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Articles by Kuldeep Dhama
Total Records ( 93 ) for Kuldeep Dhama
  Amit Kumar Verma , Kuldeep Dhama , Sandip Chakraborty , Amit Kumar , Ruchi Tiwari , Anu Rahal , Mahima and Shoor Vir Singh
  Since, last several years, efforts are going on to eradicate or eliminate a number of infectious diseases of animals, with mixed success. Basically for eradicating, eliminating or controlling any infectious disease isolation and quarantine of sick animals as well as animals suspected for disease; strengthening disease monitoring and surveillance, effective vaccines and vaccination strategies along with other control measures including of treatment are of utmost importance. Most importantly a significant knowledge is required for countering infectious diseases and assessing the criteria for selection of disease to be eradicated next. The role of environmental factors in the process of disease dynamics need to be understood which further plays a contributory role in the process of combating and elimination of diseases. Despite continuous efforts against animal diseases like Rinderpest, Contagious bovine pleuropneumonia (CBPP) and Foot-and-mouth disease, Rinderpest (cattle plague) is the only one that is successfully eradicated till date in India. However, control programmes on CBPP also brought a significant reduction in the incidence of the disease but eradication status is yet to be declared. While the other disease control programmes viz., Foot-and-Mouth Disease Control Programme (FMDCP), National Control Programme on Brucellosis (NCPB), National Control Programme of Peste des Petits Ruminants (NCPPPR) and Avian Influenza: Preparedness, Control and Containment could not achieve the desired success. Nowadays, with the achievement of the global eradication status on rinderpest there is again a renewed interest in disease eradication and control of infectious diseases of animals and alleviating their public health concerns. The focus is also being given in the 12th five year plan of the country on monitoring and control of certain animal diseases of economic importance. In view of above facts, this is right time to discuss the strategies for combating and eradicating important infectious diseases of animals with particular reference to India, achievements of global rinderpest eradication programme and reasons thereof and possibly apply lessons while planning for the future activities. This article describes various prevention and control strategies for controlling the infectious diseases of animals that have been or should be targeted for eradication or elimination, direct and indirect benefits from control programmes, issues and opportunities for the future.
  Ruchi Tiwari , Kuldeep Dhama , Sandip Chakraborty and Sanjay Kapoor
  As promising antibacterials, endolysins own several pertinent features viz., diverse novel mode of action, antibacterial spectrum, low probability of developing resistance and being highly active with explicit specificity against host bacteria. Bacteriophage endolysins are mureolytic enzymes which facilitate direct targeting of peptidoglycan bonds in the bacterial cell wall. Encoded by the bacteriophage genome they are synthesized at the end of the phage lytic life cycle, headed for lysing host cell and releasing newly produced virions. In addition to this “lysis from within”, endolysins from phages of gram-positive hosts are also able to swiftly lyse bacteria upon exogenous application. Lysozyme as well as endopeptidase like lysostaphine have been recommended in neonatal streptococcal and staphylococcal infection, respectively. Literature reveals strong potential of phage enzymes in human health care and veterinary medicine for control of pathogens and treatment of diverse systemic infections. They have wide applications in pathogen detection and development of diagnostics, as a means of biodefence, eliminating food pathogens and in control of phytopathogens. The defensins and cathelicidins can be exploited as enzybiotics among other families of antimicrobial peptide gene. In innate immunity such antibiotic peptides that are endogenous in nature play crucial role and forms first line of defense for protecting internal as well as external body surfaces of the host. The important portals of enzybiotics (EnzyBase and phiBIOTICS) are playing crucial role for disseminating the state of knowledge of enzybiotics. The present review discusses the widespread potential of various bacteriophage lysins/enzybiotics in the perspective of future antibacterial drug development.
  Thadiyam Puram Ramees , Ramswaroop Singh Rathore , Prashanth Suresh Bagalkot , Hosakote Venkatappa Mohan , Ashok Kumar and Kuldeep Dhama
  In recent years, the frequency of isolation and detection of Arcobacter organisms from animals and humans with enteritis and food samples, highlights the importance of arcobacters worldwide as emerging food-borne pathogens. Reports are very scanty regarding prevalence of arcobacters from India. Therefore, the present study aimed to know the prevalence of Arcobacter spp. (Arcobacter butzleri and Arcobacter cryaerophilus) in humans and foods of animal origin by employing cultural and multiplex PCR (mPCR) methods. A total number of 353 samples were collected from human hospitals, retail meat shops and milk suppliers [human stools (102), chicken meat (151), milk (100)] from in and around Bareilly region, Uttar Pradesh, India. By cultural method the overall prevalence rate of Arcobacter spp. was found to be 10.20% (36/353) while it was 18.13% (64/353) with mPCR which revealed mPCR to be a more efficient technique in detecting arcobacters. The highest prevalence rate was observed in chicken meat, followed by human stool and milk samples with A. butzleri having more prevalence. For simultaneous detection and differentiation of arcobacters at species level the cultural methods possess limitations while mPCR gave rapid and confirmatory detection of A. butzleri and A. cryaerophilus species. The results of the study add to the epidemiological data available for arcobacters. Extensive epidemiological studies employing the utility of mPCR are suggested for knowing the magnitude of Arcobacter infection animals, humans and various food sources in the country. This would help in designing appropriate prevention and control strategies for this important pathogen having public health concerns.
  Amit Kumar Verma , Ruchi Tiwari , Sandip Chakraborty , Neha , Mani Saminathan , Kuldeep Dhama and Shoor Vir Singh
  Bovine tuberculosis (bTB) is a zoonotic disease transmitted from animals to human and makes significant economic impacts due to high cost of eradication programs, trade restriction and serious consequences regarding public health thereby causing human tuberculosis. Mycobacterium bovis is the main etiological agent of bTB which is an acid fast staining bacterium due to waxy substance (mycolic acid) present in its bacterial cell wall. The bacteria can be transmitted by both aerogenous and enterogenous routes. Disease causes development of miliary tubercular lesions, chronic cough, obstructions of air passages and alimentary tract or blood vessels and enlargement of lymph nodes. A spectrum of Cell-Mediated Immune responses (CMI) predominate infection, projecting the role of macrophages and T-cell populations. In advanced stage, there is increased humoral response. Polymerase Chain Reaction (PCR) and real time quantitative PCR (RT-qPCR) have been widely used for the detection of M. tuberculosis complex in clinical samples. Single intradermal test, short thermal test and Stormont tests are the valuable delayed type of hypersensitivity tests. Gamma interferon assay, lymphocyte proliferation assay, Enzyme Linked Immune Sorbent Assay (ELISA), multiantigen print immunoassay (MAPIA), Fluorescent Polarization Assay (FPA), immunochromatographic lateral flow test, single antigen as well as multiplex chemiluminescence assays are the various blood-based laboratory tests. Attenuated bovine-strain of tuberculosis bacterium, known as Bacillus of Calmette and Guerin (BCG) is used as vaccine. The present review addresses important insights into the bovine TB, a complex and multi-species disease, the etiological agent, advances and trends in its diagnosis, vaccine development and treatment options and the public health significance of this important disease which would altogether help devising effective strategies for prevention and control of tuberculosis in cattle as well as in wildlife.
  Sukantu Hajra , Shoor Vir Singh , Ashok Kumar Srivastava , Sandip Chakraborty and Kuldeep Dhama
  The present study was aimed to diagnose early cases of paratuberculosis in goats by demonstration of Acid Fast Bacteria (AFB) in faecal and tissue samples; isolation of organisms from faecal and tissue samples, enzyme linked immunosorbent assay (ELISA) and patho-morphological lesions in experimental infection using “Indian Bison Type” biotype strain S-5 of Mycobacterium avium ssp. paratuberculosis (MAP). Faecal samples from 142 goats from various farm herds of North India were subjected to smear (using centrifugation and decontamination) and cultural examinations. Isolation of MAP was performed in all faecal and 74 tissue samples by inoculation on Herrold’s Egg Yolk (HEY) medium with or without Mycobactin-J after decontamination with 0.9% Hexadecylpyridinium Chloride (HPC). Experimental study was conducted on 13 young goats (10 infected, 3 controls) where pathogenicity of the strain S-5 was tested by gross and histopathological lesions and plate-ELISA test. Characteristic gross and microscopic lesions were observed at 90 Days Post Infection (DPI) and onwards. Lesions showing infiltration of macrophages with AFB without granuloma formation, simulating lepromatous form of human leprosy and typical granuloma as in tuberculoid form were observed. Positive humoral immune response was observed at 90 DPI onwards showing antibody titer above the cut off value. There was apparent linear correlation between the antibody levels and days post infection. Performance of different diagnostic tests like examination of faecal smear by direct microscopy, faecal culture, scraping smear examination for MAP from tissue, pathomorphology and plate ELISA test had linear relationship among them. Such study ultimately may help the researchers to select the specific series of tests for detection of MAP from clinical samples.
  Hosakote Venkatappa Mohan , Ramswaroop Singh Rathore , Kuldeep Dhama , Thadiyam Puram Ramees , Anil Patya , Prashanth Suresh Bagalko , Mohd. Yaqoob Wani , Kiran Narayan Bhilegaonkar and Ashok Kumar
  Arcobacter is an important emerging food and water borne pathogen having worldwide public health concern. The present study reports the prevalence of Arcobacter spp. in humans, animals and foods of animal origin based on cultural isolation, antibiogram, Polymerase Chain Reaction (PCR) and multiplex PCR detection. A total of 400 samples were collected as human diarrheal stool (50), faecal swabs of poultry (50), pig (50), cattle (50) and foods of animal origin [Raw milk (60), chicken meat (60), beef (40) and pork (40)]. The overall prevalence rate of Arcobacter spp. was found to be 6.75% (27/400) by cultural isolation with highest prevalence in pig faeces (12%), followed by cattle faeces (10%), chicken meat (10%), poultry faeces (8%), beef (5%), pork (5%), human diarrheal stools (2%) and milk (1.67%). PCR screening revealed prevalence of Arcobacter spp. to be 7.75% (31/400) with highest in pig faeces (12%), followed by cattle faeces (12%), chicken meat (11.67%), poultry (10%), beef (7.5%), pork (5%), human stools (2.00%) and raw milk (1.67%). Multiplex PCR assay enabled detection of A. butzleri (21/27) and A. skirrowii (6/27). In vitro antibiotic sensitivity profile of 27 Arcobacter isolates revealed most of these to be sensitive to azithromycin, gentamycin, nalidixic acid, kanamycin, streptomycin, ciprofloxacin and tetracycline. Higher resistance was observed for cephalothin, novobiocin and vancomycin with notable intermediately resistance against erythromycin and chloramphenicol. The present study demonstrated high prevalence of Arcobacter spp. in pig, cattle and poultry faecal samples which may play important role in contamination of environment, water and human food chain, thus could be of public health concerns. The PCR was found to be more rapid, sensitive, specific and efficient than cultural methods for detection of Arcobacter spp.
  Rekha Khandia , Sandeep Bhatia , Kh. Victoria Chanu , Richa Sood and Kuldeep Dhama
  Anthrax is a zoonotic disease and its lethality is due to two secreted exotoxins; lethal toxin and edema toxin. The receptor for anthrax toxin is called Anthrax Toxin Receptor (ATR). Two distinct cellular Anthrax toxin receptors, ANTXR1 (also known as tumour endothelial marker 8, TEM8) and ANTXR2 (also known as capillary morphogenesis protein 2, CMG2) have been identified. TEM8 and CMG2 both are ubiquitous in nature. Apart from their function as anthrax toxin receptor, their ubiquitous presence is suggestive of their physiological role. TEM8 is preferentially expressed in blood vessel of tumours and in vasculature, indicating its probable role during angiogenesis and regulation of neovasculature. CMG2 is present in capillary cells and is associated with capillary morphogenesis. Both the TEM8 and CMG2 are present in different isoforms, share homology in amino acid residues and apart from their role in angiogenesis regulation, are also involved in interaction with extracellular matrix. Mutation in TEM8 result in a condition appeared to alter physical characters in form of growth retardation, alopecia, pseudoanodontia and progressive visual impairment known as GAPO syndrome. Mutation in CMG2 result in autosomal recessive disorder in humans called Hyaline Fibromatosis Syndrome (HFS) and Infantile Systemic Hyalinosis (ISH). Because of the role in physiological functions and participation as toxin receptor, these receptors could be target for several curative therapies both for the anthrax disease as well as for receptor associated physiological disorders. This review presents a detailed insight into isoforms, functions, diseases and therapeutic implications of anthrax toxin receptors.
  Sartaj Ahmad Bhat , Mohd Yaqoob Wani , Jatinder Kumar Khojuria , Rajesh Katoch and Kuldeep Dhama
  Backyard poultry farming plays an important role in rural people by providing eggs, meat and employment. The production of backyard poultry is generally affected by ecto and endo-parasites due to their free range feeding habit and housing practices. The present study was designed to study the prevalence of ectoparasites in back yard poultry in Jammu region of India during October 2010 to September 2011. The results showed that out of 710 birds examined, 373 (52.53%) were found infested with different ectoparasites. The highest prevalence was recorded for Menopon gallinae (16.05%) followed by Menacanthus stramineus (12.95%), Goniocotes gallinae (9.58%), Goniodes gigas (5.91%), Lipeurus caponis (2.95%), Argas persicus (3.38%) and Dermanyssus gallinae (1.69%). Seasonal prevalence indicated, Menopon gallinae was predominant in all seasons except in pre monsoon, highest during winter and lowest during post monsoon. While Menacanthus stramineus had the highest prevalence during pre monsoon, Argas persicus during monsoon and Dermanyssus gallinae had the lowest prevalence during all the seasons. The study is first in its nature from Jammu, the north Indian region and will provide valuable information on ectoparasites in back yard poultry. However, further investigation is required in this regard so as to reduce the production losses by ectoparasites.
  Mahmoud Mohamed Alagawany , Mayada Ragab Farag and Kuldeep Dhama
  The present study was planned to evaluate the effects of turmeric (Curcuma longa) for protection against alterations resulted from exposure to endosulfan in broiler chicks. A total of 180 day old chicks were divided into 6 groups of 30 chicks with 3 replicates. First group was fed basal diet while the other five groups were fed basal diet supplemented with 5 g turmeric, 10 g turmeric, 30 mg endosulfan, 30 mg endosulfan plus 5 g turmeric and 30 mg endosulfan plus 10 g turmeric/kg diet during the experimental period. Growth performance, carcass traits, blood parameters, oxidative status and viability of the broilers chicks were used as criteria of response. The results showed that endosulfan significantly decreased the levels of Total Protein (TP), albumin (ALB), globulin (GLB), HDL-cholesterol, catalase (CAT), superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration but significantly increased albumin/globulin (A/G) ratio, total cholesterol (TCHO), LDL-cholesterol, triglyceride (TRG), malondialdehyde (MDA) concentration and hepatic transaminases (alanine amino-transferase, ALT and aspartate amino-transferase, AST) and exhibited different alterations to the hepatic structure in comparison with control and both turmeric groups. Dietary supplementation of turmeric at different levels could ameliorate these effects but not restored to control level. It is recommended that regular consumption of turmeric in the diet of broiler chicks provides a constant supply of potential antioxidants that could reduce these alterations.
  Dharmender Singh , Yashpal Singh Malik , Kuldeep Sharma and Kuldeep Dhama
  In this study we performed the sequence and phylogenetic analysis of peste des petits ruminants (PPR) virus isolates recovered from natural disease outbreaks in goats of central India. A total of 58 clinical samples comprised of blood, nasal/oral/rectal swabs were collected from 3 natural PPR disease outbreaks. The samples were tested by using N protein based MAb based sandwich ELISA (sELISA) and subsequently RT-PCR targeting Fusion (F) and Nucleoprotein (N) genes of PPR virus. The F and N gene specific PCR amplicons were sequenced and assessed for sequence variations with existing and circulating PPR virus strains and vaccine isolates. The results of this study presents PPR virus antigen in 48.27% clinical samples (28/58) using sELISA confirming this outbreak of PPR in goats. Amplification with primers F1/F2 for F gene yielded an expected amplicon of 372 bp and N1/N2 primer sets yielded an amplicon of 463 bp for N gene in reference vaccine virus as well as 28 field samples. In phylogeny, different patterns of branching based on N and F gene sequences and clustering of many of the central Indian PPR virus isolates with isolates from bordering countries was seen. The results confirm that heterogeneous population of PPR virus isolates is circulating in India which moreover emphasize the significance of molecular methods to understand the epidemiology and diversity of PPR virus in the country. The information from such studies will help in achieving the target of controlling and eradicating the disease, especially when the country is planning to launch the control programs in many states after the successful stamping out of the Rinderpest.
  Brajesh Singh , Mukta Jain , S.V. Singh , Kuldeep Dhama , G.K. Aseri , Neelam Jain , Manali Datta , Neeraj Kumar , Parul Yadav , Sujata Jayaraman , Saurabh Gupta , Kundan Kumar Chaubey and Jagdip Singh Sohal
  Mycobacteria are dreadful human and animal pathogens causing range of mycobacterioses in different tissues. Due to their cell wall composition and their adaptability mycobacteria can survive in different habitats for years. Emergence of Multi-drug Resistant (MDR) and extensively drug resistant (XDR) strains has complicated the problem of mycobacterial disease control. Therefore new drugs should evolve to fight drug resistance. Medicinal plants may offer a new hope as source of bioactive molecules for developing alternative medicines for the mycobacterial diseases. Presently used anti-mycobacterial medicines produce serious side-effects and cannot be used in animals because of risk of entry into food chain. Plant derived medicines may help solving this problem and fighting the drug resistance. The present study reviews the literature available on anti- mycobacterial plants and their bioactive molecules with hope that this effort will expedite the research on development of a novel plant derived drugs against mycobacterial diseases.
  B.J. Stephen , S.V. Singh , Manali Datta , Neelam Jain , Sujata Jayaraman , K.K. Chaubey , S. Gupta , Manju Singh , G.K. Aseri , Neeraj Khare , Parul Yadav , Kuldeep Dhama and J.S. Sohal
  Tuberculosis, an infectious bacterial disease that affects the lungs is caused by Mycobacterium tuberculosis (MTB). It is the second most infectious disease after AIDS, which can affect both animals and humans. Johne’s Disease (JD) or paratuberculosis caused by in intracellular bacterium Mycobacterium avium subspecies paratuberculosis (MAP) is an incurable wasting disease known to affect a large number of domestic animals and poses serious threat to livestock industries through huge economic losses. Conventional diagnostic methods like enzyme linked immunosorbat assay (ELISA), Polymerase Chain Reaction (PCR), cultural isolation are identification for use in MAP detection while sputum smear microscopy and PCR techniques remain the gold standards for TB detection despite advancement in pathogen detection most of these diagnostic methods are time consuming and have low efficacy and this become a heavy burden to developing and underdeveloped countries. When nanoscale particles are used as tags or labels, measuring the activity or presence of an analyte becomes faster, flexible and highly sensitive. These advantages nanomaterials possess, research have now focused their attention to nanotechnology based detection. Though research have shown these test to be more sensitive, less laboratorious and less time consuming, more needs to be done to introduce point of care diagnostics into the global market. This review highlights the prospects of nanotechnology based diagnostic tests as valuable alternative for rapid detection of this economically important pathogen with high accuracy and precision.
  Tarun Kumar Sachan , Virendra Kumar , ShoorVir Singh , Saurabh Gupta , Kundan Kumar Chaubey , Sujata Jayaraman , Mukesh Sikarwar , Sunil Dixit and Kuldeep Dhama
  Mycobacterial biofilm is a structured community of bacterial cells enclosed in a self-produced polymeric matrix and adherent to an inert or living surface, which constitutes a protected mode of growth that allows survival in hostile environment. Biofilms can be defined as communities of mycobacteria attached to a surface. It is clear that microorganisms undergo profound changes during their transition from planktonic (free-swimming) organisms to cells that are part of a complex, surface-attached community. These changes are reflected in the new phenotypic characteristics developed by biofilm mycobacteria and occur in response to a variety of environmental signals. The biofilm-forming microorganisms have been shown to elicit specific mechanisms for initial attachment to a surface, formation of micro colony leading to development of three-dimensional structure of mature biofilm. They differ from their free-living counterparts in their growth rate, composition and increased resistance to biocides, antibiotics and antibodies by virtue of up regulation and/or down regulation of approximately 40% of their genes. This makes them highly difficult to eradicate with therapeutic doses of antimicrobial agents. A greater understanding of mechanism of their formation and survival under sessile environments may help in devising control strategies.
  Rakesh Kumar , Shailesh Kumar Patel , B.V. Rami Reddy , Mukesh Bhatt , K. Karthik , Ravi Kumar Gandham , Yashpal Singh Malik and Kuldeep Dhama
  The normal cell has its own homeostatic mechanism. A slight deviation in this mechanism leads firstly to an adaptive response in the form of hypertrophy, atrophy etc. But sometimes when adaptive response exceeds a limit also culminates to cell injury which ultimately leads to cell death. Irreversible form of cell injury leads to cell death in the form of necrosis, apoptosis and autophagy and by other alternative ways of necroptosis, anoikis, entosis and cornification. Necrosis and apoptosis are main mechanisms of cell death in mammalian cells. Necrosis is accidental, uncontrolled and un-programmed cell death which leads to cellular swelling, pyknosis, karyolysis, karyorrhexis, disruption of cell membrane and inflammation. Apoptosis is a programmed and energy dependent pathophysiological phenomenon leading to cellular shrinkage but no cell membrane rupture and no inflammatory response. Apoptosis can be mediated by extrinsic, intrinsic and perforin/granzyme pathways, leading to activation of execution caspases and finally protein cleavage, cross linking and DNA-fragmentation. Extrinsic pathway involve ligand (FasL, TNFα) and receptors (FasR, TNFR) interaction which bind to adapter proteins Fas Associated Death Domain (FADD) and TNFα Receptor Associated Death Domain (TRADD) with activation of initiator caspases-8. Intrinsic pathway involves cytochrome c release along with pro-apoptotic proteins and inhibits anti-apoptotic proteins, leads to cytochrome c interaction with Apaf-1, thus activation of pro-caspase-9. Overall, cell death have clarified many aspects of this fundamental process and brought to the attention of scientists its role in a large number of different diseases. The present review describes apoptosis and other alternate mechanisms of cell death with biomedical and veterinary perspectives.
  Mohamed Ezzat Abd El-Hack , Mahmoud Alagawany , Mayada Ragab Farag and Kuldeep Dhama
  Distiller’s Dried Grains with Solubles (DDGS) as untraditional feedstuff has been available for feed industry for many years and became a nutritional and economical feed ingredient. According to recent studies, DDGS is usually used at low concentrations (10 or 15%) as a feed ingredient in laying hen diets without adverse effects on laying performance, feed utilization, nutrient digestibility, egg quality criteria and economics. Because DDGS became available in feed market in large amounts, the ability of using higher DDGS inclusion rate in poultry feed has become an interest for several researchers and poultry producers. Using such untraditional feedstuffs aims mainly to decrease the feed costs. Researchers assured that feeding higher levels of DDGS could have a significant effect on the cost of feed for poultry producers because of higher availability of DDGS and the current price fluctuations of feed ingredients. On the other hand, beneficial effects of DDGS on the environment have also been reported. These beneficial effects could be represented through mitigating harmful emissions and pollution from manure which provides production within clean atmosphere. Findings from different researches on the use of DDGS as feed ingredient for laying hens are illustrated in this review. Moreover, this study describes advanced information regarding the use of corn DDGS as untraditional feedstuff for laying hens involving its production process and nutritive value along with its useful effects on laying hens production traits, egg quality, apparent digestibility, economics and the impact on the surrounding environment in poultry house.
  Kundan Kumar Chaubey , Shoor Vir Singh , Saurabh Gupta , Sujata Jayaraman , Manju Singh , Bjorn John Stephan , Krishna Dutta Rawat , Anjali Pachoori , Kuldeep Dhama and Ashok Kumar Bhatia
  Cross reactivity of three antigens of Mycobacterium avium subspecies paratuberculosis with sera of sheep endemic for Johne’s disease was evaluated. Out of 40 sheep tested by fecal microscopy, 72.5% were shedding MAP. Using protoplasmic antigens (PPA) from three MAP strains isolated from different livestock species and geographical regions, 90, 77.5 and 2.5% sheep were positive in goat (Indigenous g-ELISA) and cattle (b-ELISA) based ELISA kits and ELISA kit for small ruminant (sr-ELISA), respectively. Only 2.5 and 10% sheep were positive and negative in all the four tests. Native species specific (goat origin novel ‘Indian Bison Type’ MAP) semi-purified whole cell PPA based ELISA (Indigenous g-ELISA) was superior in reacting with sera of native sheep than the commercial PPA of bovine origin (Allied Monitor Inc., USA) and commercial ELISA kit for small ruminants (ID Vet, France). Lower cross reactivity of antigens originated from US and France emphasized the need to develop tests based on local strain of MAP than strains from different livestock species and geographical regions. This is an important finding against the use of ‘Global kits’ without validating in local conditions. Study showed that kits developed from local strains of MAP were not only superior but also cost effective and will significantly contribute in programs for the control of JD in native sheep population.
  B.J. Stephen , Mukta Jain , Kuldeep Dhama , S.V. Singh , Manali Datta , Neelam Jain , Sujata Jayaraman , Manju Singh , K.K. Chaubey , S. Gupta , G.K. Aseri , Neeraj Khare , Parul Yadav and J.S. Sohal
  Johne’s Disease (JD) is a contagious fatal granulomatous enteritis, known to affect ruminants and is caused by the acid-fast Mycobacterium avium subspecies paratuberculosis (MAP). The bacterium has also been linked to Crohn’s Disease (CD) in humans. Treatment options are scarce with culling practiced in the case of Johne’s Disease (JD) and administration of anti-inflammatory drugs for pain and inflammation in case of CD. In both cases antimicrobial therapy against MAP does not have the ultimate potential. The very promising, yet untapped potential of nanotechnology offers a suitable platform for developing new therapeutic strategies for diseases caused by the bacteria. Uniformity, specificity and reproducibility are some of the characteristics of nanotechnology that can be exploited for the treatment of infectious diseases. Factors like cost, efficacy, safety and bioavailability of drugs can be greatly improved when the drugs are delivered with precision and at a controlled delivery rate to the target location. Nanotechnology can help in achieving these targets. This review discusses the current scenario of available therapeutic approaches and proposes drugs targeting strategies and vaccine development methods for the treatment and prevention of MAP related diseases.
  Shoor Vir Singh , Sachin Digambar Audarya , Manju Singh , Bjorn John Stephen , Daljeet Chhabra , Kundan Kumar Chaubey , Saurabh Gupta , Sahzad , Anjali Pachoori , Sujata Jayaraman , Gajendra Kumar Aseri , Jagdip Singh Sohal , Ashok Kumar Bhatia and Kuldeep Dhama
  Johne’s disease is endemic in the domestic riverine buffalo population of the country and bio-load of Mycobacterium avium subspecies paratuberculosis is increasing in the absence of indigenous diagnostic kits and control programs. A new ‘dot-ELISA kit’ has been developed and validated with indigenous plate ELISA for the screening of buffaloes against Johne’s disease. Out of 156 serum samples screened 41.0 (64), 85.8 (134) and 85.2% (133) were positive for MAP infection by indigenous plate ELISA kit condition (A), condition (B) and indigenous dot ELISA, respectively. Dot-ELISA kit detected 85.2 (133) and 90.3% (141) buffaloes as positive together with indigenous plate ELISA kit in condition A and B, respectively. Comparison of ‘Indigenous plate-ELISA’ with ‘Indigenous dot-ELISA’ revealed substantial agreement between two tests. Study showed that ‘Indigenous dot-ELISA test’ has potential to be sensitive and cost effective ‘Field based herd screening test’ for the large scale screening of the domestic livestock population against Johne’s disease. The study also showed that despite high slaughter rate, incidence of Johne’s disease was high in native population of riverine buffaloes (Bubalus bubalis) and call for immediate control of disease.
  Sana Ullah , Maryam Begum , Kuldeep Dhama , Saeed Ahmad , Said Hassan and Ibrar Alam
  The current study was aimed to investigate the genotoxic effect of an organophosphate pesticide malathion in the gills of a freshwater teleost rohu, Labeo rohita using alkaline Single Cell Gel Electrophoresis (SCGE)/comet assay. The 96 h LC50 of malathion was estimated for rohu in a semi-static system and was found to be 5 μg L–1. Specimens of rohu were exposed to LC50 of malathion. Gill tissues were sampled after 24, 48, 72 and 96 h of exposure. DNA damage was evaluated by studying different indices, including tail length (μm), percentage of DNA in tail, tail moment and olive tail moment using TriTek CometScoreTM. A linear relation was observed between exposure time and DNA damage in the gill cells. The current study revealed malathion as a potent inducer of DNA damage and comet assay as a reliable and sensitive assay for investigating and detecting DNA damage in vivo, induced in fish by genotoxic pesticides. In order to conserve the vanishing populations of rohu in natural aquatic bodies across the country, indiscriminate use of genotoxic pesticides such as malathion should be minimized.
  Ahmed Abdelbaset-Ismail , Mudasir Bashir Gugjoo , Alaa Ghazy , Mohamed Gomaa , Ahmed Abdelaal , Amarpal , Ahmed Behery , Abdel-Basit Abdel-Aal , Mohamed-Tayiser Samy and Kuldeep Dhama
  There is no doubt that the donkey, as a drafting animal, plays a critical role in the developing communities for both agriculture production and riding purposes. Therefore, to maintain healthy skeleton in these animals, the understanding of radiographic anatomy of ossification centers and growth plates (locations, types and closure times), need to be advanced. It is imperative that an appropriate maturation point is reached to avoid early overexertion of the donkey and the resulting irreparable damage. It is therefore the aim of this review is to highlight the importance of expanding the limited dataset on epiphyseal growth plate maturation and begin to define its ossification times in the donkey. Moreover, it has been recently proposed that the receptors of gonadal sex hormones including estrogen androgen as well as pituitary sex hormones including luteinizing hormone and prolactin are localized in human and animal growth plates. This indicates that these hormones actively participate in the chondroregulation mechanisms at the ossification growth plates. A connection with that, we noticed that the more primitive stem cells as well as hematopoietic stem cells and mesenechymal stem cells express these receptors as well. Therefore, it would be very interesting to address the link between sex hormones and ossification time of growth plates, as well as the sharing activities of these stem cells during the ossification process.
  Rekha Khandia , Pratibha Vishwakarma , Abhinav Dwivedi , Anshumala Kujur , Kuldeep Dhama and Ashok Munjal
  Objective: Angiogenesis plays critical and essential role in various physiological processes of animals and humans. Present study reports the potential angiogenic modulatory effects of the two different molybdenum salts [molybdenum trioxide (MoO3) and sodium molybdate dihydrate (Na2MoO4.2H2O)] on chorioallantoic membrane (CAM) of embryonated chicken eggs. Methodology: The three groups of the embryonated chicken eggs (1 control and 2 treated groups) were taken and 200 μL of 0.5 M of each of MoO3 and Na2MoO4.2H2O were directly introduced on to the CAM. The resealed eggs were incubated for 72 h in a humid incubator chamber at 37±1°C. Then the eggs were opened to observe the gross and histopathological alterations for angiogenesis modulation. Results: Gross examination revealed reduced number of secondary and tertiary blood vessels in MoO3 treated group, while Na2MoO4.2H2O treated group showed reduction in number of blood vessels with occasional haemorrhages. Histopathological analysis indicated pro-angiogenic effect of MoO3, with presence of numerous mesodermal blood vessels with normal CAM tissue architecture. However, Chorionic Ectoderm (CE) was absent at few places, with intact CE at most places, indicating requirement of critical dose optimization. The Na2MoO4.2H2O was observed as anti-angiogenic, causing inflammation in CAM tissue with hemorrhage and thus can’t be used for therapeutics. Conclusion: The pro-angiogenic properties of MoO3 can be explored to treat ailments related to insufficient angiogenesis like coronary artery disease, chronic wounds, stroke and myocardial infarction. However, to avoid any kind of side effects, further qualitative and quantitative analysis and critical dose determination is required before going for clinical trials.
  Mayada Ragab Farag , Mahmoud Alagawany and Kuldeep Dhama
  Objective: The present study was designed to investigate the hepatic and renal toxicity of acephate (ACE) insecticide in broiler chicks by studying the hematological, biochemical, oxido-inflammatory and pathological changes after subacute exposure to ACE in diet and to evaluate the modulatory role of flaxseed oil (FSO) on these changes. Materials and Methods: Two hundred and forty day-old un-sexed broiler chicks (average body weight of 45.52±0.25 g) were randomly assigned into 4 groups with 4 replicates of 15 chicks based on a completely randomized design. The first group was fed a basal diet, 2nd group fed basal diet supplemented with 85.2 ppm acephate, while the 3rd group fed basal diet supplemented with 1000 ppm flaxseed oil, while the 4th group fed basal diet supplemented with 85.2 ppm ACE+1000 ppm FSO for 4 weeks. Results: The ACE significantly (p<0.05) decreased hemoglobin content, erythrocytic count and packed cell volume while increased white blood cells, lymphocyte and granulocyte counts. Moreover, there was a significant increase in lipid profile (total cholesterol, LDL and triglyceride) and serum biomarkers related to hepatic and renal functions including aspartate transaminase (AST), alanine aminotransferase (ALT), urea and creatinine with no change in alkaline phosphatase (ALP) and albumin while, serum total protein, globulin and HDL-cholesterol levels were significantly reduced with ACE group in comparison with other treatment groups. The ACE significantly (p<0.05) decreased the antioxidant capacity of liver and kidney and increased lipid peroxidation, interleukine-2 (IL-2) tumor and necrosis factor-alpha (TNF-α) in the two organs while increased the activity of cytochrome P450 in liver only. Diet supplemented with FSO showed promising modulatory effects on these undesirable changes however, some did not restored to normal levels. Conclusion: It is recommended to use FSO regularly as a dietary supplement for broiler chicks to provide them powerful antioxidants required to protect these birds against environmental pollution.
  Ahmed Abdelaal , Ahmed Abdelbaset-Ismail , Mohamed Gomaa , Shaimaa Gouda and Kuldeep Dhama
  Background and Objective: Diagnosis of the internal abscesses is important to relieve the cost burden on animals’ owners that comes from long duration of unspecific and conservative medications and to nourish the animals welfare and hence their productivity. Therefore, this study aimed to evaluate the role of ultrasound, as non-invasive and decision-making tool, in addressing this issue. Materials and Methods: Nineteen buffalo cases were employed in this study and subjected to critical clinical and ultrasonographic examination: pre- and post-therapeutic interventions. Results: Emaciation, inappetance, scanty feces, ruminal atony, systemic disturbances and dull demeanor were found general clinical findings. Specifically, recurrent tympany and abdominal pain (n = 9; 47.4%) and abdominal distension (n = 2; 10.5%) were observed in abdominal abscesses, while respiratory manifestations (n = 6; 31.6%) and cardiac manifestations (n = 4; 21.1%), were recorded in thoracic abscesses. Ultrasonographically, abdominal (n = 13; 68.4%) and thoracic (n = 6; 31.6%) abscesses were diagnosed and the treatment strategies were consequently determined. Of 19 cases, 10 animals (52.6%) were of bad prognosis and advised to undergo slaughter, 6 cases (31.6%) were locally and systemically treated and 3 buffaloes (15.8%) were only subjected to systemic treatment. Of 9 treated animals, 4 cases (44.4%) responded and showed a clear improvement post-treatment. Conclusion: This study concludes that abdominal and thoracic ultrasound is a beneficial tool in diagnosis of buffaloes in which the internal abscessations are obscured. Additionally, it could efficiently provide clinicians with the therapeutic decision for a proper and economical intervention.
  Mahmoud Alagawany , Mohamed Ezzat Abd El-Hack , Mayada Ragab Farag , Ruchi Tiwari , Swati Sachan , Kumaragurubaran Karthik and Kuldeep Dhama
  Protein plays an important role in the diet formulation of poultry to maintain/improve growth, feed utilization, immune functions and maximize productive performance, ensure bird welfare, as well as mitigate environmental risks and pollution by optimizing the use of this nutrient. Also, proteins assist in the biosynthesis of tissues and have many biological functions for growth and renewal of the body. Moreover, proteins exist in forms of hormones and enzymes which play crucial roles in the physiological processes in the body. Layer birds have low dietary Crude Protein (CP) requirements, thus identification of the optimum level of CP in layer diets, for either maximizing productive performance or economic returns of laying hens, requires more and more information/knowledge about birds needs of protein and its impacts on performance parameters and environmental pollution. This biomolecule plays active role in physiological dynamics, in stabilizing the immune barrier and to drive the forces for maintaining the enhanced production performance of layers. The broad goal of the current review is to highlight the importance of CP-diet and its positive and negative effects on body weight change, performance, feed and nutrient utilization, egg production parameters, egg quality criteria as well as chemical composition of egg and its fractions, egg shell quality, blood biochemical parameters, immune function, nutrient digestibility and nitrogen pollution. The discussed concepts and knowledge would be useful for both backyard poultry rearers and poultry industry holders by optimizing the level of crude protein in the fed diet and will definitely be helpful for gaining the economic profits and consumers satisfaction.
  Mani Saminathan , Ram Bahal Rai , Kuldeep Dhama , Ruchi Tiwari , Sandip Chakraborty , Amarpal , Gopikunte Jayaramaiah Ranganath and Kandasamy Kannan
  The miracle medicinal plant Morinda citrifolia L., also called as Noni, Great Morinda or Indian mulberry, belongs to the family Rubiaceae. Its fruit has been used traditionally for more than 2000 years by native Polynesians. However, all parts of the plant have medicinal properties. More than 160 phytochemicals have been isolated from the plant Noni which makes it an amazing herbal remedy for the treatment of numerous disorders including cancer. Recently, the Noni juice has been in high demand in market as Complementary and Alternative Medicine (CAM) for its multi-dimensional health benefits. It is a potent antibacterial, antiviral, antifungal, antihelminthic, anticancer, analgesic, anti-inflammatory, anti-oxidant, hypotensive, cardiovascular protective, wound healer, anxiolytic, sedative, antigout, antiobesity and immune enhancing agent. Anticancerous activity of Morinda citrifolia is attributable to its anti-inflammatory, antioxidant and apoptosis-inducing effects. Based on toxicological and mutagenicity assessment, Noni juice has been considered as safe. Few reports of hepatotoxicity exist, although there are many evidences suggesting hepatoprotective effects of Noni. Even though large number of in vitro studies has been carried out but only few clinical trials exist in the literature to suggest real beneficial effects of Noni in humans. Recently, Noni fruit juice has been accepted as a novel food element in the European Union. A number of scientific studies have been conducted to elucidate the mechanism of action of phytoconstituents of Noni. In this review, active phytochemical constituents, pharmacological properties, mechanism of action and various immunomodulatory and therapeutic potentials of Noni usage as a useful herbal medicine are discussed in detail which could be very helpful in safeguarding health of humans and their companion animals. A special focus has been made on the potent utility of this wonderful herbal plant in preventing and treating the deadly malady of cancer.
  M. Yaqoob Wani , Tapas Kumar Goswami , Raies Ahmad Mir , Pallab Chaudhuri and Kuldeep Dhama
  Gram negative sepsis and septic shock are among the leading causes of death, both in humans and animals. Statins, 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase inhibitors are said to have immune modulating effects. In the present study, it was hypothesized that amelioration of hyper immune activation by pravastatin can improve the immunoapthological status of acute sepsis. Pasteurella multocida Pm52 strain was used as a source of Lipopolysaccharide (LPS) and the pathogenic organism for induction of septicaemia in mice. In vitro trials showed that LPS extracted from P. multocida stimulated Nitric Oxide (NO) production in time and dose dependent manner in Mouse Embryonic Fibroblast (MEF) cultures. Addition of pravastatin to MEF culture supernatant significantly reduced Pm52 LPS induced NO production (p<0.05). In vivo studies showed that administration of pravastatin in combination with cefotaxime to P. multocida induced septicaemic mice significantly increased both mean survival time and survivability percentage compared to antibiotic and pravastatin treatments regimes. Furthermore, the serum TNF-α : IL-10 levels were significantly improved and near to normal healthy ratios in septicaemic mice treated with pravastatin+cefotaxime combination at 24 h post infection. Gross and histopathological findings revealed moderate lesion in pravastatin treated mice as compared to untreated and cefotaxime alone treated groups. The findings conclude that pravastatin stabilizes the immune compromised status of the septicaemic animals during early septic stages by stabilising the NO production, regulating the TNF-α: IL-10 ratio and reducing histopathological lesions. Although the mortality was not prevented, the immunopathological signs were ameliorated to a greater extent by this new treatment combination, further investigations are suggested to explore its possible therapeutic utility against sepsis and for septicaemic patients.
  Kuldeep Dhama , Ruchi Tiwari , Sandip Chakraborty , Mani Saminathan , Amit Kumar , K. Karthik , Mohd. Yaqoob Wani , Amarpal , Shoor Vir Singh and Anu Rahal
  Owing to rising incidences of antimicrobial resistance against various chemotherapeutic and antimicrobial agents, the treatment of bacterial infections requires special consideration that may otherwise lead to grave prognosis. Simultaneously, evolution of many a Multiple Drug Resistant (MDR) bacterial strains have further aggravated the present situation. In this scenario, scrutinizing for some alternative yet effective antibacterial therapeutics like herbs, nutritional immunomodulators, bacteriophages, avian egge antibodies and others have become need of the day. Herbs have been a valuable source of medication in virtually all cultures and societies worldwide due to their important antimicrobial principles and phytoconstituents and wider therapeutic potentials. As various extracts of herbs and medicinal plants are being reported with antibacterial activities, much effort should be made in their identification, studying biologically active ingredients, efficacy and potency testing and scientific validation for their significant and practical multi-beneficial uses. The present review elaborates the potential role and applications of several herbs in treating bacterial infections and various types of bacterial diseases for safeguarding health of humans and their companion animals. It highlights the salient beneficial applications of traditional herbs and novel phytomedicines, from ancient periods to modern usages. Due emphasis has been given regarding scientific approaches to be followed and future perspectives with a vision to counter the emerging antimicrobial resistance. The review will certainly promote and popularize herbs as alternatives to conventional antimicrobials, particularly in the event of emerging MDR bacterial infections. Global usages of herbs as alternative and complementary medicines to various antimicrobials would lead not only to safeguard health issues and obtain optimum production from animals but will also ensure the public health issues including of food safety concerns viz., antibiotic residual effects in animal products (milk, meat) and zoonotic threats.
  Mani Saminathan , Ram Bahal Rai , Kuldeep Dhama , Babu Lal Jangir , Subramaniyam Suresh , Gopikunte Jayaramaiah Ranganath , Inbaraj Sophia , Kuppusamy Karuppanasamy , Singaram Barathiraja and Arumugam Gopalakrishnan
  N-Methyl-N-Nitrosourea (NMU) is a highly specific mammary gland carcinogen that act directly and does not require metabolic activation. The novel medicinal plant Morinda citrifolia, also called as Noni, has broad therapeutic effects such as antibacterial, antiviral, antifungal, anticancer, analgesic, anti-inflammatory, anti-oxidant and immune enhancing effects. The present study was conducted to assess the beneficial effects of M. citrifolia fruit juice on antioxidant, hematological and biochemical alterations caused by NMU induced mammary carcinogenesis in Sprague-Dawley rats. The rats were divided into five groups viz., vehicle control group-A (n = 8), M. citrifolia control group-B (n = 8), NMU control group C (n = 15), M. citrifolia prevention group-D (n = 15) and M. citrifolia treatment group-E (n = 15). By the end of the 28 weeks experimental period all the animals were euthanized, blood was collected by heart puncture. M. citrifolia treatment significantly (p<0.05) increased the anti-oxidant enzymes such as catalase, superoxide dismutase and significantly (p<0.05) decreased the lipid peroxidation activity when compared to NMU control group-C. M. citrifolia exhibited a preventive effect against anaemia, lymphocytosis and neutrophilia in group-D and group-E when compared to group-C. Biochemical analyses showed normal levels of enzymes of liver and kidney in M. citrifolia treated groups- B, D and E rats, whereas NMU control group-C showed significant (p<0.05) decrease in albumin and total protein levels. These findings indicate that M. citrifolia fruit juice did not show any hepatotoxic or nephrotoxic effects. It was concluded that the M. citrifolia fruit juice ameliorates the adverse effects of NMU carcinogenesis and could be useful to treat mammary tumours in humans and animals.
  Kuldeep Dhama , Ruchi Tiwari , Rifat Ullah Khan , Sandip Chakraborty , Marappan Gopi , Kumaragurubaran Karthik , Mani Saminathan , Perumal Arumugam Desingu and Lakshmi Tulasi Sunkara
  A substantial growth in poultry industry has been observed mainly due to exploitation of various modern growth promoting strategies and appropriate disease preventive and control measures. The present review describes the various essential growth promoters and novel feed supplements, their salient features, classical examples, bioactive principles, pharmacological and modes of action and useful applications for improving poultry production and health. It highlights antibiotics, probiotics, prebiotics, synbiotics, organic acids, vitamins and minerals, oils, enzymes, amino acids, betaine, carnitine, L-arginine, ractopamine, nucleotides, electrolytes, herbs, panchgavya elements. Apart from boosting poultry production and safeguarding general health of birds some of these have been found to possess beneficial immunomodulatory and stress relieving properties and also have added advantages to help produce lean meat and designer poultry products taking into account health awareness and preferences of the consumers. It is a comprehensive and an updated review compilation focusing the salient aspects of various important growth promoters and feed additives having potential applications to promote poultry production and health. Due care has been taken to cover the ongoing trends and recent advances with a perspective vision and their holistic usages and beneficial applications in poultry production system. The contents of the review will be highly useful for researchers, scientists, pharmacists, veterinary professionals, pharmaceutical industries, poultry producers/owners and poultry industry as well as for perspective applications in livestock industry. It would enrich the knowledge of researchers and help the scientific community to conduct more research on such daily essential requirements for boosting poultry production in a better way. It will also shed light regarding the management and production aspects of poultry especially broilers which will enlighten farmers and poultry producers for better economic growth.
  Rifat Ullah Khan , Shabana Naz and Kuldeep Dhama
  Heat stress has been associated with depressed growth in meat-type birds and a decline in egg production and quality in laying hens. During heat stress, feed intake tends to decrease, thus the availability of certain important minerals is reduced. Chromium (Cr) is one such mineral which is required for maintaining growth performance in poultry due to its role in growth, metabolism and alleviation of lipid peroxidation. The available scientific literature on Cr has documented the beneficial effects of this essential mineral in improving poultry performance under conditions of environmental heat stress. In the present study, past and present information about the specific role of Cr in heat-stressed poultry is presented.
  M. Yaqoob Wani , Tapas Kumar Goswami , Divya Chaudhary , Rajendra Singh and Kuldeep Dhama
  Lipopolysaccharide is the most important component of Gram negative bacteria that activates immune system through TLR-4 pathway. In the present study, the adjuvant effects of Pasturella multocida 52 strain (Pm52) on Hen Egg-white Lysozyme (HEL) and the possible attenuation of septic signs by pravastatin were investigated. In vitro results showed that Pm52 LPS stimulates nitric oxide (NO) production from splenocytes in time and dose dependent manner where as pravastatin (10 μM) inhibited the LPS induced NO production to basal levels (p<0.05). Furthermore, presence of pravastatin (10 μM) does not inhibit the in vitro proliferative responses of splenocytes by graded doses of Pm52 extracted LPS. The co-administration of Pm52 LPS with HEL by subcutaneous route in mice significantly increased TNF-α and NO levels at 2 and 6 h, respectively, as well as the HEL specific IgG development at 14th day Post Inoculation (PI). Administration of pravastatin by intraperitoneal route significantly reduced serum TNF-α and NO levels, the pro-inflammatory mediators responsible for induction of septic shock as well as stabilized TNF-α: IL-10 ratio without affecting HEL specific adaptive immune responses. However, further studies are required in this direction to determine the long term immune modulating effects of LPS and pravastatin on the host animals so as to be used in a beneficial way.
  Rifat Ullah Khan , Shabana Naz , Kuldeep Dhama , Mani Saminathan , Ruchi Tiwari , Gwang Joo Jeon , Vito Laudadio and Vincenzo Tufarelli
  Trace elements supplementation is now widely considered not only essential but also beneficial to avian species. In the last few decades, chromium (Cr) has been considered to play important role in livestock and poultry nutrition, production and health and also as a potent toxin depending on the dosage levels. It has been documented that chromium may enhance growth rate and egg quality in meat and egg type chickens, respectively. Chromium is identified as an essential nutritional supplement and it has been utilized for weight gain, to improve Feed Conversion Ratio (FCR), increase relative organ weight, muscle development and relative breast mass, that’s why Cr has been a popular mineral supplement. It is also a potent antioxidant and hypocholesterimic agent. It increases the retention of other essential elements in blood and decreases their excretion. The beneficial effects of Cr have been linked with improved nutrient digestion and enhanced metabolism. Chromium (Cr) supplementation may improve function of various digestive organs such as liver and pancreas with regards to secretion of digestive enzymes. Supplementation of Cr has promising effects on the immune system by way of relative increase in lymphoid organ weight (bursa of Fabricius, spleen and thymus), decreased heterophil:lymphocyte ratio, enhanced antibody response against infectious diseases and increased Cell-Mediated Immune (CMI) response. In the current review some of the beneficial aspects of Cr in poultry nutrition and their possible mechanisms of actions are discussed with a view to explore and promote its optimum utilization in poultry production and health.
  Rekha Pathak , Amarpal , P. Tamilmahan , Kuldeep Dhama and Netrapal Sharma
  The ability of the osteoblasts to lay the extracellular matrix and mineralize determines the efficiency of bone formation. Vitamin D injections are used to enhance bone mineralization in clinical cases. The present study was designed to evaluate the in vitro efficacy of Vitamin D on the osteoblastic activity in both fetal and adult osteoblasts. The long bone was collected from fetal and adult rabbits and cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) containing 10% fetal bovine serum and antibiotics. The passaged cells, after attaining more than 80% confluence were induced for mineralization through osteogenic media with or without 1, 25-dihydroxyvitamin D3 (Vit D3). Fetal and adult cells were harvested after 7, 14, 21, 28 days for observation of osteoblastic differentiation and mineralization. Relative transcripts abundance of mRNA of alkaline phosphatase (ALP) and osteocalcin (OCN) were measured to assess the osteoblastic activity using quantitative real-time polymerase chain reaction (RT-qPCR) at different time intervals. The mineral accumulation was assessed by Von-Kossa staining. Fetal osteoblasts compared to adult osteoblasts showed a marked significant increase in mineralization on addition of Vit D. However, the adult osteoblasts reflected transcript abundance of ALP only after 14th day and OCN genes after 21 days post induction whereas fetal osteoblasts showed the same by 7th day post induction. This reflects a great therapeutic potential of fetal osteoblasts along with Vit D3 in bone regeneration. Further studies are required to correlate the influence of Vit D3 on ALP/OCN expression and also whether there is a comparative increase in the receptors of Vit D3 and osteocalcin protein in fetal cells as compared to adult osteoblasts.
  Mayada R. Farag , Mahmoud M. Alagawany and Kuldeep Dhama
  This study was conducted to verify whether Turmeric (Curcuma longa) has the potential to modulate the cytogenotoxic and immunotoxic effects resulting from exposure to endosulfan in broiler chicks. For this purpose, 180 one day old chicks were divided randomly into 6 groups of 30 chicks each, divided into 3 replicates. First group was fed basal diet, while the other five groups were fed basal diet supplemented with 5 g turmeric, 10 g turmeric, 30 mg endosulfan, 30 mg endosulfan plus 5 g turmeric and 30 mg endosulfan plus 10 g turmeric/kg diet, respectively, during the experimental period. At the end of the experiment, blood and spleen samples were collected and evaluated for genotoxicity, cytotoxicity and immunotoxicity biomarkers induced by endosulfan. Also, histopathological investigation of the spleen tissue was conducted. A significant increase in genotoxicity and cytotoxicity biomarkers (micronucleusfrequency, DNA fragmentation, 8-hydroxy-2-deoxyguanosine level (8 OHdG) and lactate dehydrogenase activity (LDH)) was recorded in endosulfan treated chicks. In addition, the immunotoxicity biomarkers showed a significant decrease in phagocytic percentage, stimulated Nitric oxide (NO) production and decrease in the serum lysozyme activity. Histopathological findings supported the cytotoxicity results. Dietary supplementation of turmeric at different levels ameliorated deleterious effects of endosulfan and restored them to be near control level. The results of the study suggested that regular consumption of turmeric in the diet is a promising approach in attenuating the disturbances induced by endosulfan in the most studied biomarkers.
  Mahmoud M. Alagawany , Mayada R. Farag , Kuldeep Dhama , Mohamed E. Abd El-Hack , Ruchi Tiwari and Gazi Mahabubul Alam
  The polyphenol resveratrol is an antioxidant nutrient, used to enhance growth performance through activation and modification of gut function and structure and to inhibit cancer initiation and promotion. The main application of resveratrol is in animal and poultry nutrition, in particular as a feed additive to reduce free radicals in a wide variety of animal species. Several studies carried out on diets supplemented with additives containing natural antioxidants as resveratrol demonstrated its capability to improve the productive performance, immune response and health of livestock besides reducing the risks of various animal diseases such as cancer and other degenerative diseases. Such activities could be attributed to its powerful antioxidant, immunomodulatory and anti-inflammatory effects by preventing free radicals from interacting with cellular DNA and its ability to alter the intestinal microbiota, increased digestibility and absorbance of nutrients. This review describes the modes of action, metabolism, the biological activities, natural sources and beneficial aspects/potential applications of resveratrol in animal and poultry nutrition, production and health.
  Kuldeep Dhama , Shyma K. Latheef , Saminathan Mani , Hari Abdul Samad , K. Karthik , Ruchi Tiwari , Rifat Ullah Khan , Mahmoud Alagawany , Mayada R. Farag , Gazi Mahabubul Alam , Vito Laudadio and Vincenzo Tufarelli
  Herbal medicine or herbalism is a time-honored practice of natural medicine that is older than mankind itself. The practice of using traditional herbal medicine based therapy is nowadays gaining more attention worldwide in both human and animal health care systems. Among the livestock sectors, poultry production systems are the most intensively reared with developments especially in the areas of nutrition, disease control, genetic improvement, management and organization of dietary requirements along with the pressure of increasing demand for poultry products as well as threats of emerging pathogens. So this sector is badly in need of sustainable therapeutic and production aids especially based on herbs because of the advantages like, low cost, easy availability, no residual effect, free from the threat of antibiotic resistance etc. Many herbs have been recorded to be fruitfully used by veterinarians to treat a variety of disease conditions in animals. The present study discusses the various useful and practical applications of the rich heritage of herbal wealth for safeguarding poultry health in general, combating infectious as well as non-infectious diseases caused by microbes and parasites )both ecto-and endo parasites( along with immunomodulatory actions for countering immunosuppressive diseases. Moreover, highlighting herb-based poultry growth promoters for increasing production performances use of herbs as antioxidants and their role in organic egg and meat production is a special attraction of the review that will draw the attention of the poultry specialists as well as farming community. The information will be useful to increase poultry production and protect the health of birds in a better way from traditional ways towards modern perspectives and also would promote and popularize usage of herbs amongst poultry producers.
  Kuldeep Dhama , Mani Saminathan , Siju Susan Jacob , Mithilesh Singh , K. Karthik , Amarpal , Ruchi Tiwari , Lakshmi Tulasi Sunkara , Yashpal Singh Malik and Raj Kumar Singh
  In veterinary and medical sciences, immunomodulation is an area wherein extensive studies have been conducted to devise methods to improve disease resistance as well as to prevent or control immune disorders of host by optimum regulation of the immune system. Today, most infectious diseases of man and animals are treated and controlled mainly by using broad-spectrum antibiotics and vaccines. However, the antibacterial agents are becoming increasingly ineffective due to rapid emergence of resistant microbial strains. So, there is high requirement for novel and improved alternative therapeutic and prophylactic strategies to manage several diseases which are flaring at alarming pace because of the increase in international traffic, globalization and changing food habbits. Immunomodulation is focused on manipulation of immune system to control the infections and other adverse health effects with precise regulation to avoid any complications while suppressive or potentiating efforts are made to benefit the animal and human health. The main aim of this review is to give a closer insight into the potential immunomodulatory molecules, synthetic and natural, that are capable of modifying the immune responses including conventional and novel immunomodulators like adjuvants, cytokines, hormones, glucocorticoids, host defense peptides, microbial products, toll like receptors, synthetic compounds, probiotics, nutrients, vitamins, minerals, herbs, panchgavya, polysaccharides, helminths, vaccines and others. These immunomodulatory regimens could successfully offer the health industries with the most natural methods for enhancement of disease resistance, boosting vaccination immunity and prevention of various infections, disorders, cancer and stress related diseases. The updated information will be highly useful for scientists, veterinary/medical professionals, pharmaceutical industries, livestock and poultry industry to create a healthier future for people and their companion animals.
  Gopal Krishan , Santosh Kumar Shukla , Prakash Bhatt , Rajesh Kumar , Ruchi Tiwari , Yashpal Singh Malik and Kuldeep Dhama
  The present investigation was undertaken to assess the role of a polyherbal immunomodulator with additional elements (Immon) against the chicken infectious anemia virus (CIAV) infection. A total of 60 broiler chicks (day old age) were divided into three groups (n= 20) and vaccinated against Newcastle disease (ND). The group I chicks were kept as healthy control while group II and III chicks were infected with 1 ml CIAV (104.5 TCID50/0.1 ml) per chicken intramuscularly. Group III chicks were supplemented with Immon (1 ml / 10 birds in the drinking water) for 21 days. Subsequently, chicks of all three groups were monitored for hematological (Hb, PCV, TEC, TLC and DLC) and biochemical parameters (AST, ALT, ALP and uric acid) along with ND antibody titers, organ: body weight ratios, and mean live body weight at on 7th, 14th, 21st, 28th and 35th day of the experiment. At 7 - 24 days of CIAV infection, the group II birds showed a significantly lower count of erythroid and myeloid cells; increase in enzyme activities and uric acid; decline in mean live body weight and organ: body weight ratios of lymphoid organs, and decline in ND antibody titers. However, at these day intervals the CIAV immunosuppression was less severe in Immon supplemented chicks which showed significantly (P<0.05) higher values of all the test parameters as compared to virus control group II chicks. Thus, the present findings support that Immon is an effective immunomodulating agent in CIAV affected birds, reduces pathogenicity of the virus, ameliorate the depressed immune responses and protects the virus induced adverse effects on growth performances.
  Mohamed E. Abd El-Hack , Samir A. Mahgoub , Mahmoud Alagawany and Kuldeep Dhama
  This study evaluated the effect of dietary supplementation of antimicrobial cold pressed oils mixture [1:1:1 of Nigella sativa, cloves and rosemary (NCR)] at levels of 0.75 and 1.5 g kg–1 diet, on growth performance, carcass traits and some microbiological aspects for growing Japanese quails. A total number of 225 growing Japanese quails one week old were used in a complete randomized design experiment with three treatments. Final live body weight was significantly (p<0.01) higher by 2.89% in quails fed diet supplemented with 1.5 g NCR oil compared to those fed the control diet. Feed intake increased statistically (p<0.01) as the level of oil mixture supplement increased. The best feed conversion of 2.87 was associated with 1.5 g oil during period 3-6 weeks of age, whilst the control group gave the best feed conversion within the whole period (1-6 weeks of age) followed by the experimental group treated with 1.5 g NCR oil. Feeding quails on a diet enriched with 1.5 g NCR oil resulted in the best carcass percentage which increased by 3.72% compared to those fed the control diet. The populations of Total Bacterial Count (TBC), coliforms and Escherichia coli in ileum, ceca and feces were fewer (p<0.05) in quails fed diet supplemented with NCR oil mixtures (1.5 g w/w) compared with the control diet. In conclusion, the dietary supplementation of antimicrobial cold pressed oils mixture by 1.5 g kg–1 showed the potential to enhance the growth performance and reduce intestinal and excreta pathogenic bacteria in quails.
  Sana Ullah , Zaigham Hasan and Kuldeep Dhama
  The current study was designed to investigate the behavioural and biochemical changes induced by endosulfan in brain, gills, liver and muscle of rohu, Labeo rohita. Behavioural changes observed after exposing fish to LC50 of endosulfan, were erratic swimming, jumping, loss of equilibrium and balance, hyperactivity, increased air gulping and surface activity. These changes were observed to be more pronounced with length of exposure time. Longer exposure made the fish lethargic, with the lesser operculur beat, adopted a vertical position sometimes and motionless state before dying. Internal hemorrhage was conspicuous. A time dependent decrease in total protein contents and increase in antioxidant enzymes, including catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione reductase (GR), reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and glutathione-s-transferase (GST) was observed in the brain, gills, liver and muscles of rohu. A time dependent increase in malondialdehyde (MDA) concentration was also observed in different tissues. The current study reports endosulfan as highly toxic to L. rohita. Its indiscriminate use should be controlled in order to conserve the population of rohu and other Cyprinids in natural aquatic systems.
  Mayada Ragab Farag , Mahmoud Alagawany , Mohamed Ezzat Abd El-Hack and Kuldeep Dhama
  Spirulina (Arthrospira) is a microscopic blue-green algae and it is considered as one of the richest sources of organic nutrients that are making it a good nutritional supplement for human and animal feed worldwide. Spirulina contains good quality proteins, vitamins and minerals in addition to a wide variety of natural carotene and xanthophyll phytopigments. Owing to its unique and impressive nutrient composition, Spirulina is used as a dietary inclusion in a large scale of food products not only to enhance their nutritional qualities but also for therapeutic purposes. On this aspect, many researchers studied the beneficial effects of Spirulina and reported its enhancing potential on the productive and reproductive performance, improving general health as well as lowering the problems of different animal diseases like arthritis, diabetes, anaemia, hypertension and cardiovascular disorders. Other studies have demonstrated that Spirulina possess some promising biological activities such as antitumor, antimicrobial, antiviral, anti-inflammatory, hypocholesterolemic, radio protective and metalloprotective effects. These pharmaceutical and medicinal properties of Spirulina could be attributed to some natural constituents such as phycocyanin, carotene, tocopherols, linolenic acid and phenolic compounds that had been shown to have strong antioxidant properties and powerful scavenging activities against Reactive Oxygen Species (ROS) like superoxide and hydrogen peroxide radicals. This review illustrates the beneficial effects of Arthrospira on poultry, animals and human health and throws the light on its ability to protect the body physiological system against oxidative damage and as nutraceutical and source of potential pharmaceuticals based mainly on the highest levels of evidence available in the literature.
  Mohamed Ezzat Abd El-Hack , Mahmoud Alagawany , Mayada Ragab Farag , Ruchi Tiwari , Kumaragurubaran Karthik and Kuldeep Dhama
  In the present era of emerging antibiotic/drug resistance against pathogenic organisms and food safety concerns of their toxic residues as well as slow process of discovering newer antibiotics, there is a dire need for using natural and effective alternatives. In this regard, herbal and aromatic plants and/or their extracts are gaining attention of worldwide researchers. Studies on Nigella sativa (black cumin) seeds show promising results that it could provide a suitable alternative to antibiotics as growth promoter and safeguard various health issues of animals and humans. The seeds of black cumin with thymoquinone as its main active constituent are mainly used for medicinal purposes and could be used as food spice and nutritional supplements. These have beneficial antinociceptive, antimicrobial, growth enhancing, antiparasitic, immunomoulatory, hepatoprotective, analgesic, anti-inflammatory, antioxidative and bronchodilating effects. Blood pressure regulating as well as bile flow stimulating effects have also been observed. Black cumin seeds have been used widely against several diseases, disorders and ailments of humans and animals including bronchial asthma, cough, bronchitis, lung inflammation, microbial infections, fever, dysentery, gastrointestinal problems, gastric ulcers, hypertension, neurodegenerative diseases, epilepsy, alzheimer disease, headache, diabetes, allergy, obesity, back pain, skin diseases, eczema, jaundice, anorexia, conjunctivitis, dyspepsia, rheumatism, diabetes, intrinsic hemorrhages, amenorrhea and immune disorders, which altogether indicate their potent therapeutic values and biomedicinal perspectives. The aim of this study is to provide comprehensive and recent information about the nutritional, healthical, pharmaceutical, therapeutic and biomedical applications and prospects of Nigella sativa seeds in feeding humans, animals and poultry.
  Sana Ullah , Maryam Begum , Saeed Ahmad and Kuldeep Dhama
  The current study was designed to determine the genotoxic effect of endosulfan at sublethal concentrations (66, 50 and 33% of LC50, 1.5 μg L–1) in peripheral blood erythrocytes of an economically important indigenous Indian major carp Mori, Cirrhinus mrigala . A total of 180 fish were divided into four groups, each group received 45 individuals. Group 1st served as control (received no endosulfan), while group 2nd (0.5 μg L–1), 3rd (0.75 μg L–1) and 4th (1 μg L–1) were exposed to endosulfan. For investigating the induced DNA damage, the blood samples were collected from the caudal veins of the fingerlings in all the groups after 7, 14, 21 and 28 days of endosulfan exposure. Endosulfan induced DNA damage in all the treated groups at all concentrations, in terms of percentage of damaged cell (% damage cell) and Genetic Damage Index (GDI) based on visual classification of the extent of damage (Class 0-4) and cumulative tail length (μm). A concentration and time dependent increase was observed in DNA damage in the exposed groups, the highest damage was observed in group 4th (1 μg L–1) followed by group 3rd (0.75 μg L–1). Similarly, the highest level of DNA damage was observed in peripheral blood erythrocytes sampled after 28 days, followed by 21 days after exposure. The current study displayed the severe genotoxic potential of endosulfan in Cirrhinus mrigala , even at sublethal concentrations. Therefore, the indiscriminate and injudicious use of endosulfan should be strictly monitored and banned or at least controlled by the responsible governmental authorities.
  Mohd. Iqbal Yatoo , Umesh Dimri , Arumugam Gopalakrishan , Mani Saminathan , Kuldeep Dhama , Karikalan Mathesh , Archana Saxena , Devi Gopinath and Shahid Husain
  This study demonstrated the antidiabetic and antioxidant potential of Pedicularis longiflora Rudolph, a Himalayan wild herb, in alloxan induced diabetic rats. Seven groups of wistar rats (n = 6) were divided into healthy control (I) and diabetic control (II) groups, both without any treatment, test groups (III, IV and V) treated with varying concentration of ethanolic extract of Pedicularis longiflora and standard groups treated with N-acetyl cysteine as standard antioxidant (VI) and glibenclamide as standard antidiabetic drug (VII). Diabetic biomarkers and oxidative stress indices were evaluated on day 0, 7 and 14 of treatment. Glucose, glycated haemoglobin (GHb) and fructosamine showed a decrease of 23.08, 33.85 and 43.46%, respectively in group IV than group III (15.06, 46.13 and 23.95%) and group V (15.99, 27.77 and 24.84%) whereas, insulin showed significant (p<0.05) increase in group IV (15.43%) and group V (5.12%), but not than group III (16.82%) on day 14 of treatment. Concentration of reduced glutathione (GSH) and activity of superoxide dismutase (SOD) was increased (p<0.05) whereas, levels of lipid peroxide (LPO) and Nitric Oxide (NO) were decreased (p<0.05) in test groups on day 14 of treatment compared to diabetic control group. Liver homogenate showed lower levels (p<0.05) of LPO and NO, whereas, pancreatic homogenate showed higher levels (p<0.05) of GSH and lower levels (p<0.05) of LPO in test groups. These findings can be attributed to antidiabetic and antioxidant potential of P. longiflora Rudolph, however, group IV (500 mg kg–1 b.wt.) showing better response indicating its safe use as natural medicine.
  Ruchi Tiwari , Kumaragurubaran Karthik , Rajneesh Rana , Yashpal Singh Malik , Kuldeep Dhama and Sunil Kumar Joshi
  Microbial activity is considered as an important cause for the manifestation of food spoilage. The detection of chemical signals sharing information between food spoilage bacteria present in food products has initiated a new dimension to formulate an alternate preventive strategy against these spoilage bacteria. Quorum sensing or cell-to-cell communication is employed by a diverse group of bacteria talking to each other through the signaling autoinducer molecules. Based on potential of these molecules, Quorum-Sensing Inhibitors (QSI) or Quorum Quenching (QQ) compounds can be used as novel biopreservatives which abrupt the virulence of food spoilage microbes to uphold the nutritional quality of packaged and Ready To Eat (RTE) food and food by products. Through the pharmaceutical interventions and molecular mechanisms of intracellular, intercellular and interspecies communication via signaling molecules, preventive strategies can be formulated for production of pathogen free food products. Though identification of species specific signaling pathways is a challenging task for the food microbiologists and pharamacists but proper implementation of QSI molecules would be helpful for the food manufacturers in food processing plants through critical follow ups of Hazard Analysis and Critical Control Point (HACCP) to maintain the food quality and sound public health. This review draws the attention of researchers involved in dairy microbiology, meat and fish processing industries, packaging channels and neutraceuticals and pharmaceutical industries to explore the library of QS and QSI molecules to put forward and apply them as bio-preservatives for production of safe food products to meet the global food demands of growing world population.
  Rifat Ullah Khan , Shabana Naz , Kuldeep Dhama , K. Karthik , Ruchi Tiwari , Mutassim M. Abdelrahman , Ibrahim A. Alhidary and Arshad Zahoor
  Recently, animal food industry has shown an increasing interest in Direct-Fed Microbials (DFM) to keep the concept of safe food supply at the consumer level. In the absence of suitable growth stimulant after banning the use of antibiotics in animal feed, a positive manipulation of rumen microbes has become the field research for entrepreneurs and research scientists. Direct-fed microbials is a term reserved for naturally occurring live microbes that can be supplemented orally to produce a beneficial health response in the host animal. A number of genera of live microorganisms including; bacteria, yeast and fungi are frequently used in different combination feed as DFM for domestic ruminants. It has been documented that these live culture of microbes improve ruminant productivity, milk production, immunity, digestibility of feed, counter infectious pathogens and protect health. Possible attempts have also been undertaken to justify the mechanism of these microbes. This review tries to summarize the effect of supplementation of DFM on the production, immune response, fermentation pattern and safeguarding health. The discussed concepts and advances concerning to DFM implementation will be useful not only for the researchers, animal owners, feed manufacturers, pharmacists, pharmaceutical companies, stake holders but will also boost the economic gains and profits by promoting the ruminant health and production through feed modification.
  Mohammad Jalil Zorriehzahra , Ruchi Tiwari , Swati Sachan , Kumaragurubaran Karthik , Yashpal Singh Malik , Maryam Dadar , Muhammad Sarwar , Maryam Sayab and Kuldeep Dhama
  In the current scenario of increasing and emerging drug resistance in various microbial pathogens, traditional antibiotics are becoming less effective and thus globally research has focused on developing alternative therapeutic regimens having efficient germ killing abilities. The leading alternatives include use of phages, prebiotics, probiotics, cytokines, avian egg yolk antibodies, toll like receptors, medical herbs and various other immunomodulatory/immunotherapeutic approaches. Out of these valuable therapies, the application of oral passive immunization using avian egg yolk antibodies (Immunoglobulin Y, IgY) offers promising future avenues for designing and developing novel prophylactic and treatment strategies against infectious diseases in both humans and animals, particularly countering the enteric pathogens. Hitherto studies confirm beneficial applications of IgY antibodies in animals (Calves, lamb and goat, cats and dogs), poultry and humans, however such studies in fish and aquatic animals are comparatively less. The present study presents as overview on avian egg antibodies, their salient features, advantages and limitations and then describes the potential therapeutic applications of IgY for the prevention and treatment of infectious diseases of fish and aquatic animal species, as well as speculating the future prospects of upcoming IgY technology. Taking into account the valuable prophylactic and therapeutic applications of IgY antibodies, further explorative research in this area could pave way for designing and developing effective pharmaceuticals and treatment options for various infectious diseases of fish/aquaculture animals as well as for safeguarding health of humans and their companion animals.
  Zaib Ur Rehman , Ahsan Ul Haq , Naasra Akram , Mohamed E. Abd El-Hack , Muhammad Saeed , Shahid Ur Rehman , Chunchun Meng , Mahmoud Alagawany , Maryam Sayab , Kuldeep Dhama and Chan Ding
  Objective: The present study was performed to determine the influence of dietary Acetic Acid (AA) supplementation on growth performance, intestinal histomorphology, blood hematology and serum constituents of broilers. Methodology: A total 200 chicks were randomly divided into five experimental groups with four replicates each (10 chicks/replicate) in a complete randomized design experiment. Treatments were as follow: (AA0: control, AA1: basal diet+0.1% acetic acid kg–1, AA2: basal diet+0.2% acetic acid kg–1 and AA3: basal diet+0.3% acetic acid kg–1). Results: The results showed that AA supplementation improved weight gain (p<0.001) and feed conversion ratio (p<0.001). Generally, acetic acid supplementation at 0.3% level improved bird’s performance during 2-6 weeks of age. Increased intestinal length and higher intestinal weight were recorded in AA treated birds. Significant reduction in pH of proventriculus and ventriculus (p<0.01) was observed with in dose related manner. No significant effects were observed on dressing percentage. Histological observations revealed that intestinal morphology professed positive effects under AA treatment. Furthermore, the effect of dietary AA supplementation was significant (p<0.05) only on lymphocytes count and heterophil/lymphocyte ratio. It is obvious that blood of birds fed AA3 diet had the highest concentration of calcium, phosphorous, total protein and globulin comparing with the control diet and other levels of AA. The best results of all parameters were observed in AA3. Conclusion: Based on the results, it could be concluded that AA supplementations in feed employs positive effect on performance and intestinal histomorphology of broilers.
  Mahmoud Alagawany , Mayada Ragab Farag , Mohamed Ezzat Abd El-Hack , Elisabetta Casalino , Vincenzo Tufarelli , Maryam Sayab and Kuldeep Dhama
  Objective: The current study was conducted to assess the biological in vitro impacts of cyadox (CYA) as growth promoter on erythrocytes isolated from rabbits. Methodology: Suspensions of erythrocytes were divided into 6 groups (5 replicates each), 1st group served as control; 2nd, 3rd, 4th, 5th and 6th groups were respectively subjected to CYA at 2.5, 5, 10, 20 and 40 μg mL–1, then incubated for 3 and 6 h at 37°C and shaken gently from 3-4 times per hour. Results: The data obtained revealed that the low doses of CYA (2.5 and 5 μg mL–1) diminished the reduced glutathione (GSH) content and enhanced the catalase (CAT) and superoxide dismutase (SOD) activities even after incubation with CYA for 6 h. These concentrations also had no linear or quadratic influences on the values of malonaldehyde (MDA) and protein carbonyl (PrC) as well as the hemoglobin (Hb), adenosine triphosphate (ATP) and total protein (TP) levels in erythrocytes. Increasing the concentration of CYA (10, 20 and 40 μg mL–1) and increasing the incubation period resulted in depletion of GSH, inhibited the CAT and SOD activities and decreased the protein content in the treated RBCs while the levels of PrC, MDA, Hb, TP and ATP were increased in response to increasing the dose and incubation time. Conclusion: From these results it could be concluded that CYA may be safe at recommended doses (2.5 and 5 μg mL–1) while using at high concentrations revealed pro-oxidant properties which could in turn affect cell survival.
  Shoor Vir Singh , Saurabh Gupta , Kundan Kumar Chaubey , Saket Bhushan , Krishna Dutta Rawat , Naveen Kumar , Hari Audh Tiwari , Vinay Chaturvedi , Jagdip Singh Sohal , Kuldeep Dhama and Zahra Hemati
  Background: Johne’s disease is chronic incurable enteritis mainly responsible for reduced productivity in domestic livestock leading to extensive economic losses to the dairy industry world-wide. Therapeutic efficacy of ‘First indigenous vaccine’ developed using novel ‘Indian bison type’ biotype of Mycobacterium avium subspecies paratuberculosis (MAP) strain ‘S 5’ was evaluated for the treatment of clinical Johne’s disease in the farm herds of Jakhrana breed of goats. Farm herds of this important milch breed of semi-arid region of Rajasthan were endemically infected with Johne’s disease. Materials and Methods: Response to ‘Indigenous vaccine’ against Johne’s disease has been studied twice in this farm unit, first time in 2006-07 (Vaccine trail-I) and second time in the present study from 2013-14 (Vaccine trial-II). Data on improvement in health, clinical condition, productivity, reproductive performance, milk yield, survivability, morbidity, mortality, culling and shedding of MAP in feces were recorded before and after vaccination. In vaccine trial-II, 225 adult goats and 70 and 39 kids (above 3 months age) born to un-vaccinated and vaccinated goats were vaccinated one time between 2013 and 2014, respectively. Results: Reduction in shedding of MAP in this vaccine trial-II of infected goats and 1st generation kids was 45.5 and 100.0%, respectively. Presence of MAP in the blood of vaccinated goats was reduced by 23.0% at 360 DPV. Peak titers were achieved around 90 DPV and all vaccinated goats sero-converted by 360 DPV. High to very high morbidity, mortality and cullings encountered before vaccination in the infected Jakhrana goatherds were mainly due to Johne’s disease and were highly reduced after vaccination. Vaccination not only reduced clinical disease but also improved production performance (milk and meat production). Average gain in body weights were distinctly superior in the vaccinated goats and in the 1st generation kids born to vaccinated mothers. After vaccination there was overall improvement in the health of animals, kid survival rate, per animal productivity with respect to milk production and growth rates. Conclusion: Study concluded that ‘Indigenous JD vaccine’ developed using native MAP biotype can be employed both for the ‘Therapeutic management’ of the disease in the endemically infected goatherds and for the prevention of disease in naive and non-infected goats. The study can serve as model for the utilization of large population of non-productive domestic livestock and for the management and control of incurable Johne’s disease in endemically infected herds and flocks in the country.
  Rab Nawaz Soomro , Rujiu Hu , Yu Qiao , Mohamed Ezzat Abd El-Hack , Imtiaz Hussain Raja Abbasi , Mohamed Abdalla Elsiddig Mohamed , Bello Musa Bodinga , Mahmoud Alagawany , Xiaojun Yang , Junhu Yao and Kuldeep Dhama
  Objective: This study was conducted to evaluate the effects of dietary protein soybean meal (SBM) and cottonseed meal (CSM) sources and Amino Acid (AA) balances on performance, intestinal permeability and morphology in broiler chickens. Methodology: Five hundred and twenty broiler chickens were fed an experimental diet from 21-42 days of age. A completely randomized block design was used with four treatments of SBM+CSM with AA Balance (B) and Imbalance (I) (SBMB and SBMI, SBM+CSMB and SBM+CSMI) were replicated 10 times with 13 broiler chickens per replicate. All respective treatments were kept in the same condition provide the diet twice a day and access to water ad libitum. Results: The results showed that Daily Weight Gain (DWG), Daily Feed Intake (DFI), feed efficiency, Feed Conversion Ratio (FCR), carcass yield and dressing percentage were improved with SBMB in comparison with all treatments. Furthermore, SBMB significantly increased most of morphological findings in the intestinal parts studied. Intestinal permeability was (p<0.05) increased in SBMI and SBM+CSMI treatments. Conclusion: It is concluded that the best performance indices could be obtained by using SBMB carcasses and morphological findings in comparison with other treatments.
  Mohamed Ezzat Abd El-Hack , Mahmoud Alagawany , Mayada Ragab Farag , Muhammad Arif , Mohamed Emam , Kuldeep Dhama , Muhammad Sarwar and Maryam Sayab
  The concept of "Nanoparticle" is not applied to the individual molecules but it is usually used to indicate to the inorganic materials. These particles vary into different kinds due to their ability to carry different components and act to various conditions of the environment. The different sorts of nanoparticles are used in various sectors such as nutrition, pharmacy, medicine, drug delivery, therapeutics, vaccine formulations, diagnostics, chemical industry, biotechnology and biomedicine for safeguarding health of humans and animals as well as enhancing growth and production performances. The application of nanotechnology is very important in the 21st century to clean up the environment from contaminants by eco-friendly, sustainable, green and economically technologies. Nanotechnology became an essential element of pharmaceutical sciences and nanomaterials have found many applications in systems of drug delivery to enhance the therapeutic performance and efficacy of different drugs and medicines. Most of the current "Nano" systems of drug delivery are linage of conventional dosage forms like nanomicelles, nanoemulsions and nanosuspensions. Also, nanotechnology will have a major role in the future areas of animal nutrition research. Nano additives could be incorporated in capsules or micelles of protein or other natural feed or food component. The use of nutrient nanoparticles may improve the bioavailability of carried nutrients by the epithelial barriers of the gut and their susceptibility to gastrointestinal degradation by digestive enzymes. Offering the matter in a nano form may also improve the functionality of feed/food molecules to the benefit of final product quality.
  Muhammad Saeed , Xu Yatao , Zaib Ur Rehman , Muhammad Asif Arain , Rab Nawaz Soomro , Mohamed E. Abd El-Hack , Zohaib Ahmed Bhutto , Benazir Abbasi , Kuldeep Dhama , Muhammad Sarwar and Sun Chao
  Non-digestible oligosaccharides as well as phenolic compounds inulins and fructooligosaccharides of Smallanthus sonchifolius make it an attractive functional food. Consumption of these non-digestible oligosaccharides improves gastrointestinal metabolism, increases the growth of bifido bacteria in the colon and also acts as antioxidant, antimicrobial, prebiotic, growth promoter, hypoglycemic, hepatoprotective compounds via lowering alanine aminotransferase (ALT) and increasing mineral absorption to maintain bone homeostasis and also help to reduce cholesterol and triglyceride levels. Past to present literature have been reviewed and the results indicated that Smallanthus sonchifolius root consumption modulates the immune system by regulating the intestinal secretion of IgA and interferon IFN-γ subsequently enhancing resistance to infections and allergic reactions. This role not only facilitates the exclusion of potential pathogenic bacteria but also ultimately increases defense of the host. Previously published literature has focused on rat, human, pig and livestock but biological and clinical evidence is scarce on the same aspect in poultry. Therefore, this review article aimed to highlight the origin, chemical composition, different beneficial uses and biohazards of yacon plant (which contains 70-80% fructooligosaccharides (FOS)) that could be used as a novel natural prebiotic in poultry feed. The FOS could improve different health aspects and productive performance criteria of different poultry species. To recommend yacon plant as a natural and safe medicinal agent, more indices need to be determined in further studies on different livestock and poultry species on molecular level to assure its benefits and to give accurate recommendation for the optimal levels to be added as feed additive.
  Muhammad Saeed , Mohamed E. Abd El-Hack , Mahmoud Alagawany , Muhammad A. Arain , Muhammad Arif , Muhammad A. Mirza , Muhammad Naveed , Sun Chao , Muhammad Sarwar , Maryam Sayab and Kuldeep Dhama
  Chicory (Cichorium intybus) is a perennial herbal plant of the dandelion family Asteraceae, usually with bright blue flowers, rarely pink or white. Several varieties are cultivated for salad leaves, chicons or roots which are baked, ground and used as a coffee substitute and supplement. It is also grown as a forage plant for poultry and animal. In addition, chicory herb plays a key role as antioxidant, anti-inflammatory, sedative, immunological, productive and reproductive enhancer, cardiovascular, hypolipidemic, anticancer, anti-protozoal, gastroprotective, antidiabetic, analgesic, anthelmintic, antimicrobial, wound healing and bitter tonic without inducing therapeutic adverse effect. Regarding the hepatoprotective activity, chicory extract reduced the levels of hepatic enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Also, chicory plant is a good and very important protective source for hepatocytes and other liver cells as well as it is used as prebiotic against some species of pathogenic bacteria for both in vitro and in vivo. Moreover, it enhances immunity and feed efficiency by decreasing pathogenic microorganisms of gastrointestinal tract. Cichorium intybus roots also were used for the relief of mild digestive disorders, such as feeling of flatulence, abdominal fullness, temporary loss of appetite and slow digestion. The present study highlights the importance of chicory as a feed additive used to improve growth and productive performance of poultry as well as salient beneficial applications in animals and humans. Furthermore, it explains the mechanisms of action underlying the beneficial effects of chicory and to find the effective level in poultry that would act as liver tonic.
  Rekha Khandia , Ashok Munjal and Kuldeep Dhama
  Zika virus (ZIKV), is a member of the Flaviviridae family and cause congenital microcephaly and Guillain-Barre’ Syndrome (GBS). The fetus of the mothers infected with ZIKV during first trimester are suffered from severe neurological damage like change of head shape and circumference celled microcephaly, convoluted scalp, deformed joints and vision and hearing loss. Its capability to infect fetus caused Public Health Emergency of International Concern. The information related to ZIKV infecting pregnant women and safe drugs were retrieved from the authentic published resources available on Medline, Pubmed, Pubmed Central, Science Direct and other scientific databases. The retrieved information has been compiled and analyzed. Microcephaly is a rare paediatric condition, implicated with severe consequences on fetus. The consequences of ZIKV infection to the fetus, statistical analysis summarizing association of microcephaly with ZIKV infection with other teratogenic congenital disease manifestations like ZIKV infection and about the therapies which can work for fetus and pregnant women include the use of chloroquine, amodiaquine, sofosbuvir, macrolide antibiotic azithromycin, niclosamide, albendazole/mebendazole, palonosetron and use of convalescent serum. Present review explains techniques of virus detection in fetus. Detailed case study analysis of affected fetus and the mechanism by which virus cause damage to the tissues and the target of fetus might be helpful in future to prevent the detrimental effects of the virus.
  Farman Ali Siyal , Mohamed Ezzat Abd El-Hack , Mahmoud Alagawany , Chao Wang , Xioli Wan , Jintian He , Mingfa Wang , Lili Zhang , Xiang Zhong , Tian Wang and Kuldeep Dhama
  Background and Objective: Lecithin is a feed supplement and dietary source of several active compounds; therefore, this study evaluated the Soybean Lecithin (SL) in broiler diets by measuring performance, nutrient utilization, serum parameters and hepatic antioxidant status. Methodology: About 216 days old Arbor Acre broiler chicks were allotted into three groups as follow: the first group was fed a Basal Diet (BD) without emulsifier; the second and third groups were fed basal diet supplemented with 0.05 (SL0.05) and 0.1% (SL0.10) of SL, respectively. Results: During starter, grower and overall period, chicken fed with SL has better daily gain and feed intake compared with control, while feed conversion was improved in SL0.10 throughout the experiment compared to SL0.05 and control. At 21 and 42 days old, SL0.10 showed highest relative liver weight compared to SL0.05 and control (p<0.05). On day 21, digestibility of dry matter, ether extract and protein in chickens fed diet with SL0.10 was significantly improved in comparison with those fed SL0.05 and control. Cholesterol, triglyceride and low density lipoprotein concentrations were decreased in SL0.10 group in comparison with control. Serum glucose was higher in SL0.10 group compared to SL0.05 and control. Feeding SL0.10 resulted in the decreased hepatic malondialdehyde content and remarkably increased catalase, total superoxide dismutase and total antioxidant capacity enzyme activities. Conclusion: Feeding soy lecithin at 0.10% improved performance, reduced cholesterol and triglyceride, LDL-cholesterol concentrations in serum broilers. In addition, soy lecithin is suitable for improving antioxidant status and has ability to protect against oxidative stress.
  Asif Mehfooz , Quanwei Wei , Mohamed Babo Fadlalla , Farman Ali Siyal , Kuldeep Dhama , Dagan Mao and Fangxiong Shi
  Background and Objective: Restraint stress and hypothyroidism impair animal testicular functions. As stress is increasing gradually in our daily life, there is an increased chance of the occurrence of both stress and hypothyroidism together. Therefore, this study was designed to evaluate the effect of restraint stress on growth performance and testicular cells apoptosis in adult hypothyroid mice. Methodology: Twenty-four adult male mice were divided into four groups: control, Restraint Stress (RS), hypothyroid (HT) and RS+HT. ANOVA followed by Tukey as post hoc tests were used to determine the difference between multiple groups. Results: The results indicated that the feed and water index, body weight and testes weight, serum concentration of T3, T4 and testosterone exhibited a reduction but the TSH levels were increased in all experimental groups compared to the control. Histological observations of the testis from different experimental groups exhibited considerable interstitial edema, broken basement membrane and increased interstitial spaces compared with the control group. Seminiferous tubules were also morphologically shrinkage and deformed in RS+HT group compared to control group. Obvious suppression of spermatogenesis by restraint stress, the degenerative population of round spermatids was markedly increased due to apoptosis in the lumen of RS group as compared to the control group. Moreover, leydig cells, blood vessels, sertoli cells, primary and secondary spermatocytes are absent in large numbers and exposing apoptosis in RS+HT mice than RS and HT mice as compared to the control mice. Conclusion: Restraint stress and hypothyroidism together have adverse effects on male fertility based on increasing of the apoptotic process.
  Mohammed Hussen Bule , Faheem Maqbool , Ishtiaq Ahmed , Kuldeep Dhama and Hafiz Muhammad Nasir Iqbal
  From decades’ tuberculosis (TB) affecting individual and a huge number of people die every year. It causes ill-health among millions of individuals each year and ranks as the second leading cause of death from an infectious disease worldwide. The number of TB deaths has been unacceptably increased to a large extent and most cases are preventable if people get in time access to health care for a diagnosis and the right treatment. Multi-drug resistance is the fact that in TB patients are growing rapidly and difficult to treat. Treatment of MDR-TB is more complicated and longer than treatment of TB with no resistance. With advancements in the therapy of TB, now ideal treatments have been developed and many combination therapies are well recommended for MDR. The development of MDR-TB can be caused by a treatment that is inadequate, given the drug susceptibility pattern of the MTB strain. Few cohort studies provided information on treatment regimens and drug resistance profiles before treatment and at failure or recurrence or genotyping information at failure or recurrence. To monitor the development of acquired drug resistance, we suggest that given sufficient resources are available, TB treatment cohort studies or surveillance systems measure both the drug resistance profile and genotype information before starting treatment and at failure or recurrence. The emergence of MDR-TB and XDR-TB, the need for new TB drug regimens and rapid DST is intuiting globally. In future, more research with a focus on MDR and TB is required to avoid and counteract its associated complications.
  Muhammad Saeed , Mohamed Ezzat Abd El-Hack , Mahmoud Alagawany , Muhammad Naveed , Muhammad Asif Arain , Muhammad Arif , Rab Nawaz Soomro , MohibUllah Kakar , Robina Manzoor , Ruchi Tiwari , Rekha Khandia , Ashok Munjal , Kumaragurubaran Karthik , Kuldeep Dhama , Hafiz Muhammad Nasir Iqbal and Chao Sun
  Green tea is an important herb and its products are extensively used in the traditional Chinese medicinal system through various formulations. Several reports have revealed its beneficial usage and medicinal aspects for various ailments. Consumption of green tea has gained special attention and popularity in various sectors of the modern era of changing lifestyle. This review aimed to extend the current knowledge on the modes of action and beneficial applications of green tea in humans and animals for safeguarding different health issues. The nutritional, immunological, pharmacological and physiological functionalities of green tea are because of the available bioactive components like caffeine, L-theanine, polyphenols/flavonoids and others. It possesses multi-beneficial potential in treating and preventing various disorders of animals and humans, as well as promoting animal (dairy, piggery and goatry) and poultry industry. The present review provides insights on the modes of action and beneficial applications of green tea, which will be useful for nutritionists, pharmacists, physiologists, researchers, veterinarians and animal and poultry producers. Future research emphasis and promotional avenues are needed to explore its potential therapeutic applications for designing appropriate pharmaceuticals, complementary medicines and effective drugs to popularize and propagate its multidimensional health benefits.
  Mohd Iqbal Yatoo , Archana Saxena , Arumugam Gopalakrishnan , Mahmoud Alagawany and Kuldeep Dhama
  Diabetes is a chronic endocrine disease with global prevalence and rising incidence. Diabetes represents a major health issue in all age groups in the present times owing to its multisystem involvement and serious complications. Despite drug development and therapeutic interventions, successful treatment of diabetes still remains a challenge and worldwide research is focused on these aspects. Conventional antidiabetic medicines include injectable insulins, sulfonylureas, biguanides, glucosidase inhibitors and glinides. New class include inhalable insulins, incretin mimetics, amylin analogues, gastric inhibitory polypeptide analogues, peroxisome proliferator activated receptors and dipeptidyl peptidase-4 inhibitors. From effectiveness of synthetic drugs, chemicals or hormones to issues of cost, availability and side effects, novelty in preparations to methods of administration, all fields are explored for better management of the disease. Medicinal plants with antidiabetic potential have been recent areas of research. Asteraceae, Araliaceae, Cucurbitaceae, Lamiaceae, Leguminoseae, Liliaceae, Moraceae and Rosaceae are the major antidiabetic plant families. The most active plants are Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia and Ficus bengalensis. Their phytoconstituents have shown promising results in diabetes management; but need to be properly evaluated at molecular, physiological, pharmacological and toxicological levels for various prophylactic and therapeutic attributes, mechanisms of action, efficacy and safety before application in diabetes. The common phytoconstituents include polyphenols, flavonoids, terpenoids, tannins, alkaloids, saponins etc. Exploration of novel targets like glucagon-like peptide-1 (GLP-1), sodium-glucose co-transporter 2 (SGLT-2) and dipeptidyl peptidase 4 (DPP-4) for antidiabetic drugs and medicinal plants with emphasis on site specific effectiveness and overcoming problems of resistance, side effects, prolonged usage and high cost, are being investigated for future research.
  Li Chang Xing , Dhanasikar Santhi , Abdul Ghaffar Shar , Muhammad Saeed , Muhammad Asif Arain , Akhtar Hussain Shar , Zohaib Ahmed Bhutto , Mohib Ullah Kakar , Robina Manzoor , Mohamed E. Abd El-Hack , Mahmoud Alagawany , Kuldeep Dhama and Mo Chen ling
  Medicinal plants have gained great popularity and their importance is realized world over. Psyllium (Plantago ovata) is a native plant of India. The hydrophilic mucilloid, water-soluble fiber derived from psyllium husk and seed had been used since ancient times as vital curative agent for constipation, mainly as a part of the traditional Indian Ayurvedic medicine. Psyllium is a rich source of fiber and has numerous other therapeutic impacts such as cholesterol lowering, antidiarrhoeal, laxative, antidiabetic, energy increasing, hemorrhoid remedy, soothing inflammation and weight loss agent. Psyllium husk plays a key role in lowering serum cholesterol, so psyllium is being considered as a potential supportive agent in the therapy of hyperlipidemia. The cholesterol level is lowered in different animal models by the binding of psyllium husk with bile acids in the small intestine and thus reducing its absorption. The husk of psyllium could be used as an additive in milk replacer of the neonatal dairy calves to improve the physiological functions and enhance the performance and health status. Psyllium may also has positive impacts in growth and productive performance of different poultry species. The main aim of this review was to discuss the role of psyllium in managing the hypercholesterolemia in humans and the application of psyllium huskas a safe feed additive in poultry farming for the production of organic and low cholesterol designer egg and meat.
  Ashok Munjal , Rekha Khandia , Ruchi Tiwari , Sandip Chakraborty , Kumaragurubaran Karthik and Kuldeep Dhama
  The recent outbreaks of Zika virus (ZIKV) infections has changed the ZIKV status from a very mild self-limiting febrile virus to a highly pathogenic virus causing visual impairment, autoimmune response against myelin layer and microcephaly in affected fetus. The serious social impact on society has drawn the attention of the researchers globally. The search for an effective vaccine against ZIKV is on the way. Several researches as well as commercial organizations are indulged in developing vaccine for prophylactic and treatment purposes. In the present review, various vaccine strategies have been described including inactivated, attenuated, DNA, subunit, recombinant viral vectored and nucleic acid based vaccines. The vaccines developed should be clinically tested in animal models, which are susceptible for ZIKV infection like Stat2-/- mice, A129 (IFNAR-/-) Mice, Swiss Jim Lambert (SJL) mice or Rhesus macaques. Efficacy of each vaccination strategy is required to be meticulously evaluated. The use of vaccinomics could also help to discover appropriate vaccine candidate to induce the effective immune response. DNA and subunit vaccines may not be that much beneficial in endemic areas due to poor immunogenic potential; however, by adjuvanting or using specific devise to deliver DNA vaccine construct, efficacy may be improved. Investigations exploring the cross reaction between the already existing immunity and immunity against newly developed vaccines would be of interest and useful for researchers. Further, researches should target whether vaccines and/or antibodies against ZIKV can induce Antibody Dependent Enhancement (ADE) resulting in subsequent enhancement of flavivirus infection. There are utmost requirements of sufficient resources in terms of infrastructure, funding, manpower, along with producing effective and safe ZIKV vaccine in commercial basis.
  Rekha Khandia , Ashok Munjal , Arvind Kumar , Gaurav Singh , Kumaragurubaran Karthik and Kuldeep Dhama
  The intrinsic property of Cell Penetrating Peptides (CPP) is to deliver various molecules including nucleic acids, large plasmids, therapeutic drugs, imaging molecules, liposomes, nano-molecules to various cell and tissues, which indicates about the potential of CPP as therapeutic vehicle molecules. These are easy to prepare, well characterized, versatile and have ability to link with bioactive cargo through covalent and non-covalent bonds. The interaction between cargo and CPP is highly dependent on physiochemical properties of CPP including size, pH and presence of basic residues in the carrier peptide. Primary mechanism of transport of CPP is endocytosis; however, evidences of endocytosis independent mechanisms including carpet model, inverted micelle model, barrel stave pore model and toroidal pore model are also present. Though, the natural CPP are often non- selective and passive, these may be tuned to become specific and targeted by conjugating them with functional groups and chemicals. In fact several natural CPPs such as penetratin, Tat, polyarginies etc have been modified to achieve maximum penetration and desired characters. Linear CPPs may be brought into multi-branched topology to give dendrimeric structures having more cell penetrating capacity, lower toxicity and hemolysis and higher serum stability. Site-specific targeting of CPP might be helpful in achieving several goals including enhancement in protein expression, gene silencing, formation of pleuripotent cells, reduction in inflammation and apoptosis, trans-epithelial transport, neuroprotection, ischemia treatment, treating insulin disorders, delivery of nucleic acids and agricultural pest control. The present review encompasses the detailed information regarding different modes of entry of CPP inside the cells, designing and classes of such peptides, along with theirs versatile therapeutic applications.
  Mayada Ragab Farag , Mahmoud Alagawany , Mohamed Ezzat Abd El-Hack , Muhammad Arif , Tugay Ayasan , Kuldeep Dhama , Amlan Patra and Kumaragurubaran Karthik
  Chromium (Cr) is one of the essential minerals which is required for improving productive performance in poultry due to its important functions in metabolism, growth and reduction of lipid and protein peroxidation. Under heat stress conditions, Cr plays a crucial role in poultry nutrition, production and health as well as enhances growth performance and quality of eggs in meat and egg type chickens, respectively. Supplementation of Cr may increase body weight gain, improve feed efficiency and there is also increase in carcass yield of broilers. Chromium is also a potent hypocholesteremic and antioxidant agent. The beneficial impacts of Cr have been linked with improved the metabolism and immune system. Dietary addition of Cr has promising impacts on the immune system through increasing relative weights of lymphoid organ such as thymus, spleen and bursa of Fabricius, declined heterophil/ lymphocyte (H/L) ratio, enhancing the Cell Mediated Immune (CMI) response and improving the antibody response versus the infectious diseases. Dietary supplementation of Cr may stimulate the secretion of digestive enzymes by improving the functions of liver and pancreas. Chromium present in many forms differs greatly in stability and oxidation states; therefore the added forms and concentrations should be managed well. Further, the increase in Cr dose in the diet could produce hazardous and toxic influences in chickens as well. This paper illustrates the positive and negative impacts of Cr including its physical and chemical proprieties, practical applications in poultry nutrition, production, enhancing immunity and health and a special reference to its toxic effects.
  Kuldeep Dhama , Ashok Munjal and Hafiz M.N. Iqbal
  This special issue is published in International Journal of Pharmacology (Vol. 13, Issue 7) with twenty peer-reviewed articles on recent advances and novel strategies for the development of biomedical therapeutics, immunomodulatory agents, delivery of drugs, and vaccines for safeguarding various health issues. The topics/themes covered include: Advances and progress in developing vaccines to counter the threats of Zika virus; Quinazolinone derivatives as a potential class of compounds in Malaria drug discovery; Innovations in the treatment options towards drug-resistant tuberculosis; The role of antioxidants in designing effective drugs for life threatening ailments; Promising anti-diabetic drugs, medicines and herbs; Medicinal values and beneficial applications of Psyllium husk (Plantago ovata), Green tea (Camellia sinensis); Medicinal applications of Stevia rebaudiana, a potential zero calorie sweetener, steviol glycosides; Anticancer and nutraceutical potentialities of phytase/phytate; Cell penetrating peptides as therapeutic vehicles and their use as anti-cancer peptide; Biomedical applications of pentatricopeptide repeat directed RNA editing with regards to diseases, cancers, and drugs; Next-generation sequencing for drug designing and cancer treatment; Progress towards various approaches from drug discovery to drug targeting; Advantages of selective drug distribution in cancer treatment with special reference to Brentuximab vedotin; G-protein coupled receptors in revolutionizing drug discovery and pharma based research; Bio-inspired synthesis of silver nanoparticles to combat antimicrobial resistance and other pharmacological potentialities; Usage of biomaterials-based hydrogels in biomedical sectors and drug delivery potentialities; Biomedical applications and utilization of diverse nanomaterials; Role of nanotechnology in animal and poultry nutrition; Applications of chromium in poultry nutrition and health, and the toxic effects. The articles published would be useful for medical and veterinary professionals, clinicians, researchers, students/scholars, animal producers, the pharmaceutical industry and biomedicine experts.
  Angel M. Villalba-Rodriguez , Kuldeep Dhama and Hafiz M.N. Iqbal
  In recent years, biomaterials-based hydrogels have gained special attention and moved into mainstream applications in various biomedical sectors. The pristine or improved characteristics of biomaterials-based hydrogels offer unique dimensions in changing the dynamics of 21st-century drug delivery applications. In this context, numerous researchers and research-based organizations have reported uniqueness and novel aspects of various biomaterials for drug delivery purposes and different approaches including in vitro, in vivo and ex-vivo techniques have been exploited, so far. Among various potent biomaterials, chitosan, poly(lactic-co-glycolic acid) (PLGA) and bacterial cellulose are of supreme interests due to their tunable multi-functionalities for an enhanced and efficient delivery. In addition, several characteristics including unique chemical structure, bioactivity, non-toxicity, biocompatibility, biodegradability, recyclability, etc. all positioned them well in various biomedical, pharmaceutical and nutraceutical sectors of the modern world. Herein, we reviewed biomaterials (chitosan, poly(lactic-co-glycolic acid) (PLGA) and bacterial cellulose) based hydrogels and their drug delivery potentialities. The information is also given on considerable future directions that can help in addressing the left behind research gaps and outstanding questions in future studies.
  Umair Muhammad , Xiaoyu Zhu , Zhaoxin Lu , Jinzhi Han , Jing Sun , Sultana Tayyaba , Benazir Abbasi , Farman Ali Siyal , Kuldeep Dhama and Jabbar Saqib
  Background and Objective: Vine tea (Ampelopsis grossedentata) may potentially perform multiple pharmacological roles, including antibacterial, anti-cancer, antioxidant, hepatoprotective and anti-hypertension functions. But effects of extraction polarity, time and temperature on the recovery of bioactive compounds along their pharmacological activity of vine tea extract have not been reported yet. The present study reports on the importance of extraction variables for obtaining vine tea extract aiding in purification and isolation of functional and polyphenolic compound and their pharmacological activity (polyphenols) from vine tea. Materials and Methods: The effects of extraction variables (time, temperature and polarity) on Total Phenolic Content (TPC), Total Flavonoid Content (TFC) and Condensed Tannin Content (CTC) were evaluated using single factor experiment. Antiradical capacity assay and radical-scavenging capacity 2,2-diphenyl-1-picrylhydrazyl (DPPH) were tested for evaluating the antioxidant activities of vine tea crude extract. To analyze data, one-way analysis of variance (ANOVA) was established followed by the Tukey’s test and to test the correlation, Pearson correlation coefficient was tested. Results: Data explained that extraction polarity, extraction time and the temperature had a significant effect (p<0.05) on yield and their anti-radical activities. The optimized extraction parameters for TFA and CTC were 40% aqueous ethanol at 45 while 50 for TPC for 180 min. Whereas, maximum yield were 40.01 μg Catechin Equivalent per gram (CE g–1) of Dry Weight (DW) for TFA, 15.12 μg, Gallic Acid Equivalent per gram of DW (GAE g–1) for TPC and 12.70 μg CE g–1 DW for CTC. Ethanol concentration showed a significant effect (p<0.05) on extraction of phenolic compounds and their pharmacological activity especially antioxidant capacity and DPPH assay. Conclusion: This study showed that extraction variables were greatly influence on the pharmacological activities of vine tea crude extract and this study can be used as preliminary and key information to design central composite rotatable design for Response Surface Methodology (RSM). Moreover, this approach can be used to determine significant factors that influence functional compounds and their other pharmacological activities.
  Mahima , Amit Kumar Verma , Ruchi Tiwari , K. Karthik , Sandip Chakraborty , Rajib Deb and Kuldeep Dhama
  Earth is rich in variety of plant species including the beneficial one having some medicinal properties. The use of herbal medicines for the treatment of various diseases like hepatitis, arthritis, chronic heart diseases, skin disorders, wounds and even cancer have been mentioned in our ‘ayurveda’ and proved scientifically by many researchers of modern times. Now-a-days, fruits and vegetables are gaining popularity in medicine for treating mastitis, foot-and-mouth disease, skin allergies, hypersensitivity reaction, tympany, food poisoning, retention of placenta etc. These medicines are suitable for both the human as well as animals being cost economic and without side effects. Out of 21,000 medicinal plants listed by World Health organization, 2,500 species are found in India making India the largest potential producer of medicinal herbs. The plant or herbs particularly the fruits and vegetables are the cheapest and most common store of nutrients viz., carbohydrates, protein, vitamin, minerals and essential amino acids along with dietary fiber and thus reducing the risk of cardiovascular and metabolic diseases and obesity. Apart from this, fruits and vegetables also supply additional vitamins and minerals to the diet and are important sources of phytochemicals that play important role as antioxidants, phytoestrogens and anti-inflammatory agents and through various protective mechanisms. Fruits and vegetables have the potential to develop nutritional ingredients and supplements, causing a change in the perception of horticultural crops and products and helps in anaerobic digestion. The present review discusses the role of fiber and health benefits of fruits and vegetables for humans and their companion animals.
  Ruchi Tiwari , Sandip Chakraborty , Mani Saminathan , Kuldeep Dhama and Shoor Vir Singh
  Ashwagandha (Withania somnifera) is a well known herb possessing several health benefits. The steroidal lactones (withanolides) obtained from its roots have been implicated in a wide range of therapeutic activities and maintaining general health: Immunomodulation, combating infectious agents, anti-cancer and anti-epileptic, memory enhancer, to promote good physical and mental health, mood elevator, diuretic, general tonic and rejuvenator, stress reliever, cardiorespiratory endurance enhancer, anti-ageing, anti-oxidant, hypoglycemic, hypocholesterolemic and in common an effective adaptogen. Steroidal alkaloids and lactones are the active constituents of the plant. Withanolides as per theory occupies the receptor sites in the cell membrane thereby preventing the attachment and subsequent exertion of the effect of actual hormone. Withanolides have got analgesic and anti-inflammatory activity due to cyclooxygenase-2 inhibition property. Ashwagandha enhances nitric oxide synthatase activity of the macrophages, which in turn increases the microbial killing power of these immune cells thereby enhancing the Cell Mediated Immune (CMI) response. A glycoprotein Glycowithanolides (WSG) commonly known as W. somnifera glycoprotein is responsible for antimicrobial activity. Milk supplemented with Ashwagandha has been reported to increase total proteins and body weight and the plant alone helps in inducing tolerance and dependence. Its anti-stress and radiosensitization action; beneficial effects on cardiovascular system and sexual behavior; curative properties against neurodegenerative diseases and poisoning due to toxins and chemicals (including snake venom) has made this plant a treasure of nature. Thus the plant is an important component of many polyherbal preparations. Important for researchers and scientists is that biotechnologically advanced techniques; novel disciplines of bioinformatics and genomics can help in identifying and generating bioactive principles of the plant. All these salient health applications of this herb in biomedicine and veterinary sciences are discussed in this review focusing its potent role in maintaining sound health, immunomodulatory effects, combating infections, therapeutic usages and other beneficial applications.
  Ruchi Tiwari , Amit Kumar Verma , Sandip Chakraborty , Kuldeep Dhama and Shoor Vir Singh
  Since ancient era, herbal therapy remained as medicine’s backbone which is economic, safer and easily available to most of people in world. Among diverse herbal treasure, Azadirachta indica (Neem) is a highly esteemed tree with several beneficial properties and applications especially known for its incredible therapeutic and ethnomedicinal values for humankind. Neem is regarded as “free tree of India”, “wonder tree”, “Nature’s drug store”, Village dispensary”, “Divine tree”, “heal all”, “Materia medica” and “Panacea of all Diseases”. It is among highly exploited medicinal plant of Indian origin. It has been used in different medicinal systems: ayurveda, unani, homoeopathic medicine, therefore, considered as cynosure of modern medicine. All parts of the plant have some biological and medicinal properties hence valuable source of natural medicinal products. Compounds isolated from neem are broadly classified into two: (1) Isoprenoids (2) Non-isoprenoids. Isoprenoid compounds consists of diterpenoids, triterpenoids and steroids while while non-isoprenoids contains proteins and/or amino acids, polysaccharides, flavonoids etc. It is found beneficial in leprosy, gastro-intestinal problems, malaria, intestinal helminthiasis, tuberculosis, ringworms, skin disorders, boils, epilepsy, fever, respiratory distress, nausea, ulcers and in many other health related problems. This review gives a bird’s eye view particularly on history, classification, active principles, mechanism of action and potential uses of neem in safeguarding human and animal health along with the several commercial preparations available in the market.
  Shoor Vir Singh , Saurabh Gupta , Kundan Kumar Chaubey , Krishna Dutta Rawat , Naveen Kumar , Jagdip Singh Sohal , Sarjeet Singh , Ruchi Tiwari , Sandip Chakraborty and Kuldeep Dhama
  Bovine Johne’s Disease (BJD) is a chronic granulomatous enteritis that affects ruminants worldwide and is having significant impact on the world economy and has been frequently reported from farm and farmer’s herds. An attack of Johne’s disease in a newly established cattle dairy farm consisting of high yielding Holstein Friesian (HF) cows in the Alwar district of Rajasthan was investigated for the first time in India. Since slaughter of cows is prohibited in India therefore management of bovine JD is critical for the success of dairy industry in the country and in this aspect the research paper is significant. Out of a total of 35 fecal samples screened by microscopy, 24 (68.5%) were positive for Mycobacterium avium subspecies paratuberculosis (MAP). Screening of 26 serum and 23 milk samples by ‘Indigenous ELISA kit’ employing semi-purified antigen of native strain (‘S 5’) of MAP, 24 (92.3%) and 14 (60.8%) were positive, respectively. Sensitivity of ‘Indigenous serum ELISA’ with reference to fecal microscopy and milk ELISA was 88.2 and 90.0%, respectively. Screening of blood samples of 14 cows, by specific PCR (IS900), 5 (35.7%) were positive. Genotyping of PCR positive HF crossbred cows using IS1311 PCR-REA showed presence of highly pathogenic ‘Indian Bison type’ genotype. Comparison of 3 tests (milk ELISA, fecal microscopy and IS900 PCR) with ‘Indigenous serum ELISA’ revealed substantial agreement between tests. Study also reported serious economic losses in terms of productivity (reduced quality and quantity of milk), reduced fertility and conception, decreased body weight and growth rate which left the farmer economy devastated due to attack of Johne’s disease in high yielding cattle herd of HF crossbred cows.
  Shoor Vir Singh , Naveen Kumar , Jagdip Singh Sohal , Ajay Vir Singh , Pravin Kumar Singh , Narottam Das Agrawal , Saurabh Gupta , Kundan Kumar Chaubey , Avnish Kumar , Krishna Dutta Rawat , Rajib Deb and Kuldeep Dhama
  Bio-load of Mycobacterium avium subspecies paratuberculosis was estimated in the first mass screening of human population in Mathura region of South Uttar Pradesh. Of the 48,919 samples collected between December, 2010 and March, 2013 from Pathology laboratories, 26,390 were screened by indigenous ELISA kit, IS900 blood and stool PCR, IS1311 PCR_REA and stool microscopy. Of the 23,196 serum samples screened by indigenous ELISA, 34.0% were positive for MAP infection (Mathura-35.4% and Agra 14.2%). Percent prevalence of MAP infection was 28.3, 41.8, 37.4, 29.5, 41.1, 40.7, 42.5, 36.5 and 51.2 in patients suspected for diabetes, liver disorders, anaemia, thyroid disorder, tuberculosis, typhoid, abdominal disorders, inflammatory illness and ion imbalance, respectively. Of 3093 blood samples screened by IS900 PCR, 8.4% were positive (Mathura-9.2% and Agra-7.9%). Percent prevalence of MAP was 4.8, 7.0, 20.0, 4.9, 17.8, 7.6 and 12.7 in patients suspected for diabetic, liver disorder, skin disorders, anaemia, Malaria, typhoid and apparently normal individuals, respectively. Of the 101 stool samples screened by microscopy, 5.9% were positive and of these 2.9% were confirmed by IS900 PCR. IS1311 PCR_REA bio-typing showed ‘Indian Bison Type’ was the most prevalent biotype. Study indicated large scale exposure of human population to MAP infection in the Mathura region of South Uttar Pradesh and like in animals‘Indian Bison Type’ was the most prevalent biotype of MAP infecting human beings in this region.
  Rekha Khandia , Abhinav Dwivedi , Akanksha Sahu , Pratibha Vishwakarma , Arvind Kumar , Kuldeep Dhama and Ashok Munjal
  Background and Objective: Angiogenesis (neovascularization) is an important process of forming new blood vessels, essential for embryonic development, reproduction, wound repair and growth. Present study reports the plausible angiogenic modulatory effects of the cadmium chloride (CdCl2). Cadmium (Cd) is a toxic substance, which have many inhibitory effects but also medicinally important. There are several toxic materials which in low quantity can be used in therapeutic aspects. Keeping in view, the effects of CdCl2 salt were investigated on the process of angiogenesis in chicken chorioallantoic membrane (CAM) model by assessing gross and histopathological alterations. Materials and Methods: The two groups of the embryonated chicken eggs (10 in each group, 1 control and 1 treated group) were taken and 200 μL of 0.5 M of CdCl2 was directly introduced on to the CAM. The resealed eggs were incubated for 72 h in a humid incubator chamber at 37±1°C. Then the eggs were opened to observe the gross and histopathological alterations for angiogenesis modulation. Results: Gross examination of CAM revealed the reduction in the number of secondary and tertiary blood vessels amongst CdCl2 treated group. Histopathological analysis revealed anti-angiogenic effects of CdCl2 due to the less number of blood vessels and presence of breached mesodermal blood vessels, out of which RBCs were oozing out. Occasional abnormal thickening and accumulation of densely arranged cells at chorionic and allantoic sides was also observed. Conclusion: The anti-angiogenic properties of CdCl2 can be explored in the therapeutics of cancer and tumor related disorders. However, to avoid any kind of side effects, further qualitative, quantitative analysis and critical dose determination is required before going for clinical trials. Present investigations revealed the anti-angiogenic effect of cadmium chloride salt on chicken chorioallantoic membrane.
  Kuldeep Dhama , Shyma K. Latheef , Hari Abdul Samad , Sandip Chakraborty , Ruchi Tiwari , Amit Kumar and Anu Rahal
  Signaling molecules of immune system are cytokines that may either stimulate or suppress the responses of various cells involved in host immune mechanisms and Tumor Necrosis Factor (TNF) is one of the leading members of the group of cytokines. TNF-α from activated macrophages and LT-α/TNF-Β from T cells have now become representatives of a distinctive superfamily of cytokine ligands (TNF ligand superfamily) along with their corresponding receptors (TNF receptor superfamily); altogether constituting the TNF Superfamily. These are highly conserved proteins, found in all mammals having important ligand members which interact with the either of the two receptors, TNFR1 and TNFR2, that initiate varied signaling cascades leading to diverse cellular responses. It has been established that the appropriate regulation of TNF ligand and receptor interactions and functions are crucial for the proper immune system activity. Excessive production of various TNF cytokines has been attributed with the development of an array of autoimmune as well as inflammatory conditions. TNF cytokines help to reduce mortality due to cardiovascular diseases. Therapeutic TNF blockers include:monoclonal antibodies to TNF (Infliximab and Adalumimab) and TNF receptor fusion proteins (Etanercept and Lenercept) and are effective against rheumatoid arthritis; ankylosing spondylitis; psoriasis and asthma. Preclinical studies conducted in murine models and the pivotal role played by the TNF superfamily in cytokine mediator system will make it easier for researchers as well as scientists to develop novel drugs in near future. This review has covered all these aspects concerning TNF as mediator of inflammatory diseases and its therapeutic targeting.
  Kuldeep Dhama , Sandip Chakraborty , Ruchi Tiwari , Amit Kumar , Anu Rahal , Shyma K. Latheef , Mohd Yaqoob Wani and Sanjay Kapoor
  Avian/Bird flu, caused by Avian Influenza Virus (AIV) belonging to Orthomyxoviridae family, is the most fearful viral disease of birds. H5N1 subtype of AIV is of major concern for poultry as well as for humans due to its high economical impacts and zoonotic concerns. During the past ten years, the Highly Pathogenic Avian Influenza (HPAI) H5N1 subtype alone has affected more than 60 countries of the world. Domestic poultry is mostly affected by the disease episodes and outbreaks. Wild and migratory birds are the AIV reservoirs wherein H5N1 is found to be lethal. Major antigenic changes in Haemagglutinin (HA) or Neuraminidase (NA) result in periodic pandemics. Pigs can act as mixing vessel. The bird flu virus if gets the capability of transmitting from human to human can trigger a pandemic claiming millions of lives. A wide variety of serological tests and molecular tools have greatly aided in the diagnosis of avian flu. Disease management for the prevention of bird flu outbreaks including mass awareness and pandemic preparedness following World Health Organization (WHO) guidelines is of utmost importance. Interesting approaches of HPAI control are development of universal influenza virus vaccines and universal antibodies-based flu therapies. Vaccination using inactivated and recombinant vaccines is the common strategy adopted in different parts of the globe. Development of new generation vaccines is quiet noteworthy. Tamiflu is the drug of choice. Herbal therapy is gaining much attention to control disease in humans. All these aspects of the bird flu virus have been discussed vividly in the present review.
  Shambhu Dayal Singh , Rajamani Barathidasan , Asok Kumar , Rajib Deb , Amit Kumar Verma and Kuldeep Dhama
  Marek’s Disease (MD), caused by Marek’s Disease Virus (MDV) is a highly contagious oncogenic and neuropathic disease of chickens responsible for great economic losses to the poultry industry all around the world and characterized by development of CD4+T cell lymphomas as well as infiltration of nerves and visceral organs by lymphocytes. MD is one of the most common lymphoproliferative diseases of chickens which cause mononuclear cell infiltration in one or more of the following tissues: peripheral nerves, gonads, lymphoid organs, iris, muscle, skin and other visceral organs resulting into development of tumours in visceral organs, paralysis of legs, wings and neck, grey eye (iris) or irregular pupil, vision impairment, blindness, skin lesions and immunosuppression, all of which can be accompanied by non-specific signs such as anorexia, weight loss and poor performance. Today there are evolving highly pathogenic isolates of MDV around the world capable of overwhelming the protection from currently employed vaccines. Thus MD poses a big challenge to the welfare and wellbeing of the poultry with increased condemnation of carcass, loss of productivity and quality products, leading to huge economic losses. It is also an immunosuppressive disease and causes increased susceptibility to other infections. The present review discusses in brief about the Marek’s disease, its etiology, conventional and advance tools and techniques being used for its diagnosis, prevention and control strategies in poultry.
  Kuldeep Dhama , Amit Kumar Verma , S. Rajagunalan , Rajib Deb , K. Karthik , Sanjay Kapoor , Mahima , Ruchi Tiwari , Parmod Kumar Panwar and Sandip Chakraborty
  Flu viruses have mainly affected humans, birds and pigs worldwide. During the past 10 years these viruses are in limelight at a global level due to pandemic threats of Avian / Bird Flu and Swine Flu and their public health impacts, with added pandemic of swine flu virus recently. The current ongoing episodes of bird flu and swine flu are beyond the control, when and where or which country they start with nobody can predict. The continuous evolution and emergence of new strains indicate that the flu viruses are becoming more and more dangerous and this situation has posed a challenge to researchers to discover effective vaccines and therapeutics. Moreover, the role of pig as ‘mixing bowl’ for the virus to get reassorted has added to the complicated epidemiological scenario. The swine flu H1N1 reassorted subtype caused the first global pandemic in last 40 years, resulting in substantial illness, hospitalizations of millions of peoples and thousands of deaths throughout the world. A pace is there within these novel and emerging flu viruses and the scientific community, where the scientific community has to win the race so as to save the mankind. In this review, a brief overview on swine flu is presented highlighting the characteristics of the causative virus, the disease and its public health consequences, advances made in its diagnosis, vaccine and control, precautionary measures to be adapted in the wake of an outbreak.
  Kuldeep Dhama , Sandip Chakraborty , Mahima , Mohd. Yaqoob Wani , Amit Kumar Verma , Rajib Deb , Ruchi Tiwari and Sanjay Kapoor
  Modern medicine has helped to a great extent to eradicate and cure several diseases of mankind and animals. But the existence of incurable diseases like cancer, Acquired Immunodeficiency Syndrome (AIDS), diabetes or rheumatoid arthritis, side effects of allopathic medicine, increasing trend of antibiotic resistance and chemicals and biopesticides causing dietary risk have made the situation more critical than ever before. Thus, it has become a matter of concern for the scientists and researchers to develop novel therapies. Bacteriophage therapy to treat pathogenic bacterial infections, virophage therapy for conservation of global system and avian egg yolk antibody therapy for designing prophylactic strategies against Gastrointestinal (GI) diseases are interesting approaches. Others include the use of cytokines as adjunctive immunomodulators, gene therapy focusing on diseases caused by single gene defects, RNAi technology to suppress specific gene of interest and apoptins for cancer treatment. Stem cell therapy against several diseases and ailments has also been discussed. The use of nanoparticles for better drug delivery, even though costly, has been given equal importance. Nevertheless, immunomodulation, be it through physiological, chemical or microbial products, or through essential micronutrients, probiotics, herbs or cow therapy prove to be cost-effective, causing minimum adverse reactions when compared to allopathy. Development in the field of molecular biology has created an enormous impact on vaccine development. The present review deals with all these novel and emerging therapies essential to safeguard the health of humans and companion animals.
  Shoor Vir Singh , Kuldeep Dhama , Kundan Kumar Chaubey , Naveen Kumar , Pravin Kumar Singh , Jagdip Singh Sohal , Saurabh Gupta , Ajay Vir Singh , Amit Kumar Verma , Ruchi Tiwari , Mahima , S. Chakraborty and Rajib Deb
  Johne’s disease or Paratuberculosis has emerged as major infectious disease of animals in general and domestic livestock in particular on global basis. There have been major initiatives in developed countries for the control of this incurable malady of animals and human beings alike (inflammatory bowel disease or Crohn’s disease). Disease has not received similar attention due to inherent complexities of disease, diagnosis and control, in resource poor counties around the world. However, the rich genetic diverstiy of the otherwise low productive animal population offers opportunity for the control of Johne’s disease and improve per animal productivity. Present review aims to gather and compile information available on genetics or resistance to Johne’s disease and its future exploitation by resource poor countries rich in animal diversity. This review will also help to create awareness and share knowledge and experience on prevalence and opportunities for control of Johne’s disease in the livestock population to boost per animal productivity among developing and poor countries of the world. Breeding of animals for disease resistance provides good, safe, effective and cheaper way of controlling Johne’s disease in animals, with especial reference to domestic livestock of developing and poor countries. Study will help to establish better understanding of the correlation between host cell factors and resistance to MAP infection which may have ultimately help in the control of Johne’s disease in future.
  Kuldeep Dhama , Amit Kumar Verma , S. Rajagunalan , Amit Kumar , Ruchi Tiwari , Sandip Chakraborty and Rajesh Kumar
  Listeriosis is a disease that causes septicemia or encephalitis in humans, animals and birds. Although, the disease is rare and sporadic in poultry but if occurs then causes septicemia or sometimes localized encephalitis. Occasionally, the disease is seen in young chicks and the causative agent, like in humans and animals, is Listeria monocytogenes. The organism is capable to infect almost all animals and poultry; however, outbreaks of listeriosis are infrequent in birds. It is widely distributed among avian species and chickens, turkeys, waterfowl (geese, ducks), game birds, pigeons, parrots, wood grouse, snowy owl, eagle, canaries, which appear to be the most commonly affected. Chickens are thought to be the carriers of Listeria and also the prime reservoirs for the infection and thus contaminate the litter and environment of the poultry production units. Listeriosis is often noticed along with other poultry diseases such as coccidiosis, infectious coryza, salmonellosis, campylobacteriosis and parasitic infections, signifying the opportunistic nature of the organism. Intestinal colonization of poultry and the presence of L. monocytogenes in feces represent a potential source of the organism for listeriosis in ruminants. Man gets infection from raw broiler meat due to Listeria contamination and unhygienic conditions of the processing area, rather than acquiring direct infection from birds. With the changing food habits of the people, the health consciousness is also increasing and since listeriosis has now been recognized as an emerging food borne zoonoses. Therefore, this review has been compiled to make aware the poultry producers and the consumers of poultry meat/products regarding the importance of the disease and its public health significance.
  Mahima , Abhijeet M. Ingle , Amit Kumar Verma , Ruchi Tiwari , K. Karthik , Sandip Chakraborty , Rajib Deb , S. Rajagunalan , Rajesh Rathore and Kuldeep Dhama
  There are ongoing trends of immunomodulation to combat a vast range of human and animal diseases including the incurable diseases like viral diseases, cancers, autoimmune diseases and inflammatory conditions. Animate as well as non-animate factors, surrounding us are interacting with our immune system. A balanced diet should contain all essential components from energy to vitamin and trace minerals. Each of these constituent has a very special effect on the immune system starting from their development to active role in immunity therefore, the outcome of their deficiency often ends in disease. Edible items which we consume like various vegetables, spices, herbs, fruits etc., are also equally responsible in manipulation of our system either in positive or negative way. Water has biggest share in our body and acts as the main medium to support the activities of the different system of body without exception of immune system. Proper environmental temperature is essential to maintain body’s functions and experiments carried out regarding the effect of temperature suggest that extremes of the temperature are often cause immunosuppression directly by acting on the cells of immunity or indirectly through inducing stress and thereby increasing production of catecholamine which are potent anti-immune molecules. Various pathogenic as well as non-pathogenic bacteria cause immune suppression and immune potentiation, respectively. Proper exercise hold a prime position in the healthy life as it supports immunity and keeps disease away. The present review deals with all these immunomodulators having both positive and negative impact on the health status of an individual.
  Anu Rahal , A. H. Ahmad , Amit Kumar , Mahima , Amit Kumar Verma , Sandip Chakraborty and Kuldeep Dhama
  Every time a drug is administered to the animal to treat an ailment, no matter whether it is acute or chronic manifestation, it usually goes together with some other prescription medicine, OTC (Over the counter) formulation, herbs or even food. All the xenobiotics such as drugs, toxins and food components as well as the endogenous compound that are formed in the animal body as a routine phenomenon exert a stimulatory or inhibitory effect on the different physiological and biochemical processes going in the body. These effects may alter the normal metabolism and/or drug transport or its efficacy drastically and thus expose the man and animals to the risk of a potentially dangerous interaction. The present review discusses these potential reactions and their mechanisms that help in navigating the hazardous combinations of drugs with other medicines, food, herbs, vitamins and minerals with confidence.
  Rajib Deb , Amit Kumar , Sandip Chakraborty , Amit Kumar Verma , Ruchi Tiwari , Kuldeep Dhama , Umesh Singh and Sushil Kumar
  Mastitis (inflammation of mammary gland) is a most devastating disease condition in terms of economic losses occurring throughout the world. The etiological agents may vary from place to place depending on climate; animal species and animal husbandry and include wide variety of gram positive and gram negative bacteria; and fungi. They may be either contagious viz. Staphylococcus aureus; Streptococcus agalactiae or environmental viz. S. dysgalactiae, S. uberis, Corynebacterium bovis and Coagulase negative Staphylococcus. Conventional diagnostic tests viz. California Mastitis Test (CMT); R-mastitest and Mast-O-test methods are applied under field conditions; whereas somatic cell count and Bulk Tank Somatic Cell Count (BTSCC) are useful for early mastitis detection and detection of sub clinical or chronic mastitis respectively. In vitro culture based diagnosis require further study as they can detect only viable cells. The advent of Polymerase Chain Reaction (PCR) technology along with its various versions like multiplex and real time PCR has improved the rapidity and sensitivity of diagnosis. Circulating micro RNA (miRNA) based diagnosis; immune assay and proteomics based detection along with biochips and biosensors prove to be asset to diagnosticians for advanced diagnosis of this economically important condition. Improvement of milking hygiene; implementation of post-milking teat disinfection; regular control of the milking equipments; implementation of milking order; Improvement of bedding material are the general measures to prevent new cases of mastitis. The use of antibiotics (intramammary infusions; bacteriocins) and herbs (Terminalia spp.) are important for prophylaxis and therapeutics. Vaccines viz. cell based; Recombinant (staphylococcal enterotoxin type C mutant) or chimeric (pauA); live (S. uberis 0140J stain based) and bacterial surface extract based; DNA-based and DNA-protein based have greatly aided in management of bovine mastitis. Quorum sensing and disease resistant breeding using novel biomarkers viz. toll like receptors (TLR) 2 and 4, interleukin (IL) 8; breast cancer type 1 susceptibility protein (BRCA1) and calcium channel voltage-dependent alpha 2/delta sub unit 1 (CACNA2D1) are also indispensable. This mini review gives an overview of all these different aspects that act as trend setters as far as the diagnosis and control of bovine mastitis is concerned to help the diagnosticians; epidemiologists and researchers not to remain ignorant about this grave condition.
  Kuldeep Dhama , Sandip Chakraborty , Amit Kumar Verma , Ruchi Tiwari , Rajamani Barathidasan , Amit Kumar and Shambhu Dayal Singh
  Fungal/mycotic diseases cause significant economic losses to the poultry industry either due to their direct infectious nature or due to production of mycotoxins, the secondary fungal metabolites produced in grains or poultry feed. Several fungi have created havoc in the poultry industry and some of them cause direct harm to human health due to their zoonotic implications. They are responsible for high morbidity and mortality, especially in young birds and cause stunted growth and diarrhea; and fatal encephalitis. Mycotic dermatitis is a possible health hazard associated with poultry houses. Mycotoxins are the leading cause of producing immunosuppression in birds, which makes them prone to several bacterial and viral infections leading to huge economic losses to the poultry industry. In comparison to bacterial and viral diseases, advances in diagnosis, treatment, prevention and control of fungal diseases in poultry has not taken much attention. Recently, molecular biological tools have been explored for rapid and accurate diagnosis of important fungal infections. Effective prevention and control measures include: appropriate hygiene, sanitation and disinfection, strict biosecurity programme and regular surveillance/monitoring of fungal infections as well as following judicious use of anti-fungal drugs. Precautionary measures during crop production, harvesting and storing and in feed mixing plants can help to check the fungal infections including health hazards of mycotoxins/mycotoxicosis. The present review describes the fungal pathogens causing diseases in poultry/birds, especially focusing to their diagnosis, prevention and control measures, which would help in formulating appropriate strategies to have a check and control on these unwanted troubles to the poultry producers/farmers.
  Ruchi Tiwari , Sandip Chakraborty , Kuldeep Dhama , Mohd. Yaqoob Wani , Amit Kumar and Sanjay Kapoor
  Darwin’s theory of natural selection and concept of survival of fittest of Wallace is a universal truth which derives the force of life among all live entities on this biosphere. Issues regarding food safety along with increased drug resistance and emerging zoonotic infections have proved that multidisciplinary efforts are in demand for human and animal welfare. This has led to development of various novel therapies the list of which remains incomplete without mentioning about phages. Homologous and non-homologous recombination along with point mutation and addition of new genes play role in their evolution. The rapid emergence of the antibiotic resistant strains of bacteria have created keen interest in finding necessary alternatives to check microbial infections and there comes the importance of phages. Phages kill the bacteria either by lysis or by releasing holins. Bacteriophages; the viruses that live on bacteria are nowadays considered as the best biocontrol agents. They are used as replacers of antibiotics; food industry promoter; guard of aquatic life as well as of plants; pre-slaughter treatment agents; Generally Recognized As Safe (GRAS) food additives; Typing agent of bacteria; active tool of super bug therapy; in post harvest crops and food and during post infection and also to combat intracellular pathogens viz. Mycobacteria and Mycoplasma. Cyanophages/phycophages are particularly useful in controlling blooms produced by various genera of algae and cyanobacteria. By performing centrifugation studies and based on electron microscopy certain virus like particles containing ds RNA have been confirmed as mycophages. They are well proven as threat to pathogenic fungi (both fungal hyphae and yeast). Those that infect yeasts are called zymophages. Virophages have exquisite specificity for their viral host, hence can extensively be used for genetic studies and can also act as evolutionary link. After the discovery of very first virophage till now, a total of 3 virophages have been discovered including the Sputnik virophages that are used to study genetic recombination. Virophages also find their application in antiviral therapy; as engineer of ecological system etc. In brief, present review deals with various dimensions of these beneficial viruses that are being used and can be successfully used in future for safeguarding biosphere including animal and human health.
  Ruchi Tiwari , Kuldeep Dhama , Sandip Chakraborty , Amit Kumar , Anu Rahal and Sanjay Kapoor
  Since the discovery of bacteriophages at the beginning of the 19th century their contribution to bacterial evolution and ecology and use in a variety of applications in biotechnology and medicine has been recognized and understood. Bacteriophages are natural bacterial killers, proven as best biocontrol agents due to their ability to lyse host bacterial cells specifically thereby helping in disease prevention and control. The requirement of such therapeutic approach is straight away required in view of the global emergence of Multidrug Resistant (MDR) strains of bacteria and rapidly developing resistance to antibiotics in both animals and humans along with increasing food safety concerns incuding of residual antibiotic toxicities. Phage typing is a popular tool to differentiate bacterial isolates and to identify and characterize outbreak-associated strains of Salmonella, Campylobacter, Escherichia and Listeria. Numerous methods viz. plaque morphology, ultracentrifugation in the density gradient of CsCl2, and random amplified polymorphic DNA (RAPD) have been found to be effective in detection of various phages. Bacteriophages have been isolated and recovered from samples of animal waste products of different livestock farms. High titer cocktails of broad spectrum lytic bacteriophages are usually used for clinical trial for assessing their therapeutic efficacy against antibiotic unresponsive infections in different animals. Bacteriophage therapy also helps to fight various bacterial infections of poultry viz. colibacillosis, salmonellosis and listeriosis. Moreover, the utility of phages concerning biosafety has raised the importance to explore and popularize the therapeutic dimension of this promising novel therapy which forms the topic of discussion of the present review.
  Narayan Mohapatra , Jag Mohan Kataria , Sandip Chakraborty and Kuldeep Dhama
  Egg Drop Syndrome-76 (EDS-76) is a recognized disease of chickens and Japanese Quails, which is of high economic importance due to its drastic negative effects on egg production in laying birds. The aim of the present study was to better understand the EDS-76 viral disease process in Japanese quails (Coturnix coturnix japonica), since very limited studies have been conducted in this species of birds. For this purpose, an experimental study was conducted with infection of EDS-76 virus in laying Japanese quails to reveal pathology, effect on egg production/quality and immune responses of this virus in these birds. By 7, 9 and 13-15 Days Post Infection (DPI), drop as well as aberrant egg production and lower mean egg quality were observed compared to control birds. Significant histopathological changes were observed in genitalia and spleen. Haemagglutination Inhibition (HI) and Enzyme Linked Immunosorbant Assay (ELISA) titres rose rapidly by 2nd week when it became maximum; thereafter declined and maintained at low levels up to 10 week post infection. The mean total protein values in infected quail gradually increased to 4.10±0.05/100 mL without any change in mean albumen value at 12 DPI. In conclusion, the course of the EDS-76 is significant not only in chickens but also in quails even though it occurs occasionally in quails. Explorative pathological, blood biochemical and immunological studies are suggested during EDS-76 viral disease course in quails. This would aid in formulating effective disease prevention and control measures for this economically important disease of poultry.
  Rajib Deb , Sandip Chakraborty , Mahima , Amit Kumar Verma , Ruchi Tiwari and Kuldeep Dhama
  Nutrigenomics a novel era in genomics research is based on puzzling issue on how nutrition and genes re-interacts. Perusal of literature reveals that very few information are available in this field and especially when it is associated with puberty in cattle which is a multigenic trait of great economic importance. Thus it opens a new area of research interest. Various markers like-gonadotropin releasing hormone/GNRH (responsible for sexual differentiation and reproduction), interstitial growth regulating factor/IGF1 (having signal controlling reproduction function linked to somatic growth); circulating metabolic hormones viz., leptin apart from GnRH and IGF1 (having impact on testicular development in peripubertal bull) are proved to be associated with male puberty in cattle. Various minerals (copper, selenium, manganese, zinc, chromium, iron and molybdenum) and vitamins (Vit. A, D, E and C) are directly or indirectly linked to male puberty. But no research till today initiated how the nutrients effect on the transcriptome/proteome/ metabolome level of marker genes associated with male puberty in cattle. Application of nanotechnology to make food safer for promotion of good health has created much excitement and nanoparticles has been developed against infectious diseases (e.g., Campylobacteriosis) affecting puberty along with certain nanocarriers that can facilitate the uptake of essential nutrients associated with puberty. Much of nutrigenomics research is however in infancy and hence the present mini-review will allow building the concept among researchers and scientists to initiate research in this interesting area.
  Kuldeep Dhama , K. Karthik , Sandip Chakraborty , Ruchi Tiwari , Sanjay Kapoor , Amit Kumar and Prasad Thomas
  Diagnosis is an important part in case of animal husbandry as treatment of a disease depends on it. Advancement in molecular biology has generated various sophisticated tools like Polymerase Chain Reaction (PCR), its versions along with pen-side diagnostic techniques. Every diagnostic test however has both advantages and disadvantages; PCR is not an exception to this statement. To ease the odds faced by PCR several non-PCR techniques which can amplify DNA at a constant temperature has become the need of hour, thus generating a variety of isothermal amplification techniques including Nucleic Acid Sequence-Based Amplification (NASBA) along with Self-Sustained Sequence Replication (3SR) and Strand Displacement Amplification (SDA) and Loop mediated isothermal amplification (LAMP) test. LAMP stands out to be a good and effective diagnostic test for empowering in developing countries as it does not require sophisticated equipments and skilled personnel and proves to be cost-effective. Performance of LAMP mainly relies on crafting of six primers (including 2 loop primers) ultimately accelerating the reaction. LAMP amplifies DNA in the process pyrophosphates are formed causing turbidity that facilitates visualisation in a more effective way than PCR. The Bst and Bsm polymerase are the required enzymes for LAMP that does not possess 5'-3' exonuclease activity. Results can be visualized by adding DNA binding dye, SYBR green. LAMP is more stable than PCR and real-time PCR. Non-involvement of template DNA preparation and ability to generate 109 copies of DNA are added benefits that make it more effective than NASBA or 3SR and SDA. Thus, it fetches researcher’s interest in developing various versions of LAMP viz., its combination with lateral flow assay or micro LAMP and more recently lyophilized and electric (e) LAMP. Availability of ready to use LAMP kits has helped diagnosis of almost all pathogens. LAMP associated technologies however needs to be developed as a part of LAMP platform rather than developing them as separate entities. This review deals with all these salient features of this newly developed tool that has enlightened the world of diagnosis.
  Mohd Yaqoob Wani , Kuldeep Dhama , Shyma K. Latheef , Rajamani Barathidassan , Ruchi Tiwari , Sandip Chakraborty , Milind Madhukar Chawak and Shambhu Dayal Singh
  Chicken Infectious Anaemia Virus (CIAV) is one of the potent immunosuppressive and economically important agents affecting poultry industry worldwide. Recent reports indicate the emergence of this virus in the poultry flocks of the country. The present study aimed to investigate the pathogenic potential of a recent isolate of CIAV obtained from poultry flock of Uttaranchal State, India. Twenty first day-old age Specific Pathogen Free (SPF) chicks were inoculated intramuscularly with 104.5 median tissue culture infective dose (TCID50) of CIAV passaged in the Marek’s disease virus transformed chicken splenic T lymphocyte (MDCC-MSB1) cell line while 15 chicks were kept as control. The CIAV isolate produced consistent clinical signs, loss in body weight gain, anaemia, low haematocrit values, bone marrow aplasia and generalized lymphoid atrophy. Mean Packed Cell Volume (PCV) value of the infected chicks was significantly low (18.22±2.22) compared to control group (34.12±4.72) at 14 day post infection (dpi). The establishment of virus infection in chicks was confirmed both at molecular and antigenic levels by Polymerase Chain Reaction (PCR) and Indirect Immunofluorescent Test (IIFT), respectively. Characteristic apoptotic pattern was also detected in the affected organs and the virus was re-isolated successfully in MDCC-MSB1 cell cultures. The present results revealed that the virus circulating in poultry flocks of Uttaranchal state is both pathogenic and immunosuppressive in nature. Extensive epidemiological studies are suggested in the poultry flocks of the country along with adaptation of appropriate diagnostic, prevention and control strategies so as to prevent economic losses caused by this important poultry pathogen.
  Kuldeep Dhama , Shambhu Dayal Singh , Rajamani Barathidasan , P.A. Desingu , Sandip Chakraborty , Ruchi Tiwari and M. Asok Kumar
  Growth in poultry sector is being challenged due to increased incidence and re-emergence of diseases caused due to evolution of several viral pathogens and use of live vaccines. Piles of economic losses are encountered due to these diseases. Avian Infectious Bronchitis (IB), caused by Corona virus, is OIE-listed disease and characterized by respiratory, renal and urogenital involvements, causing high mortality. Economic losses are encountered due to loss of productive performance of both egg and meat-type chickens. Variant viruses evolve due to spontaneous mutations and recombinations, causing disease in vaccinated flocks of all ages. Serotyping and genotyping are the common methods of classification of IBV strains. The virus has 4 clusters, grouped into 7 serotypes and the most important strains are Massachusetts, Connecticut, Arkansas, Gray, Holte and Florida along with numerous others, distributed round the globe. Several conventional and molecular diagnostic methods have been described for the diagnosis of IB in chickens. 'All-in/all-out' operations of rearing along with good biosafety measures forms the basis of prevention, whereas vaccination forms the backbone of IB control programme. Both live and inactivated (oil emulsified) conventional vaccines are available. The new generation vaccines (recombinant and vector-based) developed against locally prevailing IBV strains may be more helpful and avoid the reversion of virulence in live vaccine viruses. The present review deals with all these perspectives of this important emerging poultry pathogen.
  Naveen Kumar , Yashpal Singh Malik , Kuldeep Sharma , Vinayagamurthy Balamurugan , Sathish Bhadravati Shivachandra and Kuldeep Dhama
  Rotaviruses of group A (RVA) are foremost cause of diarrhoeal diseases in neonates of animals and humans worldwide leading to substantial economic losses. The RVA non-structural protein-4 (NSP-4), a viral enterotoxin, is known to be associated with infantile gastroenteritis/secretory diarrhoea by inducing pathological changes in the mature enterocytes. In this study, the carboxyl terminus of NSP4 protein (73M to 175M) from a bovine RVA was expressed in Escherichia coli Tuner (DE3) pLysS cells. The fusion protein (rNSP4ct, ~31 kDa) with hexa-histidine tags on its both termini was purified by affinity chromatography under native condition using Nickel-Nitrilotriacetic acid (Ni-NTA) agarose resin. The purified soluble recombinant NSP4ct was confirmed by Western blot. The structural analysis of rNSP4 protein revealed similarity between bovine RVA and human RVA (central tetrameric coiled-coil region) and confirmed that it was composed of mainly alpha helix (85%), lacking the beta strands. The rNSP4ct protein of bovine RVA has the potential of being used in developing diagnostics, assessing the biological activity (enterotoxin property) of rNSP4ct in understanding the pathogenesis in intestinal mucosa which would reveal the role of anti-NSP4 antibodies in protection against rotavirus infection and stimulation of mucosal immunity in animal model.
  Sana Ullah , Said Hassan and Kuldeep Dhama
  The current study was designed to assess heavy metals’ concentration in muscle tissues of two Chinese carps, common carp (Cyprinus carpio) and silver carp (Hypophthalmichthys molitrix), available to consumers in markets at district Lower Dir, Khyber Pakhtunkhwa, Pakistan. Fish specimens were collected from three main markets in the study area namely; Chakdara, Timergara and Khall. Heavy metals including; manganese (Mn), lead (Pb), iron (Fe), copper (Cu), zinc (Zn), cadmium (Cd) and cobalt (Co) were investigated using atomic absorption spectrophotometer. Cobalt was not detected in any of the fish specimens while the rest of the metals were lying within the permissible limits suggested by FAO/WHO and ITS for food/fish consumption. The results showed a statistically significant (p<0.05) difference between both species with respect to the concentration of the accumulated heavy metals. In common carp, the heavy metal accumulation was in order of Fe>Mn>Zn>Pb>Cu>Cd, while in silver carp the order was Fe>Mn>Zn>Pb>Cd>Cu. Higher concentration of Pb, Mn, Zn, Cu and Cd was recorded in muscle of common carp while the concentration of Fe was higher in silver carp, indicating higher potential of accumulation of heavy metals in common carp. Statistically significant (p<0.05) correlation was observed between Pb and Zn in common carp while between Cu and Cd in silver carp. The concentration of heavy metals was in the suggested permissible limits and poses no threat if consumed. In order to maintain the heavy metals level within permissible limits, proper care should be taken along with regular assessment.
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