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Articles by Mahmoud Kandeel
Total Records ( 5 ) for Mahmoud Kandeel
  Iman Abdelaziz and Mahmoud Kandeel
  Amikacin is a valuable aminoglycoside in serious infections. However, its use is associated with undesirable renal toxicity. This study was designed to check the effect of Nigella sativa oil and Allium sativum extract in ameliorating amikacin-induced renal damage by using a rat model of nephrotoxicity. Rats received nephrotoxic dose of amikacin and the amelioration of amikacin-induced nephrotoxicity was assessed through microscopic lesion scoring of damaged renal tissue and estimating the changes in biomarkers of tissue damage. Nigella sativa oil and Allium sativum extract significantly decreased the levels of NO, malondialdehyde and total antioxidant capacity. Furthermore, they increased the level of reduced glutathione. These changes are indicative for lower tissue damage and reduced free radical formation. These results were coinciding with the lower levels of urea, uric acid and creatinine (which were significantly elevated in amikacin treated groups). Semi-quantitative analysis of cellular infiltration, necrosis of tubular cells and tubular cellular damage indicated the protective effect of the used plant materials in reducing renal damage induced by amikacin. By using a rat model, Nigella sativa oil and Allium sativum extract efficiently ameliorated the renal toxic effect of amikacin. Further studies are required for applications in other animals or human subjects.
  Mahmoud Kandeel
  Coccidiosis and its following infection with clostridia in chicken are two common diseases in chicken. Ampicillin is a highly recommended therapy in clostridia infections in chicken. However, the effect of coccidiosis on ampicillin pharmacokinetics is not known. In this study, chicken infected with Eimeria tenella showed significant changes in ampicillin bioavailability and pharmacokinetics. Compared with noninfected chicken, intravenous injection of ampicillin in the infected chicken showed higher distribution and elimination constants and statistically significant higher AUC and MRT. Furthermore, oral administration in the infected chicken produced higher mean absorption time, delayed tmax, lower Cmax, smaller AUC value and lower bioavailability. Coccidiosis is the major predisposing factor for clostridia infections. Therefore, the use of ampicillin is highly expected following coccidiosis. Based on these results, monitoring and adjustment of ampicillin dosing could be practiced during the presence of coccidiosis.
  Abdullah Al- Taher , Mahmoud Kandeel , Hye-Sook Kim and Yukio Kitade
  The identification of extra-functional activities of enzymes is an attractive strategy for development of new antiparasitic drugs. In this study, the nuclease properties of Plasmodium Nucleoside Diphosphate Kinase (PfNDK) were demonstrated. The classical effect of PfNDK is the production of nucleotides for DNA/RNA synthesis. Such new nuclease activity of PfNDK implies the incrimination of the enzyme in functions other than its classical kinase activity. Such functions include apoptosis, regulation of cell cycle, cell division and repair of DNA damage. We have investigated the nuclease activity of Plasmodium falciparum Nucleoside Diphosphate Kinase (PfNDK). The nature of the nucleotide sequence and the length of the DNA substrate were critical factors in PfNDK’s nuclease activity. The PfNDK was unable to bind to oligonucleotides, although it formed aggregates with oligonucleotides that contained repeated pyrimidine nucleotides in their sequence. The enzyme was unable to cleave a supercoiled plasmid, whereas DNA substrates of various lengths were cleaved in a time- and concentration-dependent manner. Furthermore, ATP at a concentration of 1 mM was able to inhibit the nuclease activity. These data is valuable in highlighting the possible role of PfNDK in cellular functions other than its classical nucleotide kinase activity. Specific PfNDK inhibition is expected to modulate parasites cell cycle and induction of apoptosis.
  Yousef Altaher , Masayuki Nakanishi and Mahmoud Kandeel
  While camels rapidly evoluted several genes to adapt their environment, contemporary studies recorded that camels are sensitive to toxicity with some drugs as monensin, narasin and maduramicin ionophores compounds, which are extensively used in veterinary medicine. Recently, camel genome was resolved, which will allow for discovery of secrets of camel life. To this end, it is not known whether camel cytochrome enzymes were specially developed or adapted to camel environment or it has been associated with increasing the susceptibility of camels to toxicity with drugs. The objectives of this work are annotation of camel genome and retrieval of camel for cytochrome P450 1A2 (CYP 1A2) for phylogenetic, molecular modeling studies, docking studies and determination of its drug binding power. Results indicated poor efficiency of camel CYP 1A2 in binding with drugs. Furthermore, despite the high evolution of many camel genes to adapt camel environment, CYP 1A2 was found to be phylogenetically retarded gene showing lower rate of evolution compared with subset of data from 100 different organisms. These results suggests the potential toxicity of camels with drugs undergoing oxidation by CYP 1A2.
  Mahmoud Kandeel , Iman Abdelaziz , Nagwan Elhabashy , Hanaa Hegazy and Yasmin Tolba
  Gentamicin (GS) is a potent antimicrobial exhibiting concentration dependent bacterial killing. A high dose of gentamicin (10 mg kg-1) is required to reach sufficient concentrations in specific fluids as cerebrospinal fluid and to be effective on antibiotics resistant bacteria as well as treatment of acute and dangerous illness. Using a rat model, the renal toxicity and oxidative stress of administering gentamicin (10 mg kg-1 daily for 7 days) either in a single dose or divided into 2 doses was investigated. The safety of dose regimens was assessed through oxidant-antioxidant parameters as well as renal function tests. Typical renal damage and high oxidative stress were evident in the control group receiving 100 mg kg-1 gentamicin daily for 7 days. This was verified by high serum urea, uric acid, creatinine as well as increase in the levels of oxidative stress biomarkers as malondialdehyde, NO, total antioxidant capacity and decrease in reduced glutathione level. At any of the used regimen, 10 mg kg-1 gentamicin did not provide high compromise for renal functions nor significantly increased the oxidative stress and tissue damage. Based on microscopic lesions scores and biochemical analysis, there were no significant differences between single or two divided dosages of gentamicin at dose rate of 10 mg kg-1 day-1. Further studies are required for applications in other animals of human subjects.
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