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Articles by Srikumar Chakravarthi
Total Records ( 10 ) for Srikumar Chakravarthi
  Srikumar Chakravarthi , Choo Zhen Wei , H.S. Nagaraja , Wong Shew Fung , Mak Joon Wah and Shalini Sreekumar
  Candidiasis is a fungal infection which is prone to occur in people with immunosuppression due to debilitating diseases and nosocomial causes. While few studies have shown evidence of this disease co-existing with malignancy-induced immunosuppression disease, there never were any exclusive animal studies demonstrating this relationship, especially cerebral candidiasis with breast cancer. In fact, the exact causative mechanism of candidiasis is by and large still under much speculation. This study aims to demonstrate this relationship by observing the histopathological changes of the brain harvested from female Balb/c mice which were experimentally induced with breast cancer and inoculated with Candida. The mice were randomly assigned to 5 different groups (n = 12). The first group (Group 1) was injected with Phosphate Buffer Solution (PBS), the second group (Group 2) with Candida, third group (Group 3) with breast cancer and the final two groups, fourth and fifth group (Group 4 and 5) having co-existence of candidiasis and breast cancer at 2 different doses of candidiasis respectively. Inoculation of mice with candidiasis was done by intravenous injection of Candida albicans via the tail vein after successful culturing methods. Induction of mice with breast cancer is via injection of 4T1 cancer cells at the right axillary mammary fatpad after effective culturing methods. The prepared slides with the brains were stained with Haematoxylin and Eosin (H and E), Periodic Acidic Schiff (PAS) and Gomori Methenamine Silver (GMS) stains for histopathology analysis. Grading of primary tumour and identification of metastatic deposits were done. Scoring of inflammation and congestion in the brains was done. Statistical tests done to compare group 2 and 4 showed that group 4 exhibited a highly statistically significant increase in inflammation and congestion (p<0.01), especially in the cerebral areas. The median severity of candidiasis was also increased in group 4 as compared to group 2. In conclusion, based on the above evidences, cerebral candidiasis was significantly increased in mice with breast cancer.
  Nagaraja Haleagrahara , Tan Jackie , Srikumar Chakravarthi and Anupama Bangra Kulur
  The present study was designed to investigate the effects of alpha Lipoic Acid (LA) against lead acetate induced changes in free radical scavenging enzymes and lipid hydroperoxides in bone marrow of rats. Rats were exposed to lead acetate in their drinking water (500 ppm) for 14 days and alpha lipoic acid was given concurrently (25, 50 and 100 mg kg-1). Blood lead levels, lipid hydroperoxides, protein carbonyl contents and oxidative marker enzymes were estimated. Lead acetate in drinking water had elicited a significant (p<0.05) increase in bone marrow lipid hydroperoxides (LPO) (p<0.05) and Protein-Carbonyl-Contents (PCC). There was a significant (p<0.05) decrease in total antioxidants, superoxide dismutase (p<0.05), glutathione peroxidase (p<0.05), glutathione S-transferase (p<0.05) and catalase levels with lead ingestion. Supplementation of alpha lipoic acid was associated with reduced serum LPO and PCC and a significant (p<0.05) increase in total antioxidants and antioxidant enzyme levels . There was more significant protective effect of bone marrow with 100 mg kg-1 b.wt. LA. The potency of alpha lipoic acid on the reversal of lead induced changes in oxidative biomarkers in bone marrow confirms the importance of lead induced oxidative stress in bone and suggests a therapeutic approach.
  Shonia Subramaniam , Ammu Radhakrishnan , Srikumar Chakravarthi , Uma Devi Palanisamy and Nagaraja Haleagrahara
  This study investigated the antidiabetic effects of the rind of Nephelium lappaceum extract in a high fat-induced diabetic rat model. Ethanolic N. lappaceum rind extract was prepared and standardised with geraniin using high performance liquid chromatography. Male Sprague Dawley rats were fed on a high fat diet followed by 210 mg kg–1 nicotinamide and 55 mg kg–1 streptozotocin injection to induce type 2 diabetes. The diabetic rats were treated with N. lappaceum rind at concentrations of 500 and 2000 mg for 28 days. Positive control rats were treated with 200 mg metformin. A 41.1% yield of ethanolic extract was obtained from powdered N. lappaceum rind while geraniin present in the extract was quantified to be 33.0±0.2 mg geraniin/g extract. Our study also showed that the diabetic rats treated with 2000 mg N. lappaceum had reduction in blood glucose level and improved insulin levels which were similar to the metformin-treated group. Pancreas histology showed that the group treated with 2000 mg of N. lappaceum had healthy pancreas morphology and the treatment was comparable to the effects observed in the metformin-treated group. In conclusion, N. lappaceum rind extract showed anti-hyperglycaemic activity at a dose of 2000 mg kg–1 without any major toxic effects in high-fat diet induced diabetic rats.
  Shashi Kumar , Srikumar Chakravarthi , Gan Seng Chiew , Thavamanithevi Subramaniam , Umadevi Palanisamy , Ammu Radhakrishnan and Nagaraja Haleagrahara
  Pathogenic mechanisms of arthritis are studied using Collagen-Induced Arthritis (CIA) animal models. Plant derived antioxidants are known to reduce the inflammatory response in CIA. The aim of the study was to assess the protective efficacy of Nephelium lappaceum ethanol extract against Collagen-Induced Arthritis (CIA) in dark agouti rats. Arthritis was induced with 4 mg kg-1 of collagen in complete Freund's adjuvant. CIA rats were orally treated with 100 and 200 mg kg-1 per oral of N. lappaceum from day 25-50. Changes in body weight, joint thickness, C-reactive protein were recorded and immunohistochemistry for matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) was done. N. lappaceum (100 and 200 mg kg-1) significantly reduced (p<0.05) the arthritis-induced changes in body weight and paw edema. There was a significant reduction (p<0.05) in the C-reactive protein in the treatment groups. A significant reduction (p<0.05) in the arthritis-induced histopathological changes was seen after treatment with N. lappaceum. Treatment with N. lappaceum showed dose dependent effects on MMP-13 and TIMP-1 levels. N. lappaceum rind extract significantly suppressed the physiological, biochemical and histopathological changes produced during collagen-induced arthritis in dark Agouti rats. N. lappaceum extract supplementation may be beneficial in preventing the tissue damage and inflammatory conditions in arthritis.
  Shonia Subramaniam , Srikumar Chakravarthi , Uma Devi Palanisamy , Ammu Radhakrishnan and Nagaraja Haleagrahara
  Nephelium lappaceum is a tropical fruit native to Malaysia. The rind of N. lappaceum, is having extremely high antioxidant and free radical scavenging activities. The ethanol extract from the rind of Nephelium lappaceum was evaluated for acute and sub-chronic toxicity study in Sprague Dawley rats. In the acute study, a single oral administration of N. lappaceum rind extract (50, 200, 1000 and 2000 mg kg-1) was administered to rats for 14 days. In the sub chronic toxicity study, the extract was administered to rats (500, 2000 mg kg-1) for 28 days. There was no mortality, or adverse effects observed in rats. There was no significant difference observed in relative organ weights and the biochemical analysis (serum urea, creatinine, ALP, AST and total protein). Histological observation of liver and kidney also did not reveal any significant changes. In conclusion, present study showed that the lethal dose of ethanol extract of Nephelium lappaceum rind is more than 2000 mg kg-1 and there is a huge margin of safety for the therapeutic use. No-observed-adverse-effect-level (NOEL) of the extract is considered to be up to 2000 mg kg-1 day-1 for 28 days in rats.
  Srikumar Chakravarthi , Linda Tjoa Husin , P.M. Thani and Nadeem Irfan Bukhari
  Benign Prostatic Hyperplasia (BPH) is an enlargement of the prostate gland caused by an increase in the number of glandular units. Apoptosis is a programmed cell death necessary for the regulation of the size of organs in adult life. Disruption of apoptotic pathways has been suggested as an important regulatory mechanism in BPH. A high level of the BCL-2 protein suppresses apoptosis by preventing the activation of the enzymes that carry out the process. In this study, an attempt was made to observe the abnormal expression of BCL-2 protein in BPH tissues in paraffin sections and to demonstrate the disruption of apoptotic pathways in BPH. Prostatic tissue from 30 patients with BPH and no prior prostatic carcinoma were obtained by transurethral resection of prostate procedure. Apoptotic index was compared in the H and E sections. Expression of BCL-2 was analyzed by immunohistochemistry and evaluated. Apoptotic index in BPH tissues was found to be twice lower than that of normal tissues. Wilcoxon signed rank test was employed and the p-value proved that the results were highly significant (p<0.01). This data supported the research hypothesis that apoptotic index is decreased in benign prostatic hyperplasia. Out of 30 tissue samples, 20 (67%) shown positivity for BCL-2 expression. Kendall’s Tau-B test was applied and the result showed negative correlation between the intensity of BCL-2 expression and apoptosis, however not significantly. This proves, the theory that BCL-2 regulates individual cell death up to a certain extent.
  John Paul Judson , Lee Pui Fun , Vishna Devi Nadarajah , Sivalingam Nalliah , Srikumar Chakravarthi , P. Thanikhacalam and L. Santhanaraj
  Gestational hypertension and preeclampsia account for 5-7% of the maternal mortality and morbidity worldwide. Gestational hypertension and preeclampsia is characterised by blood pressure of 140/90 mm Hg or greater after the 20th week of gestation. The aetiology of gestational hypertension and preeclampsia is closely related to the disorder of placenta implantation. It is thought that shallow trophoblast invasion into maternal decidua causes malfunction of the utero-placental arteries, thus leading to both the diseases. The exact cause of shallow trophoblast invasion remains controversial. Placenta implantation involves activation and migration of trophoblast into the decidua and myometrium. These processes are dependent on keratin expression where activation of appropriate adhesion molecules and integrins are essential for appropriate trophoblast activity. This integrated study aimed to detect and analyse the trophoblastic keratin expression, as well as to examine the placenta ultrastructure for presence of degenerative changes in normal, gestational hypertensive and preeclamptic placenta. Immunofluorescence double staining method was performed on placental sections and trophoblastic expression of keratin 19 (K19) and keratin 18 (K18) were analysed qualitatively and quantitatively in normal (n = 10), gestational hypertensive (n = 10) and preeclamptic (n = 10) placenta. Statistical analysis of means was performed using one-way ANOVA. Representative placental samples from each of three groups were analysed via electron microscopy. Immunofluorescence results showed that both K19 and 18 expression in gestational hypertension and preeclampsia were reduced compared to normal but significant reduction was observed only for K19 expression in gestational hypertensive placenta. Gestational hypertensive placenta showed more reduction than preeclampsia for both keratins. Electron microscopic results demonstrated obvious degeneration and significant changes in the placental ultrastructure in all representative samples of gestational hypertension and preeclampsia when compared to normal. The redearchers conclude that the fundamental link exists between keratin expression and placental ultrastructural changes. The present keratin findings, especially in gestational hypertension, need to be confirmed by larger studies in future.
  Srikumar Chakravarthi , Ang Seng Long , Beh Hannien , Thani Pasupati , Kandasamy Palayan and Arni Talib
  For evaluation of the prognostic relevance of p53 expression in gastric cancer, the immunohistochemical tissue status of 66 primary gastric cancer patients was investigated for p53 expression and the association between p53 tissue status and clinicopathological parameters was analyzed. p53 immunoreactivity was detected in the nuclei of cancer cells in 42 cases (63.7%). The nuclear p53 immunoreaction was closely associated with tumour location, lymph node metastasis and curability. Tumours with positive p53 stain reactions frequently metastasized to lymph nodes (metastatic rate: 88.3%) in contrast to tumors with negative p53 stain reactivity (59.4%, p<0.005). Immunohistochemical analysis of primary gastric cancer appears to be an accurate and simple method of screening for p53 expression. In combination with common prognostic parameters, determination of p53 tissue status might help to detect prognostically unfavourable subgroups of gastric cancer patients.
  Srikumar Chakravarthi , Nagaraja Haleagrahara , Chong Fu Wen , Nagaraja Lee and P.M. Thani
  Cyclosporine-A (CsA) is an immunosuppressant prescribed in organ transplants to prevent rejection. It is a calcineurin inhibitor produced by the fungi Trichoderma polysporum and Cylindrocarpon lucidum, its adverse effect of renal dysfunction has limited its use in a clinical setting. Apigenin (4', 5',7'-Trihydroxyflavone), a herbal extract, with anti-inflammatory and anti-tumour properties has shown to reverse this adverse effect. This research was conducted to study the effects of apigenin on reversal of Cyclosporine-A induced damage and this was assessed by immunohistochemical estimation of expression of c-myc and estimation of apoptosis in histopathological sections. Rats were divided into groups and administered with CsA with Apigenin in different doses. The kidneys from the rats were harvested, weighed and observed for gross pathology changes. The renal tissue was processed and stained for haemotoxylin and eosin staining, to assess the apoptotic index and stained by immunohistochemistry, for the analysis of the apoptosis regulatory gene c-myc. The apoptotic index was then compared with the c-myc intensity to observe for any correlation. It was found that there was a high apoptotic index and c-myc intensity in the Cyclosporine-A group. Apigenin managed to reduce the values of both parameters. The apoptotic index correlated with the c-myc intensity, especially in the glomeruli. The study proved that Cyclosporine-A enhanced the expression of c-myc in the rat kidney, which signifies accelerated apoptosis. Therefore, c-myc and apoptotic index may be used to assess apigenin and its effect on Cyclosporine-A induced renal damage.
  Srikumar Chakravarthi , H.S. Nagaraja , Choo Zhen Wei and Wong Shew Fung
  Candidiasis is a fungal infection which patients with solid malignancies are at high risk. While few studies have shown evidence of this disease co-existing with malignancy-induced immunosuppression disease, there never were any exclusive animal studies demonstrating this relationship, especially cardiac candidiasis with breast cancer. In fact, the exact causative mechanism of candidiasis is by and large still under much speculation. This study aims to demonstrate this relationship by observing the histopathological changes of the hearts harvested from female Balb/c mice which were experimentally induced with breast cancer and inoculated with candida. The mice were randomly assigned to 5 different groups (n = 12). The first group (group 1) was injected with Phosphate Buffer Solution (PBS), the second group (group 2) with candida, third group (Group 3) with breast cancer and the final two groups, fourth and fifth group (Group 4 and 5) having co-existence of candidiasis and breast cancer at 2 different doses of candidiasis, respectively. Inoculation of mice with candidiasis was done by intravenous injection of Candida albicans via the tail vein after successful culturing methods. Induction of mice with breast cancer is via injection of 4T1 cancer cells at the right axillary mammary fatpad after effective culturing methods. The prepared slides with the livers were stained with Haematoxylin and Eosin (H and E), Periodic Acidic Schiff (PAS) and Gomori Methenamine Silver (GMS) stains for histopathology analysis. Grading of primary tumour and identification of metastatic deposits were done. Scoring of inflammation and congestion in the liver was done. Statistical tests done to compare group 2 and 4 showed that group 4 exhibited a highly statistically significant increase in inflammation and congestion (p<0.01). The median severity of candidiasis was also increased in group 4 as compared to group 2. In conclusion, based on the above evidences, cardiac candidiasis was significantly increased in mice with breast cancer.
 
 
 
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