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Jarouliya U.,Jiwaji University | Anish Zacharia J.,Jiwaji University | Kumar P.,Defence Research and Development Establishment DRDE | Bisen P.S.,Jiwaji University | And 2 more authors.
Indian Journal of Medical Research | Year: 2012

Background & objectives: Diabetes mellitus is a metabolic disorder characterized by hyperglycaemia. Several natural products have been isolated and identified to restore the complications of diabetes. Spirulina maxima is naturally occurring fresh water cyanobacterium, enriched with proteins and essential nutrients. The aim of the study was to determine whether S. maxima could serve as a therapeutic agent to correct metabolic abnormalities induced by excessive fructose administration in Wistar rats. Methods: Oral administration of 10 per cent fructose solution to Wistar rats (n=5 in each group) for 30 days resulted in hyperglycaemia and hyperlipidaemia. Aqueous suspension of S. maxima (5 or 10%) was also administered orally once daily for 30 days. The therapeutic potential of the preparation with reference to metformin (500 mg/kg) was assessed by monitoring various biochemical parameters at 10 day intervals during the course of therapy and at the end of 30 days S. maxima administration. Results: Significant (P<0.001) reductions in blood glucose, lipid profile (triglycerides, cholesterol and LDL, VLDL) and liver function markers (SGPT and SGOT) were recorded along with elevated level of HDL-C at the end of 30 days therapy of 5 or 10 per cent S. maxima aquous extract. Co-administration of S. maxima extract (5 or 10% aqueous) with 10 per cent fructose solution offered a significant protection against fructose induced metabolic abnormalities in Wistar rats. Interpretation & conclusions: The present findings showed that S. maxima exhibited anti-hyperglycaemic, anti-hyperlipidaemic and hepatoprotective activity in rats fed with fructose. Further studies are needed to understand the mechanisms. Source

Khan Z.,Jiwaji University | Khan Z.,French Institute of Health and Medical Research | Khan Z.,Madhav Institute of Technology and Science | Tiwari R.P.,RFCL Ltd | And 5 more authors.
Current Gene Therapy | Year: 2012

Survivin is known to be highly-expressed in various carcinomas; and is associated with their biologically aggressive characteristics and drug resistance. We have previously reported survivin as an important anti-apototic protein involved in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and providing resistance to conventional cancer therapies. The purpose of present study was to investigate the potential of survivin as a therapeutic target in HNSCC. This study was designed to explore the effect(s) of survivin-siRNA therapy on the apoptosis in HNSCC cells, and its influence on cisplatin-sensitivity. Lentivirus vector was developed to deliver survivin specific siRNA into cancer cells. The data indicates that silencing of survivin-mediated by Lentivirus-siRNA therapy effectively suppressed cancer cell proliferation and induced caspase-dependent apoptosis in HNSCC cells. The study also shows that the response of HNSCC cells to cisplatin drug treatment at clinically relevant level was limited. We observed survivin to be a key factor involved in this cisplatin-resistance mechanism, and down-regulation of survivin significantly increased sensitivity of cancer cells to cisplatin-mediated apoptosis. Thus, this combination therapy acts as a multimodality regimen with significant potential to improve clinical outcomes in head and neck cancers. © 2012 Bentham Science Publishers. Source

Srivastava A.,Indian Institute of Toxicology Research | Yadav S.,Indian Institute of Toxicology Research | Sharma A.,Indian Institute of Toxicology Research | Dwivedi U.,University of Lucknow | And 2 more authors.
Xenobiotica | Year: 2012

Freshly prepared peripheral blood lymphocytes (PBL) are known to express cytochrome P450s (CYPs) and glutathione S-transferases (GSTs) involved in the bioactivation and detoxification of organic components of diesel exhaust particles (DEPs). To validate that blood lymphocyte expression profiles could be used as a biomarker to predict exposure to vehicular emissions, similarities in the alterations in the mRNA expression of CYPs and GSTs were studied in PBL and lungs of rats exposed to DEPs. Adult male Wistar rats were treated transtracheally with different doses of DEPs (3.75- or 7.5- or 15- or 30-mg/kg b.wt.). The animals were anaesthetized after 24h and blood was drawn and lungs were taken out and processed. DEP produced a similar pattern of increase in the mRNA expression of CYPs (CYP1A1, 1A2, 1B1, 2E1), associated arylhydrocarbon receptor (Ahr) and arylhydrocarbon nuclear translocator (Arnt) and GSTs (GSTPi, GSTM1 and GSTM2) at all the doses in lungs and PBL. The protein expression of CYP1A1/1A2 and 2E1 and catalytic activity of CYPs and GSTs also showed a similar pattern of increase in blood lymphocyte and in lungs isolated from DEP treated rats. Our data indicating similarities in the alterations in the expression of carcinogen metabolizing CYPs and GSTs in PBL with the lung enzymes suggests the suitability of using expression profiles of blood lymphocyte CYPs and GSTs as a biomarker to predict exposure to vehicular emissions. © 2012 Informa UK, Ltd. Source

Reddy V.,National Institute of Mental Health and Neuro Sciences | Ravi V.,National Institute of Mental Health and Neuro Sciences | Desai A.,National Institute of Mental Health and Neuro Sciences | Parida M.,Defence Research and Development Establishment DRDE | And 2 more authors.
Journal of Medical Virology | Year: 2012

Chikungunya fever a re-emerging infection with expanding geographical boundaries, can mimic symptoms of other infections like dengue, malaria which makes the definitive diagnosis of the infection important. The present study compares the utility of four laboratory diagnostic methods viz. IgM capture ELISA, an in house reverse transcription PCR for the diagnosis of Chikungunya fever, TaqMan real-time PCR, and a one step reverse transcription-loop mediated isothermal amplification assay (RT-LAMP). Out of the 70 serum samples tested, 29 (41%) were positive for Chikungunya IgM antibody by ELISA and 50 (71%) samples were positive by one of the three molecular assays. CHIKV specific nucleic acid was detected in 33/70 (47%) by reverse transcription PCR, 46/70 (66%) by TaqMan real-time PCR, and 43/70 (62%) by RT-LAMP assay. A majority of the samples (62/70; 89%) were positive by at least one of the four assays used in the study. The molecular assays were more sensitive for diagnosis in the early stages of illness (2-5 days post onset) when antibodies were not detectable. In the later stages of illness, the IgM ELISA is a more sensitive diagnostic test. In conclusion we recommend that the IgM ELISA be used as an initial screening test followed one of the molecular assays in samples that are collected in the early phase of illness and negative for CHIKV IgM antibodies. Such as approach would enable rapid confirmation of the diagnosis and implementation of public health measures especially during outbreaks. © 2012 Wiley Periodicals, Inc. Source

Tiwari R.P.,RFCL formerly Ranbaxy Fine Chemical Ltd. | Jain A.,RFCL formerly Ranbaxy Fine Chemical Ltd. | Khan Z.,Institute Pasteur Paris | Kumar P.,RFCL formerly Ranbaxy Fine Chemical Ltd. | And 2 more authors.
Journal of Immunological Methods | Year: 2013

HIV (human immunodeficiency virus) infection has now become endemic worldwide and AIDS ranks fourth among the world's top killers of mankind. A rapid and accurate HIV testing assay is a pre-requisite for practical applicability of diagnostic tests. The aim of this present study was to design peptide cocktail as an antigen and to develop ELISA test for HIV-1/2 antibody detection, with enhanced sensitivity and specificity. A novel peptide stretch V3-I, covering immunodominant epitope corresponding to V3 hypervariable loop of gp120 antigens of selected Indian isolates, has been studied and incorporated in an antigenic cocktail of gp36, gp41, and rp24 of HIV-1/2. Peptides from these antigens were chemically synthesized and an additional cysteine residue was added at both amino- and carboxyl-terminal sequences of each peptide in order to form inter and intramolecular disulfide bond for the folding of peptides. This generated conformational epitopes with increased oligomericity and stability of peptide sequences; and attachment of antigen to the solid support of ELISA plates. The use of antigenic cocktail of folded peptides and recombinant p24 enhanced sensitivity and specificity of the ELISA test. Evaluation of the test using 1123 serum samples in comparison with Boston Biomedical Incorporation (BBI) panels showed 100% sensitivity and 99.3% specificity with no cross reactivity tribulation. In conclusion, "HIV screen test" detects HIV 1/2 antibodies with a high degree of sensitivity and specificity and could be a promising tool for seroscreening of blood during transfusion, counseling and diagnosis of HIV-1/2. © 2012 Elsevier B.V. Source

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