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Anthony J.,Piramal Enterprises Ltd | Kelkar A.,Piramal Enterprises Ltd | Wilankar C.,Piramal Enterprises Ltd | Ranjith V.,Piramal Enterprises Ltd | And 7 more authors.
PLoS ONE | Year: 2013

Insulin resistance is a characteristic feature of Type 2 diabetes. Insulin resistance has also been implicated in the pathogenesis of cardiovascular disease. Currently used thiazolidinedione (TZD) insulin sensitizers although effective, have adverse side effects of weight gain, fluid retention and heart failure. Using fat cell-based phenotypic drug discovery approach we identified P1736, a novel antidiabetic molecule that has completed Phase II clinical trials. The present study evaluated the in vitro and in vivo pharmacological properties of P1736. P1736 is a non-TZD and it did not activate human PPAR(Peroxisome Proliferator Activated Receptor Gamma)receptors. P1736 caused dose dependent increase in glucose uptake (EC50-400nM) in the insulin resistant 3T3 adipocytes. The compound (10μM) induced translocation of GLUT-4 (Glucose Transporter type 4) transporters in these adipocytes while metformin (1.0mM) was inactive. In diabetic db/db mice, P1736 (150mg/kg) was more efficacious than metformin in lowering plasma glucose (35% vs 25%) and triglyceride levels (38% vs 31%). P1736 tested at 5mg/kg, twice daily doses, reduced glucose by 41% and triglycerides by 32%, in db/db mice. These effects were not associated with adverse effects on body weight or liver function. Rosiglitazone (5mg/kg, twice daily) caused 60% and 40 % decreases in glucose and triglyceride levels, respectively. However, rosiglitazone induced 13% weight gain (p<0.05) in db/db mice. P1736 was also efficacious in ob/ob mice wherein 30-35% decrease in glucose and significant improvement in hyperinsulinemia were observed. Administration of P1736 to ob/ob mice resulted in 70% increase in glucose uptake in soleus muscles while metformin caused 38% increase. P1736 exhibited excellent safety profile and was weight neutral in all preclinical models of diabetes. Thus, P1736 with its unique pharmacology coupled with PPAR- independent mode of action could represent an alternative option in the management of insulin resistant Type 2 diabetic patients. © 2013 Anthony et al. Source

Taishete S.,Ministry of Petroleum and Natural Gas | Chowdhary A.,Haffkine Institute For Training
Indian Journal of Medical Microbiology | Year: 2016

Context: HCWs all over the world carry occupational risk of getting infected with major blood borne infections through needle stick injuries (NSIs). As health care industry has been expanding, risk of nosocomial infections is increasing proportionately. Measures to prevent it and put in place a mechanism to control these injuries are needed urgently, especially in India where there is not only increase in domestic demand but impetus in health tourism. Aim: To determine HBs Ag, HBc IgM level and to assess anti-HBs level prevalence in HCWs, in a tertiary care hospital and to study the influence of factors like age and sex in the vaccinated HCWs and formulate mechanism to increase awareness to create a safe working environment in the hospitals. Settings and Design: 437 HCWs, working in Laboratories, Surgical, Medical or Dental departments in 11 Civil Hospitals and Sub-district Hospitals covering 8 circles of the State. Methods and Material: Qualitative and Quantitative estimation of HBs Ag and Anti-HBs by sandwich ELISA technique and qualitative HBc IgM level by antibody-capture, non-competitive test. Liver profile (SGPT, SGOT and Alkaline Phosphatase) by IFCC method done. Statistical Analysis Used: Tabulation and Pie Circle Result: 193 of the total 229 vaccinated HCWs tested positive for core antibody, meaning that they were infected prior to HBs Ag vaccination, leaving a total of 36 'truly' vaccinated HCWs. 11 HBs Ag positive HCWs were tested for Liver Profile and all had ALAT, ASAT and ALP within normal range. Out of total number of 141 HCWs having 10 and below IU/L anti HBs, 5 HCWs were positive for HBS Ag, showing a positivity of 3.5%. Conclusion: Need of vaccination and for post-vaccination serological testing of all HCWs considering the high rates of non-responders and low responders (anti-HBs-34.2%). Importance of educating the HCWs of safety precautions while handling body fluids, and the management of ' sharps ' injuries. © 2016 Indian Journal of Medical Microbiology Published by Wolters Kluwer-Medknow. Source

Netravathia M.,National Institute of Mental Health and Neuro Sciences | Udani V.,Hinduja Hospital | Manic R.S.,National Institute of Mental Health and Neuro Sciences | Gadada V.,National Institute of Mental Health and Neuro Sciences | And 7 more authors.
Journal of Clinical Virology | Year: 2015

Background: Rabies is fatal encephalitis which is a major public health problem in Asian and African countries. Till date, only 12 cases have been reported who have survived after rabies. Case Report: In this communication we report a patient who is unique as the first documented long term rabies survivor with PCR positivity even after 41/2 years of illness. Child sustained dog bite following which he received adequate prophylaxis. Within two weeks, child developed encephalopathy requiring evaluation. Child continues to have persistent myoclonic jerks, seizures, is dependent on all activities with severe neurological deficits. Nested reverse transcriptase PCR (RT-PCR) specific for rabies nucleoprotein gene in CSF and nuchal skin biopsy were positive for rabies viral RNA. The nuchal skin biopsy was also positive for rabies nucleoprotein antigen by fluorescent antibody test (FAT). We describe the clinical evolution and sequential MRI brain changes in this child. Conclusions: Despite the uniformly dismal prognosis of human rabies, these unusual reports of survival of rabies patients may provide an impetus to explore newer therapeutic strategies for this otherwise fatal disease. © 2015 Elsevier B.V. Source

Rege A.A.,Haffkine Institute For Training | Ambaye R.Y.,Institute of Chemical Technology | Deshmukh R.A.,Haffkine Institute For Training
Indian Journal of Natural Products and Resources | Year: 2012

Three tropical medicinal plants, Ocimum sanctum Linn., Withania somnifera Dunal and Tinospora cordifolia (Willd.) Miers ex Hook. f. & Thoms. and two mangrove medicinal plants, Avicennia officinalis Linn. and Rhizophora mucronata Lam. were taken up in the present study along with Shilajit. Three extracts, petroleum ether, ethanol (successive) and aqueous were prepared from each plant, whereas, only 2 extracts of Shilajit, ethanol (successive) and aqueous were included for the in vitro study. Thus a total of 17 extracts were evaluated for their effect on HIV-reverse transcriptase of 2 clinical isolates, designated as non-antiretroviral therapy (non-ART, from drug naïve patient) and antiretroviral therapy (ART, from drug-treated patient), by reverse transcriptase inhibition assay. The virus stocks were prepared by standard co-cultivation method. Eleven of the 17 extracts showed more than or equal to 50% (≥50%) inhibition of non-ART isolate whereas, only 9 of the 17 extracts showed ≥50% inhibition of ART isolate. In general, Shilajit extracts showed ≥50% inhibition of both the clinical isolates. Furthermore, different combinations of aqueous extracts were assessed for their effect on reverse transcriptase of non-ART isolate. Combination of A. officinalis and Shilajit showed the highest inhibition of viral enzyme. However, the lowest inhibition was noted with combination of W. somnifera and T. cordifolia. Source

Rege A.A.,Haffkine Institute For Training | Ambaye R.Y.,Institute of Chemical Technology | Deshmukh R.A.,Haffkine Institute For Training
Indian Journal of Natural Products and Resources | Year: 2010

Medicinal plants namely Ocimum sanctum Linn., Withania somnifera Dunal, Tinospora cordifolia (Willd.) Miers. ex Hook.f. & Thoms., Avicennia officinalis Linn. and Rhizophora mucronata Lam. were screened for anti-HIV activity in the present study. O. sanctum, T. cordifolia, A. officinalis and R. mucronata showed anti-HIV potential by inhibiting the virus by 2 different mechanisms. Interference with the gp120/CD4 interaction and inhibition of viral Reverse Transcriptase (RT) contributed to the overall anti-viral activity in vitro. Among these plants A. officinalis and R. mucronata are mangrove plants and their medicinal properties are rarely reported. Source

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