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Banerjee A.G.,Banaras Hindu University | Das N.,Banaras Hindu University | Shengule S.A.,National Toxicology Center | Srivastava R.S.,Banaras Hindu University | Shrivastava S.K.,Banaras Hindu University
European Journal of Medicinal Chemistry | Year: 2015

A series of triazin-3(2H)-one derivatives bearing 1,3,4-oxadiazole (4a-4o) were synthesized, characterized and evaluated for anti-inflammatory and analgesic activities. Preliminary in vitro anti-inflammatory activity was assessed using an albumin denaturation assay. The promising compounds were further evaluated in acute, sub-chronic and chronic animal models of inflammation. Derivatives 4d, 4e, 4g, 4j and 4l exhibited significant anti-inflammatory activity with reduced ulcerogenic, hepatotoxic and renotoxic liabilities compared to standard indomethacin. These potential derivatives were also evaluated for in vivo analgesic activity using a writhing model and the formalin-induced paw licking response in mice. Compounds 4d, 4e and 4g exhibited comparable analgesic activity, whereas 4j and 4l yielded moderate effects. The specificity of compounds 4d, 4e, 4g, 4j, and 4l to inhibit (cyclooxygenase-1) COX-1 and (cyclooxygenase-2) COX-2 isozymes and their kinetics were also determined via an in vitro COX inhibition assay. In silico docking studies were performed using a molecular dynamics simulation of the most active compound 4d (COX-2 IC50: 3.07 μM) at the COX-2 active site. The outcome of this exercise helped to verify the consensual interaction of these compounds with the enzyme. © 2015 Elsevier Masson SAS. Source

Gonzalez N.,CQB | Paredes B.,Biomolecular Chemistry Center | Perez S.,National Toxicology Center | Mirabal M.,Finlay Institute | And 11 more authors.
MEDICC Review | Year: 2015

INTRODUCTION Pneumococcal infections are a major cause of mor bidity and mortality and are associated with considerable economic burden on health systems. To prevent pneumococcal infections, 7-valent conjugate vaccines have been available for over a decade; more recently, 10-and 13-valent conjugate vaccines have been for mulated, which are more immunogenic than vaccines with capsular polysaccharides only. In Cuba, a new vaccine candidate has been developed, PCV7-TT, a conjugate of tetanus toxoid with antigens of seven of the serotypes of Streptococcus pneumoniae with highest circu lation in Cuba and in the world: 1, 5, 6B, 14, 18C, 19F and 23F. OBJECTIVE Assess the safety of the vaccine candidate PCV7-TT in healthy adults and conduct a preliminary assessment of its immunogenicity. METHODS A phase I, double-blind clinical trial was performed at the National Toxicology Center in Havana, Cuba. Healthy male volunteers aged 18-35 years were randomly assigned to two groups: 20 received the vaccine candidate PCV7-TT and 20 the polyvalent antipneumococcal vaccine PNEUMO-23 used as control, each in a single intramuscular dose. To assess safety, the occurrence of adverse events was monitored for 30 days following inoculation. To explore immunogenicity, concentrations of serotype-specific antibodies was quantified before and 30 days after inoculation, as well titers of opsonophagocytic antibodies. (National Clinical Trial Registry RPCEC00000133) RESULTS Local adverse events were pain, redness, induration, increased sensitivity to touch, and warmth in the injection area. Pain was registered in 70% of individuals who received PCV7-TT and in 75% of those vaccinated with PNEUMO-23. Reported systemic adverse events were general malaise, headache and drowsiness. All adverse events appeared in the first 72 hours post inoculation and lasted no lon ger than 3 days. One event was reported that was classified as severe in intensity and serious in consequences, but it was unrelated to vacci nation-acute appendicitis in one individual inoculated with the control vaccine. Before vaccination, all participants but one had antibody con centrations ?0.20 ?g/ml against the vaccine strains; after vaccination 100% of individuals were positive and the concentrations of antibodies increased in previously positive volunteers. Some individuals had opso nophagocytic antibodies against serotypes 1, 14, 19F and 23F before vaccination, with highest concentrations against serotypes 14 and 19F. After vaccination, the percent of individuals with opsonophagocytic titers ?1:8 for all serotypes in the vaccine was >50% in both groups. CONCLUSIONS A single dose of candidate vaccine PCV7-TT was safe when used in healthy adults. Preliminary results showed that it was able to activate an immune response against the serotypes of Streptococcus pneumoniae used. Source

Ameri A.,Ahvaz Jundishapur University of Medical Sciences | Rajive B.B.,Armed Force Medical College Dalanwala | Vaidya J.G.,University of Pune | Apte K.,National Toxicology Center | Deokule S.S.,University of Pune
International Journal of Applied Research in Natural Products | Year: 2013

Topical antimicrobial therapy is one of the most important methods of wound care. In this investigation, we evaluated topical gel preparations of Ganoderma praelongum and Glycyrrhiza glabra aqueous extracts alone and in combination for antimicrobial and wound healing activities in MRSA - infected excision and incision wound models in mice. Gel formulations containing 0.3% G. praelongum, 2.5% G. glabra and combination of the two were prepared and tested for their influence on wound infection, wound contraction and epithelization phases of wound healing. Mupirocin ointment was applied as a standard treatment antibiotic. Results indicated that all three gel formulations promoted wound healing in both models by influencing wound contraction and epithelization phases. Examination of wounds at the end of our study period revealed that wounds treated with G. praelongum and G. glabra gel formulations (combination gel) showed considerable contraction and epithelization as compared to the gel base - treated group (negative control). Assumption could be made that this wound promotion is due to the anti - Staphylococcal activity of Ganoderma and wound healing activity of G. glabra. Industrial relevance. Medicine using fungal metabolites is now recognized. A mushroom that has gained worldwide attention is Ganoderma lucidum and has been used to treat a wide spectrum of ailments including fungal and bacterial infections for long periods of time throughout history of ancient traditional medicine. Previous reports indicate that ganoderma lucidum mycelia are usually prescribed in the form of soup, syrup, tea, tablets, capsules, tincture or bolus or injected as a solution of powdered spores.In this study, the combination gel containing aqueous extracts of G. praelongum and G. glabra effectively inhibited the growth of methicillin resistant Staphylococcus aureus and promoted wound healing in mice. Further phytochemical studies are needed to pinpoint the active components of the extracts. Moreover, various topical formulations containing combination of the two extracts are suggested to be prepared and evaluated for wound healing in clinical trials. © 2008-2013. IJARNP-HS Publication. Source

Sonawane H.B.,University of Pune | Ghole V.S.,University of Pune | Garad S.,University of Pune | Bapat G.,University of Pune | And 2 more authors.
Journal of Natural Remedies | Year: 2013

Phansomba (Phellinus badius Berk ex Cooke) G. Cunn., family Hymenochetaceae, is a folk medicine used by local practitioners for various types of ailments. The hypoglycemic effect of aqueous extract of fruit body and mycelial biomass were investi gated in alloxan-induced diabetic rats. The diabeticrats were orally administered with aqueous extracts of Phellinus badius, basidiocarp, and mycelial biomass at the doses of 800 mg/kg and 1000 mg/kg each. The blood glucose level changed at 6-hr interval at a dose of 1000 mg/kg in case of basidiocarp and mycelial biomass. The food intake of diabetic control was increased by 33.6% as compared to normal control, and the body weight gain was significantly decreased at a dose of 1000 mg/kg of both the samples. The blood glucose levels of the diabetic rats were significantly reduced after fourteen days. The plasma triglyceride and cholesterol level also significantly decreased as compared to diabetic rats (positive control). There was a considerable increase in the weight of body organs on administration of aqueous extract of Phansomba sample as compared to the normal rats (negative control). It also demonstrated a marked reduction in the level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The study reveals the potential of Phansomba samples as hypoglycemic agents with its aqueous extracts from fruit body and mycelial biomass. Source

Hardikar A.A.,University of Sydney | Satoor S.N.,University of Sydney | Satoor S.N.,National Center for Cell Science | Karandikar M.S.,Dy Patil Medical College | And 20 more authors.
Cell Metabolism | Year: 2015

People in developing countries have faced multigenerational undernutrition and are currently undergoing major lifestyle changes, contributing to an epidemic of metabolic diseases, though the underlying mechanisms remain unclear. Using a Wistar rat model of undernutrition over 50 generations, we show that Undernourished rats exhibit low birth-weight, high visceral adiposity (DXA/MRI), and insulin resistance (hyperinsulinemic-euglycemic clamps), compared to age-/gender-matched control rats. Undernourished rats also have higher circulating insulin, homocysteine, endotoxin and leptin levels, lower adiponectin, vitamin B12 and folate levels, and an 8-fold increased susceptibility to Streptozotocin-induced diabetes compared to control rats. Importantly, these metabolic abnormalities are not reversed after two generations of unrestricted access to commercial chow (nutrient recuperation). Altered epigenetic signatures in insulin-2 gene promoter region of Undernourished rats are not reversed by nutrient recuperation, and may contribute to the persistent detrimental metabolic profiles in similar multigenerational undernourished human populations. © 2015 Elsevier Inc. Source

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