PHARMACOLOGY

The colossal rise in antimicrobial resistance has led to treatment failures and so mastitis has become cumbersome to treat. The objective of this study was to evaluate the antibacterial effect of non-antibiotic drug, atorvastatin in combination with antimicrobial, ampicillin against two commonly isolated bacterial species Staphylococcus spp and E. coli from bovine mastitis. Milk samples were collected from mastitis cows, visiting Veterinary Clinical Complex. Bacterial isolation was performed using Eosin Methylene Blue (EMB) agar and Mannitol Salt Agar (MSA), followed by characterization and identification by biochemical tests and gram staining. Genotypic confirmation was done by Polymerase Chain Reaction (PCR) with subsequent screening for resistant genes-mec A, blaTEM. Antibiotic Sensitivity Test (ABST) of the isolates against 12 different antimicrobials, atorvastatin only, and combination of atorvastatin with ampicillin were performed using Kirby-Bauer disc diffusion method. Minim...

Seaweeds are considered as a valuable source of bioactive compounds produced as secondary metabolites having a broad spectrum of biological activities. Recently seaweed has been extensively utilized by pharmaceutical, chemical and nutraceutical industries as valuable sources of raw material of natural origin. The present study aimed at evaluating the mutagenic and genotoxic effects of methanolic extract of brown seaweed Stoechospermum marginatum. The test extract was assessed for its potential mutagenic effect using in vitro bacteria reverse mutation assay (Ames test) and for its potential clastogenic and DNA damaging effects using in vivo rodent bone marrow micronucleus and alkaline comet assay respectively. The test extract did not produce a twofold increase or a reproducible dose-dependent increase in the number of revertant colonies in all the bacterial tester strains at the highest dose of 5000 µg/plate tested both with and without metabolic activation. No significant clastogenic and DNA damaging effects were observed at the highest dose of 2000 mg/kg body weight when the test extract was assayed in-vivo in mice bone marrow erythrocytes and peripherally in lymphocytes respectively. The result obtained from this study revealed that methanolic extract of Stoechospermum marginatum is safe to living cells genome and does not produce significant mutagenic and genotoxic effect when assayed in both in vitro and in vivo testing systems.

Please cite this article in press as: Sukumaran SV, et al. TRPV4 channel activation leads to endothelium-dependent relaxation mediated by nitric oxide and endothelium-derived hyperpolarizing factor in rat pulmonary artery. Pharmacol Res (2013),

Background: The aim of the present study was to assess the effect of seven days daidzein pretreatment in cecal ligation and puncture (CLP) model of sepsis. Methods: We assessed the survival benefit of daidzein and its effect on lung injury in CLPinduced sepsis in mice and determined the bacterial load in peritoneal fluid, blood, and lung homogenates. Tumor necrosis factor a (TNF-a) and corticosterone levels were measured by enzyme-linked immunosorbent assay; relative mRNA expression was estimated by real-time polymerase chain reaction, and standard biochemical techniques were used to measure nitrite level, myeloperoxidase activity, and vascular permeability. Results: Daidzein pretreatment for seven days at a dose of 1 mg/kg body weight subcutaneously increased the survival time of septic mice. Daidzein decreased the bacterial load in peritoneal fluid, blood, and lungs, reduced the tumor necrosis factor a and nitrite level in plasma, and partially suppressed lung injury by reducing vascular permeability and myeloperoxidase activity in septic mice. Further, it restored the relative mRNA expressions of inducible nitric oxide synthase, glucocorticoid receptor a, and glucocorticoid receptor b genes in septic lungs were restored by daidzein pretreatment. Conclusions: Daidzein pretreatment for 7 d in sepsis increased the survival time in mice, which may be relate to decrease in bacterial load, anti-inflammatory effect, and protection from lung injury.

We have recently reported that pre-treatment, but not the post-treatment with atorvastatin showed survival benefit and improved hemodynamic functions in cecal ligation and puncture (CLP) model of sepsis in mice. Here we examined whether combined treatment with atorvastatin and imipenem after onset of sepsis can prolong survival and improve vascular functions. At 6 and 18 h after sepsis induction, treatment with atorvastatin plus imipenem, atorvastatin or imipenem alone or placebo was initiated. Ex vivo experiments were done on mouse aorta to examine the vascular reactivity to nor-adrenaline and acetylcholine and mRNA expressions of α 1D AR, GRK2 and eNOS. Atorvastatin plus imipenem extended the survival time to 56.00 ± 4.62 h from 17.00 ± 1.00 h observed in CLP mice. The survival time with atorvastatin or imipenem alone was 20.50 ± 1.89 h and 27.00 ± 4.09 h, respectively. The combined treatment reversed the hyporeactivity to nor-adrenaline through preservation of α 1D AR mRNA/protein expression and reversal of α 1D AR desensitization mediated by GRK2/G βγ pathway. The treatment also restored endothelium-dependent relaxation to ACh through restoration of aortic eNOS mRNA expression and NO avalability. In conclusion, combined treatment with atorvastatin and imipenem exhibited survival benefit and improved vascular functions in septic mice.