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Using bioinformatics techniques and sequence analyses algorithms, we identified that tumor necrosis factor-α (TNF-α) and nitric oxide (NO) have a significant role in the pathobiology of insulin resistance syndrome, a condition that is common in subjects with abdominal obesity, hypertension, dyslipidemia, atherosclerosis, and coronary heart disease and are accompanied by endothelial dysfunction due to reduced endothelial nitric oxide generation. TNF-α has neurotoxic actions, stimulates inducible NO synthase activity, and modulates the expression of neurotransmitters involved in the control of feeding and thermogenesis. NO is a neurotransmitter and influences secretion and actions of various hypothalamic peptides and neuropeptides. Insulin suppresses the production of TNF-α but stimulates that of endothelial NO. This close interaction between TNF-α, NO, hypothalamic peptides, and insulin suggests that regulation of TNF-α and NO production and action could be critical in the management of insulin resistance syndrome and its associated conditions.

The study was undertaken to evaluate the effect of Quercetin on the pharmacokinetics of Atorvastatin Calcium. In-vivo Pharmacokinetic studies were performed on rats in a single dose study and multiple dose study. Rats were treated with Quercetin (10 mg/kg) and Atorvastatin Calcium (20 mg/kg) orally and blood samples were collected at (0) pretreatment and 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 24 hours post treatment. Plasma concentrations of Atorvastatin were estimated by HPLC method. Quercetin treatment did not significantly alter the pharmacokinetic parameters of atorvastatin like AUC(0-24), AUC(0-α) , T(max), C(max) and T(½) in both single dose and multiple dose studies of Atorvastatin Calcium. Quercetin does not alter the oral bioavailability of Atorvastatin Calcium in rats.

One of the biggest challenges for discovering more efficacious drugs for the control of neuropathic pain has been the diversity of chronic pain states in humans. It is now acceptable that different mechanisms contribute to normal physiologic pain, pain arising from tissue damage and pain arising from injury to the nervous system. To study pain transmission, spot novel pain targets and characterize the potential analgesic profile of new chemical entities, numerous experimental animal pain models have been developed that attempt to simulate the many human pain conditions. Among the neuropathic pain models, surgical models have paramount importance in the induction of pain states. Many surgical animal models exist, like the chronic constriction injury (CCI) to the sciatic nerve, partial sciatic nerve ligation (pSNL), spinal nerve ligation (SNL), spared nerve injury (SNI), brachial plexus avulsion (BPA), sciatic nerve transaction (SNT) and sciatic nerve trisection. Most of these models induce responses similar to those found in causalgia, a syndrome of sustained burning pain often seen in the distal extremity after partial peripheral nerve injury in humans. Researchers most commonly use these surgical models in both rats and mice during drug discovery to screen new chemical entities for efficacy in the area of neuropathic pain. However, there is scant literature that provides a comparative discussion of all these surgical models. Each surgical model has its own benefits and limitations. It is very difficult for a researcher to choose a suitable surgical animal model to suit their experimental set-up. Therefore, particular attention has been given in this review to comparatively provide the pros and cons of each model of surgically induced neuropathic pain.

Valsartan is a potent, orally active non-peptide tetrazole derivative and selectively inhibits angiotensin II receptor type 1 which causes reduction in blood pressure and is used in treatment of hypertension. The risk of heart disease mortality decreased significantly as flavonoid intake increased. Interestingly, the flavonoid-containing foods contain a high amount of Quercetin. The objective of this study was to evaluate the influence of quercetin on the pharmacokinetics of valsartan. In vivo studies were performed on rats. Rats were treated with quercetin (10 mg/kg) and valsartan (10 mg/kg), blood samples were collected at 1, 1.5, 2, 2.5, 3, 3.5, 4, 6 and 8 h. Plasma concentration of valsartan was estimated by Reverse Phase (RP-HPLC). Quercetin significantly increases the plasma concentration of valsartan and peak concentration (70.45 µg/mL) was achieved at 3.5 h. In vitro studies were performed on rat intestinal everted sacs. The transport of valsartan from serosal side to mucosal side decreased from 53.12 ± 1.27 to 40.15 ± 0.45 µg/mL in the presence of quercetin and from 53.12 ± 1.27 to 28.68 ± 0.31 µg/mL in the presence of verapamil (standard P-glycoprotein (P-gp) inhibitor) at 120 min. Verapamil is a potent P-gp and CYP3A4 inhibitor. Quercetin is a P-gp inhibitor and may be an inhibitor of CYP3A4. The simultaneous administration of quercetin significantly increases the intestinal absorption and decreases the efflux of valsartan. The observed effect may be beneficial to develop oral valsartan dosage forms using safe P-gp inhibitor (quercetin) to improve its oral bioavailability.

Reperfusion injury is remarkable clinical issue that needs to be resolved as ischemia-reperfusion is a common phenomenon encountered in numerous clinical situations. The present communication report the involvement of nitric oxide (NO) in cardioprotection offered by flavonoids (rutin and quercetin) against myocardial ischemia reperfusion. Rutin produced better cardioprotection than quercetin in normal and diabetic rats. The observed cardioprotection offered with quercetin and rutin was partially abolished by prior administration of nitric oxide synthase inhibitor, L-NAME (N-nitro-L-arginine methyl ester) in both normal and diabetic rats. L-NAME abolished the cardioprotective actions of rutin more strongly than the cardioprotective actions of quercetin. However, mechanistic study with NOS inhibitor implied the possible partial role of nitric oxide in infarct size limiting effect of quercetin and rutin

Introduction Testicular torsion and detorsion causes reperfusion injury which damages the testicular tissue and affects the quality of sperm. Deterioration in the quality of sperm worldwide is the recent scenario and one of its reasons is testicular ischemic/ reperfusion (IR) injury. Therefore the present study aims at producing new drugs for the treatment of testicular IR injury. Methods 42 animals were selected for the study and divided into 7 groups, each containing 6 rats. Bioflavonoids were tested for their efficacy in reversing the damage done to the testicular tissue by causing testicular torsion and detorsion in rats. As oxidative stress produced in the above condition causes tissue damage, MDA level was measured and antioxidant enzymes SOD and catalse were evaluated. Histological examination was conducted to find the extent of damage and the protective effect of rutin and naringin. One-way ANOVA and Tukey's post-hoc test were used for data analysis. A p-value

Diabetes mellitus is an independent risk factor for cardiovascular disease and is also associated with increased susceptibility to cardiovascular complications. It has been suggested that alterations in glucose metabolism and glucose flux via the aldose reductase pathway make the diabetic heart more sensitive to ischemic-reperfusion injury. Previous studies have found sulindac to have inhibitory and anti-inflammatory effects on aldose reductase. The use of aldose reductase inhibitors for the protection of ischemic myocardium is still in an exploratory state.To evaluate the therapeutic potential of sulindac in an in vivo rat model of acute ischemia (30 min) and reperfusion (4 h) in diabetic and nondiabetic rats.Diabetes was induced in rats by administering streptozotocin (45 mg/kg, intravenously). Myocardial infarction was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured using the staining agent 2,3,5-triphenyltetrazolium chloride. A lead II electrocardiogram was monitored at various intervals throughout the experiment. Sorbitol dehydrogenase levels in heart tissue, as well as lipid peroxide levels in serum and heart tissue, were estimated spectrophotometrically.Infarct size was increased in diabetic rats in comparison with normal rats. Pretreatment with sulindac significantly reduced infarct size, lipid peroxidation and sorbitol dehydrogenase levels in both diabetic and nondiabetic rats. The degree of cardioprotection was greater in diabetic rats than in nondiabetic rats.The present study indicates that the observed cardioprotection provided by sulindac in terms of reducing infarct size in normal rats may be due to its combined antioxidant and anti-inflammatory activities. The inhibition of aldose reductase may be responsible for the enhanced cardioprotection observed in diabetic rats treated with sulindac.

Objective: The study was aimed to assess the incidence and characteristics of drug-related problems (DRPs). Methods: A prospective, observational study was conducted among 133 patients with stroke disease who were aged 18 years or older and admitted to the general medicine ward. During the 6 months study period, the incidence of DRPs was identified using the Pharmaceutical Care Network Europe Foundation classification system, version 6.2. Findings: A total of 133 patients were screened for DRPs. Among them, 120 patients have at least one DRP. A total of 254 DRPs were identified (on average, 2.015 DRPs per each patient case). Conclusion: Increasing the evidence of the incidence of medication-related problems in tertiary care hospitals indicates the need for the establishment of a clinical pharmacist in hospital settings.

Diabetic retinopathy is the leading cause of blindness among patients with diabetes mellitus. We evaluated the role of several proteins that are likely to be involved in diabetic retinopathy by employing multiple sequence alignment using ClustalW tool and constructed a phylogram tree using functional protein sequences extracted from NCBI. Phylogram was constructed using Neighbor-Joining Algorithm in bioinformatics approach. It was observed that aldose reductase and nitric oxide synthase are closely associated with diabetic retinopathy. It is likely that vascular endothelial growth factor, pro-inflammatory cytokines, advanced glycation end products, and adhesion molecules that also play a role in diabetic retinopathy may do so by modulating the activities of aldose reductase and nitric oxide synthase. These results imply that methods designed to normalize aldose reductase and nitric oxide synthase activities could be of significant benefit in the prevention and treatment of diabetic retinopathy.