Background and Objectives : Exaggerated production of superoxide and inactivation of nitric oxide have been implicated in pathogenesis of hypertension. NAD(P)H oxidase is one of the major source of reactive oxygen species in vasculature. In the present study, we aimed to determine the effect of chronic administration of Apocynin an NAD(P)H oxidase inhibitor on endothelial function and hypertension in fructose-fed rat. Materials and Methods : Endothelial function, vascular superoxide, and nitric oxide production/bioavailability in aortas from fructose-fed rats and age-matched controls treated with or without apocynin were assessed using isometric tension studies in organ chambers. Systolic blood pressure was measured by the tail cuff method. Results : In fructose-fed rats, acetylcholine-induced relaxation was impaired, vascular superoxide production was increased, and nitric oxide bioavailability was decreased along with an increase in systolic blood pressure compared to controls. Apocynin treatment prevented the increased generation of superoxide, decreased nitric oxide bioavailability, impaired acetylcholine-induced relaxation, and elevation of systolic blood pressure. Conclusion : Chronic administration of apocynin improves the endothelial function by reducing oxidative stress, improving NO bioavailability, and prevents the development hypertension in fructose-fed rat.

Objectives : The objective of this study was to investigate the effects of pentoxifylline (PTX), a drug that is mainly used for indications related to tissue hypoxia, on hypoxia-induced inhibition of skeletal muscle contractility and neuromuscular transmission in mice. We hypothesized that chronic PTX treatment alters skeletal muscle contractility and hypoxia-induced dysfunction. Materials and Methods : Mice were treated with 50 mg/kg PTX or saline intraperitoneally for a week. Following ether anesthesia, diaphragm muscles were removed; isometric muscle contractions and action potentials were recorded. Time to reach neuromuscular blockade and the rate of recovery of muscle contractility were assessed during hypoxia and re-oxygenation. Results : The PTX group displayed 90% greater twitch amplitudes (P < 0.01). Hypoxia depressed twitch contractions and caused neuromuscular blockade in both groups. However, neuromuscular blockade occurred earlier in PTX-treated animals (P < 0.05). Muscle contractures developed during hypoxia were more pronounced in the PTX group (P < 0.05). Re-oxygenation reduced contracture and indirect muscle contractions resumed. The rate of recovery of contractions was faster (P < 0.05) and the amplitude of contractions was greater (P < 0.01) in the PTX group. PTX treatment increased amplitude (P < 0.05) and shortened action potential (P < 0.05) without altering resting membrane potential, excitation threshold, and neurotransmitter release. Conclusion : Chronic PTX treatment increases diaphragm contractility, but amplifies hypoxia-induced contractile dysfunction in mice. These results may implicate important clinical consequences for clinical usage of PTX in hypoxia-related conditions.

Objectives : Clonidine, a known antihypertensive, is currently used for many purposes including diabetic gastroparesis, postmenopausal hot flushes, opioid/nicotine/alcohol withdrawal. Its effects on carbohydrate metabolism appear to be variable. Hence, the present study was undertaken to evaluate the influence of clonidine on euglycemic and alloxan -induced diabetic rats and its interaction with glibenclamide. Materials and Methods : Alloxan - induced (150 mg/kg, i.p) diabetic rats were divided into six groups of six animals each. Group I - Normal Control; Group II - Nondiabetic + Clonidine (25 μg/kg); Group III - Diabetic Control; Group IV - Diabetic + Glibenclamide (5 mg/kg); Group V - Diabetic + Glibenclamide + Clonidine. All drugs were given orally once daily. Blood glucose was estimated from rat tail vein using glucometer before start of the experiment and at the end of 30 days. Results : After 30 days of treatment, clonidine (25 mg/kg) produced significant hyperglycemia in both euglycemic and diabetic rats. It also reduced the hypoglycemic effect of glibenclamide in diabetic rats. Conclusion : The results of present study indicate that clonidine has hyperglycemic effect and it also interacts with glibenclamide to reduce its hypoglycemic activity. If these findings are true to human beings then clonidine should not be used in diabetic patients on sulfonylureas.

Objectives : The aim of the present study was to investigate the involvement of nitric oxide in 5-HT ₃ receptor agonist-induced fluid accumulation in jejunum and colon of anesthetized rats. Materials and Methods : Fluid movement in jejunum and colon were determined simultaneously in the same rat, by modifying the Beubler method. Nv-nitro-L-arginine (L-NNA, 20 mg/kg, s.c) alone and in combination with L-arginine (L-Arg, 150 mg/kg s.c) or D-arginine (D-Arg, 150 mg/kg, s.c) were administered 30 min before administration of 1-PBG (18.5 μg/kg, i.v). Results : Intravenous administration of 1-phenylbiguanide (1-PBG) induced a net secretion of fluid in both jejunum and colon. 1-PBG had a more prominent secretory effect in the colon, causing a three-fold increase in volume of fluid secreted/g of colon than in the jejunum. Pretreatment with (L-NNA) prevented the 1-PBG-induced fluid accumulation in both jejunum and colon. The inhibitory effect of L-NNA on 1-PBG-induced fluid accumulation was reversed by L-Arg but not by D-Arg. Conclusion : These results provide evidence that nitric oxide plays an important role in 5-HT ₃ receptor agonist-induced fluid accumulation in jejunum and colon of anesthetized rats.

Objective : To assess the adverse effects of antiretroviral therapy (HAART) and its adherence in HIV-infected patients, in remote and tribal area with restricted resources. Materials and Methods : This was a prospective, observational study carried out at Department of Medicine, Government Medical College, Jagdalpur. A set of questions were asked and adverse drug reactions (ADRs) were recorded for every patient. Results : 79 HIV positive patients were analyzed. Among them, 68 (86%) had at least one ADR. The mean ADR per patient was 1.64 (±1.09). The most common ADR in our study was peripheral neuropathy (20.83%), followed by skin rashes (15.83%). Twenty-one patients (26.58%) had severe (grade-3 and grade-4) ADRs. Female patients had more ADRs (45.71%) than males (11.36%); severe ADRs had a statistically significant positive correlation with sex and CD4 cell count of the patients. Conclusion : In spite of high ADRs, HAART is the only answer to HIV/AIDS; thus, management requires a highly precise balance between benefits of durable HIV suppression and the risks of drug toxicity to achieve the therapeutic goals, with conventional drugs or with newer less toxic agents.

Objectives : To evaluate the ethanolic and aqueous extracts of Bauhinia variegata Linn. for in vitro antioxidant and antihyperlipidemic activity. Materials and Methods : Ethanolic and aqueous extracts of the stem bark and root of B. variegata Linn. were prepared and assessed for in vitro antioxidant activity by various methods namely total reducing power, scavenging of various free radicals such as 1,2-diphenyl-2-picrylhydrazyl (DPPH), super oxide, nitric oxide, and hydrogen peroxide. The percentage scavenging of various free radicals were compared with standard antioxidants such as ascorbic acid and butylated hydroxyl anisole (BHA). The extracts were also evaluated for antihyperlipidemic activity in Triton WR-1339 (iso-octyl polyoxyethylene phenol)-induced hyperlipidemic albino rats by estimating serum triglyceride, very low density lipids (VLDL), cholesterol, low-density lipids (LDL), and high-density lipid (HDL) levels. Result : Significant antioxidant activity was observed in all the methods, (P < 0.01) for reducing power and (P < 0.001) for scavenging DPPH, super oxide, nitric oxide, and hydrogen peroxide radicals. The extracts showed significant reduction (P < 0.01) in cholesterol at 6 and 24 h and (P < 0.05) at 48 h. There was significant reduction (P < 0.01) in triglyceride level at 6, 24, and 48 h. The VLDL level was also significantly (P < 0.05) reduced from 24 h and maximum reduction (P < 0.01) was seen at 48 h. There was significant increase (P < 0.01) in HDL at 6, 24, and 48 h. Conclusion : From the results, it is evident that alcoholic and aqueous extracts of B. variegata Linn. can effectively decrease plasma cholesterol, triglyceride, LDL, and VLDL and increase plasma HDL levels. In addition, the alcoholic and aqueous extracts have shown significant antioxidant activity. By the virtue of its antioxidant activity, B. variegata Linn. may show antihyperlipidemic activity.

Objective : To evaluate the antibacterial and antioxidant activity of methanol extract of Evolvulus nummularius (L) L. Materials and Methods : Disc diffusion and broth serial dilution tests were used to determine the antibacterial activity of the methanol extract against two Gram-positive bacterial strains (Bacillus subtilus NCIM 2718, Staphylococcus aureus ATCC 25923) and three Gram-negative bacterial strains (Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae ATCC 70063 and Escherichia coli ATCC 25922). The methanol extract was subjected to preliminary phytochemical analysis. Free radical scavenging activity of the methanol extract at different concentrations was determined with 2, 2-diphenyl-1picrylhydrazyl (DPPH). Results : The susceptible organisms to the methanol extract were Escherichia coli (MIC=12.50 mg/ml) and Bacillus subtilus (MIC=3.125 mg/ml) and the most resistant strains were Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa. The methanol extracts exhibited radical scavenging activity with IC50 of 350 μg/ml. Conclusion : The results from the study show that methanol extract of E.nummularius has antibacterial activity. The antioxidant activity may be attributed to the presence of tannins, flavonoids and triterpenoids in the methanol extract. The antibacterial and antioxidant activity exhibited by the methanol extract can be corroborated to the usage of this plant in Indian folk medicine.

Objective : Objective: To evaluate diclofenac-induced biochemical and histopathological changes in White Leghorn birds. Materials and Methods : Six-week-old birds were equally divided into three groups of six birds each. Group I served as control and received vehicle orally. The birds of Group II and III were orally administered with a single low (2 mg/kg) and high dose (20 mg/kg) of diclofenac sodium, respectively, and were observed for 7 days. The acute toxicity was assessed by observing the clinical signs and symptoms, mortality, alterations in blood biochemistry, and necropsy findings. Results : The birds of Group II showed only mild symptoms of diarrhea. In Group III, 50% of birds died in between 24 and 36 h post-treatment showing the symptoms of segregatory behavior, lethargy, terminal anorexia, and severe bloody diarrhea. The birds of Group II and the surviving birds of Group III showed a significantly (P<0.05) increased plasma uric acid, creatinine and plasma glutamic pyruvic transaminase (PGPT), and decreased total protein and albumin at 12 and 24 h post-treatment which returned to the normal levels at 36 h post-treatment. The dead birds of the high-dose group also showed similar pattern of biochemical changes at 12 and 24 h post-treatment and revealed extensive visceral gout with characteristic histopathological lesions in liver, kidney, heart, spleen, and intestine on post-mortem. Conclusion : The results indicate that diclofenac sodium has hepatotoxic, nephrotoxic, and visceral gout inducing potentials in White Leghorn birds, especially at higher dose.