Tumor necrosis factor-alpha (TNF-a), a proinflammatory cytokine is involved in the pathophysiology of a number of disorders including Crohn’s disease, rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. AntiTNF-a strategies target this pathogenic element to provide clinical benefit. The various strategies are in preliminary stage of experimentation and much remains to be elucidated before these are applied clinically. Though antiTNF-a therapy is currently approved only for rheumatoid arthritis and Crohn’s disease, the future of this therapeutic paradigm holds much promise. The number of official indications for strategies against this biologic agent are likely to increase to include congestive heart failure, psoriasis, asthma, septic shock, stroke and malignancy. This will make it a truly broad spectrum therapeutic weapon currently available to us.

Objective: To conduct the economic analysis of drug expenditure in the Government Medical College Hospital, Nagpur and to identify the categories of drugs needing stringent management control. Material and Methods: A matrix based on the coupling of cost (ABC) analysis and vital/essential/desirable (VED) criticality analysis was formulated for prioritization, to narrow down the group of drugs requiring greater managerial monitoring. The difference between actual expenditure and the inflation factor-derived expenditure was found. Expenditure for forthcoming years was forecasted by regression analysis using NCSS software. Results: The annual drug expenditure was found to be only 11.59 % of the total hospital budget. The division of the drug inventory into two priority categories resulted in identifying the priority I drugs (56) for stringent control. The percentage cost of each drug helped in determining the economic order quantity and the schedule of placing the purchase orders for drugs of high value but low criticality. Using the cost inflation index, it was observed that the overtly seen increase in annual drug expenditure was just 2.84% when the inflation factor-based expenditure was derived. Conclusion: Categorization of drugs by the ABC-VED coupling matrix model helps to narrow down on fewer drugs. The application of the cost inflation index justified the increased annual budget.

Objective: To study the effect of the combined treatment of phenytoin and piracetam on seizure control, cognitive and motor functions in mice. Material and Methods: Increasing current electroshock seizure (ICES) test was used to evaluate the effect of the combination of phenytoin and piracetam on convulsions. Cognitive functions in mice were assessed by spontaneous alternation in behavior on a plus maze while motor functions were screened using rolling roller apparatus and by counting the number of arms entries on a plus maze. Brain acetylcholinesterase (AChE) activity was measured using the Ellman et al method. Results: The study showed that piracetam when co-administered with phenytoin, significantly reversed phenytoin-induced reduction in spontaneous alternation without altering the efficacy of phenytoin against ICES in both acute and chronic studies. Further, it also reversed phenytoin-induced increase in AChE activity. Conclusion: Piracetam alleviated the phenytoin–induced cognitive impairment without compromising its antiepileptic efficacy.

Objective: To evaluate the acute effect of a-cypermethrin (a-CP) on antioxidant activities, oxidants, biochemical and histopathological changes at LD50 dose level. Material and Methods: a-CP at single LD50 (145 mg/kg) dose was administered orally to Wistar rats while controls received an equal volume of the vehicle, DMSO. The antioxidants, oxidants, biochemical and histopathological changes in some visceral organs were studied following a-CP. Results: A single LD50 dose of a-CP increased the malondialdehyde (MDA) level and decreased the activities of catalase (CAT), superoxide dismutase (SOD) and glycogen in the liver. It also increased the serum aminotransaminases (AST, ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities, and blood glucose level. It produced some cytotoxic effect on the lungs, liver, stomach, intestine, testes and cerebellum. The vehicle DMSO may have influenced the determination of LD50 of a-CP in rats. Conclusion: A single, oral LD50 dose of a-CP decreased antioxidant status, and altered biochemical parameters, which correlated with histopathological changes in rats.

Objective: To determine the bioequivalence of two marketed test formulations (A, B) as compared to a reference formulation (R) of slow release theophylline in healthy volunteers. Material and Methods: The study was conducted as an open label, balanced, randomized, three-treatment, three-period, three-sequence single-dose crossover study to determine the bioequivalence of Phylobid 200 mg SR tablets (A) and Theobid 200 mg SR tablets (B) as compared to Theostan CR 200 mg capsule (R) under fasting conditions. A group of 12 healthy, adult, male human subjects participated in this study. The bioavailability was compared using pharmacokinetic parameters Cmax, Tmax, AUC0-t, and AUC0-¥. Moreover, the 90% confidence interval (CI) for the ratio of logarithmic transformed Cmax, AUC0-t and AUC0-¥ was also used to determine bioequivalence. A washout period of seven days was kept between each study period. Serial blood samples were collected at 0, 0.5, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21 and 24 h during each study. Results: The 90% CI for the log transformed data forCmax, AUC0-t, and AUC0-¥ for both the test products fell outside the prescribed limits of bioequivalence for narrow therapeutic index drugs i.e. 90-111%. The T/R (test/reference) ratio of product A was quite close to the prescribed limits of bioequivalence (95-105%), while for product B the T/R ratio was not satisfactory. Conclusions: None of the test products of theophylline were bioequivalent to the reference product. The finding is of special significance since substitution of one brand of theophylline, a drug with a narrow therapeutic index, with another brand may result in sub-therapeutic response in patients.

Objective: To investigate the protective effect of ambrex in ethanol-induced gastric mucosal lesions in rats. Material and Methods: Ethanol-induced gastric mucosal lesions in male Wistar rats were used to evaluate gastric ulcer protective effect of ambrex (40 mg/kg/day p.o. for 15 days). The response to ambrex was assessed from ulcer index, cell proliferation, histopathological changes and alkaline phosphatase (ALP) activity. Results: Ambrex pretreatment showed protection against ethanol-induced gastric mucosal damage, a significant reduction in the ulcer index and ALP activity, and an increase in the DNA content. Conclusion: Ambrex offers protection against ethanol-induced gastric ulcers.

Objective: To evaluate the antitumor activity of the ethanol extract of Indigofera aspalathoides (EIA) in mice. Material and Methods: The antitumor activity of EIA was evaluated against the Ehrlich ascites carcinoma (EAC) tumor model. The activity was assessed using survival time, peritoneal cell count, hematological studies, solid tumor mass and in vitro cytotoxicity. Results: Oral administration of EIA increased the survival time and normal peritoneal cell count. Hematological parameters, protein and PCV, which were altered by tumor inoculation, were restored. Solid tumor mass was also significantly reduced. EIA was found to be cytotoxic in the in vitro model. Conclusion: EIA possesses significant antitumor activity.