Role of antioxidant therapy in management of type – 2 diabetes mellitus.

Introduction: Diabetes Mellitus is a heterogeneous group of disorders characterized by variable degrees of insulin resistance, impaired insulin secretion and increased glucose production. Free radical injury is important contributing factor for the development of Insulin resistance and impaired insulin secretion. Recently it has been suggested that glycation of antioxidant enzymes could alter the structure and function of antioxidant enzymes such that they are unable to detoxify free radicals. Intake of vitamin E and vitamin C, due to antioxidant property, is associated with reduced risk of development of Diabetes Mellitus Type 2. With this background, this study was planned to explore the role of antioxidant therapy in the management of Diabetes Mellitus Type 2. Objectives: (1) To demonstrate increased oxidative stress in newly diagnosed Type 2 Diabetes Mellitus patients by measuring antioxidant enzymes activities. (2) To study the effect of oral hypoglycaemic agents on oxidative stress in Type 2 Diabetes Mellitus patients. (3) To evaluate the effects of vitamin C, vitamin E and their combination in patients having Type 2 Diabetes Mellitus managed with oral hypoglycaemic agents. Materials and Methods: The study included two groups consisting of 60 euglycemic healthy subjects and 64 newly diagnosed Diabetes Mellitus Type 2 patients. After 3 months of treatment with oral hypoglycaemic drug, the second group was divided into 4 subgroups with 16 subjects in each subgroup and were treated with oral hypoglycaemic agent alone, oral hypoglycaemic agent + vitamin C, oral hypoglycaemic agent + vitamin E, and oral hypoglycaemic agent + vitamin C + vitamin E respectively for further 3 months. Results : Hyperglycemia in patients with Diabetes Mellitus Type 2 is associated with reduced antioxidant status (superoxide dismutase and catalase activities, and reduced glutathione level). Treatment with oral hypoglycaemic agent for 3 months produced euglycemia with partial but statistically significant elevation of catalase activity and reduced glutathione level in blood. Following additional antioxidant therapy with vitamin C and vitamin E produced further significant increase in reduced glutathione level, however fasting plasma glucose level and activities of superoxide dismutase and catalase enzymes were found to be statistically non-significant.Conclusion: Antioxidant therapy with vitamin C and vitamin E in addition to oral hypoglycaemic agent reduces oxidative stress in patients having Type 2 Diabetes Mellitus.

Study of prescribing patterns of antimicrobial agents in the medicine department at tertiary teaching care hospital in Gujarat.

Prescription of drugs which needs to be continuously assessed and refined accordingly. It is not only reflects the physician’s knowledge of pharmacology and pathophysiology of diseases but also his/her skill in diagnose and attitude towards selecting the most appropriate cost effective treatment. Antimicrobials are among the most commonly prescribed drugs in hospital. As per literature, they account for nearly 20% of all new and repeat prescription each year. Hospital purchase of these drugs is thought to be about 25 to 30 % of the total annual drug budget. Such studies have been sparse from Gujarat and hence, this study was undertaken. Objective: This study was carried out to find out the prescribing patterns of antimicrobial drugs in the medicine department at tertiary teaching care hospital, Vadodara (Gujarat). Methods: Retrospective study was carried out by collecting 350 prescriptions containing antimicrobial agents of the indoor patients admitted (Oct 2005 to June 2006) in the wards of medicine department at Sir Sayajirao General (SSG) Hospital, Vadodara to assess the prescribing patterns of antimicrobial agents. All the information about drugs details were recorded in pre-tested proforma. Results: In our study, total 350 prescriptions containing 539 antimicrobial drugs were prescribed in-patients during study. Of them β –lactam (except CP) (159; 29.49%) and cephalosporin (156; 28.94%) groups were commonly prescribed. Average number of antimicrobials per prescription was 1.54.Out of 539 antimicrobial agents prescribed, 486 (90.16%) were prescribed by generic name, while only 53(9.53%) were prescribed by trade name. Total numbers of antimicrobial prescribed by parenteral route were 313(58.07%), while 226(41.93%) antimicrobial agents were prescribed by oral route. Conclusion: Results indicate that noticeable controlled over the prescribing habits of the physicians for indoor patients at our hospital. It is suggested that further detail analysis to judge the rationality of the therapy is necessary.

Effect of Withania somnifera on forced swimming test induced immobility in mice and its interaction with various drugs.

The objective of the present study was to evaluate the antidepressant action of Withania somnifera (WS) as well as its interaction with the conventional antidepressant drugs and to delineate the possible mechanism of its antidepressant action using forced swimming model in mice. Effect of different doses of WS, fluoxetine and imipramine were studied on forced swimming test induced mean immobility time (MIT). Moreover effect of WS 100 mg/kg, i.p. was observed at different time intervals. Effect produced by combination of sub therapeutic doses of WS with imipramine (2.5 mg/kg, i.p.) as well as fluoxetine (2.5 mg/kg, i.p.) were also observed. Effect of WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) were observed in mice pretreated with reserpine (2 mg/kg, i.p.) and clonidine (0.15 mg/kg, i.p.). Effects of prazosin (3 mg/kg, i.p.) or haloperidol (0.1 mg/kg, i.p.) pre-treatment were also observed on WS induced decrease in MIT. WS produced dose dependent decrease in MIT. Maximum effect in MIT was observed after 30 min of treatment with WS 100 mg/kg, i.p. Combination of WS (37.5 mg/kg, i.p.) with imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) also produced significant decrease in the MIT. Clonidine and reserpine induced increase in MIT, was significantly reversed by treatment with WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.). Pre-treatment with prazosin but not haloperidol, significantly antagonized the WS (100 mg/kg, i.p.) induced decrease in MIT. It is concluded that, WS produced significant decrease in MIT in mice which could be mediated partly through a adrenoceptor as well as alteration in the level of central biogenic amines.

Comparative study of beta-adrenoceptor blocking efficacy of two formulations of esmolol in vivo and in vitro.

The objective of the present study was to compare the cardiovascular beta-blocking activity of two different formulations of esmolol. Spontaneously beating guinea-pig isolated atria and the heart rate and blood pressure of anaesthetized cat were employed in the study to compare the beta-blocking efficacy of the two formulations of esmolol using isoprenaline as an agonist. In guinea-pig isolated atria the standard esmolol formulation (Brevibloc) reduced basal atrial rate more significantly than the indigenously formulated esmolol (test formulation). Both the formulations produced similar parallel rightward shift of cumulative concentration response curves of isoprenaline with closely comparable pA2 values. In anaesthetized cats, only indigenous esmolol formulation significantly decreased basal heart rate. Both the formulations did not modify the basal blood pressure and isoprenaline-induced fall in blood pressure, despite significantly blocking isoprenaline-induced tachycardia. It is suggested that both the formulations produced similar degree of beta-1 adrenoceptor blocking activity.

Antagonism of calcium-induced contractions by some non-specific spasmolytics in depolarized smooth muscles.

The effects of papaverine MgCl2, cocaine, DNP, KCN and khellin on responses of some rabbit and rat tissues to CaCl2 were studied in vitro in a depolarizing medium. Guinea pig taenia coli preparation was used for comparison. In rabbit tracheal chain and vas deferens and guinea pig taenia coli preparations all spasmolytics shifted the concentration-response curves of CaCl2 to the right without affecting the maxima or slopes. In rat tracheal chain and vas deferens preparations all spasmolytics shifted the concentration-response curves of CaCl2 to the right. Furthermore all agents (except cocaine in tracheal chain preparations) depressed the maximum responses. The slopes were unaffected in either preparations. The initial competition and subsequent noncompetition observed in certain tissues is discussed in the light of the reported poor capacity of some tissues to retain Ca++ and the absence of releasable firmly bound Ca++ (11).