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.

Comparative study of platelet histamine and serotonin with their corresponding plasma oxidases in asthmatics with normals.

OBJECTIVE: Asthma is well controllable but non-curable disease. Exact pathophysiology involved is unresolved till today. Role of allergic hypersensitivity reaction in asthmatic on-set is well established. Present work is an effort to elucidate some basic points of unresolved pathophysiology of asthma taking platelets as marker. MATERIAL AND METHODS: A group of 52 normal human subjects in the age group of 20-60 years were studied for platelet histamine and serotonin levels and also for their plasma metabolising enzymes diamine oxidase (DAO) and monoamine oxidase (MAO). The data was collected for 79 asthmatic patients at different stages of asthma and accordingly were studied as four different groups of seventy nine asthmatics those were on regular treatment and were comfortable with drugs and were free from symptomatic attack formed gr. I; these (79) patients were followed-up during their symptomatic phase (gr. II) and same (79) patients immediately after their recovery from symptomatic stage studied as gr. III members. All the 79 asthmatic patients fall in gr. I, II and III in a serial manner i.e. all (n = 79) in each group. A separate group of thirty seven patients with known history of asthma but were symptom free and also off drugs for last 2-4 years formed gr. IV. RESULTS: Results showed mean platelet count in asthmatics at all four stages were in the normal range but were slightly low in comparison with normals. Both the enzymatic levels (DAO and MAO) in gr. I, II and III were significantly higher than normals but were same in the case of gr. IV patients. Low levels of platelet biogenic amines were observed in asthmatics (gr. I to gr. IV) than normals. CONCLUSIONS: Thus, study parameters showed significant difference in asthmatics and normals. Findings of the study have been utilized to understand unanswered hypersensitivity shown by the asthmatics over normal individuals (non-asthmatics).

Evaluation of serum lipids in patients of acute stroke.

Stroke, though considered a thromboembolic disorder, is known to be associated with hyperlipidaemia. In Western country, some workers have performed studies exploring the role of lipids in stroke in their country. Such a study is lacking in Indian population. This study was therefore conducted to observe the role of lipids in stroke by evaluating 13 parameters of lipids in 48 patients of non haemorrhagic cerebral stroke hospitalised in acute condition and compared with those of 70 age matched normal subjects. Results revealed that phospholipids and arachidonic acid were significantly altered in patients of acute stroke.

Effect of gugulipid on bioavailability of diltiazem and propranolol.

The effect of single oral dose of 1 gm gugulipid was studied on bioavailability of single oral dose of propranolol (40 mg) and diltiazem (60 mg) in 10 and 7 normal healthy male volunteers respectively. It was a randomised within group crossover study. Blood samples were collected at hourly intervals upto 8 hrs. Gugulipid significantly reduced (P < .01) peak plasma concentration (Cmax) and area under curve (AUC 0-8 hrs) of both the drugs in normal volunteers. Such interaction in patients receiving propanolol or diltiazem with gugulipid may lead to diminished efficacy or nonresponsiveness due to significant reduction in bioavailability.

Modulation of Kupffer cell activity by Tinospora cordifolia in liver damage.

Kupffer cells are major determinants of outcome of liver injury. Their activity was therefore studied in a model of chronic liver disease. The effect of Tinospora cordifolia, an indigenous agent with proven hepatoprotective activity, was evaluated on Kupffer cell function, using carbon clearance test as a parameter. Rats were divided into two major groups. In Gp I which served as normal control t1/2 of carbon was 9.48 +/- 4.14 min. GpII received horse-serum in a dose of 0.5 ml/100 gm b.w. i.p. for a period of 12 weeks and was divided into three sub-groups. In Gp IIA at the end of 12 weeks half-life of carbon was found to be significantly increased to 19.86 +/- 7.95 min (p < 0.01). Indicating suppressed Kupffer cell function in chronic liver damage. In Gp IIB treated with vehicle for 4 more weeks there was significant prolongation of half-life to 38.32 +/- 10.61 min (p < 0.01), indicating perpetuation of damage in absence of damaging agent. Whereas in Gp IIc, treated with Tinospora cordifolia t 1/2 was decreased to 14.24 7.74 min (p < .01), as compared to vehicle control indicating a significant improvement in Kupffer cell function and a trend towards normalization.

Immunotherapy with Tinospora cordifolia: a new lead in the management of obstructive jaundice.

OBJECTIVE: Immunosuppression associated with deranged hepatic function and sepsis results in poor surgical outcome in extrahepatic obstructive jaundice. The effect of an ayurvedic agent, Tinospora cordifolia (TC), which has been shown to have hepatoprotective and immunomodulatory properties in experimental studies, on surgical outcome in patients with malignant obstructive jaundice was evaluated. METHODS: Thirty patients were randomly divided into two groups, matched with respect to clinical features, impairment of hepatic function (as judged by liver function tests including antipyrine elimination) and immunosuppression (phagocytic and killing capacities of neutrophils). Group I received conventional management, ie vitamin K, antibiotics and biliary drainage; Group II received Tinospora cordifolia (16 mg/kg/day orally) in addition, during the period of biliary drainage. RESULTS: Hepatic function remained comparable in the two groups after drainage. However, the phagocytic and killing capacities of neutrophils normalized only in patients receiving Tinospora cordifolia (28.2 +/- 5.5% and 29.47 +/- 6.5% respectively). Post-drainage bactobilia was observed in 8 patients in Group I and 7 in Group II, but clinical evidence of septicemia was observed in 50% of patients in Group I as against none in Group II (p < 0.05). Post-operative survival in Groups I and II was 40% and 92.4% respectively (p < 0.01). CONCLUSION: Tinospora cordifolia appears to improve surgical outcome by strengthening host defenses.

Antipyrine and doxycycline pharmacokinetics in patients with thyroid disorders.

Pathological conditions are known to affect pharmacokinetics of many drugs. Antipyrine half-life is used as a marker of liver microsomal enzyme function. Antipyrine pharmacokinetics, therefore, was investigated in 23 thyrotoxic and 11 euthyroid goitre patients. Of these, 11 thyrotoxic and 9 euthyroid goitre patients also participated in doxycycline bioavailability studies. In thyrotoxic patients, antipyrine half-life and AUCo infinity and doxycycline Cpmax and AUCo infinity were found to be reduced as compared to those of healthy euthyroid normal subjects. Following treatment of thyrotoxicosis, the antipyrine half-life and AUCo infinity returned to normal. Doxycycline AUCo infinity returned to near normal range but Cpmax did not.

Antipyrine clearance: prognostic marker for obstructive jaundice.

A prospective study was undertaken to determine prognostic markers for patients with obstructive jaundice. Along with routine liver function tests, antipyrine clearance was determined in 20 patients. Four patients died after basal investigations. Five patients underwent definitive surgery. The remaining 11 patients were subjected to percutaneous transhepatic biliary decompression. Four patients died during the drainage period, while surgery was carried out for seven patients within 1-3 weeks of drainage. Of 20 patients, only six patients survived. Basal liver function tests were comparable in survivors and nonsurvivors. Discriminant analysis of the basal data revealed that plasma bilirubin, proteins and antipyrine half-life taken together had a strong association with mortality. A mathematical equation was derived using these variables and a score was computed for each patient. It was observed that a score value greater than or equal to 0.84 indicated survival. Omission of antipyrine half-life from the data, however, resulted in prediction of false security in 55% of patients. This study highlights the importance of addition of antipyrine elimination test to the routine liver function tests for precise identification of high risk patients.

Suitability of laboratory animals for screening anti-hyperlipidemic agents.

The present study was undertaken to evaluate and compare the lipid profiles of various laboratory animals to that of human beings. The human subjects and animals included in the study were from three age groups based on key physiological states. A record of the usual dietary constituents and their daily consumption was maintained. The results indicated that the lipid profile of pigs and dogs bears similarity to that of human beings. Results also revealed that lipid profile was labile in the second group of these animals indicating that this age is suitable to bring about the required changes to produce a hyperlipidemic animal.