Interrelationship between coagulation factor VII and obesity in diabetes mellitus (type 2).

We explored the interrelationships of coagulation FVII activity levels with obesity, leptin and insulin resistance in diabetes mellitus (DM Type 2) and in non-diabetic control subjects. We found FVII hypercoagulant activity levels in DM not associated with obesity, leptin levels or insulin resistance. It was found independently associated with hypertriglyceridemia.

Chikungunya encephalomyeloradiculitis: report of 2 cases with neuroimaging and 1 case with autopsy findings.

Chikungunya, an alphavirus presenting with fever, rash, and polyarthritis, is derived from the Makonde word that means "that which bends up," in reference to the crippling manifestations of the disease. Most often it is a self-limiting febrile illness. Neurologic complications of Chikungunya infection have been reported. We are reporting the clinical and neuroimaging data in 2 patients with Chikungunya encephalomyeloradiculitis and brain autopsy findings in 1 patient.

Role of endothelial cell dysfunction in essential hypertension.

BACKGROUND: Hypertension is associated with functional and morphological alterations of the endothelium, which disturbs delicate balance of endothelium-derived factors resulting in endothelial dysfunction. The endothelial dysfunction could then facilitate the maintenance of elevated peripheral resistance, which would favor the occurrence of atherosclerosis. AIMS AND OBJECTIVES: The aim of the present study was to determine the circulating levels of vasodilators [nitric oxide (NO) and prostacyclin (PGI2)] and vasoconstrictors [endothelin I (ET-I) and thromboxane (TX)A2)], which reflect endothelial cell dysfunction. METHOD: Nitric oxide as nitrites and nitrates (NOx) were measured spectrophotometrically; ET-I, TXA2 (as TXB2) and PGI2 (as 6 keto PGFIalpha) were measured using enzyme immunoassay methods in 54 male subjects having predominantly untreated, mild hypertension and compared with age-matched 75 healthy controls. RESULTS: Significantly higher levels of ET-I (p<0.001) and TXB2 (p<0.001) were found in essential hypertension subjects (EHT) as compared to controls. No significant difference was observed in NOx and 6 keto PGFIalpha between the two groups. There was significant increase (p = 0.005) in the ratio of TXB2/6 keto PGFIalpha in EHT subjects as compared to controls. CONCLUSIONS: Elevated levels of vasoconstrictors in untreated essential hypertension subjects as compared to controls confirmed the presence of endothelial dysfunction, even in mild cases of hypertension. Early detection of endothelial dysfunction may be a useful measure to guide therapy before the damaging effects of hypertension manifests.

Non-drug therapy in prevention and control of hypertension.

Non-drug therapy is a very vital aspect in prevention and treatment of hypertension. The successive reports of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension, WHO scientific report on primary prevention of essential hypertension and national High Blood Pressure Education Program's working groups report on primary prevention of hypertension have stressed on the non-drug therapy. Today a busy family physician does not spend enough time to explain to the patient various dietary and lifestyle modifications but straightaway prescribes the drugs. Every patient of hypertension from the stage of pre-hypertension to grade 2 hypertension should follow non-drug therapy. If non-drug therapy is strictly adhered, one can prevent cases of pre-hypertension from progressing to hypertension stage and one can reduce or stop the medications in Grade I (mild) hypertension. We have discussed the role of low salt, high potassium diet, role of caffeine intake, calcium and magnesium supplements, fish oil intake, cigarette smoking, alcohol consumption, role of physical exercise, stress reduction and bio-feedback, yoga, meditation and acupuncture. These recommendations regarding diet and lifestyle modifications should be targeted to population at large through public health authorities, non-government organisations and news media.

Homocysteine and its role in the pathogenesis of atherosclerotic vascular disease.

Homocysteine has been recently recognised as a risk factor for atherosclerotic vascular disease. Numerous studies have studied adverse influence of homocysteine on endothelial cells, vascular smooth muscle cells, connective tissue, interactions with plasma lipoproteins, clotting factors and platelets. It has been suggested that endothelial damage is mediated by hydrogen peroxide, a by-product of auto-oxidation of homocysteine. Human studies have shown that high levels of homocysteine are associated with impaired endothelial dependent vasodilatation in healthy subjects indicating that the bio-availability of nitric oxide (NO) is decreased in those with hyper-homocysteinemia. Homocysteine thialactone (a by-product of homocysteine auto-oxidation) combines with native LDL to form oxidized LDL which is taken up by intimal macrophages to form foam cells which is the beginning of atheromatous plaques. Homocysteine has also influence on proliferation of vascular smooth muscle cells and collagen deposition in atheromatous plaque. In addition several retrospective and prospective studies have shown that hyperhomocysteinaemia is associated with atheromatous and vascular events. Observations in 80 clinical and epidemiological studies have indicated that hyper-homocysteinaemia is a risk factor for atherosclerotic disease. However there are some studies which conclude that homocysteine is not a major risk factor for coronary heart disease.

Effects of cyclo-oxygenase and thromboxane synthetase inhibitors on right atrial prostaglandins.

OBJECTIVES: The aim of this study was to find out the effects of cyclo-oxygenase and thromboxane synthetase inhibitors on right atrial prostacyclin and thromboxane A2 levels. METHODS: The study consisted of a total of 50 patients subjected to coronary bypass surgery. These patients were divided into two groups, Group I and Group II each consisting of 25 patients. In Group I patients, the right atrial tissues were studied for effects of indomethacin and U63557A on the prostaglandin levels. In Group II patients, the right atrial tissues were studied for effects of Aspirin and U63557A on the prostaglandin levels. RESULTS: In Group I patients, the atrial tissues pretreated with indomethacin showed a fall in the levels of 6 keto PGF1 alpha from 153.5 +/- 28.4 pg/0.1 mg to 59.7 +/- 11.6 pg/0.1 mg and of TXB2 from 41.6 +/- 1.2 pg/0.1 mg to 17.2 +/- 3.2 pg/0.1 mg. In the atrial tissues of Group I treated with U63557A the levels of 6 keto PGF1 alpha fell to 145.4 +/- 26.8 pg/0.1 mg and the levels of TXB2 fell to 14.7 +/- 2.8 pg/0.1 mg. In Group II patients, the atrial tissues pretreated with aspirin, showed a fall in the levels of 6 keto PGF1 alpha from 142.1 +/- 2.8 pg/0.1 mg to 17.5 +/- 0.8 pg/0.1 mg. In the atrial tissues pretreated with U63557A, the levels of 6 keto PGF1 alpha fell to 131.2 +/- 2.9 pg/0.1 mg and the levels of TXB2 fell to 14.4 +/- 0.7 pg/0.1 mg. CONCLUSIONS: The study showed that human right atrial tissues are capable of producing TXA2 in addition to prostacyclin. Indomethacin and aspirin by inhibiting generation of cyclic endoperoxides inhibited synthesis of both prostacyclin and TXA2. In contrast a thromboxane synthethase inhibitor U63557A selectively inhibited TXA2 without significant effects on prostacyclin synthesis.

Diet and lifestyle guidelines and desirable levels of risk factors for the prevention of diabetes and its vascular complications in Indians: a scientific statement of The International College of Nutrition. Indian Consensus Group for the Prevention of Diabetes.

BACKGROUND: There has been a rapid increase in the prevalence of diabetes and cardiovascular disease in India, in association with rapid changes in diet and lifestyle. In adults, the prevalence of diabetes, hypertension and coronary artery disease is two- to threefold greater in the urban population than in rural populations; it is associated with modest insulin resistance in urban groups. METHODS: In response to a proposal by the International College of Nutrition that specialist experts should develop consensus recommendations for the prevention of chronic diseases, Indian specialists in diabetes and vascular disease have collaborated to produce guidelines relevant to the population of India. RECOMMENDATIONS: Because Indian urban populations have a modest increase in overweight and low rates of obesity in association with the rapid emergence of diabetes and cardiovascular risk, a body mass index of 21 kg/m2 should be considered safe, with a range of 19-23 kg/m2 acceptable; > 23 kg/m2 should be considered overweight, and > 25 kg/m2 should be taken to indicate obesity. A waist:hip ratio > 0.88 in males and > 0.85 in females should be considered to indicate central obesity, because the prevalence of coronary disease, hypertension and associated disturbances of insulin resistance are more common above these limits. For the prevention of vascular disease, there is general international consensus that the desirable serum concentration of cholesterol should be < 170 mg/dl (> 4.42 mmol/l), which may also be optimal for Indians; values between 170 and 200 mg/dl (4.42-5.2 mmol/l) should be considered borderline. The critical values for low density lipoprotein cholesterol may be < 90 mg/dl (ideal), 90-110 mg/dl (borderline high) and > 110 mg/dl (high) (< 2.32, 2.32-2.84 and > 2.84 mmol/l, respectively). Fasting triglycerides should be < 150 mg/dl (< 1.69 mmol/l) and high-density lipoprotein cholesterol > 35 mg/dl (> 0.9 mmol/l). The limit for the total energy derived from fat intake should be < 21%/day (7% each for saturated, polyunsaturated and mono-unsaturated fatty acids). The carbohydrate intake should provide more than 65% of daily energy, mainly from complex carbohydrates. A daily dietary intake of 400 g fruits, vegetables and legumes, 400 g cereals, in conjunction with 25 g soya bean or mustard or canola oils (rich in n-3 fatty acids) in place of fats rich in saturated fat, may be protective against diabetes and vascular disease. Moderate physical activity with the aim of burning 300 Kcal/day (> 1255 KJ/day), and cessation of tobacco and alcohol consumption, may provide an effective programme for prevention of diabetes and its vascular complications in Indians.

Serum angiotensin converting enzyme activity in sarcoidosis and pulmonary tuberculosis.

Serum angiotensin converting enzyme (SACE) was estimated in 18 cases of sarcoidosis, 15 patients suffering from pulmonary tuberculosis and in 12 normal healthy individuals. SACE was elevated in the patients suffering from sarcoidosis. (33.2 +/- 12.9). SACE values for the pulmonary tuberculosis patients were 18.8 +/- 7.9 and those for the normal healthy individuals were 17.1 +/- 4.7. Compared to pulmonary tuberculosis and normal healthy individuals, the SACE levels were significantly elevated (P < 0.01) in sarcoidosis patients.

Effect of aspirin treatment on plasma levels of keto PGF 1 alpha and thromboxane B2.

A study was carried out on the effect of aspirin 175 mg/day on the plasma levels of 6 keto PGF 1 alpha and TXB2 in patients with acute myocardial infarction and in patients subjected to coronary artery bypass surgery. Our results showed a fall in the levels of both the prostagladins from day one to day seven and further from seven to day nine in patients with myocardial infarction treated with aspirin 175 mg/day. In patients with myocardial infarction accompanied by arrhythmias the TXB2 levels dominated over the 6 Keto PGF 1 alpha levels. In the group of patients subjected to coronary bypass surgery but after treatment with aspirin 175 mg/day for a period of five days both 6 keto PGF 1 alpha and TXB2 levels fell significantly.

Evaluation of oxidative stress in diabetics with or without vascular complications.

An excess of Oxidative Stress can occur either through an increase in the generation of free radicals and their metabolites (which overwhelm the protective capacity of the normal defence mechanisms of the body) or through a decrease in the protective ability of the body to withstand normal Oxidative Stress or both. Excessive Oxidative Stress plays an important role in the pathogenesis of diabetes and its chronic complications like retinopathy and nephropathy. Through various mechanisms, it plays a prominent role in the progression and acceleration of atherosclerosis. Free radicals being highly unstable due to their high reactivity are very difficult to measure accurately. Recourse is therefore taken to measure the compounds that are formed due to the activity of these free radicals. These compounds are relatively more stable and therefore can be measured as diene congugate and lipid peroxides. Another valuable measurement is to measure the levels of reduced glutathione in serum. Measurements of these products can be an excellent parameter to judge the metabolic control of diabetes.

HLA association with sarcoidosis and diffuse interstitial pulmonary fibrosis.

HLA typing was performed on 18 patients suffering from sarcoidosis and 30 patients suffering from diffuse interstitial pulmonary fibrosis. One hundred normal healthy people ethnically matched served as the controls. On statistical analysis, the corrected 'p' value of all the HLA antigens for both the patient groups was non significant. The results therefore suggest that there is no particular HLA antigen associated with sarcoidosis and diffuse interstitial pulmonary fibrosis.

Changes in 6 keto PGF1 alpha and TXB2 in patients with myocardial infarction.

A study was carried out on the plasma levels of 6 Keto PGF1 alpha and Thromboxane B2 (TXB2) in patients with acute myocardial infarction. Our results showed a generalized increase in the levels after acute myocardial infarction. The 6 Keto PGF1 alpha levels increased twice as compared to control values while the TXB2 levels increased nine times as compared to control values. The prostaglandin levels were found to increase from day 1 to day 3 and further from day 3 to day 7. In most of the patients with uncomplicated myocardial infarction the 6 Keto PGF1 alpha levels were higher than the TXB2 levels. In patients with myocardial infarction accompanied by arrhythmias the TXB2 levels dominated over the 6 Keto PGF1 alpha levels.

Apolipoproteins A-1 and B as predictors of angiographically assessed coronary artery disease.

Serum lipids, lipoproteins, apolipoproteins (A-1 and B) were determined in 225 patients with angiographic evidence of coronary artery disease (having abnormal coronary angiogram and positive exercise stress test), and 112 patients without any clinical and/or angiographic evidence of coronary artery disease. The variable with the strongest association with coronary artery disease was the ratio of apo B/A-1. Thus, the determination of apolipoproteins yielded complementary information in this case control study and warrants further study in a prospective setting.