Circulating thrombotic and haemostatic components in patients with coronary artery disease.

The study aimed to analyze the circulating levels of thrombotic and haemostatic components; tissue factor, tissue factor pathway inhibitor, tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with acute myocardial infarction at presentation (Group 1, n=49), unstable angina and Non-ST elevated MI after treatment (Group 2, n=22), stable angina (Group 3, n=18) and healthy individuals (Group 4, n=31). Significant finding was increase in tissue factor not only in Group 1 (2.0 fold, P=0.001), Group 2 (2.2 fold, P=0.015) but also in Group 3 (1.8 fold, P=0.018) as compared to controls. In Group 1 Plasminogen activator inhibitor-1 increased significantly (35.8%, P=0.02). Tissue factor pathway inhibitor and tissue plasminogen activator demonstrated increase in Group 1 of age<40 years while insignificant changes in elder patients. Increased thrombotic and decreased fibrinolytic conditions in acute myocardial infarction patients were observed. Increase TF in stable angina demonstrates procoagulant status in these patients as well.

Matrix metalloproteinase-3 (MMP-3) -1612 5A/6A promoter polymorphism in coronary artery disease in Indian population.

Matrix metalloproteinases (MMPs) play important role in the pathogenesis of coronary artery disease (CAD). 5A allele of -1612 5A/6A polymorphism of MMP-3 is associated with two fold higher activity than 6A allele. Present study was designed to analyse the association of this polymorphism with CAD in Indian population. Subjects included in the study were patients with stable angina (n=35), unstable angina (n=53), patients with recent event of myocardial infarction (MI) (MI Group-1, n=56) and patients at presentation of the acute MI (MI Group-2, n=49). Controls were healthy individuals (n=99). Genotyping of MMP-3 5A/6A polymorphism was carried out by PCR-based restriction digestion method. The genotype distribution of patient groups did not deviate from controls. Serum MMP-3 levels were significantly elevated at presentation of the acute MI by 36.8% (P=0.031) as compared to controls and more associated with 6A genotype suggesting discrepancy between in vitro transfection experiment and peripheral MMP-3 levels.

Subclinical hypovitaminosis D among exclusively breastfed young infants.

OBJECTIVE: To determine Vitamin D status of mother-newborn diads at birth and of their exclusively breastfed (EBF) infants at 3 months. DESIGN: Longitudinal study. METHODS: Exclusively breastfed infants born at term with birth weight > 2.5 kg to normal, healthy mothers followed till 3 months. Serum calcium, phosphorous, heat labile alkaline phosphatase (HLAP) and 25(OH)D estimated in 42 mother / cord blood diads and in 35 (EBF) infants followed up at 3 months. Twenty five (OH)D < 15 ng/mL was considered low and 15 to 25 ng/mL low to normal. RESULTS: Ca, P, HLAP were significantly higher in cord blood (P < 0.001) but mean 25 (OH)D, 19.36 ng/mL was comparable to maternal level of 22.9 ng/mL (r = 0.82, P < 0.001). At 3 months only HLAP was significantly higher compared to cord blood. Higher 25 (OH)D at 3 months correlated with higher 25 (OH)D values in cord blood (r = +0.616, P < 0.001) as well as higher antenatal maternal levels (r = + 0.552, P < 0.001). Serum 25 (OH)D values < 25 ng/mL was observed in 50 % mothers, 62 % cord blood specimens and 80 % infants at 3 months. CONCLUSIONS: Subnormal maternal vitamin D status is associated with vitamin D deficiency in newborns and persists in exclusively breastfed infants.

Association of insulin resistance to electrocardiographic changes in non obese Asian Indian subjects with hypertension.

To investigate the relationship between insulin resistance and electrocardiographic changes in hypertension in the absence of confounding influences, plasma glucose and insulin responses to oral glucose were studied in 26 normotensive and 38 hypertensive subjects. Resting ECG was taken and classified into normal or abnormal using the Minnesota code. Among the 38 subjects, 16 had ECG abnormalities. All the hypertensive subjects had normal glucose tolerance. Serum insulin response of hypertensive subjects with ECG changes was 43% higher than those of hypertensive subjects without ECG changes and of normotensive subjects. The ratio AUC glucose/AUC insulin, a measure of insulin sensitivity was significantly reduced in subjects with abnormal ECG. Serum LDL cholesterol was significantly elevated and was the highest in hypertensive subjects with abnormal ECG. The ratio, Total Cholesterol/HDL Cholesterol was elevated to 5.81+/-0.47. I(125)-insulin binding to erythrocytes from 6 normotensive subjects, and 16 hypertensive subjects (8 with and 8 without ECG abnormalities) indicated 50% reduction in insulin receptor number in both the groups of hypertensive subjects compared to normotensive subjects. Multiple logistic regression analysis using mean blood pressure, serum total cholesterol, LDL cholesterol/HDL cholesterol, sex, insulin level at 60 min in OGTT, treatment, serum triglyceride, presence of family history of diabetes, CHD, hypertension and tobacco as independent variables causing ECG changes, revealed correct classification in 84% of cases. Among the variables, insulin level in OGTT contributed the most to ECG abnormalities. The data suggest that in the non obese, non diabetic Asian Indian hypertensive subjects, the presence of electrocardiographic abnormalities might be partly related to hyperinsulinemia or insulin resistance in them.

A clinicopathologic profile of adrenocortical tumors.

OBJECTIVE: To study the clinical, biochemical, hormonal, radiological and histopathological profile of adrenocortical tumors in children; to assess the clinicopathological correlations and note the future outcome. DESIGN: Retrospective and prospective study. SETTING: Hospital based; Endocrine Service of our institution and other institution based services. SUBJECTS: 14 children (Females = 11, Males = 3) with adrenocortical tumor, aged 8 months to 13 years (mean age 5.1 +/- 3.42 years), seen over a period of 9 years. RESULTS: Females predominated (F:M = 3.7:1). Majority (64%) had a mixed picture with cushingoid features and virilization, whereas 36% presented only for virilization. Elevated serum cortisol levels with loss of diurnal variation was noted only in those with mixed clinical presentation. Adrenal androgen elevation was noted in majority of cases as virilization was common to all. CT confirmed the diagnosis of tumor, 7 on either side. Thirteen cases were operated. Histopathologic diagnosis was carcinoma in 7 and adenoma in 6 cases. Three of the seven with carcinoma died within 3 months to 2 years but two of these with small tumours (weight 60-65 g and diameter < 6 cm) were well at 2 and 5 years, while as one of the six with a large adenoma had recurrence and metastasis after three years. CONCLUSION: Female preponderance was marked (4 times), 43% of tumors had occurred by 3 years of age and 64% by 6 years. Neither the hormonal parameters nor the histopathology correlated well with the biological behavior and outcome. Prolonged and vigilant follow up is essential.

Modulation of sperm membrane conformation by pentoxifylline in oligospermia: a biophysical investigation of sperm membrane in vitro.

Low superoxide anion radical levels, low membrane fluidity and high superoxide dismutase activity are some of the defects existing in oligospermia. The phosphodiesterase inhibitor pentoxifylline has been used as a motility stimulant in the treatment of oligospermia in vitro. The mechanism of its action is unclear. Our results show significant inhibition of superoxide dismutase, increase in lipid peroxidation and membrane fluidity after pentoxifylline treatment. A biophysical modulation of the sperm membrane by an oxyradical mechanism in oligospermia is discussed.

Free radical induced biophysical modification of membrane lipids: a novel mechanism proposed for a haemorheological alteration induced by 4,5' 8-trimethyl psoralen.

Haemostasis is the spontaneous arrest of bleeding from damaged blood vessel. Platelet aggregation is the major event in this process. A number of drugs are known to inhibit this process of platelet aggregation. 4,5' 8-trimethyl psoralen a naturally occurring furocoumarin is used as a photochemotherapeutic agent in PUVA therapy. It shows antithrombotic action by preventing platelet aggregation induced by adenosine diphosphate in vitro. It is proposed that a free radical induces a lipid phase transition of the membrane lipids, the platelet membrane undergoes certain biophysical alteration leading to increased membrane fluidity resulting in a loss of aggregating ability.