Biomedical subjects

S Khilnani

Publications and source records attributed to S Khilnani.

16 recordsLinked to original sources

PubMed1996

Risk factors for hepatotoxicity from antituberculosis drugs: a case-control study.

BACKGROUND: Several risk factors for the development of hepatotoxicity during short course antituberculosis therapy have been suggested. A case-control study was undertaken to assess the role of age, sex, disease extent, nutritional status, past history of liver disease, infection with hepatitis viruses, acetylator status, and high alcohol intake as risk factors in the development of hepatotoxicity in patients with pulmonary tuberculosis receiving antituberculosis treatment. METHODS: The cases comprised 86 consecutive patients who were diagnosed as having hepatitis induced by antituberculosis drugs and who were negative for any of the hepatitis markers (HAV-IgM, HBsAg, HBc-IgM, and anti-HCV). The control group comprised 406 consecutive patients attending the chest clinic who completed antituberculosis treatment without developing hepatitis. The variables analysed were age, sex, body mass index (BMI), history of high alcohol intake, radiological extent of the disease, acetylator status, and serum proteins. RESULTS: The cases were older and their serum albumin levels were lower than in the control group. High alcohol intake was more common among the cases, they had more extensive disease radiologically, and the proportion of slow acetylators was higher. No differences were observed between the two groups in the other risk factors analysed. CONCLUSIONS: Of the various risk factors analysed, only advanced age, hypoalbuminaemia, high alcohol intake, slow acetylator phenotype, and extensive disease were risk factors for the development of hepatotoxicity. The risk of hepatitis in the presence of one or more of these risk factors may be increased.

Adolescent↗

PubMed1994

Changes in plasma lipoproteins during lipolysis in vivo in the hypertriglyceridemic state.

We investigated the effects of the severity of the hypertriglyceridemic state on lipolysis of very-low-density lipoproteins (VLDLs) in vivo. In six patients with mild (Mild, fasting triglyceride 2.54 +/- 0.27 mmol/L) and six with moderate hypertriglyceridemia (Mod, fasting triglyceride 4.63 +/- 0.47 mmol/L), heparin infusion decreased plasma triglycerides in direct correlation with the baseline triglyceride (r = 0.92 in Mild, r = 0.96 in Mod) concentration. Fasting VLDL-triglyceride correlated inversely with postheparin lipoprotein lipase (LPL) (r = -0.85). A decrease in VLDL-triglyceride correlated with baseline VLDL-triglyceride (r = 0.93), but not with postheparin LPL. In the Mild group, low-density-lipoprotein (LDL) cholesterol steadily increased (baseline, 2.90 +/- 0.18 mmol/L; 30 min, 3.03 +/- 0.23 mmol/L; 2 h, 3.15 +/- 0.18 mmol/L) in correlation with the decrease in VLDL-triglyceride (r = 0.89). In the Mod group, LDL cholesterol initially decreased (baseline, 2.51 +/- 0.34 mmol/L; 30 min, 2.30 +/- 0.23 mmol/L) and then increased (2 h, 2.82 +/- 0.28 mmol/L). These results demonstrate a delay in conversion of VLDLs into LDLs in pronounced hypertriglyceridemia, which may contribute to the etiology of low plasma LDL cholesterol.

Adult↗

PubMed1993

Prothymosin alpha gene expression correlates with proliferation, not differentiation, of HL-60 cells.

Accumulating evidence suggests that prothymosin alpha has an as yet undefined intracellular, perhaps intranuclear, function related to cell proliferation. Prothymosin alpha mRNA and/or peptide levels increase when cells are stimulated to proliferate. Because proliferation and differentiation events are often inversely correlated, we examined prothymosin alpha gene expression during proliferation and differentiation of HL-60 myeloid leukemia cells. Steady-state levels of prothymosin alpha mRNA, which are high in exponentially growing HL-60, decrease within hours after induction of HL-60 to differentiate along the neutrophil pathway with dimethylsulfoxide (DMSO) or along the macrophage lineage with either tetradecanoylphorbol acetate (TPA) or bryostatin 1. The decline in prothymosin alpha mRNA in response to these differentiation signals parallels that of c-myc mRNA under the same conditions. We then determined whether the downregulation of prothymosin alpha and c-myc mRNA were due to differentiation or cessation or proliferation. Recombinant human gamma-interferon induces monocytic differentiation of HL-60, but permits continued proliferation, and, under these conditions, expression of prothymosin alpha, as well as of c-myc, mRNA remains elevated. We conclude that prothymosin alpha and c-myc expression are coregulated in differentiating HL-60 and that their expression correlates with the proliferative state of HL-60 cells, rather than with the differentiated state.

Cell Differentiation↗

PubMed1993

Effect of lovastatin on the secretion of very low density lipoprotein lipids and apolipoprotein B in the hypertriglyceridemic Zucker obese rat.

Recent studies demonstrated that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase lower plasma triglyceride primarily by decreasing hepatic secretion of very low density lipoproteins (VLDL). A possible mechanism is that inhibition of cholesterol synthesis interferes with the assembly of VLDL particles. Since one molecule of apolipoprotein (apo) B is required for the proper assembly and secretion of each VLDL and secretion of apo B may be regulated by various lipid components of the lipoproteins, question arises whether HMG-CoA reductase inhibitors also decrease the secretion of apo B. To address this issue, we investigated the effect of lovastatin on the secretion rate of VLDL-apo B and on the composition of VLDL in the Zucker obese rat; a model for genetic hypertriglyceridemia. Lovastatin treatment (4 mg/kg day x 13 days), as compared with placebo, decreased the concentrations of fasting plasma triglyceride (1740 +/- 170 vs. 3130 +/- 790 micrograms/ml) and VLDL-triglyceride (1379 +/- 59 vs. 3082 +/- 715 micrograms/ml). There was a small but non-significant decrease in VLDL-apo B (19 +/- 2 micrograms/ml vs. 26 +/- 7 micrograms/ml). Thus, lovastatin significantly decreased the ratio of triglyceride to apo B in VLDL (76 in lovastatin vs. 124 in placebo group). Secretion rates of VLDL-lipids and VLDL-apo B were measured after intravenous injection of Triton WR-1339.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Dietary and anthropometric determinants of plasma lipoproteins during a long-term low-fat diet in healthy women.

Long-term (1 y) effects of dietary fat intake on lipoprotein metabolism were determined in 72 healthy women receiving either a 15%-fat diet (n = 34) or usual diet (n = 38). Every three months food records, weight, waist-hip ratio (W:H), percent body fat, fasting plasma triglyceride, cholesterol (C), high-density-lipoprotein cholesterol (HDL-C), HDL2-C, and HDL3-C; apolipoprotein B and A-I, and postheparin lipoprotein lipase (LPL) and hepatic triglyceride lipase activities were determined. In one year, the low-fat-diet (LFD) group had 17% and the non-intervention-diet group had 36% dietary fat. The LFD group showed decreases in cholesterol: 7% TC, 13% low-density lipoprotein (LDL), and 8% HDL. Apolipoprotein A-I, decreased early. Apolipoprotein B did not change. Plasma triglyceride correlated with weight. Percent body fat and W:H correlated with the total and LDL-C. Changes in HDL-C and/or HDL2-C and LPL correlated directly with the changes in dietary fat and inversely with dietary carbohydrate. Changes in total-C or LDL-C correlated with the changes in weight and W:H, but not with the changes in nutrient intake.

Adipose Tissue↗

PubMed1992

Effect of the prostaglandin E1 analog enisoprost on glucose and lipid metabolism in patients with type II diabetes mellitus.

Short-term studies have suggested that analogs of prostaglandin E may have favorable effects on the carbohydrate and lipid metabolism in patients with type II diabetes mellitus. The present study was undertaken to investigate the long-term effects of a prostaglandin E1 analog on the regulation of glycemic control and plasma lipids. Twenty patients with type II diabetes received enisoprost, 300 mcg/day, for three months. Fasting serum glucose, glycosylated hemoglobin, insulin and C-peptide levels as well as triglyceride, total cholesterol, high density lipoprotein cholesterol and its subfractions, apolipoproteins B and AI and post-heparin lipoprotein lipase and hepatic triglyceride lipase activities were determined. During the first month, enisoprost treatment caused significant decreases in plasma glucose (baseline = 8.72 +/- 0.39 mmol/L, 4 week = 7.78 +/- 0.5 mmol/L, change = -0.94 +/- 0.28 mmol/L, p less than 0.01) and total cholesterol (baseline = 5.30 +/- 0.23 mmol/L, 4 week = 5.01 +/- 0.26 mmol/L, change = -0.28 +/- 0.06 mmol/L, p less than 0.05). The decrease in cholesterol level was due to a reduction in high density lipoprotein, specifically in high density lipoprotein2 fraction (baseline = 1.29 +/- 0.1 mmol/L, 4 week = 1.12 +/- 0.08 mmol/L, change = -0.018 +/- 0.04 mmol/L, p less than 0.05 for the former and baseline = 0.40 +/- 0.06 mmol/L, 4 week = 0.27 +/- 0.03 mmol/L, change = -0.12 +/- 0.03 mmol/L, p less than 0.05 for the latter): All of these values returned to the pretreatment levels despite continuation of enisoprost.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1992

Effects of inspiratory loading on left ventricular myocardial blood flow and metabolism.

With airways obstruction, mean pleural pressure decreases. It has been postulated that associated increases in left ventricular afterload increase myocardial O2 demand (MvO2) and coronary blood flow (CBF). We tested this hypothesis in 12 anesthetized mixed-breed dogs. Through a median sternotomy, dogs were instrumented for the measurement of mean arterial pressure, cardiac output, and left anterior descending CBF. A catheter placed in the coronary sinus allowed sampling of left ventricular venous blood. MvO2 was calculated as CBF x (arteriovenous content difference), and coronary resistance was calculated as (mean arterial pressure)/CBF. After closure of the thoracotomy, animals were studied before and during inspiratory threshold loading (IL) of -20 to -25 cmH2O while breathing 100% O2 before and after bilateral cervical vagotomy. During IL, heart rate fell [approximately 20 beats/min (NS prevagotomy, P less than 0.05 postvagotomy)], arterial PCO2 increased [45 to 66 Torr prevagotomy, 45 to 50 Torr postvagotomy (P less than 0.01)], and arterial O2 content was unchanged. CBF increased with IL:41% prevagotomy (P less than 0.01), 18% postvagotomy (P less than 0.02). However, with IL, MvO2 did not increase significantly either pre- or postvagotomy. Coronary resistance decreased with IL [30% prevagotomy, 24% postvagotomy (P less than 0.01)]. In eight dogs, PCO2 was increased by increasing dead space while the animals were mechanically ventilated and paralyzed. Although there was little change in CBF, heart rate fell by an amount equal to that with IL. We conclude that 1) IL causes coronary vasodilation not related to changes in MvO2, PCO2, or vagal tone; 2) MvO2 does not increase with IL; and 3) decreased heart rate with IL is related to hypercapnia and/or acidosis.

Airway Obstruction↗

PubMed1992

Erythropoietin response to acute normobaric hypoxia in humans.

Hypoxia causes an increased production of erythropoietin (EPO), but the time course of the EPO response in humans has not been well characterized. This study examines the relationship between the duration of normobaric hypoxic exposure and plasma EPO levels in healthy human subjects. Six volunteers breathed a gas mixture of 10.5% O2-89.5% N2 continuously for 5, 60, and 120 or intermittently for 240 min. O2 saturations were maintained between 75 and 85% during the exposure. Arterial pH was 7.467 +/- 0.019, PO2 37.05 +/- 2.43 Torr, and PCO2 36.69 +/- 2.05 Torr. O2 half-saturation pressures of hemoglobin were normal for all subjects. Plasma EPO was measured every 30 min for 360 min by radioimmunoassay. No increase in EPO was seen after the 5- and 60-min exposures. However, a 50% increase was seen 240 min after the initiation of the 120-min hypoxic exposure (P less than 0.01). Intermittent exposure resulted in an increase of EPO by 52% 360 min after the onset of exposure (P less than 0.05). Therefore, exposing humans continuously to an inspiratory O2 fraction of 0.105 for 120 min or intermittently for 240 min provides a sufficient stimulus to increase production of EPO.

Adult↗

PubMed1992

Respiratory phasic effects of inspiratory loading on left ventricular hemodynamics in vagotomized dogs.

Exaggerated inspiratory swings in intrathoracic pressure have been postulated to increase left ventricular (LV) afterload. These predictions are based on measurements of LV afterload by use of esophageal or lateral pleural pressure. Using direct measurements of pericardial pressure, we reexamined respiratory changes in LV afterload. In 11 anesthetized vagotomized dogs, we measured arterial pressure, LV end-systolic (ES) and end-diastolic transmural (TM) pressures, stroke volume (SV), diastolic left anterior descending blood flow (CBF-D), and coronary resistance. Dogs were studied before and while breathing against an inspiratory threshold load of -20 to -25 cmH2O compared with end expiration. Relative to end expiration, SV and LVES TM pressures decreased during inspiration and increased during early expiration, effects exaggerated during inspiratory loading. In all cases, LV afterload (LVES TM pressure) changed in parallel with SV. LV end-diastolic TM pressure did not change. CBF-D paralleled arterial pressure, and there were no changes in coronary resistance. In two dogs, regional LVES segment length paralleled calculated changes in LVES TM pressure. We conclude that 1) LV afterload decreases during early inspiration and increases during early expiration, changes secondary to those in SV; 2) changes in CBF-D are secondary to changes in perfusion pressure during the respiratory cycle; and 3) the use of esophageal or lateral pleural pressure to estimate LV surface pressure overestimates changes in LV TM pressures during respiration.

Animals↗

PubMed1992

Mechanisms of triglyceride-lowering effect of an HMG-CoA reductase inhibitor in a hypertriglyceridemic animal model, the Zucker obese rat.

Inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase have been approved for treatment of hypercholesterolemia in humans. This class of therapeutic agents, in addition to lowering plasma cholesterol, reduces plasma triglyceride levels. We have investigated the mechanism of triglyceride-lowering effect of lovastatin in the hypertriglyceridemic state by using a rodent model of hypertriglyceridemia and obesity, the Zucker obese (fa/fa) rat. Lovastatin treatment (4 mg/kg), as compared to placebo, caused a 338% reduction in plasma triglyceride (146 +/- 5 vs. 494 +/- 76 mg/dl), a 58% decrease in total cholesterol (99 +/- 13 vs. 156 +/- 18 mg/dl), and a 67% reduction in high density lipoprotein (HDL)-cholesterol (69 +/- 8 vs. 115 +/- 15 mg/dl). The fall seen in plasma triglyceride was due to a decrease in hepatic secretion of very low density lipoproteins (VLDL), determined after blocking the clearance of triglyceride-rich lipoproteins with Triton WR-1339. Lovastatin treatment did not affect either the activities of hepatic lipogenic enzymes, glucose-6-phosphate dehydrogenase, or malic enzyme, or the activities of the lipolytic enzymes of adipose tissue, lipoprotein lipase, or liver, hepatic triglyceride lipase. Supplementation of mevalonolactone in the diet partially reversed the changes in plasma triglyceride (265 +/- 37 vs. 146 +/- 5 mg/dl), but not in total or HDL-cholesterol. These data demonstrate that, in the hypertriglyceridemic Zucker rat model, HMG-CoA reductase inhibitors reduce the rate of secretion of VLDL and this effect can be partially reversed by administration of mevalonolactone.

Adipose Tissue↗

PubMed1991

Relationships between the amount of weight loss and post-heparin lipoprotein lipase activity in patients with type II diabetes.

The objective of this study was to investigate the changes in plasma post-heparin lipoprotein lipase activity, as it relates to the total amount of weight loss and the changes in plasma lipoproteins, during acute weight reduction and after weight maintenance in type II diabetic patients. Twenty-eight severely obese (mean weight = 106 +/- 21.7 kg, BMI = 36.4 +/- 6.0 kg/m2), diabetic patients lost, on the average, 13.3 kg on a 500 kcal (2100 kJ) diet in eight weeks. Weight loss was maintained throughout the study, which lasted 24 weeks. At the baseline, post-heparin lipoprotein lipase activity did not correlate with degree of obesity, but correlated inversely with fasting plasma glucose (r = -0.64, P less than 0.0001) and triglyceride (r = -0.63, P less than 0.0001). Both during acute caloric restriction and after weight maintenance suppression in post-heparin lipoprotein lipase activity correlated directly with the amount of weight reduction (r = 0.37, P less than 0.05 during weight loss and r = 0.42, P less than 0.03 during weight maintenance). At the end of the study patients were divided into tertiles according to the amount of weight loss achieved and baseline characteristics of the highest and lowest weight loss groups were compared. Before weight loss, despite having similar weights, the highest weight loss group had higher lipoprotein lipase activity (211 +/- 32 mU/ml vs 166 +/- 35 mU/ml, P less than 0.05) and lower plasma triglyceride (1.64 +/- 0.62 mmol/l vs 2.81 +/- 1.28 mmol/l, P less than 0.05) as compared to the lowest weight loss group.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗

PubMed1990

Amiodarone-induced changes in lipid metabolism.

Hypothyroidism is a major cause of secondary hypercholesterolemia. Amiodarone treatment alters both the levels of serum lipids and thyroid hormones. We investigated whether the amiodarone-induced changes in lipid metabolism are related to the changes in thyroid hormone levels. Eighteen patients received amiodarone (31 +/- 3 g cumulative dose) for six weeks. Serum triglyceride, total-cholesterol, high density lipoprotein-cholesterol and its subfractions, apolipoproteins B and AI, and plasma post-heparin lipoprotein lipase and hepatic triglyceride lipase activities were determined. Amiodarone treatment caused significant increases in serum total-cholesterol (baseline 4.4 +/- 0.21 (SE), 6 weeks 5.12 +/- 0.26 mmol/l, P less than 0.01), in low density lipoprotein cholesterol (baseline 2.61 +/- 0.26, 6 weeks 3.36 +/- 0.21 mmol/l, P less than 0.05) and in apolipoprotein B (baseline 1.95 +/- 0.15, 6 weeks 2.26 +/- 0.13 mmol/l, P less than 0.01) concentrations. Serum high density lipoprotein and its subfractions, or apolipoprotein AI levels did not change. Plasma post-heparin lipoprotein lipase activity increased (baseline 137 +/- 21, 6 weeks 168 +/- 21 U/ml, P less than 0.01) while hepatic triglyceride lipase did not change. Amiodarone also caused an increase in serum thyroxine (baseline 110 +/- 8, 6 weeks 136 +/- 6 mmol/l, P less than 0.05), although values remained in euthyroid range. In summary, amiodarone therapy increased the concentrations of atherogenic lipoproteins in the serum similar to that seen in hypothyroidism. On the other hand the effect of amiodarone on lipoprotein lipase was opposite to that seen in hypothyroidism. Therefore, amiodarone-induced changes in lipid metabolism cannot be explained solely on the basis of the changes in circulating thyroid hormone levels.

Aged↗

PubMed1988

Effects of omega-3 fish oils on lipid metabolism, glycemic control, and blood pressure in type II diabetic patients.

We investigated the effects of omega-3 fish oil (FO) supplementation on lipid metabolism, glycemic control, and blood pressure (BP) in patients with type II diabetes mellitus. In 22 diabetic patients without overt hyperlipidemia, serum triglyceride, total cholesterol, high density lipoprotein (HDL)-cholesterol, HDL2-cholesterol, HDL3-cholesterol, and apolipoprotein A-I (apo A-I) levels did not change during omega-3 FO supplementation for 8 weeks. The mean serum apo B concentration increased significantly [baseline, 2.56 +/- 0.11 (+/- SEM) mmol/L; 4 weeks, 2.82 +/- 0.13 mmol/L; 8 weeks, 2.80 +/- 0.13 mmol/L; P less than 0.01]. The mean plasma postheparin lipoprotein lipase activity increased transiently during the fourth week (baseline, 168 +/- 17 U/mL; 4 weeks, 182 +/- 18 U/mL; P less than 0.05), whereas postheparin hepatic triglyceride lipase activity did not change. Glycemic control worsened transiently during the fourth week, (baseline, 7.7 +/- 0.4%; 4 weeks, 8.4 +/- 0.3%; P less than 0.05). Both systolic and diastolic BP decreased significantly throughout the study (systolic BP: baseline, 142 +/- 5 mm Hg; 8 weeks, 128 +/- 5 mm Hg; diastolic BP: baseline, 88 +/- 4 mm Hg; 8 weeks, 80 +/- 3 mm Hg; P less than 0.01). These findings suggest that in type II diabetics without overt hyperlipidemia, omega-3 FO supplementation does not improve either the glycemic control or serum lipids, and it is associated with a potentially detrimental rise in serum apo B concentrations. Until more information is available, use of such supplementation should be discouraged.

Apolipoproteins↗

PubMed1987

Effect of amiodarone on serum lipids, lipoprotein lipase, and hepatic triglyceride lipase.

We have determined the effects of chronic amiodarone treatment on lipid metabolism and compared them with those of hypothyroidism in the rat. Serum triglyceride was lower in both amiodarone-treated and hypothyroid rats; total cholesterol was higher in hypothyroid rats, and serum high density lipoprotein cholesterol remained unchanged. Amiodarone increased adipose tissue lipoprotein lipase activity. Hepatic triglyceride lipase activity was decreased in both hypothyroid and amiodarone-treated groups. The effects of amiodarone on serum triglyceride and adipose tissue lipoprotein lipase were reversed by concomitant administration of T3. The activity of hepatic triglyceride lipase, however, was not increased. Our findings indicate that amiodarone causes marked changes in lipid metabolism which are similar to those found in hypothyroidism.

Adipose Tissue↗

PubMed1987

Significance of hepatic triglyceride lipase activity in the regulation of serum high density lipoproteins in type II diabetes mellitus.

We investigated the regulation of serum high density lipoprotein (HDL) cholesterol metabolism in patients with type II diabetes mellitus by determining the activities of the two lipolytic enzymes that play major roles in the production and degradation of HDL. The activity of lipoprotein lipase (LPL), the enzyme responsible for HDL cholesterol production, and the activity of hepatic triglyceride lipase (HTGL), the enzyme that facilitates the catabolism of HDL, were measured in plasma obtained after iv injection of heparin. Thirty patients were selected to represent a wide range of serum HDL cholesterol concentrations (low, normal, and high HDL cholesterol groups). Mean lipoprotein lipase activity was similar in all three groups [122 +/- 10 (SEM) U/mL in the low HDL, 141 +/- 11 U/mL in the normal HDL, and 148 +/- 30 U/mL in the high HDL group]. Mean HTGL activity was markedly decreased in the high HDL group; the mean values were 346 +/- 28 U/mL in the low HDL, 320 +/- 25 U/mL in the normal HDL, and 191 +/- 23 U/mL in the high HDL groups, respectively. Body weight and insulin requirement correlated directly with HTGL activity and inversely with serum HDL cholesterol levels. These findings suggest that in type II diabetes mellitus low serum HDL cholesterol levels may be due to an increased rate of clearance by HTGL.

Aged↗

PubMedDate not supplied

Peak expiratory flow rate in school-going children.

Peak expiratory flow rate (PEFR) was measured with mini Wright's peak flow meter in 783 children (aged 6-17 years) from a school in urban Delhi and 523 children (aged 6-15 years) from another school in Nellore, Andhra Pradesh. In all the children, age in completed years, sex, height, weight, chest circumference at full inspiration and maximum chest expansion were recorded. Age, sex, height and weight were independent predictors of PEFR in children from Nellore. Age, sex and height, were independent predictors of PEFR in boys from Delhi while height alone was an independent predictor of PEFR in Delhi girls. Common prediction equations for predicting PEFR in boys and girls have been developed for both regions based on age and height. For the same height and age, boys had higher PEFR than girls. In the females, the PEFR seemed to have a plateaux effect after the age of 14 years; such an effect was, however, not seen in the boys in the age range studied. The PEFRs of children from both parts of the country were similar, and were lower than those reported for American white children.

Adolescent↗