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S Jacob

Publications and source records attributed to S Jacob.

At least 145 records · Page 8Linked to original sources
PubMed1996

Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid.

Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore, pharmacological intervention should aim to improve insulin sensitivity. Thioctic acid (TA), a naturally occurring compound, was shown to enhance glucose utilization in various experimental models after acute and chronic administration. It also increased insulin-stimulated glucose disposal in patients with NIDDM after acute administration. This pilot study was initiated to see whether this compound also augments glucose disposal in humans after repeated treatment. Twenty patients with NIDDM received TA (500 mg/ 500 ml NaCl, 0.9%) as daily infusions over a period of ten days. A hyperinsulinaemic, isoglycaemic glucose-clamp was done on day 0 and day 11. Parenteral administration of TA resulted in a significant increase of insulin-stimulated glucose-disposal by about 30% (metabolic clearance rate for glucose, 2.5 +/- 0.3 vs. 3.2 +/- 0.4 ml/kg/min and insulin-sensitivity-index: 3.5 +/- 0.5 vs. 4.7 +/- 0.4 mg/kg/microU/ml; p < 0.05, Wilcoxon-Rank-Sum-Test). There were no changes in fasting plasma levels for glucose or insulin; this can be explained, however, by the short period of treatment and observation. This is the first clinical study to show that a ten day administration of TA is able to improve resistance of insulin-stimulated glucose disposal in NIDDM. Experimental data suggest several mechanisms in the mode of action. As the present investigation was an uncontrolled pilot trial, the encouraging results call for controlled studies to further elucidate the clinical relevance of the findings and the mode of action of this compound.

Aged↗
PubMed1996

Sustained antiplatelet properties of nitroglycerin during hemodynamic tolerance in rats.

Organic nitrates possess important antiplatelet actions that are useful in the treatment of unstable angina and myocardial infarction, but the susceptibility of platelets to nitrate tolerance has not been extensively studied. In normal conscious rats, we showed that continuous infusion of nitroglycerin (NTG) at 10 micrograms/min had no significant effect on mean arterial pressure (MAP) as compared with control, but hemodynamic tolerance could be demonstrated by MAP response to a bolus intravenous (i.v.) NTG challenge. By this criterion, continuous 8-h NTG infusion produced hemodynamic tolerance (a decrease in MAP response of 45.7 +/- 19.9%, p < 0.05), whereas D5W control and S-nitroso-N-acetylpenicillamine (SNAP) infusions did not. During NTG infusion, platelet-rich plasma (PRP) cyclic GMP was increased by 41.4 +/- 13.6% as compared with control and remained increased throughout the infusion (p < 0.05). Bleeding time during a 2-h infusion of NTG was 8.9 +/- 1.2 min as compared to 3.8 +/- 0.4 min in controls (p < 0.05). After 8-h of NTG infusion, the bleeding time was 10.2 +/- 1.4 min versus 4.4 +/- 0.4 min in controls (p < 0.05). NTG also decreased the PRP platelet concentration by 30% in 8 h, whereas D5W had no effect. In vitro experiments showed that platelets in themselves do not produce significant amounts of cyclic GMP. These data indicate that the biochemical and antiaggregation effects of NTG on platelets are not diminished during hemodynamic tolerance and that these effects may be dependent on extraplatelet production of nitric oxide (NO).

Animals↗
PubMed1996

Renal functional reserve in kidney donors assessed in different settings using scintigraphy.

Glomerular filtration rate (GFR) was measured in 9 voluntary male kidney donors by scintigraphy. In the basal state, the mean GFR was 96.1 +/- 22 ml/min/1.73 m2. Four weeks after donor nephrectomy, the GFR of the remaining kidney had increased by 22.8 +/- 20.7% (p < 0.05). A protein meal given at this time failed to significantly augment the GFR. The GFR of the grafted kidney increased by 59.7 +/- 24.4% after 6 months (p < 0.01). Renal functional reserve was thus demonstrated in the remaining kidney and the allograft, though a further reserve could not be elicited in the remaining kidney.

Adult↗
PubMed1996

Potential role of bradykinin in forearm muscle metabolism in humans.

Using the euglycemic-hyperinsulinemic glucose clamp and the human forearm technique, we have demonstrated that the improved glucose disposal rate observed after the administration of an angiotensin-converting enzyme (ACE) inhibitor such as captopril may be primarily due to increased muscle glucose uptake (MGU). These results are not surprising because ACE, which is identical to the bradykinin (BK)-degrading kininase II, is abundantly present in muscle tissue, and its inhibition has been observed to elicit the observed metabolic actions via elevated tissue concentrations of BK and through a BK B2 receptor site in muscle and/or endothelial tissue. These findings are supported by several previous studies. Exogenous BK applied into the brachial artery of the human forearm not only augmented muscle blood flow (MBF) but also enhanced the rate of MGU. In another investigation, during rhythmic voluntary contraction, both MBF and MGU increased in response to the higher energy expenditure, and the release of BK rose in the blood vessel, draining the working muscle tissue. Inhibition of the activity of the BK-generating protease in muscle tissue (kallikrein) with aprotinin significantly diminished these functional responses during contraction. Applying the same kallikrein inhibitor during the infusion of insulin into the brachial artery significantly reduced the effect of insulin on glucose uptake into forearm muscle. This is of interest, because in recent studies insulin has been suggested to elicit its actions on MBF and MGU via the accelerated release of endothelium-derived nitric oxide, the generation of which is also stimulated by BK in a concentration-dependent manner. This new evidence obtained from in vitro and in vivo studies sheds new light on the discussion of whether BK may play a role in energy metabolism of skeletal muscle tissue.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Glucose transport activity in insulin-resistant rat muscle. Effects of angiotensin-converting enzyme inhibitors and bradykinin antagonism.

Insulin resistance of skeletal muscle glucose disposal underlies the pathogenesis of NIDDM and is associated with hypertension, obesity, and dyslipidemia. Angiotensin-converting enzyme (ACE) inhibitors are used primarily in antihypertensive therapy but also are known to improve whole-body insulin-mediated glucose disposal. However, the exact site of action is not well characterized. We have used the isolated epitrochlearis muscle from a well-established animal model of skeletal muscle insulin resistance, the obese Zucker rat, to test the effect of oral administration of ACE inhibitors on insulin-sensitive muscle glucose transport activity. Both acute and chronic administration of a sulfhydryl-containing ACE inhibitor (captopril) or a non-sulfhydryl-containing ACE inhibitor (tran-dolapril) significantly enhanced in vitro insulin-mediated muscle glucose transport activity. In addition, the acute effect of oral captopril administration was completely abolished by pretreatment of the animal with a bradykinin B2 receptor antagonist (HOE 140). These findings indicate that ACE inhibitors may improve whole-body glucose metabolism by acting on the insulin-sensitive skeletal muscle glucose transport system. In addition, bradykinin or one of its metabolites may be involved in the action of the ACE inhibitor captopril on insulin-resistant muscle.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

The antioxidant alpha-lipoic acid enhances insulin-stimulated glucose metabolism in insulin-resistant rat skeletal muscle.

Insulin resistance of muscle glucose metabolism is a hallmark of NIDDM. The obese Zucker (fa/fa) rat--an animal model of muscle insulin resistance--was used to test whether acute (100 mg/kg body wt for 1 h) and chronic (5-100 mg/kg for 10 days) parenteral treatments with a racemic mixture of the antioxidant alpha-lipoic acid (ALA) could improve glucose metabolism in insulin-resistant skeletal muscle. Glucose transport activity (assessed by net 2-deoxyglucose [2-DG] uptake), net glycogen synthesis, and glucose oxidation were determined in the isolated epitrochlearis muscles in the absence or presence of insulin (13.3 nmol/l). Severe insulin resistance of 2-DG uptake, glycogen synthesis, and glucose oxidation was observed in muscle from the vehicle-treated obese rats compared with muscle from vehicle-treated lean (Fa/-) rats. Acute and chronic treatments (30 mg.kg-1.day-1, a maximally effective dose) with ALA significantly (P < 0.05) improved insulin-mediated 2-DG uptake in epitrochlearis muscles from the obese rats by 62 and 64%, respectively. Chronic ALA treatment increased both insulin-stimulated glucose oxidation (33%) and glycogen synthesis (38%) and was associated with a significantly greater (21%) in vivo muscle glycogen concentration. These adaptive responses after chronic ALA administration were also associated with significantly lower (15-17%) plasma levels of insulin and free fatty acids. No significant effects on glucose transporter (GLUT4) protein level or on the activities of hexokinase and citrate synthase were observed. Collectively, these findings indicate that parenteral administration of the antioxidant ALA significantly enhances the capacity of the insulin-stimulatable glucose transport system and of both oxidative and nonoxidative pathways of glucose metabolism in insulin-resistant rat skeletal muscle.

Animals↗
PubMed1996

Differential effect of chronic treatment with two beta-blocking agents on insulin sensitivity: the carvedilol-metoprolol study.

BACKGROUND: Hypertensive patients frequently show resistance to insulin-stimulated glucose uptake and hyperinsulinemia. Diuretics and beta-adrenoceptor blocking agents have been found to decrease insulin sensitivity, whereas alpha 1-blockers and angiotensin converting enzyme inhibitors seem to improve it. OBJECTIVE: To compare the effects of a 3 months' antihypertensive treatment with carvedilol, a non-selective beta-adrenoceptor blocker with alpha 1-blocking properties, with the beta 1-selective receptor blocker metoprolol on insulin sensitivity in non-diabetic hypertensive patients. DESIGN: A multicenter double-blind randomized study. SUBJECTS AND METHODS: Seventy-two non-diabetic hypertensive patients were randomly assigned to treatment with either carvedilol or metoprolol. An isoglycemic, hyperinsulinemic glucose clamp was conducted before and after 12 weeks of treatment; the metabolic clearance rate for glucose was taken as an indicator of insulin sensitivity. RESULTS: The two groups did not differ in age, sex, body mass index, blood pressure or lipids, and treatment effectively lowered blood pressure. In both groups, insulin sensitivity was impaired at baseline. After metoprolol treatment, insulin sensitivity further decreased significantly by about 14%, whereas it increased after carvedilol. There was also a decrease in high-density lipoprotein and an increase in triglycerides levels in patients in the metoprolol-treated group, whereas these parameters remained unchanged in patients in the carvedilol-treated group. CONCLUSION: This study confirms previous findings of a reduction in insulin sensitivity after chronic metoprolol treatment. Carvedilol treatment, however, resulted in a small amelioration of insulin resistance and a better lipid profile [corrected]. We thus demonstrate that a beta-blocker with alpha 1-blocking properties has favorable effects on glucose metabolism, suggesting a potentially important role of peripheral blood flow in regulating glucose uptake. These findings imply that beta-blocker treatment, when combined with alpha 1-blocking activity has advantageous effects on insulin sensitivity and lipids and could therefore be suitable for patients with the metabolic syndrome.

Adrenergic beta-Antagonists↗
PubMed1996

Birthweight standards for south Indian babies.

OBJECTIVE: To obtain birthweight standards for south Indian babies. DESIGN: Prospective cohort study. SETTING: A tertiary care hospital in south India. PATIENTS AND METHODS: Data from 11, 641 singleton live births between 1991 and 1994 were used to calculate smoothed gestation specific birthweight centiles for four categories based on sex of the infant and birth order. Smoothed gestation specific birthweight centiles were also calculated for all births between 37-41 weeks without adjustments for sex of infant or birth order. Data for births between 37 and 41 weeks were reanalysed using non-adjusted birthweight centiles and birthweight centiles adjusted for sex and birth order to determine misclassification of data. Multiple regression analysis was used to determine the influence of various variables on birthweight. RESULTS: Factors influencing birthweight were gestation at birth, sex of infant, birth order and maternal height. A quadratic equation including these variables and the square of the gestational age explained 18% of variation in birthweight. Female infants were on the average 113 g (95% CI 26-200 g) lighter than male infants. Later born babies were on the average 130 g (95% CI 40-220 g) heavier than first born babies. Therefore significant misclassification of infants occurred when non-adjusted birthweight centiles were used. Babies born to women whose heights were outside the interquartile range (150-158 cm) were 81 g lighter or heavier than those born to women within this range. CONCLUSIONS: Birthweight centiles for gestation when used should be adjusted for birth order, sex of infant and maternal height.

Birth Order↗
PubMed1996

Improvement of glucose metabolism in patients with type II diabetes after treatment with a hemodialysate.

Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore, pharmacological intervention should aim to improve insulin sensitivity. Previous studies have shown that Actovegin, a hemodialysate of calf blood, which has been used for treatment of circulatory disorders for many years, improves glucose tolerance in NIDDM without affecting insulin levels; in vitro studies found an improvement of insulin-stimulated glucose uptake in adipocytes. This pilot study was initiated to see whether this compound augments insulin sensitivity after repeated treatment. Ten patients with NIDDM received the hemodialysate (Actovegin 2.000 pro infusions, 500 ml as daily infusions) over a period of 10 days. A hyperinsulinaemic, isoglycaemic glucose-clamp was done on day 0 and day 11; oral glucose tolerance test (oGTT) was done on day -4 and day 12. Parenteral administration of the hemodialysate markedly augmented insulin stimulated glucose disposal (glucose infusion rate and metabolic clearance rate) by more than 80% (p < 0.003 day 11 vs. day 0). Although tested 44 h after the last infusion, oGTT also improved significantly, as documented by the diminished area under the curve (AUC) for glucose, whereas the AUC for insulin remained unchanged. This is the first clinical study to show that parenteral administration of the tested hemodialysate results in a significant increase of insulin-stimulated glucose disposal in NIDDM. The exact mode of action of the hemodialysate in improving insulin sensitivity is currently not known. The hemodialysate possibly acts via a supplementation of inositol-phosphate-oligosaccharides (IPO), as in experimental studies IPOs isolated from the hemodialysate improved glucose uptake in adipocytes in an insulin-independent manner. Further studies are needed to elucidate the underlying mechanisms.

Aged↗
PubMed1996

Mediastinal enterogenic cyst presenting as paraplegia--a case report.

A rare case of a mediastinal enterogenic cyst with an intraspinal extension through a anterior vertebral defect presenting with paraplegia in a 10 year boy is presented. Laminectomy and the trans-thoracic excision of the cyst resulted in the complete recovery of the neural deficit.

Abnormalities, Multiple↗
PubMed1995

[Incidence of insulin resistance in peripheral arterial occlusive disease patients. Pilot study in a general medicine practice].

UNLABELLED: Few data are available on the correlation between peripheral occlusive arterial disease and metabolic syndrome. The present pilot study therefore investigated patients with and without PAOD and compared their vascular risk pattern with that of healthy controls. METHOD: With the aid of Doppler US measurements of blood pressure differences (tibiobrachial Doppler Index [DI], 59 patients were divided up into three groups: "healthy" (DI > 0.8 to < 1.0), "suffering from PAOD" (DI < 0.8) and "endangered" (DI > 0.8 to < 1.0). In each patient an oral glucose test (100 g) was done and insulin levels measured; in addition, the lipid fractions and fibrinogen were determined in the fasting patient. RESULTS: The groups, matched for age and weight, showed typical differences between patients with PAOD and healthy controls: lowered HDL cholesterol, elevated systolic blood pressure, triglycerides, total and LDL cholesterol and insulin. In addition, disorders of the glucose tolerance test were also more common. This shows that the patients with vascular disease have the typical risk factor pattern for metabolic syndrome as compared with controls in which point they are similar to patients with CAD. CONCLUSION: In patients with PAD, intensive non-medical therapy, such as weight reduction and physical exercise are likely to reduce the vascular risk-as has been shown for CAD patients.

Aged↗
PubMed1995

Effects of captopril on glucose transport activity in skeletal muscle of obese Zucker rats.

This study tested whether the angiotensin-converting enzyme (ACE) inhibitor captopril can modify the glucose transport system in insulin-resistant skeletal muscle. Obese Zucker (fa/fa) rats (approximately 300 g)--a model of insulin resistance--were administered by gavage either a single dose (50 mg/kg body weight) or repeated doses (50 mg/kg/d for 14 consecutive days) of captopril. Corresponding groups of age-matched, vehicle-treated lean (Fa/-) littermates (approximately 170 g) were also studied. Glucose transport activity in the epitrochlearis muscle was assessed by in vitro 2-deoxyglucose (2-DG) uptake. The increase in 2-DG uptake due to insulin (2 mU/mL) in muscles from vehicle-treated obese rats was less than 50% (P < .05) of the increase observed in muscles from lean rats. Short-term captopril treatment improved insulin-stimulable 2-DG uptake in muscles from obese rats by 46% (P < .05), and this enhanced insulin action due to captopril was completely abolished by pretreatment with the bradykinin antagonist HOE 140 (100 micrograms/kg). Long-term treatment with captopril produced a 60% improvement in insulin-stimulated 2-DG uptake (P < .05). Contraction-stimulated 2-DG uptake was significantly impaired (-31%, P < .05) in the obese rat, but was not altered by long-term captopril treatment. These findings indicate that both short- and long-term treatments with captopril significantly improve insulin-stimulated glucose transport activity in skeletal muscle of the obese Zucker rat, and that this improvement involves bradykinin metabolism. These data therefore support the hypothesis that captopril-induced improvements in glucose disposal result in part from an enhancement of the skeletal muscle glucose transport system.

Animals↗
PubMed1995

Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid.

Insulin resistance of skeletal muscle glucose uptake is a prominent feature of Type II diabetes (NIDDM); therefore pharmacological interventions should aim to improve insulin sensitivity. Alpha-lipoic acid (CAS 62-46-4, thioctic acid, ALA), a natural occurring compound frequently used for treatment of diabetic polyneuropathy, enhances glucose utilization in various experimental models. To see whether this compound also augments insulin mediated glucose disposal in NIDDM, 13 patients received either ALA (1000 mg/Thioctacid/500 ml NaCl, n = 7) or vehicle only (500 ml NaCl, n = 6) during a glucose-clamp study. Both groups were comparable in age, body-mass index and duration of diabetes and had a similar degree of insulin resistance at baseline. Acute parenteral administration of ALA resulted in a significant increase of insulin-stimulated glucose disposal; metabolic clearance rate (MCR) for glucose rose by about 50% (3.76 ml/kg/min = pre vs. 5.82 ml/kg/min = post, p < 0.05), whereas the control group did not show any significant change (3.57 ml/kg/min = pre vs. 3.91 ml/kg/min = post). This is the first clinical study to show that alpha-lipoic acid increases insulin stimulated glucose disposal in NIDDM. The mode of action of ALA and its potential use as an antihyperglycemic agent require further investigation.

Aged↗
PubMed1995

Primary malignancies of the corpus uteri retrospective five year analysis.

Primary malignant tumours of the body of the uterus are less common in India compared to carcinoma of the cervix. This study analyzed 86 primary malignant tumours of the body of the uterus over a 5 year period with regard to incidence of the various tumours, age group, gravidity, any predisposing factor, and the incidence of carcinoma of the cervix in the same period. Adeno-carcinomas were found to be the most common type of tumour. Tropho-blastic malignancies and mixed mullerian tumours also formed a significant number of cases. Compared to Western studies our patients with adenocarcinoma, adenosquamous carcinoma, squamous cell carcinoma and mixed mullerian tumour, were younger. Patients with adeno-carcinomas had a higher parity and patients with choriocarcinoma had a lower parity. Diabetes, hypertension and obesity were not as common as in the West. Carcinoma of the cervix was found to be commoner than primary malignant tumours of the body of the uterus.

Adult↗
PubMed1994

Quantitative whole body autoradiographic disposition of glycol ether in mice: effect of route of administration.

Glycol ethers such as ethylene glycol monomethyl ether (EGME) are common solvents used in many industrial products. A large number of individuals are exposed to EGME through different exposure routes. We investigated the differential distribution of EGME following various routes of administration using whole body autoradiographic (WBA) techniques. Male B6C3F1 mice were treated with tracer iv or oral doses of [2-14C]EGME (4.05 micrograms EGME/kg equivalent to 0.8 mCi/kg) and euthanized at 1 and 24 hr following treatment. In both groups of animals the highest levels of radioactivity were detected in the liver, urinary bladder, bone marrow, kidney, and epididymis, at 1- and 24-hr time periods. Computer-assisted quantitation of WBA indicated that there was markedly higher deposition of [2-14C]EGME and/or its metabolites in various tissues of the orally treated animals than in animals treated intravenously. Our studies also suggest that [2-14C]EGME is rapidly distributed either from blood or stomach to various tissues. Preferential deposition of radioactivity in the peripheral tissues of the bone, with a progressive inward accumulation in the bone marrow, was observed. Selective permeability of EGME and/or its metabolites was indicated by the higher uptake by the epididymis than that by testis. The high levels of radioactivity in biosynthetically active tissues, e.g., the liver, bone marrow, and gastric mucosa, is an indication of persistent interaction of the compound with cellular components of these tissues. These interactions may lead to EGME toxicity.

Administration, Oral↗