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Biomedical subjects

I Raz

Publications and source records attributed to I Raz.

At least 55 records · Page 3Linked to original sources
PubMed1997

Effect of acute N-nitro-L-arginine methyl ester (L-NAME) hypertension on glucose tolerance, insulin levels, and [3H]-deoxyglucose muscle uptake.

This study was conducted to test the hypothesis that acute, widespread N-nitro-L-arginine methyl ester (L-NAME) induced vasoconstriction and hypertension may affect glucose tolerance and insulin sensitivity in normal rats. Comparisons were made of blood pressure, intravenous glucose tolerance, and insulin response and [3H]-deoxyglucose tissue uptake between L-NAME and control treated rats. Chronically instrumented, awake rats were administered L-NAME (30 mg/kg) (n = 8) or saline (0.3 mL) (n = 8) intravenously. After blood pressure stabilized, a bolus injection containing glucose (300 mg/kg) and trace [3H]-deoxyglucose was administered. Arterial blood was sampled for evaluation of glucose tolerance, insulin response, and [3H]-deoxyglucose muscle uptake. L-NAME treated rats had a persistent 54 +/- 4 mm Hg blood pressure rise while fasting, and postload plasma glucose and insulin responses did not differ, nor did heart and striated muscle [3H]-deoxyglucose uptake differ. In conclusion, acute L-NAME induced hypertension does not result in glucose intolerance, hyperinsulinemia, or decreased [3H]-deoxyglucose muscle uptake.

Animals↗
PubMed1996

A patient with hypoparathyroidism, dysmorphic features and mental retardation.

There have been various reports in the medical literature concerning children with syndromes of congenital hypoparathyroidism, seizures, dysmorphic features and mental retardation. We describe a patient with hypoparathyroidism, mental retardation, micrognathia, deep-set eyes and pes cavus in a 31-year-old man. This combination of abnormalities in an adult is unique.

Adult↗
PubMed1996

Pre-clinical Cushing's syndrome: an unexpected frequent cause of poor glycaemic control in obese diabetic patients.

OBJECTIVE: Autonomous cortisol secretion without clinical stigmata of Cushing's syndrome (CS) has been recently recognized and termed pre-clinical or sub-clinical CS. The common assumption is that CS is an extremely rare cause of uncontrolled diabetes; however, the prevalence of this entity has not been studied. We assessed the prevalence of pre-clinical CS among obese patients with uncontrolled diabetes. PATIENTS AND DESIGN: (1) In a retrospective analysis, the medical records of 63 patients with endogenous CS were reviewed. (2) In a cross-sectional study, 90 obese patients (BMI > 25 kg/m2) followed in a University Hospital and the local Health Fund endocrine and diabetes clinics, with poorly controlled diabetes (glycosylated haemoglobin > 9%), underwent an overnight 1 mg dexamethasone suppression. In patients with non-suppressible cortisol levels (> 140 nmol/l), Liddle's 2 and 8 mg dexamethasone suppression tests and imaging studies were performed. MEASUREMENTS: The prevalence of poorly controlled diabetes, the major presenting symptom of CS, was assessed in the retrospective analysis. The prevalence of "true' CS and the false positive rate in the overnight dexamethasone suppression test were calculated. The endocrine evaluation of the patients with pre-clinical CS and the effects of surgical cure on glycaemic control are described. RESULTS: In the retrospective analysis, 11 (17.5%) had diabetes and 2 (3.2%) lacked the classic physical characteristics of the syndrome. In the cross-sectional study, 4 patients failed to suppress plasma cortisol (< 140 nmol/l). In one patient the diagnosis of CS was not confirmed by a standard Liddle's test and was therefore considered false positive. In the other 3, the diagnosis of CS was confirmed (prevalence of 3.3%, 95% confidence interval 1-9%). In all other patients the overnight cortisol suppression test was normal (cortisol level 47.3 +/- 2.5 nmol/l (mean +/- SEM)). After surgical treatment of CS, glycaemic control was markedly improved in all 5 patients (2 from retrospective and 3 from cross-sectional studies). CONCLUSIONS: The prevalence of pre-clinical Cushing's syndrome in obese patients with poorly controlled diabetes appears to be considerably higher than previously believed. The overnight dexamethasone suppression test proved to be a simple, sensitive and highly specific screening test for Cushing's syndrome despite the presence of obesity and hyperglycaemia.

Adult↗
PubMed1996

Dyslipidaemia in polycystic ovarian syndrome: different groups, different aetiologies?

The objective was to study the pathophysiology of the dyslipidaemia in polycystic ovarian syndrome (PCOS) patients, and to determine how it is related to hyperinsulinaemia, hyperandrogenism and dehydroepiandrosterone sulphate (DHEA-S) concentrations. The lipoprotein lipid profile, anthropometric measurements, endocrine profile and the presence of insulin resistance were evaluated in 31 PCOS patients and 20 age-matched healthy women, who served as controls. PCOS patients had higher fasting insulin concentrations, higher body mass indexes (BMI) and were hyperlipidaemic, with higher total cholesterol, low density lipoprotein (LDL) and triglyceride (TG) concentrations. There were no relationships between plasma lipids and anthropometric variables in the patient group as a whole. Insulin-resistant (IR) and non-IR (NIR) PCOS patients were then evaluated separately. Obesity with marked hyperandrogenism were the predominant features in patients with IR. NIR patients were not obese and had significantly less hyperandrogenism. The adrenal androgen DHEA-S was at the upper limit of its normal range in both groups. However, both PCOS subgroups exhibited similar significant abnormalities in terms of their lipid parameters. Insulin and DHEA-S concentrations were positively correlated with total cholesterol, LDL and TG, and negatively correlated with high density lipoprotein, in IR patients. In NIR subjects, insulin was not correlated with any of the lipids and DHEA-S was negatively related to cholesterol and LDL. Anthropometric variables were related to lipids in only the NIR patients. Thus PCOS subjects as a group exhibit dyslipidaemia, characterized by increased total cholesterol, LDL and TG concentrations. When divided into IR and NIR subjects, there were no differences in the degree of lipid abnormalities, despite significant variations in the BMI and androgen status. Thus, in PCOS subjects, dyslipidaemia may occur irrespective of insulin resistance. Insulin and DHEA-S concentrations were positively correlated with an atherogenic lipid profile in the IR group only. As distinct from syndrome X when IR was present, dyslipidaemia was not related to body weight or the waist:hip ratio. In the NIR group there was no relationship between lipids and insulin; DHEA-S, on the other hand, was negatively related to cholesterol and LDL concentrations. Thus, dyslipidaemia in PCOS patients may occur irrespective of insulin resistance, and may have different metabolic aetiologies depending on DHEA-S metabolism. It remains to be seen whether the two types of PCOS are associated with different risks for ischaemic heart disease.

Adult↗
PubMed1996

Role of reactive oxygen species in diabetes-induced embryotoxicity: studies on pre-implantation mouse embryos cultured in serum from diabetic pregnant women.

Sera from diabetic patients or sera with high levels of diabetic metabolic products, were found to affect mouse and rat blastocysts. In the present study we examined the earliest developmental stages at which human diabetic serum will be lethal to mouse pre-implantation embryos, and whether reactive oxygen species (ROS) are involved in these diabetes-induced injuries. We cultured 2-4 cell-stage embryos and blastocysts in a medium containing 30 or 50% serum obtained from pregnant women with diabetes Type I, Type II and gestational diabetes (GDM) for 72 h. The development of the 2-4 cell-stage embryos was delayed when cultured in 30% diabetic serum, but the viability was impaired to a lesser extent. Viability was reduced in blastocysts cultured in 50% diabetic serum, but the development of the living embryos was not delayed. Cyclic voltametry measures the oxidation potential of the tissue and the concentration of antioxidants, thus reflecting the total antioxidative activity of the embryos. Pre-implantation embryos cultured in diabetic serum had a lower concentration of antioxidants than embryos cultured in non-diabetic serum. It seems, therefore, that diabetic metabolic factors may induce embryotoxicity in pre-implantation embryos through derangement of the antioxidant defense mechanism. A similar mechanism is suggested for the diabetes-induced teratogenicity in post-implantation embryos.

Animals↗
PubMed1995

Rapid activation of glycogen synthase and protein phosphatase in human skeletal muscle after isometric contraction requires an intact circulation.

The effects of isometric contraction (66% of maximal force) and recovery on glycogen synthase fractional activity (GSF) in human skeletal muscle have been studied. Biopsies were taken from the quadriceps femoris muscle at rest, at fatigue and 5 min postexercise on two occasions: after one of the contractions, the circulation to the thigh was occluded during the 5 min recovery (OCC), and after the other contraction, the circulation was intact (control, CON). During CON, GSF decreased from (mean +/- SE) 0.34 +/- 0.05 at rest to 0.24 +/- 0.02 at fatigue and then increased to 0.74 +/- 0.04 at 5 min postexercise; corresponding values for OCC were 0.37 +/- 0.04, 0.25 +/- 0.04 and 0.48 +/- 0.05 (P < 0.001 vs. CON for 5 min postexercise only). Compared with the value at fatigue, protein phosphatase activity (PP) increased by 79 +/- 16% during CON recovery (P < 0.01), whereas no change was observed during OCC recovery. Uridine diphosphate glucose increased by approximately 2.5-fold at fatigue, remained elevated during OCC recovery, but reverted to the preexercise level during CON recovery (P < 0.001 vs. OCC recovery). Glucose 6-P increased approximately 5-fold at fatigue and was higher at 5 min postexercise in OCC vs. CON recovery (8.6 +/- 1.5 vs. 4.1 +/- 0.9 mmol/kg dry wt; P < 0.01). It is concluded that the rapid increase in GSF after intense exercise with an intact circulation may be at least partly attributed to an increase in the specific activity of PP. The increase in GSF during recovery in OCC may be at least partly attributed to the high glucose 6-P content in vivo, which enhances the substrate suitability of GS for PP. Thus, separate mechanisms exist for the activation of PP and GS during recovery from intense short term exercise.

Adult↗
PubMed1995

Insulin-like growth factor-I (IGF-I) and IGF-I receptor gene expression in the kidney of the chronically hypoinsulinemic rat and hyperinsulinemic rat.

Acute streptozotocin (STZ)-induced diabetes in rats causes a transient increase in insulin-like growth factor-I (IGF-I) in the kidney, followed by a rapid renal hypertrophy and constant renal hyperperfusion. However, renal IGF-I levels return to normal within 4 days. Thus, hyperperfusion, which is independent of renal hypertrophy of the chronically diabetic kidney, is not explained by increased renal IGF-I. We studied IGF-I and IGF-I receptor gene expression in the kidney of rats with long-standing STZ-induced diabetes. IGF-I mRNA level in the chronically diabetic kidney was approximately 50% of that in control rats, whereas IGF-I receptor mRNA was increased approximately threefold. Ten days' treatment with insulin 65 days after induction of diabetes resulted in a glucose-dependent decrease in IGF-I receptor mRNA. Chronic hyperinsulinemia with near normoglycemia did not change gene expression of either IGF-I or IGF-I receptor. The studies suggest that glucose levels per se, independent of insulin levels, play an important role in the regulation of IGF-I receptor gene expression in the chronically diabetic kidney. Furthermore, kidney hyperperfusion in chronic diabetes is coupled with the increase in IGF-I receptor mRNA, despite normal kidney IGF-I levels.

Animals↗
PubMed1995

Insulin resistant and non-resistant polycystic ovary syndrome represent two clinical and endocrinological subgroups.

We studied the clinical and endocrine features of 35 patients with polycystic ovary syndrome (PCOS) who are either insulin resistant or non-insulin resistant. The occurrence of insulin resistance was determined by measuring insulin and glucose concentrations following a standard 75 g oral glucose load. All patients were evaluated by anthropometric measurements: body mass index (BMI), percentage of body fat (BCF) and waist-to-hip ratio (W/H), degree of hirsutism (Ferriman-Gallwey method) and endocrine profile. Fourteen patients had insulin resistance of unknown origin whereas four were due to a type A insulin receptor mutation, and 17 were non-insulin resistant. The insulin resistant patients were significantly more obese (higher BMI P < 0.0001, BCF P < 0.002 and W/H ratio P < 0.005) and were more hirsute (P < 0.002) than the non-insulin resistant patients. Testosterone concentrations were significantly higher in the insulin resistant group than in the non-insulin resistant group (2.65 versus 1.37 nmol/l; P < 0.027), whereas sex hormone-binding globulin was lower in insulin resistant patients (30.61 versus 19.48 nmol/l; P < 0.02). Non-insulin resistant patients showed a high luteinizing hormone to follicle stimulating hormone ratio, while a normal ratio was found in the insulin resistant subpopulation (2.94 versus 1.34; P < 0.0001). We concluded that PCOS comprises two subpopulations, one with insulin resistance of different aetiologies and the other which has no insulin resistance. These two groups differ in their anthropometric and endocrine features. The diagnosis of insulin resistance in PCOS can be easily determined by the insulin response to an oral glucose tolerance test.

Adult↗
PubMed1995

Medical students' contribution to the development of a smoke-free hospital policy in a university medical centre: a relevant learning experience.

In a research methodology course, second-year medical students conducted a survey on 'Enforcing a Smoking Ban in the Soroka Medical Center: a Survey of Hospital Employees on Facilitating Factors and Obstacles'. They defined the study objectives and design, developed the study instrument, carried out the survey, coded and entered the data into mainframe computers, analysed the computer output, and prepared oral and written reports. The aims of the project were twofold: to survey employees' attitudes to a hospital smoking ban and to train medical students in the planning and conduct of a research project on public health or preventive medicine. Twelve students conducted a cross-sectional survey of 208 hospital employees (10% of the hospital staff). Employees were surveyed regarding smoking status, interest in quitting smoking, knowledge of the law banning smoking in public places, knowledge of the health effects of passive smoking, attitudes towards a hospital smoking ban and potential obstacles to its implementation. The students rated the course as excellent. They gained important research skills, as well as practical medical and public health experience through active participation in the design and execution of a study project with public health implications. At the first meeting of the hospital committee appointed to enforce a smoke-free hospital, the students' findings were reported in full, and their recommendations have guided policy decisions.

Health Policy↗
PubMed1995

Chronic exogenous hyperinsulinaemia accelerates the development of hypertension in spontaneously hypertensive rats.

1. An association between hyperinsulinaemia, insulin resistance and hypertension was previously described in spontaneously hypertensive rats (SHR). We therefore tested whether chronic exogenous hyperinsulinaemia, which did not affect blood pressure of normotensive rats, may aggravate hypertension in young SHR. 2. Insulin was administered for 4 weeks by a graded increase of a sustained release insulin implant, without carbohydrate supplementation. 3. Initial bodyweight of seven SHR and five sham-implanted control SHR, aged 6-8 weeks, was not different between the groups or by week 4. 4. Glucose levels decreased in the treated rats [2-way ANOVA F(1:10) = 18.7. P < 0.005] and were 7.3 +/- 0.1 mmol/L in the controls and 4.4 +/- 0.7 mmol/L in the treated SHR, respectively. Insulin levels were comparable at baseline and increased to 1002 +/- 978 pmol/L in treated rats at week 4 while remaining 270 +/- 78 pmol/L in the controls [F(1:10) = 6.1, P < 0.05]. The systolic blood pressure (tail-cuff) was significantly increased in insulin treated SHR in weeks 1-3[F(1:10) = 5.1, P < 0.05] though it was comparable at baseline and week 4. 5. In the presence of a hypertensive predisposition, chronic exogenous hyperinsulinaemia accelerates the time course of the development of hypertension without affecting its severity.

Animals↗
PubMed1995

Insulin-induced renal dysfunction in regular Sabra rats.

1. We tested the effects of chronic hyperinsulinaemia on renal function. Hyperinsulinaemia, in the range of 1.5-4 times the control levels, was achieved using a sustained-release insulin implant. Sham-treated rats served as controls. 2. Experiment 1. Acute saline loading: seven sham and seven hyperinsulinaemic rats received an acute saline load (4 mL/100 g). Two h post-load urea and creatinine excretion rats were (mu mol/min) 15 +/- 5 and 9 +/- 4, and 0.17 +/- 0.05 and 0.10 +/- 0.04, respectively; P < 0.05 for both. 3. Experiment 2. Chronic saline loading: 12 sham- and 24 insulin-treated rats drank saline for 8 weeks plus 4% NaCl in the food for 2 more weeks. By week 10 plasma creatinine (mu mol/L) was 62 +/- 12 and 78 +/- 13, and creatinine clearance (mL/min) was 1.9 +/- 0.5 and 1.5 +/- 0.4, respectively; P < 0.05 for both. 4. Experiment 3. Regular diet: 10 sham- and 14 insulin-treated rats had, by week 8, plasma creatinine (mu mol/L) of 75 +/- 34 and 96 +/- 37 and creatinine clearance (mL/min) of 1.260 +/- 0.025 and 0.97 +/- 0.22, respectively; P < 0.02 for both. Bodyweight, resting blood pressure and urinary Na+ and K+ excretion were comparable in sham- and insulin-treated rats. 5. In three experimental settings long-term hyperinsulinaemia was associated with a subtle but significant renal dysfunction. This finding may be related to the aetiology of renal complications of hypertension and diabetes mellitus, both of which are insulin-resistant and hyperinsulinaemic states.

Animals↗
PubMed1995

Insulin-like growth factor-1 (IGF-1) enhances recovery from HgCl2-induced acute renal failure: the effects on renal IGF-1, IGF-1 receptor, and IGF-binding protein-1 mRNA.

Several growth factors have been found to play an important role in the recovery from acute renal failure (ARF). The effect of the continuous subcutaneous infusion of human recombinant insulin-like growth factor (IGF)-1 (125 micrograms daily by osmotic minipumps) in a rat model of mercuric chloride (HgCl2)-induced ARF was examined. HgCl2 (4 mg/kg) induced ARF with a mortality that was unaffected by IGF-1. However, IGF-1 significantly enhanced functional and histologic recovery in the survivors, as measured by serum creatinine and creatinine clearance and by histologic scoring. Solution hybridization RNAase protection assays showed that renal IGF-1 mRNA, IGF-1 receptor (IGF-1R) mRNA, and IGF-binding protein-1 (IGFBP-1) mRNA were unaffected by exogenous IGF-1, but this treatment significantly increased renal IGF-1 in ARF rats compared with normal rats and ARF rats not receiving IGF-1. After ARF renal mRNA for IGF-1 was decreased, IGF-1R was unchanged and IGFBP-1 was increased. Similar changes occurred in IGF-1-infused ARF rats. Thus, (1) IGF-1 enhances recovery from nephrotoxic ARF both functionally and histologically; (2) in nephrotoxic ARF, there is (a) a reduction in IGF-1 mRNA expression that is not prevented by IGF-1 infusion, and (b) an increase in renal IGFBP-1 mRNA. This may allow a significant increase in renal IGF-1 levels in IGF-1-infused ARF rats, despite the decrease in renal IGF-1 mRNA. A local increase in renal IGFBP-1 and IGF-1 may explain the accelerated recovery from ATN in this model. It was concluded that HgCl2-induced ARF is amenable to improvement by IGF-1 infusion and that the increase in renal IGFBP-1 mRNA may be an important modulator in the recovery of the kidney.

Acute Kidney Injury↗
PubMed1995

Blood pressure and insulin in Ethiopian immigrants: longitudinal study.

Immigration from Ethiopia to Israel exposed subjects from an underdeveloped environment to that of a westernised, developed country. In previous cross-sectional analyses we found that residence in Israel for more than 2 years was associated with a rise in blood pressure which, in turn, was associated with a rise in lipids and insulin levels. Herein we report longitudinal follow-up and baseline examination of 53 young male Ethiopians who resided in a relatively controlled environment (agricultural boarding schools) for 2 years after immigration. Their mean age, when re-examined, was 23 +/- 3 years. Body mass index (20 +/- 2 kg/m2) and triceps' skinfold (71 +/- 32 mm) were not different from baseline values. However, over the 2 years blood pressure rose from 118 +/- 9/62 +/- 11 to 129 +/- 13/71 +/- 10 mmHg, P < 0.0001 for both systolic and diastolic pressures. At 2 years 11 of 53 subjects (20.7%) had hypertension. Total high-density lipoprotein cholesterol and triglyceride levels increased from 131 +/- 27, 36 +/- 8 and 65 +/- 22 mg/dl to 146 +/- 29, 43 +/- 10 and 98 +/- 42 mg/dl, respectively; P < 0.00001 for all. Surprisingly, glucose tolerance (to oral 75 g load) improved and the sum of insulin (first and second hour post-load) decreased significantly and was not correlated with blood pressure changes. Only systolic blood pressure was an independent predictor of incident hypertension (r2 = 0.33, P < 0.0001) in multiple regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Prediction of hypertension by the insulinogenic index in young Ethiopian immigrants.

OBJECTIVE: Hyperinsulinaemia may be associated with hypertension, hyperlipidaemia and glucose intolerance. In the present study we compared the consequence of immigration from Ethiopia to Israel in order to elucidate environmental effects on these variables. DESIGN: A cross-sectional analysis of 337 young, male Ethiopian immigrants who were placed in boarding schools were divided into two groups: group I was in Israel for < 3 months (n = 180) and group II was in Israel for > 2 years (n = 157). Both groups were attending the same schools and were fed from the same kitchens. METHODS: Sitting blood pressure, body mass index, triceps skinfold width, fasting lipids insulin and glucose levels were measured and a standard (75-g) oral glucose-tolerance test was performed. RESULTS: Both groups had similar body mass index. Group I was younger than group II. Both systolic and diastolic blood pressure were significantly higher in group II than in group I. Hypertension was more prevalent in group II. Impaired glucose tolerance (from the oral glucose-tolerance test) prevalence did not differ between the groups, neither did the glycosylated haemoglobin nor fructosamine level. The insulinogenic index (ratio of the areas under the curve of the insulin to that of the glucose level during the oral glucose-tolerance test) was significantly higher in group II. Total and high-density lipoprotein-cholesterol levels were significantly higher in group II. In stepped multiple regression analysis, belonging to group II and having higher insulinogenic index predicted hypertension. CONCLUSIONS: This cross-sectional comparison of young, very lean Ethiopian immigrants found those with longer residence in Israel and higher insulinogenic index to have a threefold increase in the prevalence of hypertension in addition to acquiring higher cholesterol levels, indicating that in this ethnically distinct population environmental factors significantly affected the cardiovascular risk.

Adult↗
PubMed1994

Oral administration of insulin in solid form to nondiabetic and diabetic dogs.

It was previously demonstrated that a biologically active insulin could cross the mucosal membrane in the gut by using surface active substances. In this report we describe studies in which insulin administered orally, in a solid formulation, was effectively absorbed in the canine model. The insulin was mixed with cholate and soybean trypsin inhibitor. It was delivered orally, as enterocoated microtablets, to nondiabetic and diabetic (pancreatectomized) dogs in a fasting state. The time interval between the administration of the drug and the beginning of a decrease in the plasma glucose levels was 60-140 min. This decrease reached a minimum level of 20-40 % of the initial values and lasted for more than 90 min following administration of the drug. In this model a pronounced increment in plasma insulin levels was shown prior to the drop of plasma glucose concentrations. It is concluded that with this novel oral insulin formulation a beneficial biological effect can be achieved in the treatment of diabetes.

Administration, Oral↗
PubMed1994

The effect of hyperglycaemia on the absorption of glibenclamide in patients with non-insulin-dependent diabetes mellitus.

We have studied the absorption of glibenclamide 10 mg as a single morning dose in 7 patients with non-insulin-dependent diabetes mellitus, comparing normoglycaemic and hyperglycaemic states. The maximal glibenclamide plasma concentrations were significantly higher in the normoglycaemic than in the hyperglycaemic state (448 vs 228 mg.l-1) and these peak concentrations were attained faster in normoglycaemia than in hyperglycaemia (3.7 vs 5 h). We conclude that the absorption of glibenclamide in the two states is different.

Adult↗