PubMed Health⌕ Search

Biomedical subjects

S H Schneider

Publications and source records attributed to S H Schneider.

At least 19 recordsLinked to original sources
PubMed2002

Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes.

OBJECTIVE: To evaluate whether simultaneous initial treatment of both insulin resistance and impaired beta-cell insulin secretion with glyburide/metformin tablets is superior to monotherapy with each component agent. RESEARCH DESIGN AND METHODS: In this randomized, parallel-group, placebo-controlled, multicentre study, 806 patients with type 2 diabetes (mean duration, 3 years) who had failed diet and exercise were randomly assigned to 4 weeks of therapy with placebo, glyburide 2.5 mg, metformin 500 mg, glyburide/metformin 1.25/250 mg, or glyburide/metformin 2.5/500 mg once daily. Doses were then titrated over 8 weeks based on glycaemic response. The primary outcome measure was change from baseline in mean HbA1c after 20 weeks. Changes in fasting plasma glucose, lipids and body weight were also assessed along with 2-h postprandial glucose and insulin values after a standardized meal. RESULTS: At week 20, patients taking glyburide/metformin 1.25/250 mg or 2.5/500 mg tablets had greater reductions in HbA1c levels (-1.48% and -1.53% respectively) compared with placebo (-0.21%; both p < 0.001), glyburide (-1.24%; p = 0.016 and p = 0.004 respectively) or metformin (-1.03%; both p < 0.001). Fasting plasma glucose concentrations were reduced more in both glyburide/metformin groups compared with placebo and metformin (p < 0.001); patients in both combination therapy groups also had significantly lower postprandial glucose concentrations compared with placebo, glyburide and metformin. CONCLUSIONS: Initial combination treatment with glyburide/metformin tablets produces greater improvements in glycaemic control than either glyburide or metformin monotherapy. The superiority of initial therapy with glyburide/metformin tablets may arise from simultaneous treatment of both pathophysiological defects of type 2 diabetes.

Blood Glucose↗
PubMed2000

The role of exercise in type II diabetes mellitus.

A number of studies have demonstrated a beneficial effect of regular physical activity on levels of HgbA(1)C in patients with type II diabetes mellitus, largely due to an increase in insulin sensitivity. Benefits are related to short-term improvements in insulin sensitivity following individual exercise bouts. Regular exercise can prevent or delay the onset of type II diabetes in high-risk populations. The insulin resistant state is associated with a cluster of cardiovascular risk factors all of which improve with regular physical activity. Because of the high incidence of occult coronary disease, patients need a cardiovascular evaluation when initiating an exercise program. High intensity exercise may result in retinal hemorrhage and transient worsening of diabetic proteinuria. The most common complication is hypoglycemia. A combination of aerobic and light resistance exercise is appropriate. Patients should exercise a minimum of three times a week for 30-60 minutes at 50% to 75% of their VO(2max). (c) 2000 by CHF, Inc.

Journal Article↗
PubMed1999

Glycation of high-density lipoprotein does not increase its susceptibility to oxidation or diminish its cholesterol efflux capacity.

In vitro oxidation of high-density lipoprotein (HDL) diminishes its capacity to mediate cholesterol efflux from J774 macrophages. To investigate the possible role of HDL glycation in the increased atherosclerotic risk in diabetes, we studied the effects of in vitro glycation of HDL on its susceptibility to oxidation and capacity to mediate cholesterol efflux. HDL isolated from normal volunteers was incubated with 25 mmol/L glucose for 70 hours, resulting in 6.1% additional derivatization of apoproteins as determined by trinitrobenzene sulfonic acid (TNBS) reactivity. Unmodified HDL and glycated HDL (glyHDL) were tested for susceptibility to oxidation by incubation with various concentrations of copper and three assays of lipid oxidation. GlyHDL produced 51% to 64% less lipid peroxide than HDL as determined by reaction with xylenol orange (P < .02), indicating decreased susceptibility to oxidation. However, glycation of HDL did not result in significant changes in the formation of conjugated dienes or thiobarbituric acid-reactive substances (TBARS), two other indices of oxidation. To study cholesterol efflux, J774 macrophages were labeled with 3H-cholesterol followed by incubation with the various HDL preparations. HDL and glyHDL had a similar capacity to mediate efflux. The efflux mediated by oxidized HDL (oxHDL) and oxidized glyHDL was reduced to a similar extent compared with the efflux mediated by HDL and glyHDL. These data indicate that in vitro glycation of HDL does not increase its susceptibility to oxidation and does not diminish its capacity to mediate cholesterol efflux.

Cholesterol↗
PubMed1999

Red wine inhibits the cell-mediated oxidation of LDL and HDL.

OBJECTIVE: We compared the in vitro effects of red wine, white wine and ethanol on the cell mediated oxidation of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) by three frequently-used assays. METHODS: LDL and HDL isolated from normolipidemic human serum were incubated with J774.A1 macrophages in DMEM with copper, with or without red wine, white wine or ethanol (equivalent to 0.2 mg ethanol/ml). Lipoprotein oxidation was assessed by conjugated diene formation as measured by changes in absorbance at 234 nm (deltaA234), thiobarbituric-acid-reactive-substance (TBARS) production and trinitrobenzene-sulfonic-acid (TNBS) reactivity. RESULTS: Red wine (0.2 mg ethanol/mL) inhibited LDL oxidation as indicated by an 85.7% decrease in absorbance at 234 nm, a 96.5% decrease in TBARS production and complete prevention of the decrease in TNBS reactivity. White wine and ethanol did not have any significant effect at 0.2 mg/mL. White wine at 1.0 mg ethanol/mL inhibited TBARS production from LDL by 84.1%. Red wine (0.2 mg ethanol/mL) inhibited HDL oxidation as indicated by a 78.9% decrease in deltaA234, an 81.7% decrease in TBARS production and by no change in TNBS reactivity. White wine and ethanol had no effect at 0.2 mg/mL. White wine at 1.0 mg ethanol/mL inhibited TBARS production from HDL by 66.4%. CONCLUSIONS: These results indicate that red wine inhibits the cell mediated oxidation of lipoproteins, that white wine is not as effective as red wine and that the effect of the red wine is not due to its ethanol content.

Animals↗
PubMed1998

Bone turnover and insulin-like growth factor I levels increase after improved glycemic control in noninsulin-dependent diabetes mellitus.

It is unclear whether both bone resorption and formation are affected by glycemic control, and contribute to diabetic osteopenia. In this study, 20 patients with noninsulin-dependent diabetes mellitus (12 men and 8 postmenopausal women) and 20 healthy control subjects (10 men and 10 postmenopausal women) were examined at baseline and 2 months. The diabetic patients showed an improvement of glycemic control (decreased HbA1c) at the second measurement. Analysis of variance showed that there was no effect of gender on the variables that increased with improved glycemic control, and therefore results are presented for both male and female subjects. Baseline values of serum osteocalcin, a marker of formation, were significantly lower in diabetic patients compared with healthy subjects (2.5 +/- 1.3 versus 4.4 +/- 1.4 ng/ml; P = 0.0006), but markers of bone resorption [urinary pyridinoline (PYD), deoxypyridinoline (DPD)] did not differ. Improved glycemic control in diabetic patients resulted in increased values of PYD (P = 0.012), DPD (P = 0.049), serum osteocalcin (P = 0.001), and serum insulin-like growth factor I (IGF-I, P = 0.003), but no change in serum parathyroid hormone or 25-hydroxyvitamin D. In diabetic patients there were inverse correlations for the percent change from baseline to improved glycemic control for osteocalcin and HbA1c (r = -0.53; P = 0.016) and glucose (r = -0.46; P = 0.050). These data suggest that improved glycemic control is accompanied by an increase in bone turnover for male and female diabetic patients, possibly mediated by increased levels of circulating IGF-I.

Adult↗
PubMed1997

Effect of obesity and feeding on the growth hormone (GH) response to the GH secretagogue L-692,429 in young men.

GH secretion and the response to GH secretagogues are significantly diminished in obese individuals. Previous studies have shown that L-692,429 (L), a nonpeptide mimetic of GH-releasing peptide, selectively stimulates GH release in normal young men and in the elderly, who also have diminished GH secretion. A paired, two-site study examined the effects of L on GH release in 12 healthy obese (part A; mean +/- SD: age, 26.1 +/- 3.3 yr; body mass index, 35.0 +/- 3.1 kg/m2) and 10 nonobese (part B; age, 22.2 +/- 2.3 yr; body mass index, < or = 27.0) young men. In part A, placebo, low dose L (0.2 mg/kg), or high dose L (0.75 mg/kg) was administered iv over 15 min on 3 separate occasions after an overnight fast. Samples for GH, PRL, and cortisol determinations were obtained every 15 min. GH release (mean +/- SE) was significantly increased by both doses of L compared to the effect of placebo: 12.6 +/- 1.8 micrograms/L (low dose), 18.5 +/- 2.7 micrograms/L (high dose), and 0.84 +/- 0.1 microgram/L (placebo), respectively (P < 0.05). In a subset of 6 obese men, in samples collected every 5 min, the GH response to both doses of L was significantly greater than that to 1 microgram/kg GHRH. To compare the response to low dose L in the obese and to determine the effects of feeding on this response, 0.2 mg/kg L was administered as described in part A to nonobese young men after an overnight fast (fasted) or a standardized breakfast (fed; part B). Low dose L was an effective GH secretagogue in nonobese young men; however, this effect was attenuated with feeding [43.6 +/- 7.9 (fasted) vs. 17.7 +/- 4.8 (fed) micrograms/L]. Of note, the response to low dose L in fasted obese individuals was similar to that in fed nonobese individuals. The administration of L was well tolerated in both groups. We conclude that L is an effective GH secretagogue in obese and nonobese young men and may have therapeutic benefits when administered to relative (obese or elderly) or absolute GH-deficient individuals.

Adult↗
PubMed1997

Dexamethasone increases leptin expression in humans in vivo.

The effect of 2 days of oral dexamethasone administration (0.75 mg twice daily) on leptin expression in healthy volunteers was tested. Dexamethasone increased the relative abundance of leptin messenger RNA in abdominal and gluteal adipose tissues by approximately 70% (P < 0.05). Dexamethasone also significantly increased serum leptin (+ 80%) and insulin concentration (+ 83%) but did not affect serum glucose. We conclude that a hypercortisolemic/hyperinsulinemic state up-regulates leptin expression at the messenger RNA level in humans.

Adipose Tissue↗
PubMed1997

Administration of antioxidant vitamins does not alter plasma fibrinolytic activity in subjects with central obesity.

In vitro studies suggest that oxidized low density lipoprotein inhibits fibrinolysis by stimulating the production of plasminogen activator inhibitor -1 (PAI). We assessed the effects of dietary antioxidant vitamins for four weeks on three indices of copper mediated oxidation of very low and low density lipoproteins (VLDL+LDL) and plasma fibrinolytic activities in 15 male subjects with central obesity, a condition associated with increased PAI activity. Vitamin administration resulted in a decrease in production of thiobarbituric acid reactive substances from 29.3 +/- 3.9 to 13.6 +/- 3.5 nmoles/mg VLDL + LDL protein (mean +/- SE, p <0.003), an increase in the lag phase of conjugated diene formation from 94.8 +/- 5.5 to 225.0 +/- 31.9 min (p <0.001) and an increase in reactivity of lysine residues from 73.6% +/- 4.8% to 86.8% +/- 3.6% (p <0.034) demonstrating a reduction in the susceptibility of the lipoproteins to oxidation. However, antioxidant vitamins had no effect on plasma PAI activity, PAI antigen, tissue-type plasminogen activator activity and antigen, fibrinogen and fibrin degradation products. These results do not support the hypothesis that lipoprotein oxidation is a significant cause of impaired fibrinolysis in men with central obesity.

Antioxidants↗
PubMed1996

Sweet taste and diet in type II diabetes.

The relationship between sweet taste function and dietary intake was studied in 21 patients with type II diabetes mellitus and 16 age-, weight-, and sex-matched controls. Subjects rated the sweetness intensity and pleasantness of a series of beverage samples sweetened with sucrose: 1.5-24%, fructose: 1-18%, or aspartame: 0.25-4%. They also kept 7-day food records. No group differences were found in sweet taste perception, pleasantness ratings, daily energy intakes, or macronutrient composition of the diets. However, subjects with diabetes consumed less sucrose but 3.5 times more alternative sweeteners than did controls. Peak pleasantness ratings for the beverage samples were positively correlated with dietary sweetness content in the subjects with diabetes but not the controls. These findings suggest that in diabetes, hedonic ratings for a sweetened beverage were related to dietary sweetness intake rather than changes in sweet taste perception.

Adult↗
PubMed1994

Stimulation of low-density lipoprotein oxidation by insulin and insulin like growth factor I.

Hyperinsulinemia has been implicated as an independent risk factor for atherosclerosis. We measured the effect of insulin and related hormones on the oxidation of low density lipoproteins (LDL) and superoxide anion production by peripheral blood mononuclear cells (MC). LDL oxidation was measured by the production of thiobarbituric acid reactive substances (TBARS). Insulin and IGF-I at 10(-7) M caused a 33% and 48% increase in TBARS production, respectively. At 10(-6) M the corresponding values were 63% and 67%. Proinsulin and IGF-II at 10(-6) M had no effect. Glucose caused a concentration dependent (up to 10 mM) stimulation of LDL oxidation reaching 85% and 77% at insulin concentrations of 10(-7) M and 10(-6) M, respectively. The stimulatory effect of insulin was confirmed by measurements of other indices of LDL oxidation, i.e. absorbance at 234 nm, trinitrobenzene sulfonic acid reactivity and electrophoretic mobility. Insulin-stimulated LDL oxidation was inhibited by superoxide dismutase (SOD), but insulin had no effect on MC superoxide production. MC were isolated from five subjects before and after a 5 h hyperinsulinemic, euglycemic clamp. Insulin infusion had no effect on TBARS or superoxide production by MC. Our in vitro experiments suggest that high levels of insulin and IGF-I stimulate MC-mediated oxidation of LDL, an effect that is potentially atherogenic.

Cells, Cultured↗
PubMed1994

Pharmacodynamics of MK-0963, a new 5 alpha-reductase inhibitor: effects on serum androgen concentrations.

The hormonal effects after a 10-day administration of a 4-azasteroid inhibitor of 5 alpha-reductase, MK-0963 (previously L-654,066), were evaluated in 35 healthy male volunteers in an increasing-dose, five-panel design. Marked suppression of serum dihydrotestosterone was observed after the once-daily administration at each active dose level (placebo, 0.1, 0.5, 1.0, 10, and 25 mg). Maximum dihydrotestosterone suppression occurred at doses greater than or equal to 10 mg. The mean percentage (+/- SE) decreases in dihydrotestosterone at 24 hours after the last dose in the groups treated with the 10 and 25 mg doses were 78% +/- 4.9% and 80% +/- 2.9%, respectively. The 25 mg dose maintained a dihydrotestosterone suppression of at least 70% for more than 6 days after the last dose. No consistent changes in serum testosterone were noted. This study shows that administration of multiple doses of MK-0963 results in a substantial suppression of serum dihydrotestosterone with no consistent influence on serum testosterone concentrations.

5-alpha Reductase Inhibitors↗
PubMed1994

The evolution of the Earth.

The formation of this planet and its atmosphere gave rise to life, which shaped the earth's subsequent development. Our future lies in interpreting this geologic past.

Atmosphere↗
PubMed1993

Growth hormone response in man to L-692,429, a novel nonpeptide mimic of growth hormone-releasing peptide-6.

L-692,429, a substituted benzolactam, is a novel nonpeptide mimic of the GH secretagogue, GH-releasing peptide-6. The safety and GH secretory activity of L-692,429 (0.001-1.0 mg/kg, i.v.) were investigated in 24 healthy nonobese young (18-26 yr old) male volunteers who demonstrated a GH response of 7 micrograms/L or more after 1 microgram/kg, i.v. GH-releasing hormone [GH-releasing hormone-(1-29)NH2]. L-692,429 was administered as a 15-min iv infusion in an incremental dose, double blind, placebo-controlled, alternating panel fashion to 3 panels of 8 subjects each. Dose-dependent GH secretion was observed with a threshold dose of 0.05 mg/kg (4 of 6 subjects responded with peak GH > 7 micrograms/L), and 0.2 mg/kg produced a response in all 14 subjects tested (mean +/- SE peak GH, 41.0 +/- 6.3 micrograms/L). The maximum dose of 1.0 mg/kg L-692,429 resulted in a pronounced GH response (peak GH, 82.5 +/- 14.9 micrograms/L; n = 8). The GH peak was seen 30-45 min after initiation of the infusion. Small transient increases in cortical and PRL were observed (increases in cortical averaged 182.1 +/- 33.1 nmol/L and peak PRL was 21 +/- 2.6 micrograms/L after 1.0 mg/kg L-692,429, respectively), whereas no significant changes occurred in LH, FSH, TSH, insulin, or glucose concentrations. Plasma pharmacokinetic analysis revealed dose-related increases in plasma concentrations of L-692,429 and a half-life of 3.8 +/- 0.2 (+/- SE) h, a plasma clearance of 214 +/- 67 mL/min, and a steady state volume of distribution of 14.2 +/- 4.8 L. Facial flushing or a warm sensation were reported in 4 subjects, primarily at dose levels of 0.2 mg/kg L-692,429 or more, but no other clinical or laboratory adverse experiences appeared related to drug treatment. L-692,429, synthesized as a specific nonpeptide mimic of GH-releasing peptide-6, is thus a well tolerated, highly effective, and selective GH secretagogue in man.

Adolescent↗
PubMed1992

Effects of pravastatin on cholesterol metabolism in Watanabe heritable hyperlipidemic rabbits.

Pravastatin, a competitive inhibitor of hydroxymethylglutaryl CoA reductase (HMG CoA reductase) is a potent hypocholesterolemic agent in humans as well as experimental animals, including the Watanabe heritable hyperlipidemic (WHHL) rabbit, lacking low density lipoprotein (LDL) receptor activity. We studied the effect of pravastatin on several aspects of cholesterol metabolism in WHHL rabbits. Cholesterol synthesis was measured by intraperitoneal injection of radioacetate and determination of its incorporation into the nonsaponifiable lipid fraction of liver, plasma, adrenal glands and gonads. A single dose of pravastatin (25 mg/kg) caused statistically significant inhibition of hepatic cholesterol synthesis at 2, 6, 12, and 24 hours following oral administration. By 48 hours, the inhibitory effect of the drug was no longer demonstrable. The pattern of radioactivity in the plasma was similar to that in the liver. The drug had no statistically significant effect on cholesterol synthesis in adrenal glands and gonads, suggesting a selective effect on the liver. Cholesterol absorption was studied after simultaneous oral administration of [3H] cholesterol and [14C] beta-sitosterol. Pravastatin, 50 mg/kg for 10 days had no effect on fecal excretion of the radiolabelled steroids over 4 days. At 24 hours the plasma level of [14C] cholesterol was 1/3 that of control in pravastatin treated animals (p < 0.05) but did not undergo an accelerated decline over 6 days. The activity of acyl CoA: cholesterol acyltransferase (ACAT) in intestinal mucosa and the concentration of hepatic cholesterol were similar in animals treated over one year with pravastatin 50 mg/kg/day or with placebo. Our data do not allow us to make definitive conclusions about the effect of pravastatin on cholesterol absorption but are compatible with the hypothesis that the drug inhibits the hepatic synthesis as well as the assembly of cholesterol into lipoproteins.

Absorption↗
PubMed1992

Diabetes, exercise, and atherosclerosis.

Regular exercise may diminish the risk for atherosclerotic vascular disease in patients with non-insulin-dependent (type II) diabetes and in the general population. The basis for this effect of exercise may be its ability to diminish or prevent hyperinsulinemia, insulin resistance, and/or increases in intra-abdominal adipose mass. These abnormalities are associated with premature atherosclerotic vascular disease, essential hypertension, type II diabetes, and certain dyslipoproteinemias, and most likely precede them. They also have been implicated in the pathogenesis of these disorders. We propose that the high prevalence of hyperinsulinemia and insulin resistance in individuals leading a western life-style accounts for the reported benefit of physical activity in preventing coronary heart disease in the general population. We also propose that exercise (and diet) are most likely to be effective when initiated in young individuals, before the onset of irreversible vascular alterations, and when life-style changes may be more acceptable. Early identification of such individuals may be possible on the basis of family history, the presence of components of the hyperinsulinemia-insulin resistance syndrome, and/or central obesity. One such group that may already have been identified is women with gestational diabetes.

Arteriosclerosis↗