PubMed Health⌕ Search

Biomedical subjects

G Crepaldi

Publications and source records attributed to G Crepaldi.

At least 163 records · Page 9Linked to original sources
PubMed1988

Abnormal erythrocyte charge in diabetes mellitus. Link with microalbuminuria.

The anionic charge on the surface of the erythrocyte and the erythrocyte membrane content of sialic acid and acid glycosaminoglycans (GAGs) were evaluated in insulin-dependent diabetic patients who had albumin excretion rates less than 300 mg/24 h. In these subjects a statistically significant reduction of erythrocyte anionic charge (RBCCh) and GAGs content in erythrocyte ghosts was shown. In view of the demonstration of a negative correlation between RBCCh and albuminuria after a lysine provocative test, these observations support the hypothesis that the onset of microalbuminuria in human diabetes is sustained by an alteration of glomerular charge and consequently of glomerular charge selectivity.

Adolescent↗
PubMed1988

Reduced in vivo biological activity of in vitro glycosylated insulin.

We evaluated the in vivo biological activity of in vitro extensively glycosylated insulin (GI) with the euglycemic-hyperinsulinemic glucose-clamp technique in postabsorptive nondiabetic subjects. Insulin-mediated glucose disposal was approximately 30% lower (P less than .03) with GI (9.2 +/- 1.2 mg.kg-1.min-1, mean +/- SE) than with the nonglycosylated hormone (12.6 +/- 0.7 mg.kg-1.min-1) at comparable plasma insulin concentrations (approximately 90 microU/ml). Binding of GI to a specific receptor on circulating cells (erythrocytes and monocytes) was normal. We conclude that in vitro extensive glycosylation of insulin reduces its biological activity in vivo, as reflected by insulin-mediated glucose disposal, probably at a postreceptor level.

Adult↗
PubMed1988

Efficacy and safety of dexfenfluramine in obese patients: a multicenter study.

We have evaluated the effects of dextrofenfluramine treatment on body weight control during a 90 day period, in obese patients on a calorie-restricted diet. The weight loss in dextrofenfluramine-treated patients was significantly higher than in placebo group. The rate of weight loss was linear up to the end of the trial in d-fenfluramine patients. Neural disturbances (vertigo, headache, depression) were the most frequent side effects observed in both the d-fenfluramine and in the placebo-treated groups, without significant differences between the groups. A total number of 23 patients in the dextrofenfluramine group and 20 patients in the placebo group complained side effects. Six patients (five in the d-fenfluramine group and one in the placebo group) discontinued the treatment, due to the side effects. No modifications of the biochemical parameters considered (fasting blood glucose, bilirubin, alkaline phosphatase, creatinine, blood cell counts, asparate-amino transferase (AST), alanine-amino transferase (ALT), total plasma and HDL cholesterol, and triglycerides) were observed at the end of the trial. A significant reduction of total serum cholesterol was observed in both groups at the end of the period of treatment. In conclusion, dextrafenfluramine was proved to be in short term trials an effective and safe tool in overweight control in obese patients.

Adult↗
PubMed1988

Atherogenic factors in diabetes: the role of lipoprotein metabolism.

In diabetes, altered lipoprotein metabolism is one of the factors which accelerates the process of atherogenesis. In NIDDM, plasma triglyceride levels are increased and HDL levels are, independently, decreased. In order to increase HDL levels, good metabolic control and prolonged, near perfect, control of lipoprotein metabolism are required. In NIDDM, there is a direct relationship between lipoprotein lipase activity and HDL levels. Optimal insulin therapy gives improved diabetic control, and in the long term will improve the lipoprotein profile in these diabetics. Factors affecting lipid metabolism are discussed, and the importance of improving the lipoprotein profile in diabetics is emphasized.

Arteriosclerosis↗
PubMed1987

Ketone bodies increase glomerular filtration rate in normal man and in patients with type 1 (insulin-dependent) diabetes mellitus.

The purpose of this study was to investigate whether the administration of acetoacetic and hydrochloric acids in a group of control and Type 1 (insulin-dependent) diabetic patients influenced renal haemodynamics. Renal plasma flow increased from 657 +/- 88 to 762 +/- 81 ml X min-1. 1.73 m-2 in diabetic patients (p less than 0.01) and from 590 +/- 71 to 691 +/- 135 in control subjects (p less than 0.01). Glomerular filtration rate increased from 135 +/- 9 to 180 +/- 8 ml X min-1. 1.73 m-2 in diabetic patients (p less than 0.001) and from 117 +/- 8 to 145 +/- 7 in control subjects (p less than 0.01). Similar effects on renal haemodynamics, even if less pronounced, were observed with low dose acetoacetic but not with hydrochloric acid infusion. Total protein, beta 2-microglobulin but not albumin excretion rates were increased by acetoacetic acid. We conclude that an acute increase in blood concentration of ketone bodies within the range found in diabetic patients with poor metabolic control increases renal plasma flow and glomerular filtration rate both in control subjects and diabetic patients and causes a tubular proteinuria.

Acetoacetates↗
PubMed1987

Differential effects of hyperinsulinemia and hyperaminoacidemia on leucine-carbon metabolism in vivo. Evidence for distinct mechanisms in regulation of net amino acid deposition.

The effects of physiologic hyperinsulinemia and hyperaminoacidemia, alone or in combination, on leucine kinetics in vivo were studied in postabsorptive healthy subjects with primed-constant infusions of L-[4,5-3H]leucine and [1-14C]alpha-ketoisocaproate (KIC) under euglycemic conditions. Hyperinsulinemia (approximately 100 microU/ml) decreased (P less than 0.05 vs. baseline) steady state Leucine + KIC rates of appearance (Ra) from proteolysis, KIC (approximately leucine-carbon) oxidation, and nonoxidized leucine-carbon flux (leucine----protein). Hyperaminoacidemia (plasma leucine, 210 mumol/liter), with either basal hormone replacement or combined to hyperinsulinemia, resulted in comparable increases in leucine + KIC Ra, KIC oxidation, and leucine----protein (P less than 0.05 vs. baseline). However, endogenous leucine + KIC Ra was suppressed only with the combined infusion. Therefore, on the basis of leucine kinetic data, hyperinsulinemia and hyperaminoacidemia stimulated net protein anabolism in vivo by different mechanisms. Hyperinsulinemia decreased proteolysis but did not stimulate leucine----protein. Hyperaminoacidemia per se stimulated leucine----protein but did not suppress endogenous proteolysis. When combined, they had a cumulative effect on net leucine deposition into body protein.

Amino Acids↗
PubMed1987

Alcohol impairs insulin sensitivity in normal subjects.

The effects of alcohol on insulin action are not yet clearly established. To assess the effects of intravenously administered ethanol on insulin mediated glucose disposal, euglycaemic clamps at 3 different plasma insulin levels and insulin receptor binding studies on circulating monocytes after alcohol infusion were performed. Ethanol infusion leads to a significant reduction of insulin mediated glucose disposal (7.08 +/- 0.4 vs 8.6 +/- 0.6 mg/Kg/min; 9.8 +/- 0.7 vs 13.4 +/- 0.7; 14.7 +/- 0.7 vs 18.1 +/- 0.7 at 33, 73 and 760 mU/m2/min insulin infusion rate respectively). Monocyte insulin-receptor binding was decreased in all the subjects from 30 to 60% after ethanol infusion. These results demonstrate that alcohol can adversely influence the insulin mediated glucose disposal.

Blood Glucose↗
PubMed1986

Effect of probucol treatment on lipoprotein cholesterol and drug levels in blood and lipoproteins in familial hypercholesterolemia.

Twelve patients with mild and 3 with severe hypercholesterolemia were stabilized with an isocaloric diet containing less than 300 mg cholesterol daily with a P/S ratio of 1.8, and placebo period of 4 weeks. They were administered 1000 mg probucol daily for 12 weeks, followed by placebo for 6 weeks. In patients with mild disease, a significant cholesterol reduction was achieved in serum, LDL, and HDL (maximum decrease, 17%, 13%, and 31%, respectively). While HDL3 cholesterol was reduced significantly throughout the period (P less than 0.001), HDL2 cholesterol showed a significant decrease only at the 4th week of treatment (P less than 0.001), and returned to basal levels at the 8th and 12th treatment weeks. Serum apo B levels decreased only slightly, but the HDL-apo A-I fall was significant with a reduction in the HDL-CH/HDL-apo A-I ratio throughout the treatment period. In 3 patients with severe disease, cholesterol decrease in serum and in VLDL, LDL and HDL fractions varied, but on the whole was lower than in patients with mild disease. A decrease in VLDL-CH and HDL-CH was present in all 3, but LDL-CH levels were only slightly lowered in 2 patients, and unchanged in the third. Serum probucol levels fell 66% from the 4th to the 12th treatment week, and in parallel, the percentage of lipoprotein-bound drug increased about 2-fold. It is suggested that these changes in pharmacokinetics as well as the cholesterol-lowering effect of the drug may be due to a change in lipoprotein composition or structure.

Adult↗
PubMed1986

Long term-effect of fenofibrate on lipoprotein level and composition in different types of genetic hyperlipidemias.

Fenofibrate effect on plasma lipids and lipoproteins was studied in 23 patients with primary hyperlipoproteinemias (HLP): 12 with familial hypercholesterolemia (FH), 5 with combined HLP and 6 with Type III HLP. Trial lasted from 8 to 10 months. Cholesterol and triglycerides were significantly reduced in all patients as follows: cholesterol dropped 26% in FH (p less than 0.001), 32% in combined HLP and 48% in type III HLP; triglycerides dropped 29%, 64% and 72% respectively. This drop involved LDL in FH, VLDL and LDL in combined HLP and beta-VLDL in type III HLP patients. In FH and combined HLP patients we observed a +10% (p less than 0.01) and a +9% (n.s.) increase of HDL, respectively. Two patients had a mild SGOT and SGPT increase and three had a vescicular cutaneous erythema.

Cholesterol↗
PubMed1986

Lipoprotein modifications during dietary treatment in patients with primary type V hyperlipoproteinaemia.

Type V hyperlipoproteinaemia is a disorder of lipid transport characterized by the accumulation in serum of chylomicrons and very low density lipoproteins. The purpose of the study was the analysis of serum lipids and lipoproteins by ultracentrifugation in nine patients with primary type V hyperlipoproteinaemia before and during dietary treatment. After 30 days of balanced isocaloric diet mean serum triglycerides fell from 25.4 +/- 15.0 (mean +/- SD) to 2.8 +/- 1.7 mmol l-1. At the same time the chylomicrons and the very low density lipoproteins of flotation rate higher than 100 disappeared from the serum while the remaining very low density lipoproteins maintained unaltered their normal protein-lipid composition. After 30 days the low density lipoproteins increased significantly in concentration (from 1.6 +/- 0.8 to 4.1 +/- 1.1 mmol l-1 cholesterol) and their percentage content of cholesterol and triglyceride was increased and reduced, respectively. The highest concentration of intermediate density lipoprotein cholesterol was observed after 15 days of treatment (1.2 +/- 0.6 mmol l-1. The abnormally low concentrations and the physicochemical properties of the high density lipoproteins remained unchanged throughout the study (from 0.6 +/- 0.2 to 0.8 +/- 0.2 mmol l-1 cholesterol concentration) and no high density lipoproteins two (HDL2) were observed at any time. The effects of this treatment were an increase in low density and marginal change in high density lipoproteins which are considered, respectively, a positive and a negative risk factor for atherosclerosis.

Adult↗
PubMed1986

Dose-response curves of effects of insulin on leucine kinetics in humans.

To determine the effects of physiological and pharmacological insulin concentrations on leucine-carbon kinetics in vivo, eight postabsorptive normal volunteers were infused with L-[4,5-3H]leucine and alpha-[1-14C]ketoisocaproate (KIC). Insulin concentrations were sequentially raised from 8 +/- 1 to 43 +/- 6 and 101 +/- 14 and to 1,487 +/- 190 microU/ml, while maintaining euglycemia with adequate glucose infusions. At the end of each 140-min insulin-infusion period, steady-state estimates of leucine and KIC rates of appearance (Ra), KIC (approximately leucine-carbon) oxidation, nonoxidized leucine-carbon flux [an index of leucine incorporation into protein (Leu----P)], and leucine and KIC interconversion rates were obtained. After the three insulin infusions, leucine Ra decreased by a maximum of approximately 20%. KIC Ra decreased by a maximum of approximately 50%. The sum of leucine plus KIC Ra in the basal state was 2.59 +/- 0.24 mumol X kg-1 X min-1 and decreased by approximately 30% at the maximal insulin concentrations. KIC oxidation decreased by a maximum of approximately 65%. Leu----P did not increase after hyperinsulinemia. Interconversion rates were promptly and markedly suppressed by 50-70%. Leucine clearance increased by approximately 120%. We conclude that euglycemic hyperinsulinemia, at physiological and pharmacological concentrations, decreased leucine and KIC concentrations, leucine-carbon turnover and oxidation, and leucine and KIC interconversions in a dose-dependent manner in vivo.

Adult↗
PubMed1986

Urinary glycosaminoglycans, sialic acid and lysosomal enzymes increase in nonalbuminuric diabetic patients.

Urinary excretion of glycosaminoglycans (GAGS) and sialic acid (SA), as well as the activity of two renal enzymes related to glycoprotein metabolism, N-acetyl-beta-D-glucosaminidase (NAG) and beta-galactosidase (GAL), and two others unrelated to glycosaminoglycans and glycoprotein metabolism, gamma-glutamyltranspeptidase (gamma-Gt) and angiotensin-I-converting enzyme (ACE), were evaluated in 40 insulin-dependent diabetic patients with normal range albuminuria, 21 patients with mesangial glomerulonephritis, and 30 control subjects. Diabetic and glomerulonephritic patients excreted a significantly higher amount of GAGS and SA, and showed greater NAG and GAL activities; gamma-Gt and ACE levels were within normal ranges. No correlation could be demonstrated between diabetes duration and GAGS, SA, NAG and GAL findings. Moreover, no correspondence between degree of metabolic control, as reflected by glycosylated hemoglobin (HbA1a-c) and GAGS, SA, NAG and GAL emerged.

Acetylglucosaminidase↗
PubMed1986

Defective suppression by insulin of leucine-carbon appearance and oxidation in type 1, insulin-dependent diabetes mellitus. Evidence for insulin resistance involving glucose and amino acid metabolism.

To determine whether a resistance to insulin in type 1, insulin-dependent diabetes mellitus (IDDM) is extended to both glucose and amino acid metabolism, six normal subjects and five patients with IDDM, maintained in euglycemia with intravenous insulin administration, were infused with L-[4,5-3H]leucine (Leu) and [1-14C]alpha ketoisocaproate (KIC). Steady-state rates of leucine-carbon appearance derived from protein breakdown (Leu + KIC Ra) and KIC (approximately leucine) oxidation were determined at basal and during sequential euglycemic, hyperinsulinemic (approximately 40, approximately 90 and approximately 1,300 microU/ml) clamps. In the euglycemic postabsorptive diabetic patients, despite basal hyperinsulinemia (24 +/- 6 microU/ml vs. 9 +/- 1 microU/ml in normals, P less than 0.05), Leu + KIC Ra (2.90 +/- 0.18 mumol/kg X min), and KIC oxidation (0.22 +/- 0.03 mumol/kg X min) were similar to normal values (Leu + KIC Ra = 2.74 +/- 0.25 mumol/kg X min) (oxidation = 0.20 +/- 0.02 mumol/kg X min). During stepwise hyperinsulinemia, Leu + KIC Ra in normals decreased to 2.08 +/- 0.19, to 2.00 +/- 0.17, and to 1.81 +/- 0.16 mumol/kg X min, but only to 2.77 +/- 0.16, to 2.63 +/- 0.16, and to 2.39 +/- 0.08 mumol/kg X min in the diabetic patients (P less than 0.05 or less vs. normals at each clamp step). KIC oxidation decreased in normal subjects to a larger extent than in the diabetic subjects. Glucose disposal was reduced at all insulin levels in the patients. In summary, in IDDM: (a) Peripheral hyperinsulinemia is required to normalize both fasting leucine metabolism and blood glucose concentrations. (b) At euglycemic hyperinsulinemic clamps, lower glucose disposal rates and a defective suppression of leucine-carbon appearance and oxidation were observed. We conclude that in type 1 diabetes a resistance to the metabolic effects of insulin on both glucose and amino acid metabolism is present.

Adult↗
PubMed1986

The effect of drugs on bile flow and composition. An overview.

Many drugs are eliminated via the hepatobiliary route, after biotransformation in the liver. Some of them may affect bile flow and/or the hepatic secretion of biliary lipids such as bile acids, cholesterol and phospholipids. Bile acids are the most potent agents which increase bile flow, especially unconjugated bile acids. Other drugs which increase bile flow include phenobarbitone (phenobarbital), theophylline, glucagon and insulin. In contrast, ethacrynic acid, amiloride, ouabain, oestrogens and chlorpromazine are among those agents which decrease bile flow. Biliary bile acid secretion is altered by a variety of drugs, including cheno- and ursodeoxycholic acids (CDCA and UCDA), the bile acid sequestrants cholestyramine and colestipol, and ethinyloestradiol. The composition of bile can also be altered by drug therapy. Thus, clofibrate increases biliary cholesterol secretion, and reduces bile acid concentrations, without altering biliary phospholipid concentrations. However, other clofibrate derivatives may produce changes of a different pattern, suggesting that the risk of developing gallstones may differ for each derivative. Nicotinic acid and d-thyroxine also increase biliary cholesterol saturation, while CDCA and UDCA reduce biliary cholesterol concentration. The potential consequences of drug-induced changes in bile flow and composition extend to the liver, the gallbladder and the intestine. If adverse effects are to be avoided, further study in this often overlooked area is required.

Animals↗