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Biomedical subjects

G Crepaldi

Publications and source records attributed to G Crepaldi.

At least 127 records · Page 7Linked to original sources

Forearm ketone body metabolism in normal and in insulin-dependent diabetic patients.

In insulin deficiency, there is excessive arterial delivery of free fatty acid (FFA) to muscles where they are converted to acetoacetyl-CoA and acetyl-CoA. These intermediates may be metabolized further to acetoacetate and beta-hydroxybutyrate, which can be released into the venous circulation. When ketone body (KB) tracers are infused in vivo, they are diluted across muscle tissue. This dilution may be due to 1) KB newly formed within muscle (ketogenesis); 2) exchange of tracer between labeled and unlabeled acetyl-CoA and acetoacetyl-CoA, intermediates common to the metabolism of both FFA and KB (pseudoketogenesis). Thus this study assessed whether such label exchange could be detected across the human forearm and whether an increased delivery of FFA in insulin-sufficient controls provoked dilution of labeled KB tracer comparable to that observed in insulin-deficient diabetics. Five normal and five insulin-dependent diabetic (IDDM) subjects were infused with labeled [3,4-13C2]-acetoacetate. [13C]KB enrichments were lower in forearm vein than in the artery, and dilution of labeled KB was always higher than that which could be explained by arterial-venous differences of unlabeled KB. When arterial FFA concentrations in normals were raised (Intralipid+heparin) to values comparable to those of the diabetics, no additional increase in forearm arteriovenous dilution of labeled KB was observed. Neither in the basal state nor under conditions of increased plasma FFA were we able to detect venous appearance of KB labeled in the first and in the second carbon atoms, a necessary consequence of pseudoketogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lipoprotein sub-fraction levels and composition in obese subjects before and after gastroplasty.

Obesity is frequently associated with several alterations of plasma lipid levels and lipoprotein metabolism. To evaluate the effects of severe obesity and weight loss on plasma lipoprotein sub-class levels and composition 11 grossly obese patients were examined before and six and 12 months after gastroplasty. Plasma lipoproteins were isolated by ultracentrifugation in a zonal rotor under rate flotation conditions. Mean body weight was 121.9 kg before gastroplasty, 97.6 kg after six months, and 90.7 kg after 12 months. Total plasma cholesterol was not affected by the weight reduction. Obese patients were characterized by increased levels of IDL and small dense LDL (LDL3). LDL levels, but not LDL3, were reduced following weight reduction. Plasma apo B levels of obese patients were always higher than in controls and were not affected by the weight reduction. After 12 month's weight loss total HDL cholesterol increased without modification of HDL sub-class cholesterol distribution, which was similar to that of normal controls. Plasma apo AI in obese patients was not affected by changes in body weight, and remained below normal. The percentage protein-lipid composition of LDL2 and HDL3 in obese patients was characterized by a decreased cholesterol ester content before gastroplasty which was normalized 12 months after gastroplasty. The presence of IDL and LDL3 in increased concentrations in severely obese patients may represent a vascular risk factor since similar abnormalities were recently observed in non-obese patients affected with vascular diseases.

Adult↗

Sulodexide oral administration influences blood viscosity and fibrinolysis.

The aim of this study was to verify the effects of oral administration of a new enteric-coated formulation of sulodexide on blood viscosity and fibrinolysis. Six outpatients suffering from peripheral artery occlusive disease were administered orally two enteric-coated tablets containing 50 mg of sulodexide, twice daily for seven days. On the first and seventh administration days, the following parameters were evaluated: plasminogen activator inhibitor (PAI-1) activity, PAI-1 antigen, tissue plasminogen activator (t-PA) and whole blood, serum and plasma viscosity, before (0 time) and 2, 4 and 8 hours after ingestion of the drug. Following the first administration (50 mg), a slight reduction of PAI was registered; after 7 days' administration, a clear-cut lowering of functional and antigenic PAI was observed, together with an increase of t-PA. As to the drug's influence on blood viscosity, after 7 days the most evident reduction was that registered for plasma viscosity. No side effects were observed throughout the treatment period.

Aged↗

Investigation of products arising from enzymatic digestion of advanced glycated albumin by high-performance liquid chromatography/mass spectrometry.

The structural investigation of the products arising from 28 days incubation of albumin with high glucose concentration and further enzymatic hydrolysis has been carried out by means of high-performance liquid chromatography/mass spectrometry (HPLC/MS) under plasmaspray conditions. By this approach many different compounds have been detected, and for most of them, possible structures have been proposed on the basis of literature data and molecular weight assignments.

Animals↗

Effects of the oral administration of glycosaminoglycans on cellular abnormalities associated with idiopathic calcium oxalate nephrolithiasis.

Oral administration of mixture of extractive glycosaminoglycans to a group of renal stone formers led to a significant decrease in oxalate self-exchange and in erythrocytes membrane protein phosphorylation traits that are abnormal in the majority of patients with idiopathic calcium nephrolithiasis. The action of glycosaminoglycans at the cellular level is probably due to their modulating activity on certain membrane protein kinases. The proven effect of the glycosaminoglycans opens a new pharmacological approach to the prevention of recurrent nephrolithiasis.

Administration, Oral↗

Diabetes mellitus and hypertension: a physiologic basis for a rational therapeutic approach.

The basic mechanisms that initiate and sustain hypertension in the diabetic population are poorly understood. Obesity, insulin, genetic factors, and abnormalities in calcium homeostasis may contribute, and could be related to an elevated Na+/H+ antiport activity. In the first study described in this investigation, hypertensive subjects with insulin-dependent diabetes mellitus (IDDM) who had an elevated Na+/Li+ countertransport activity were found to have a lower whole body glucose utilization, a lower insulin-stimulated forearm carbohydrate oxidation, larger ultrasound kidney volume, and increased left ventricular mass index when compared with hypertensive IDDM subjects with a normal Na+/Li+ countertransport activity or normotensive IDDM subjects. Thus an elevated Na+/Li+ countertransport activity appears to identify a subset of IDDM patients who are more susceptible to the development of the renal and cardiac complications associated with hypertension. This underlines the importance of choosing an appropriate antihypertensive therapy that will not produce a deterioration in glucose and lipid metabolism. In the second part of the report, results are presented for the treatment of hypertensive patients with non-insulin-dependent diabetes mellitus with doxazosin. The selective alpha 1-inhibitor produced a significant reduction in blood pressure, together with favorable changes in the serum lipid profile. As a result, the calculated risk of developing coronary heart disease was significantly reduced. Throughout the study no patients required a dose reduction or discontinuation of doxazosin because of side effects, and no clinically significant changes in laboratory tests were apparent. Thus doxazosin could be considered a useful antihypertensive agent in hypertensive patients with IDDM who are insulin-resistant and who have renal and cardiac abnormalities.

Antihypertensive Agents↗

Acute effects of HMG-CoA reductase inhibitors on biliary lipids in patients with interrupted enterohepatic circulation.

HMG-CoA reductase inhibitors decrease serum cholesterol by inhibiting hepatic cholesterol synthesis, but their influence on biliary lipids is not well characterized. In the present study Pravastatin (80 mg) was administered as a single oral dose to 10 patients with external bile fistula, after 1 week of interruption of the enterohepatic circulation, in order to assess the effect of inhibition of hepatic cholesterol synthesis on biliary lipids in conditions of stimulated bile acid synthesis. Bile was collected every hour for 12 h. On the day before, the same procedure was applied with a placebo, and collected bile used as control. Pravastatin decreased both bile acid and phospholipid concentration to about 60% of basal values; this change was still significant after 10 h. Cholesterol concentration was also decreased to about 70% of basal values, but this change was significant only from the 5th to the 7th h. The per cent of cholic and chenodeoxycholic acid was not affected by the drug, but the ratio of glyco- to tauroconjugated bile acids was decreased to about half the initial values. Bilirubin concentration exhibited a late increase, suggesting a reduction in the bile flow. These results suggest that, in patients with interrupted enterohepatic circulation, biliary excretion of bile acids can be largely dependent on hepatic cholesterol synthesis.

Adult↗

The epidemiology and prevalence of diabetic retinopathy in the Veneto region of north east Italy. Veneto Group for Diabetic Retinopathy.

The prevalence of diabetic retinopathy and its relationship to a number of risk factors were examined in a population-based study in the Veneto region of North East Italy. Of 1321 diabetic patients selected, 98% attended for examination. Prevalence of diabetic retinopathy was 26.2% (24.4% background and 1.8% proliferative). The prevalence of retinopathy was significantly related (p less than 0.01) to the duration of diabetes (17.3% for less than 5 years; 60.8% for greater than 20 years). Proliferative retinopathy was much more prevalent after 20 years of diabetes. After 10 years most proliferative retinopathy was found in Type 1 diabetic patients, but before 10 years from diagnosis it was most prevalent in Type 2 diabetes. The prevalence of retinopathy was significantly related (p less than 0.001) to the type of diabetes and was found predominantly in Type 1 (46.2%) and insulin-treated Type 2 (45.9%) subjects and to a lesser degree in non-insulin-treated patients (24.6%). The prevalence of retinopathy was significantly related to both fasting and post-prandial blood glucose levels (p less than 0.001), blood urea nitrogen (p less than 0.05), and systolic (p less than 0.001) and diastolic (p less than 0.01) blood pressure. No significant differences were found in the prevalence of total or proliferative retinopathy between males and females. No significant relationships were found with family history of diabetes, alcohol intake, smoking habits, cholesterol, triglycerides, and serum uric acid.

Blood Glucose↗

Myocardial metabolism in type 1 diabetic patients without coronary artery disease.

Myocardial exchange of metabolic substrates was investigated in eight Type 1 diabetic patients with angiographically normal coronary arteries and seven normal control subjects, after an overnight fast. Simultaneous samples of arterial and coronary sinus blood were collected for analysis of the major metabolic substrates. Myocardial blood flow was measured by the thermodilution technique. Although the Type 1 patients were hyperglycaemic (10.0 +/- 2.0 (+/- SE) mmol I-1) myocardial glucose uptake was lower than in control subjects (27 +/- 6 vs 42 +/- 5 mumol min-1 1.73 m-2, p less than 0.05). The net balance of lactate and pyruvate across the myocardium showed a net release in Type 1 patients (13.4 +/- 2.7 mumol min-1 1.73 m-2 and 1.3 +/- 0.2 mumol min-1 1.73 m-2, respectively) and a net uptake in control subjects (2.2 +/- 0.7 mumol min-1 1.73 m-2 and 3.5 +/- 0.3 mumol min-1 1.73 m-2, both p less than 0.01). Myocardial uptake of ketone bodies was significantly higher in diabetic patients (37.0 +/- 6.3) mumol min-1 1.73 m-2) than in control subjects (10.1 +/- 3.4 mumol min-1 1.73 m-2, p less than 0.01). Non-esterified fatty acid (NEFA) uptake was significantly greater in the diabetic patients than in control subjects (44.1 +/- 7.0) vs 24.1 +/- 5.1 mumol min-1 1.73 m-2, p less than 0.01). Net balance of glucose, lactate, and pyruvate across the myocardium was inversely and significantly related to that of NEFAs and ketone bodies (p less than 0.01). Myocardial carbohydrate uptake is markedly impaired in Type 1 diabetic patients with angiographically intact coronary vessels. Ketones and NEFA represent the major fuel for the diabetic myocardium. Thus, in diabetes, myocardial lactate metabolism may be profoundly altered independently of coronary artery disease.

Blood Glucose↗

Insulin resistance is associated with high sodium-lithium countertransport in essential hypertension.

The nature of the association between essential hypertension and insulin resistance remains unknown. We measured plasma glucose and insulin levels after an oral glucose tolerance test (OGTT), as well as insulin sensitivity (using a euglycemic hyperinsulinemic clamp), glucose turnover (Rd; using [6,6-2H2]- and [3-3H]glucose isotopic dilution), and forearm net balance of glucose (using arterial-venous difference) in 22 hypertensive patients with high (H2) red blood cell (RBC) sodium-lithium countertransport (Na(+)-Li+ CT; greater than 0.41 mmol.l RBC-1.h-1), 21 hypertensive patients with normal (H1) Na(+)-Li+ CT, and 22 normotensive controls (C). After OGTT, H2 patients had higher plasma glucose and insulin levels than H1 and C. During euglycemic hyperinsulinemia (approximately 100 microU/ml) Rd was lower in H2 [21.7 +/- 1.4 (SE) mumol.kg-1.min-1] than in H1 (44.3 +/- 2.9; P less than 0.01) and C (48.1 +/- 3.0; P less than 0.01), and an inverse correlation was found between rates of Na(+)-Li+ CT and Rd in H1 and H2 (rs = -0.76; P less than 0.01). Forearm glucose uptake was 40-50% lower in H2 compared with H1 and C (P less than 0.01). Lactate concentration increased more in C (from 511 +/- 24 to 1,207 +/- 69 microM) and in H1 (from 564 +/- 40 to 1,122 +/- 99) than in H2 (from 581 +/- 42 to 950 +/- 102, P less than 0.05 vs. both). Forearm blood flow increased more in C (31%, P less than 0.05) and H1 (22%, P less than 0.05) than in H2 (12%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Insulin-dependent diabetes mellitus and hypertension.

Contrasting results have been reported regarding the prevalence of hypertension in insulin-dependent diabetes mellitus (IDDM), showing a slightly higher or normal percentage of IDDM patients with elevated blood pressure levels than in the general population. Most of the cross-sectional and prospective studies on the prevalence of hypertension in IDDM show an association between microalbuminuria and elevated blood pressure levels. However, it is not clear whether hypertension is simply secondary to kidney damage or whether hypertension occurs with or even before the development of impaired kidney function. Patients with IDDM have a higher exchangeable body Na+ pool. Na+ retention in IDDM is accounted for by several metabolic and hormonal abnormalities such as hyperglycemia, hyperketonemia, hyperinsulinemia, altered secretion, and resistance to atrial natriuretic peptide. High blood pressure appears to be dependent, at least at some phase, on expansion of extracellular fluid volume as a consequence of defects in the renal secretion of Na+ and water. On the other hand, a tendency toward Na+ retention characterizes all patients with IDDM, whereas hypertension develops only in a subgroup of diabetic patients. One possible explanation for these findings is that a genetic predisposition plays a role in creating susceptibility to hypertension and perhaps to diabetic nephropathy independent of diabetes, even if Na+ retention can further deteriorate this susceptibility to hypertension. With regard to this issue, it has recently been suggested that the risk of kidney disease in patients with IDDM is associated with a genetic predisposition to hypertension. Furthermore, diabetic nephropathy occurs in familial clusters, because diabetic siblings of nephropathic diabetic patients show a higher frequency of diabetic nephropathy than the diabetic siblings of nonnephropathic diabetic patients. One of the possible genetic markers that could be useful to identify the diabetic patients with susceptibility to hypertension and diabetic nephropathy is the Na+(-)Li+ countertransport activity in erythrocytes.

Biological Transport↗

Italian Consensus Conference--overweight, obesity and health.

On 5 and 6 April 1991, at the National Research Council (CNR) in Rome, a Consensus Conference on the relationship between overweight, obesity and health was held. The conference was sponsored by FATMA (Applied Project on Disease Factors of the CNR) and UICO (Italian Society for the Study of Obesity) with the purpose of establishing guidelines for health employees. The development of the conference followed the methodology set down by OMAR to obtain a rational and significant consensus on the answers to six basic questions prepared by the planning committee. The questions were the pivotal point of the conference and were brought to the attention of all the attendees and widely diffused among the medical community; they were proposed with the aim of giving an exhaustive definition of obesity, to investigate its relationship with mortality and morbidity, to highlight its social characterization, to indicate methods of evaluation and recommendations for weight loss, to select groups at risk, and to focus general guidelines for research. After the presentation of the state of the art on 18 topics by experts in the field, the 22 members of the consensus panel, impartial experts from a vast area of the scientific community, discussed a draft document representing the answers to the questions, which was subsequently submitted to the 307 attendees, discussed and then approved. This paper is the definitive document of the Consensus Conference. The introduction explains the reasons which led to the decision to promote the conference six years after the one held in the United States. The methodology is then set out. The questions are answered in the form of recommendations and backed up by data and scientific evidence from the literature.

Body Weight↗

Pravastatin vs gemfibrozil in the treatment of primary hypercholesterolemia. The Italian Multicenter Pravastatin Study I.

This study compared the efficacy and safety of pravastatin and gemfibrozil in the treatment of primary hypercholesterolemia. Three hundred eighty-five outpatients from 13 lipid clinics in Italy participated in this randomized double-blind study. Patients were assigned to receive either 40 mg once daily of pravastatin or 600 mg of gemfibrozil twice daily after an initial diet lead-in period. After 24 weeks, mean reductions from baseline values of plasma total and low-density lipoprotein cholesterol were, respectively, 23% and 30% with pravastatin and 14% and 17% with gemfibrozil. Significant lipid-lowering effects were noted within 4 weeks. Apolipoprotein B decrease was 21% with pravastatin and 13% with gemfibrozil. A statistically significant increase of high-density lipoprotein cholesterol of 5% was achieved with pravastatin compared with a 13% increase for gemfibrozil. Serum triglyceride values decreased 5% with pravastatin and 37% with gemfibrozil. Familial and polygenic hypercholesterolemic patients were also examined separately. Pravastatin effectiveness in reducing low-density lipoprotein cholesterol was greater by 6% in polygenic than in familial hypercholesterolemic patients. Treatment for 25 patients (eight treated with pravastatin and 17 treated with gemfibrozil) was discontinued during the study. The incidence of clinical symptoms and laboratory alterations was low for both treatment groups. Pravastatin and gemfibrozil were well tolerated, but pravastatin was significantly more effective in reducing total and low-density lipoprotein cholesterol levels in primary (either familial or polygenic) hypercholesterolemias than gemfibrozil.

Adult↗

Identification of furoyl-containing advanced glycation products in collagen samples from diabetic and healthy rats.

The compounds resulting from the reaction of glucose with proteins (advanced glycation products) can be important markers of chronic diabetic complications. To test the possible diagnostic value of advanced glycation products containing the furoyl moiety, collagen samples from diabetic and healthy rats were analyzed by parent ion spectroscopy. In our study, we compared normal collagen, diabetic collagen and normal collagen incubated with different glucose concentrations and we employed different hydrolysis procedures (HCl and proteinase). Mass spectroscopic measurements performed on hydrolyzed samples showed that either different samples or different hydrolysis procedures produce a similar set of furoyl-containing compounds. 2-(2-Furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI) which has been reported to be one of the advanced glycation products, was never found in any of the samples examined. Hence neither FFI nor furoyl-containing molecules can be considered markers of advanced glycation processes.

Animals↗