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Biomedical subjects

L Benzi

Publications and source records attributed to L Benzi.

At least 55 records · Page 3Linked to original sources

Intracellular insulin processing is altered in monocytes from patients with type II diabetes mellitus.

We studied total cell-associated A14-[125I]insulin radioactivity (including surface-bound and internalized radioactivity), insulin internalization, and its intracellular degradation at 37 C in monocytes from nonobese type II untreated diabetic patients (n = 9) and normal subjects (n = 7). Total cell-associated radioactivity was decreased in diabetic patients [2.65 +/- 1.21% (+/- SD) vs. 4.47 +/- 1.04% of total radioactivity; P less than 0.01]. Insulin internalization was also reduced in diabetic patients (34.0 +/- 6.8% vs. 59.0 +/- 11.3% of cell-associated radioactivity; P less than 0.01). Using high performance liquid chromatography six intracellular forms of radioactivity derived from A14-[125I] insulin were identified; 10-20% of intracellular radioactivity had approximately 300,000 mol wt and was identified as radioactivity bound to the insulin receptor, and the remaining intracellular radioactivity included intact A14-[125I]insulin, [125I]iodide, or [125I]tyrosine, and three intermediate compounds. A progressive reduction of intact insulin and a corresponding increase in iodine were found when the incubation time was prolonged. Intracellular insulin degradation was reduced in monocytes from diabetic patients; intracellular intact insulin was 65.6 +/- 18.1% vs. 37.4 +/- 18.0% of intracellular radioactivity (P less than 0.01) after 2 min and 23.6 +/- 22.3% vs. 3.9 +/- 2.3% (P less than 0.01) after 60 min in diabetic patients vs. normal subjects, respectively. In conclusion, 1) human monocytes internalize and degrade insulin in the intracellular compartment in a stepwise time-dependent manner; and 2) in monocytes from type II diabetic patients total cell-associated radioactivity, insulin internalization, and insulin degradation are significantly reduced. These defects may be related to the cellular insulin resistance present in these patients.

Aged↗

Long-term therapy with biosynthetic human insulin: importance of short-acting/intermediate-acting insulin ratio on determining efficacy of treatment.

This report describes the efficacy of biosynthetic human insulin (BHI) in long-term (one year) therapy of type I diabetic patients previously treated with conventional insulins. The results were compared with those obtained in a group of diabetic patients kept on their usual treatment. In the latter, fasting plasma glucose, HbA1, insulin dose and relative proportions of insulin formulations remained constant throughout the study. In patients switched to BHI, hypoglycaemic episodes occurred during the first week of treatment and fasting plasma glucose was higher than basally at the first two visits (7th and 30th days). Both hypoglycaemia and high fasting plasma glucose were avoided by reducing the amount of short-acting insulin and increasing that of intermediate-acting insulin, so that the short-acting/intermediate-acting insulin ratio was significantly lower during BHI therapy, although the total daily insulin dose remained unchanged. HbA1 levels remained fairly constant throughout the study. It was concluded that in order to achieve full clinical efficacy of BHI, it is important to modify the proportions of short- and intermediate-acting insulin preparations accurately when switching patients from conventional insulin to biosynthetic human insulin.

Adult↗

A14-[125I]monoiodoinsulin purified by different high-performance liquid chromatographic procedures and by polyacrylamide gel electrophoresis: preparation, immunochemical properties and receptor binding affinity.

Reversed-phase high-performance liquid chromatography (RP-HPLC) allows the rapid separation of A14-[125I]monoiodoinsulin directly from the iodination mixtures. It remains to be clarified, however, whether the RP-HPLC chromatographic conditions affect the properties of the purified tracer. In this study we prepared A14-[125I]insulin purified by polyacrylamide gel electrophoresis (PAGE) and by three different RP-HPLC mobile phases containing, respectively, ammonium acetate, sodium perchlorate and trifluoroacetic acid. The binding characteristics of all these tracers were examined using an insulin antiserum and insulin cell receptors. The specific radioactivity corresponded to the theoretical maximum for the RP-HPLC-purified tracers and was significantly lower for the PAGE-purified tracers. Significant differences were found in the binding of different tracers to the insulin antiserum: maximum binding ranged from 94 to 99% and was significantly lower for tracers purified by RP-HPLC eluents B and C; antiserum dilution giving 50% tracer binding was lower for tracers purified by RP-HPLC eluent B. The four insulin derivatives showed no difference in non-specific precipitation and in the affinity constant values calculated from the Scatchard analysis. No significant difference was found in the binding of the four insulin derivatives to the human-cultured IM-9 lymphocytes and to the human circulating monocytes. In conclusion, the present work demonstrates that the immunological properties of the A14-[125I]monoiodoinsulin purified by RP-HPLC may be partially affected by the composition of the mobile phase. In order to obtain a fully potent A14-[125I]insulin derivative and to have the possibility of comparing data from different laboratories, the chromatographic conditions must be taken into account.

Adult↗

Salivary insulin concentrations in type 2 (non-insulin-dependent) diabetic patients and obese non-diabetic subjects: relationship to changes in plasma insulin levels after an oral glucose load.

The presence of immunoreactive insulin in saliva and its relationship to plasma immunoreactive insulin was investigated in healthy subjects, newly diagnosed non-obese Type 2 (non-insulin-dependent) diabetic patients and obese non-diabetic subjects, basally and after an oral glucose tolerance test. The mean +/- SEM fasting values of plasma and salivary immunoreactive insulin were significantly higher in diabetic patients and obese non-diabetic subjects than in normal volunteers (p less than 0.05). During the glucose challenge, the increase of salivary insulin was related with that of plasma in the three groups of subjects, with a time lag in normal and obese subjects. In normal volunteers, plasma and salivary peak values were respectively 49.5 +/- 13.4 microU/ml (p less than 0.05 vs obese subjects) at 60 min and 12.0 +/- 3.3 microU/min (p less than 0.05 vs obese subjects) at 120 min; in diabetic patients, the values were 51.7 +/- 5.6 microU/ml (p less than 0.05 vs obese subjects) and 14.6 +/- 4.1 microU/min at 120 min; in obese subjects, the peak value for plasma insulin was 111.5 +/- 40.1 microU/ml at 90 min and for salivary insulin 15.6 +/- 5.1 microU/min at 120 min. A positive linear relationship was shown between plasma and salivary insulin during the oral glucose tolerance test. The identity of salivary insulin was assessed by reversed-phase HPLC. We conclude that salivary immunoreactive insulin can be found in Type 2 diabetic patients and in obese non-diabetic subjects, as well as normal volunteers, that plasma and salivary insulin are related after a glucose load, and that differences exist in salivary insulin secretion patterns among the three groups of subjects.

Adult↗

Decrease in plasma glucose concentration during storage at -20 degrees C.

We measured glucose concentrations with the Beckman Glucose Analyzer, before and after storage at -20 degrees C for various intervals, in 228 plasma samples from oral glucose tolerance tests on 17 normal subjects and 21 patients with impaired carbohydrate tolerance, and also in 82 control samples collected daily, after overnight fast, from seven insulin-dependent diabetics. We found a significantly (p < 0.001) positive relation between storage interval and percentage decrease in glucose concentration. Evidently, the longer plasma is stored, the greater the decrease in glucose.

Blood Glucose↗

Effect of plasma metformin concentrations on serum lipid levels in type II diabetic patients.

In this study we evaluated the relationships between plasma metformin levels, measured by reverse-phase high-performance liquid chromatography, and serum lipid levels in 20 metformin-treated, type II diabetic patients. Mean fasting plasma metformin concentration was 490 +/- 188 ng/ml. No correlation was found between daily dose of drug and lipid parameters. A significant correlation emerged between circulating metformin concentration and serum triglycerides (r = -0.574, p less than 0.01), HDL-cholesterol (r = 0.583, p less than 0.01) and HDL2-cholesterol (r = 0.670, p less than 0.05). Multiple linear regression analysis showed that the correlation between plasma metformin concentration and serum triglycerides still remained significant after correction for other clinical and metabolic parameters. Total cholesterol and HDL3-cholesterol were not correlated with metformin concentrations. These results demonstrate the clinical usefulness of measuring plasma metformin concentrations and indicate that some effects of metformin on lipid metabolism depend on the drug plasma levels.

Aged↗

Biosynthetic human insulin does not modify circulating lipid and apolipoprotein concentrations in type I diabetic patients.

Since insulin modulates key enzymes of lipid metabolism, different biological activities of biosynthetic human insulin (BHI) and conventional insulins might induce different plasma lipid and apolipoprotein patterns in diabetic patients chronically treated with the former or the latter insulin preparation. In this study we have evaluated the effects of 3 months of therapy with BHI on plasma lipid and apolipoprotein concentrations in a group of type I diabetics previously treated with insulin of animal origin and the results have been compared with those from diabetics maintained on conventional insulin therapy. In the latter, no change occurred in the clinical and metabolic parameters. Patients transferred to BHI showed lower HDL-cholesterol and HDL3-cholesterol levels at 30 days from the beginning of BHI treatment, and both parameters returned to, and were maintained the basal values at subsequent controls. Total cholesterol, HDL2-cholesterol, triglycerides, apolipoproteins AI, AII and B remained substantially constant throughout the study. Glycometabolic control, which was evaluated by fasting plasma glucose and glycosylated hemoglobin, exhibited a transient, moderate deterioration at the 30-day control, and returned to basal level in the following weeks. No major change was noted as far as daily insulin dosage and relative body weight were concerned. Thus, long-term BHI treatment of type I diabetics does not cause any major change in plasma lipid and apolipoprotein patterns in comparison with animal insulin therapy, so that the validity of using BHI in the treatment of type I diabetes is confirmed.

Adult↗

Metabolic control affects plasma lipid and apolipoprotein levels in women, but not in men, with IDDM.

In order to evaluate if in insulin-dependent diabetes lipid and apolipoprotein levels are differently affected by metabolic control in men and women, we measured the concentrations of fasting plasma glucose, mean plasma glucose, glycosylated hemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and apolipoproteins A and B in 94 sex matched patients. Diabetic men and women were strictly comparable as far as age, relative body weight and metabolic control were concerned. In women, total and LDL cholesterol, triglycerides and apolipoprotein A correlated positively with HbA1 but not with fasting and mean plasma glucose. In men, no correlation between metabolic control and lipid and apolipoprotein levels was found. We conclude that, in diabetic women, the degree of metabolic control may affect the concentrations of plasma lipids, thus explaining, at least in part, the increased risk for coronary atherosclerosis in these patients.

Adult↗

Effects of guar-pasta on serum lipid levels in obese diabetic and non-diabetic women with normal lipids.

Alternative medications for hyperlipidemia management have been continuously searched for above all because currently employed drugs appear not to be effective or are poorly tolerated. Fibers, such as guar-gum, seem to be able to reduce cholesterol levels, but their extensive and long-term use is beset by the high incidence of gastrointestinal side-effects. In this study the administration of guar-enriched pasta has proved to reduce fasting and post-prandial cholesterol levels significantly in 15 obese normocholesterolemic women (5 diabetics and 10 non-diabetics). The women reported good palatableness of guar-pasta without any side-effects.

Adult↗

Measurable deficit of autonomic and sensory nerve function in asymptomatic diabetic patients.

In a group of 46 consecutive outpatients attending the diabetic clinic of our Metabolic Department, 30 insulin-dependent and 16 non-insulin-dependent diabetic patients in stable metabolic control, and in 38 age-matched controls, we measured vibration perception threshold with biothesiometer and autonomic function, by means of the five classical cardiovascular tests: R-R interval variations during deep breathing, Valsalva ratio, lying-to-standing, postural hypotension, and sustained handgrip. None of the patients complained of symptoms related to diabetic autonomic neuropathy (DAN) or sensory polyneuropathy. Vibration perception threshold positively correlated with Valsalva ratio (p < 0.05) and deep breathing (p < 0.01), and all of them correlated with age (p < 0.001), but not with duration of diabetes and metabolic control. Patients scored significantly lower than controls in vibration perception threshold and all of the autonomic function tests. According to the outcomes of cardiovascular tests ["Autonomic Score" (AS)] patients were divided into two different groups: presence (DAN+ = AS > or = 3) or absence (DAN- = AS < 3) of autonomic neuropathy. The DAN- group (n = 28, 60.9%) showed no significant differences from the DAN+ group (n = 18, 39.1%) in age, duration of diabetes, glycated hemoglobin, or body mass index. DAN+ patients had vibration perception threshold measured at the first toe tip and at external malleolus significantly higher than DAN- patients (p < 0.01 and p < 0.001, respectively) and controls (p < 0.005), as well as all the other cardiovascular tests except sustained handgrip. No difference in any of these items was observed between DAN- patients and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Efficacy of sulfonylurea and sulfonylurea-benfluorex therapy in patients with type 2 diabetes treated with commercial sulfonylurea-biguanide combinations].

This study tests the possibility to avoid the use of phenformin in 40 type 2 (non insulin dependent) diabetic patients treated with the commercial sulphonylurea-phenformin combinations. In diabetic patients treated with sulphonylureas and phenformin at low dosage (glibenclamide 5 mg and phenformin 50 mg) it was possible to maintain good glycometabolic control using only the sulphonylurea gliclazide (160 mg/die). The diabetic patients on treatment with sulphonylureas and phenformin at higher dosage (glibenclamide 7.5 mg and phenformin 75 mg) may further improve their metabolic control when transferred to a gliclazide-benfluorex combination 160 mg and 300 mg/die, respectively. These results suggest the possibility of withdrawing or replacing phenformin in the therapy of type 2 diabetic patients without modifying their glycometabolic control.

Aged↗

[Reduction of intra- and post-operative bleeding after treatment with a peptide fraction derived from bovine factor VIII].

The most common post-operative complication of adenotonsillectomy is an excessive bleeding. This problem persists although the laboratory investigations may exclude hemocoagulative anomalies and the anamnesis is able to show the presence or not of genetic factors or constitutional disease. Even if the surgical operation is performed in a technical proper way, the risk of bleeding is still present. Therefore we have valued new prospects of application in pediatric O.R.L. of a peptide fraction from bovine factor VIII. This compound has proved to be able to reduce the bleeding time. We valued the action of this drug compared with that of tranexamic acid and in comparison with the results obtained before treatment. Furthermore, we have also investigated the possibility of influence of this drug on haemocoagulative parameters and we have concluded that the drug does not show any effect on them.

Adenoidectomy↗