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Biomedical subjects

M Trovati

Publications and source records attributed to M Trovati.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effect of labetalol on human platelet function.

1. The effects of the alpha-beta-adrenergic antagonist labetalol on the activation of human platelets by adrenaline and other aggregating stimuli have been investigated. 2. Labetalol inhibited platelet aggregation and secretion induced by collagen and the second phase of aggregation caused by ADP, platelet activating factor, adrenaline and ionophore A23187. Adrenaline-induced platelet activation was inhibited by the lowest labetalol concentration. The response to Na arachidonate was minimally affected and the arachidonate-induced thromboxane B2 generation was only partially prevented. 3. The pre-incubation with low concentration of ionophore A23187 overcame labetalol's inhibition of collagen-induced platelet aggregation. 4. Labetalol did not influence intraplatelet cyclic AMP levels. 5. The present investigation provided evidences that the modulation of human platelet function by labetalol could be related also to a decreased Ca2+ availability.

Adult↗
PubMed1988

Insulin directly reduces platelet sensitivity to aggregating agents. Studies in vitro and in vivo.

The aim of this study was to investigate the influence of insulin on platelet function, both in vitro and in vivo. For the in vitro investigation, we evaluated whether insulin affects platelet function at a physiological hormone concentration by incubating the platelet-rich plasma (PRP) of fasting subjects with human regular insulin at the final concentration of 40 microU/ml for 30 min; we observed a significant reduction of platelet sensitivity to all the aggregating agents employed, i.e., ADP, platelet-activating factor (PAF), epinephrine, collagen, and Na+ arachidonate. To investigate whether the insulin effect on platelets is dose dependent, we incubated the PRP of fasting subjects with different concentrations of human regular insulin (40, 80, 120, and 160 microU/ml) for 5 min, and we observed that the insulin-induced reduction of platelet sensitivity to aggregating agents is a dose-dependent phenomenon. Furthermore, the comparison between the platelet responses after 5 and 30 min of incubation with insulin showed that the insulin effect on platelet aggregation is time dependent. The lack of specificity of its inhibiting activity suggests that insulin does not interfere with the initial binding of each aggregating agent at specific sites but does influence a common step of platelet aggregation. Our study rules out the possibility that insulin reduces platelet-function-modifying intraplatelet cAMP levels or thromboxane A2 production, because this hormone decreases the platelet concentrations of cAMP--a phenomenon that, per se, promotes platelet aggregation--and does not modify collagen or Na+ arachidonate--induced platelet production of thromboxane A2, measured by radioimmunoassay of its stable-metabolite thromboxane B2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1988

Postprandial exercise in type I diabetic patients on multiple daily insulin injection regimen.

This study shows the influence on plasma glucose concentrations of 45 min of mild exercise (48 +/- 4% of maximum aerobic capacity) performed 180 min after breakfast and 195 min after a subcutaneous injection of regular insulin by six type I (insulin-dependent) diabetic patients on a three-daily insulin injection regimen (regular insulin before breakfast and lunch, regular + intermediate insulin before supper). It has been observed that such exercise does not induce a large plasma glucose decrease. Actually, plasma glucose concentrations were 99 +/- 18 mg/dl before exercise, reached a nadir of 78 +/- 17 mg/dl at 35 min, and were 81 +/- 15 mg/dl at the end of exercise. During the control study at rest, in the same 45-min time interval, plasma glucose decreased from 146 +/- 31 to 128 +/- 31 mg/dl. In the exercise study, one patient began exercising while hypoglycemic, and another patient developed asymptomatic hypoglycemia during exercise. In the control study at rest, one patient showed hypoglycemic glucose concentrations. Throughout the exercise study, plasma free-insulin concentrations decreased (from 32 +/- 5 to 20 +/- 4 microU/ml) as a result of the pharmacokinetics of subcutaneously injected insulin.

Adult↗
PubMed1986

Studies on mechanisms involved in hypoglycemia-induced platelet activation.

The aim of our study was to investigate the mechanisms involved in hypoglycemia-induced platelet activation. Sixteen healthy male subjects received a 60-min intravenous infusion of human regular insulin at the rate of 64 mU . m-2 . min-1: throughout 150 min, we serially measured plasma concentrations of glucose, insulin, and counterregulatory hormones; platelet sensitivity to ADP, thrombin and platelet-activating factor; plasma concentrations of platelet markers for specific proteins of in vivo release reaction (beta-thromboglobulin and platelet factor 4). Our study showed that insulin-induced hypoglycemia causes a significant increase in platelet sensitivity to aggregating agents in vitro and a platelet release reaction in vivo. Hypoglycemia-induced platelet activation was not correlated with plasma glucose concentrations at nadir and occurred before the increase of plasma growth hormone and cortisol. To further elucidate the mechanisms of hypoglycemia-induced platelet activation, we incubated in vitro platelet-rich plasma (PRP) of seven fasting healthy subjects with the same concentrations of insulin, epinephrine, glucagon, growth hormone, and cortisol measured in vivo during insulin-induced hypoglycemia. Only epinephrine was able to increase platelet sensitivity to aggregating agents. To investigate the role of alpha-adrenergic receptors in this phenomenon, we also studied four healthy subjects on another occasion, repeating the above-described insulin infusion together with intravenous infusion of phentolamine (-15 to +150 min), 5 mg over 2 min followed by 500 micrograms/min. alpha-Blockade was able to suppress hypoglycemia-induced increase of platelet sensitivity to aggregating agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Metformin reduces insulin requirement in Type 1 (insulin-dependent) diabetes.

The effect of metformin on Type 1 (insulin-dependent) diabetes has been assessed with the artificial pancreas. Fourteen Type 1 diabetic patients of normal body weight received in addition to their usual insulin therapy 850 mg metformin or placebo three times a day for 4-6 weeks. The sequence was placebo-metformin in eight patients and metformin-placebo in the other six. On the last day of metformin or placebo treatment, an artificial pancreas was used for about 36 h to assess insulin requirement. There was a 25.8% reduction in insulin requirement during metformin management despite slightly lower blood glucose levels (5.25 +/- 0.20 versus 5.98 +/- 0.18 mmol/l, p less than 0.01). Maximum reduction (about 50%) occurred 2 h after both lunch and dinner. There was no nocturnal effect. A marked decrease in specific insulin binding before metformin was found (0.56 +/- 0.27% to 10(7) monocytes versus 2.82 +/- 0.75 of control subjects) and significant increase after metformin (1.36 +/- 0.36%, p less than 0.05). There were no significant changes in blood lactate, total and HDL-cholesterol, triglycerides and C-peptide levels. These results show that insulin receptor binding is diminished in Type 1 diabetes, perhaps as a consequence of higher peripheral blood insulin levels and that metformin can improve binding, and so reduce the amount of insulin needed to reach euglycaemia. The insulin sparing effect is greatest after meals, and interference with intestinal absorption of sugars may also be important. It follows that metformin could be usefully administered to Type 1 diabetic patients with unimpaired liver and renal function to reduce their insulin requirement.

Adult↗
PubMed1983

Exercise-induced changes of Factor VIII complex in healthy subjects and in type-I diabetics: relation between growth hormone and Von Willebrand Factor increments.

This work aims to study the exercise-induced changes of Factor VIII Complex both in healthy subjects and in type I diabetics without vascular complications, and to investigate the possible relations between growth hormone and Von Willebrand's Factor response to exercise. Results show that maximal exercise performed by cycle ergometer causes a significant increment of the procoagulant subunit (VIII:C) and of Von Willebrand Factor (VIII:RiCoF) both in healthy controls and in type I diabetics, whereas a slight increment of Factor VIII-Related antigen (VIIIR:Ag) is observed only in diabetics. The shape of the mean GH response to exercise parallels the one of Von Willebrand's Factor: however, the presence of VIII:RiCoF increments also in GH non-responders supports the conclusion that growth hormone is not the only factor involved in the regulation of Von Willebrand's Factor exercise-induced increase.

Adult↗
PubMed1983

Insulin binding to isolated monocytes and adipocytes in the study of hypoglycemic subjects and in the follow-up of patients with insulinoma.

The present study was performed to see whether insulin receptor evaluation is useful as a diagnostic tool in the differential diagnosis of hypoglycemia. The receptor numbers and affinity constants of insulin binding to adipocytes isolated from subcutaneous tissue were determined in 5 metabolically healthy subjects, undergoing laparatomy for cholecystectomy, and in 4 patients undergoing surgery for insulinoma removal. The specific insulin binding to monocytes at physiological concentrations (1 ng/ml) was also determined in all these subjects, and in 6 patients with functional hypoglycemia. The study was repeated in insulinoma patients 7 days after surgery. Results show that insulinoma patients before tumor removal have greater than 50% fall in binding capacity on both monocytes and fat cells, in keeping with the down-regulation mechanism, whereas the values for patients with functional hypoglycemia are in the normal range. After surgery, the insulin binding to monocytes sharply increased, nearly to the lower level of the normal range when the insulinoma was removed; no change was observed when the tumor was not resected (case 3). Insulin receptor study may therefore be of diagnostic and prognostic assistance in the investigation of hypoglycemic syndromes.

Adenoma, Islet Cell↗
PubMed1981

Glycosylated hemoglobin in patients with newly discovered juvenile-onset diabetes mellitus in the days immediately following the beginning of insulin treatment.

We studied the behavior of fast hemoglobin fractions in newly discovered diabetic patients, before and in the 10 days immediately following the beginning of insulin therapy, in order to verify whether or not the rapid improvement of glycemic control involved a rapid reduction of total HbA1 and of its fractions. We observed a rapid and highly significant fall of HbA1(a+b+c) and HbA1c levels after only 1 or 2 days of insulin therapy, followed by a slower decrement in the other 3-10 days. HbA1(a+b) showed a slower decrement trend, reaching levels significantly below baseline values only after 7-10 days. These results suggest that rapid changes occurring in glycosylated hemoglobin levels after the beginning of insulin treatment in newly discovered diabetic patients involve mainly HbA1c. The kinetics of glycosylated hemoglobin reduction, with a first rapid decrement followed by a slower one, may suggest the hypothesis that rapid changes are due to reversible Schiff base de-glycosylation, the ketoamine linkage being the true index of long term glycemic control.

Adult↗
PubMedDate not supplied

Labile and stable glycosylated hemoglobin during OGTT in healthy subjects and maturity-onset diabetics.

HbA1 levels were determined by a rapid chromatographic column test in 15 healthy subjects (HS) and in 15 maturity-onset diabetics (MOD), fasting and 2 h after glucose ingestion (100 g for HS, 50 g for MOD). Chromatography was carried out both before and after 6 h of red cell incubation in saline at 37 degrees C. HbA1 in HS at 0 and 120 min of OGTT was not significantly different, either before (6.24 +/- 0.61% and 6.22 +/- 0.62%) or after red cell incubation in saline (5.85 +/- 0.61% and 5.87 +/- 0.55%). Red cell incubation in saline significantly reduced HbA1 levels both at 0 and 120 min (2p less than 0.001). HbA1 in MOD before red cell incubation in saline, was slightly but significantly higher at 120 min (8.61 +/- 1.03%) than at 0 min (8.39 +/- 1.01%): 2p less than 0.001. After incubation in saline, this difference was cancelled (7.86 +/- 0.85% at 0 min and 7.97 +/- 0.83% at 120 min: n.s.). Post-incubation levels were lower than pre-incubation ones both at 0 and 120 min (2p less than 0.001). The HbA1 increment observed in MOD is significantly correlated (p less than 0.01; r=0.64) to the blood glucose increment observed at the glycemic peak. We conclude that hemoglobin glycosylation may show rapid changes also in MOD, reflecting blood glucose changes, whereas in HS the physiological glycemic excursions are not wide enough to produce rapid HbA1 changes. Since labile and stable HbA1 co-elute in the rapid chromatographic methods, red cell incubation in saline for 6 h at 37 degrees C is recommended as a simple procedure which allows the measurement of the stable fraction alone, i.e. the real index of long-term glycemic control, independent of rapid glycemic fluctuations.

Adult↗
PubMedDate not supplied

Effect of a somatostatin analog on insulin requirement and hormone levels in 6 insulin-dependent juvenile-onset diabetics subjected to artificial pancreas.

This study was performed in order to investigate the effect of a 12-h infusion of the somatostatin selective analog D-Trp8, D-Cys14 Serono, (SRIF-A), on insuli requirement and C-peptide (CP), growth hormone (GH) and glucagon (IRG) levels in 6 insulin-dependent diabetics submitted to 60-h artificial pancreas (Biostator Miles) metabolic control from 2000 of the first day to 0800 of the fourth day. Meals were given at 1200 and 1700 of the second and third day. Before meals and 1-2 h after meals, plasma levels of CP, GH and IRG were measured. The two 12-h periods (midday-midnight) with and without continuous SRIF-A 12-h infusion (40 microgram/h) were considered. The SRIF-A infusion caused a 20% reduction in insulin requirement (p < 0.05) and a slight but significant reduction of GH levels (p < 0.05). CP and IRG were unaffected.

Adult↗
PubMedDate not supplied

Metabolic and hormonal changes during exercise in healthy, diabetic and obese subjects.

The metabolic and hormonal changes during a standard physical exercise were studied in healthy subjects and in insulin-dependent diabetics well matched for body weight, and therefore submitted to a similar work load in a physiologic range, and in obese subjects that, owing to their weight, faced a significant heavier work in the same environmental conditions. Moderate work load did not lead to significant changes in metabolic and hormonal blood parameters (blood glucose, FFA and glycerol; insulin, glucagon, growth hormone and cortisol) in healthy subjects. A similar substrate homeostatis was seen in insulin-dependent diabetics, that however showed marked hormonal alterations. In these subjects, indeed, higher levels of plasma glucagon and GH were reached during work and in the recovery phase. Obese subjects, submitted to a heavier work load, presented a marked increase in blood glucose and glycerol which agrees with high GH and cortisol levels, and a subsequent increment of IRI which corresponds to a normalization of blood glucose and glycerol. Obese subjects, therefore, show a normal sensitivity to work load. Considerations about the work load in everyday life are discussed.

Adult↗
PubMedDate not supplied

To what extent does the artificial pancreas facilitate the surgery of preoperatively not localized insulinomas?

The patient study has been performed in order to evaluate the usefulness of the artificial pancreas in the surgical management of previously not localized insulinomas. In the 4 patients studied, blood glucose was maintained both overnight and during surgery up to a preselected individualized level in order to avoid hypoglycemia. During surgery, only one patient required dextrose infusion. The continuous intrasurgical monitoring of blood glucose in the 4 cases examined showed that: (1) anesthesia induction, surgical incision and viscera mobilization were accompanied by a rise in blood glucose (10.30 mg/dl), reaching the highest levels 30-40 min after the start of the operation; (2) adenoma manipulation was followed by a drop in blood glucose (10.40 mg/dl), reaching the lowest level after 30-40 min; (3) adenoma resection was followed by a rise in blood glucose (25-40 mg/dl), particularly evident after 30-40 min. It is concluded that the artificial pancreas is certainly useful during surgery of insulin-producing tumors, allowing continuous monitoring of glycemia and avoiding dangerous blood glucose excursions: however, when the insulinoma is not identified during surgery, the periods elapsing between the surgical phases and the blood glucose changes observed can be too prolonged to ensure successful conservative serial pancreatectomy in all cases.

Adenoma↗
PubMedDate not supplied

Effect of the somatostatin analog D-Trp8,D-Cys14 on glucose insulin, pancreatic glucagon and growth hormone plasma levels in acromegalics and mild diabetics.

The effect of the somatostatin analog (GHRIH-A) D-Trp8, D-Cys14 on plasma levels of growth hormone, pancreatic glucagon, insulin and glucose was studied in four acromegalic patients and in four maturity-onset mild diabetics. Acromegalics received a bolus iv injection of 25 microgram of GHRIH-A, followed by a continuous infusion of 25 microgram in saline over an hour. Mild diabetics were submitted in two different days to two tests: arginine (30 g in 30 min) +/- GHRIH-A (bolus iv injection of 25 microgram followed by an infusion of 25 microgram/h over 120 min) and arginine + saline. GHRIH-A lead to a significant (2 p less than 0.01) fall in GH basal secretion in acromegalics, and significantly reduced the GH response to arginine in maturity-onset diabetics. The inhibitory effect of insulin secretion was less impressive, but significative in both groups. No significant changes in plasma pancreatic glucagon values were noted. In mild diabetics, GHRIH-A infusion induced a small but significant increase in the blood glucose increment due to arginine. Our data suggest that this somatostatin analog may be potentially useful only when GH suppression is the main therapeutic goal to be reached, as in acromegaly and in severe diabetic retinopathy, but not in metabolic control of mild diabetic patients with a good residual insulin secretion.

Acromegaly↗
PubMedDate not supplied

Rapid changes of glycosylated hemoglobin in diabetics submitted to artificial pancreas control.

This study was performed in order to investigate the possibility of rapid changes in glycosylated hemoglobin levels. Hb A1(a + b + c) values were evaluated by a chromatographic Column Test (Bio-Rad) in 20 insulin-dependent diabetic patients before and after 48 h of glycemic control obtained by an artificial pancreas (Biostator Miles). A significant decrease of glycosylated hemoglobin levels was observed: from 11.21 +/- 2.8% to 9.89 +/- 2.15% of total hemoglobin content (p less than 0.005). Our data bring to the conclusion that rapid changes of glycosylated hemoglobin partially reduce, but do not abolish the clinical significance of Hb A1 determination as a reliable index of long-term glycemic control in diabetic patients.

Adolescent↗
PubMedDate not supplied

Continuous subcutaneous insulin infusion and postprandial exercise in tightly controlled type I (insulin-dependent) diabetic patients.

The aim of this study was to investigate the influence of short-term submaximal postprandial exercise on plasma glucose concentrations in tightly controlled insulin-dependent diabetic patients treated by means of continuous subcutaneous insulin infusion (CSII). Two hours after breakfast, five diabetic patients and five healthy control subjects followed this protocol: 30 min of mild exercise, 30 min rest, 30 min of moderate exercise, 150 min rest. Serial determinations of plasma glucose, free insulin, and growth hormone (GH) were made. Similar control studies without exercise were also performed. In the diabetic patients, analysis of variance and covariance did not reveal any significant difference between the 2-h postbreakfast concentrations of plasma glucose and free insulin and postexercise values. A significant GH increase was observed after the exercise periods. Plasma glucose and insulin concentrations throughout the exercise study were not significantly different from the control study concentrations. Plasma free insulin concentrations of the diabetic patients were higher than the concentrations of healthy subjects. We conclude that CSII-treated, tightly controlled, insulin-dependent diabetic patients performing short-term mild and moderate exercises 2 and 3 h after breakfast do not have a high risk of hypoglycemia in spite of mild hyperinsulinemia.

Adolescent↗