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Biomedical subjects

L Misso

Publications and source records attributed to L Misso.

15 recordsLinked to original sources

Tolrestat in the primary prevention of diabetic neuropathy.

OBJECTIVE: To compare the effects of tolrestat and placebo in patients with subclinical diabetic neuropathy. RESEARCH DESIGN AND METHODS: Non-insulin-dependent diabetes mellitus (NIDDM) patients with early involvement of the autonomic nervous system were identified by only one pathological (outside the 99% confidence interval of the normal population) squatting test (vagal or sympathetic). Fifty-seven patients entered a randomized, placebo-controlled, double-blind, parallel 52-week study of tolrestat at a dose of 200 mg/day. Cardiovascular reflex tests (squatting vagal and sympathetic tests, pressure gain, deep breathing, lying-to-standing, Valsalva maneuver, and orthostatic hypertension), vibration thresholds, tendon reflexes, and muscle strength were assessed throughout the study. RESULTS: At 12 months, nerve function significantly improved in patients receiving tolrestat and deteriorated in patients taking placebo. At baseline, the squatting vagal test was normal in 16 patients in the tolrestat group and in 15 patients in the placebo group. At 12 months, 25 patients taking tolrestat had a normalized squatting test, but only 6 patients taking placebo did (P = 0.02). Vibration perception threshold improved by a value of 6 +/- 3 V in the tolrestat group (P < 0.001) and deteriorated by a value of 3 +/- 1.8 V (P < 0.001) in the placebo group. CONCLUSIONS: Tolrestat may be useful in the primary prevention of diabetic neuropathy.

Administration, Oral

[Effects of low O2 tension on platelet aggregation].

Several studies in animals suggest a link between haemocoagulative patterns and blood gas changes. Furthermore platelet functions seem to be affected by O2 concentrations. In the present study we have evaluated "in vitro" the effect of low PO2 concentrations on platelet aggregation in man. In 15 normal subjects (mean age 32 +/- 5) platelet aggregation ADP (end conc. 1,25 microM) and collagen induced 2 micrograms/Ml) was determined before and after exposition to low PO2 concentrations (O2 conc. 5,04%). The results show that low PO2 concentrations determine a significant increase (P less than 0,001) of platelet aggregation as compared to controls. Although the mechanism of the direct influence of PO2 concentrations upon human platelet is unclear, this finding suggest new therapeutic approaches in chronic lung obstructive diseases.

Adenosine Diphosphate

Rapid decrease of platelet aggregation (ADP--and collagen--induced) and of platelet circulating aggregates by the artificial pancreas in insulin-dependent diabetics.

The aim of the present study was to evaluate the role of the strict metabolic control achieved with the aid of an artificial pancreas (Biostator, Miles) on platelet functions in insulin-dependent diabetics (n = 20). Platelet aggregation responses to both ADP and collagen, as well as circulating platelet aggregates according to Wu and Hoak, were determined before and after 24 hours of complete metabolic control; as control group, 18 insulin-dependent diabetics were only monitored without attempts to normalize their blood glucose behaviour. A significant decrease in ADP induced aggregation (p less than 0.01) and circulating platelet aggregates (p less than 0.001) was observed in diabetics during the period of strict metabolic control. No changes were observed in the control group. The present data suggest that the increased platelet activity in diabetes is a consequence of the metabolic derangement of the disease.

Adenosine Diphosphate

[Changes in mean erythrocyte volume and 2,3-diphosphoglycerate in two groups of diabetic subjects].

Mean corpuscular volume and Red Blood Cell 2-3, diphosphoglycerate in insulin dependent diabetics and in non insulin dependent diabetics were evaluated. Only in insulin dependent diabetics an increased mean corpuscular volume was found while in non insulin dependent diabetics red blood cell 2-3, DPG level appears to be reduced. These findings were not correlated with the metabolic parameters neither they seemed to be dependent upon sex, age or vascular disease. The Authors suggest that the increase of mean corpuscular volume might be indicative of a tendency to macromegaloblastosis in insulin dependent diabetics; with regard to RBC 2-3, DPG level it seems to be extremely variable in dependence on oxygen request at the tissue level.

2,3-Diphosphoglycerate

Further studies on the significance of circulating platelet aggregates induced by somatostatin in man.

The aim of the present study was to further evaluate the significance of circulating platelet aggregates induced by somatostatin in insulin-dependent diabetic subjects. Eight insulin-dependent diabetics and eight normals were infused with somatostatin at increasing doses (250, 500, and 750 microgram/h), each dose for 30 min. In diabetics, somatostatin induced the appearance in blood of platelet aggregates in a dose-dependent fashion, the highest level being observed with the highest dose (750 microgram/h), p less than 0.005). In normals, circulating platelet aggregates were detected only with the infusion of the highest rate of somatostatin (p less than 0.025). This effect of somatostatin was reversible, since it tended to disappear 30 min after the infusion was stopped. In six additional insulin-dependent diabetics, a previous infusion of phentolamine (0.5 mg/min) completely prevented the appearance of platelet aggregates by somatostatin. No significant variation of the aggregation response to both ADP and collagen and the platelet count was seen in both experiments. Somatostatin, as expected, reduced the basal concentration of plasma glucose, glucagon, and C-peptide in both diabetics and normals. On the basis of these results, we suggest that somatostatin has some proaggregating capacity in vivo, probably by interacting with adrenergic mechanisms.

Adolescent

Impaired insulin secretion in human diabetes mellitus. II. A possible role for prostaglandins.

Human diabetes mellitus is characterized by impaired insulin response to intravenous glucose. In search of possible endogenous factors which impair insulin release, we have investigated the effect of lysine acetylsalicylate (LAS), an inhibitor of endogenous prostaglandin (PGs) synthesis, upon insulin responses to glucose and arginine in subjects with type II (adult-on-set) diabetes mellitus. Acute insulin response to glucose (20 g) was significantly increased by LAS (response before LAS=26 +/- 10%; during LAS=77+15%, mean+/-SEM, mean change 3-10 min insulin, % basal, n=8, p 0.01), as well as second phase insulin secretion (before LAS=1437+/-316%; during LAS=3960+/-550%, change 10-60 min, uU/ml-min, % basal, p less than 0.01). This effect was associated with an increase in glucose disappearance rates (p less than 0.01). Acute insulin response to arginine (5 g iv) was also increased by LAS infusion. These results suggest that endogenous PGs may be one of the factors which impair insulin secretion in human diabetes.

Adult

[Thromboelastographic patterns in patients suffering from chronic obstructive lung disease after hyperventilation].

In an our previous study we studied the influence of O2 therapy administration on the thromboelastographic pattern of patients suffering from chronic obstructive lung disease. We showed that basal hypocoagulability of our patients became normal after O2 administration. In this study we refer the thromboelastographic pattern observed in patients suffering from the same disease before and after hyperventilation. We don't find any changes about total coagulability either in patients or in healthy subjects after hyperventilation. Therefore we suggest that the absence of any changes is due to PCO2 and pH variations that occur at the same time of PO2 modification during hyperventilation; PCO2 and pH variations may influence the haemoglobin oxygen affinity and annul the effect of the increase PO2 on the tissue oxygenation. We suppose that the increase of patients suffering from chronic obstructive lung disease, is due to decreased fibrinolysis or to increased production of prostacycline induced by hyperventilation.

Adult

Circulating platelet aggregates induced by somatostatin in insulin-dependent diabetic subjects.

The present study was undertaken to reevaluate the influence of somatostatin on platelet function in insulin-dependent diabetics and in normal subjects. In in vivo studies, nine insulin-requiring diabetics were infused with cyclic somatostatin (250 microgram/hour) for 120 minutes or with saline, in randomized order. This dose of somatostatin, sufficient to depress the basal concentrations of plasma glucose, glucagon and C-peptide, resulted in no significant change of platelet aggregation response to either ADP or collagen. By contrast, a progressive and significant reduction of platelet aggregation response to ADP was found during saline infusion. A similar pattern of response was seen in normal subjects. In all diabetics, but not in normals, somatostatin induced the appearance of circulating platelet aggregates. In in vitro studies, somatostatin augmented the aggregation response to epinephrine in both normals and diabetics. In conclusion, somatostatin counteracts the decrease of platelet aggregation response to ADP seen in saline studies, induces the appearance of platelet aggregates in diabetics and potentiates the aggregation response to epinephrine (in vitro) in both normals and diabetics. These actions of somatostatin suggest some aggregating capacity of the peptide in man.

Adolescent

Air pollution by gasoline exhaust fumes: effect on platelet function and blood viscosity.

Air pollution induced by automobile exhaust fumes seems to be involved in increased cardiovascular and respiratory morbidity. The effects of inhalation of such pollutant gases on platelet function and blood viscosity have not been sufficiently investigated, even if these parameters seem to be in strict correlation with cardiovascular function. Twelve healthy non-smoking volunteers were exposed for 30 minutes in a closed room to air polluted by automobile fumes. Platelet aggregation, blood viscosity, HbCO levels and P50 STD were determined before and after exposure. Cardiovascular parameters (blood pressure, heart rate and ECG) were also measured. At the end of the test, HbCO levels were significantly increased, but P50 STD was significantly reduced; an impairment of both platelet function and blood viscosity was observed. No significant changes in cardiovascular parameters were recorded. The decreases in platelet aggregation and blood viscosity were not directly correlated with either the increase in carbon monoxide levels or with the reduced P50 STD levels. It can be reasonably concluded that gasoline exhaust fumes could have been responsible for the observed alterations.

Adult