Showing papers by "University of Naples Federico II published in 1992"

Abnormal sympathetic overactivity evoked by insulin in the skeletal muscle of patients with essential hypertension.

Abstract: The reason why hyperinsulinemia is associated with essential hypertension is not known. To test the hypothesis of a pathophysiologic link mediated by the sympathetic nervous system, we measured the changes in forearm norepinephrine release, by using the forearm perfusion technique in conjunction with the infusion of tritiated NE, in patients with essential hypertension and in normal subjects receiving insulin intravenously (1 mU/kg per min) while maintaining euglycemia. Hyperinsulinemia (50-60 microU/ml in the deep forearm vein) evoked a significant increase in forearm NE release in both groups of subjects. However, the response of hypertensives was threefold greater compared to that of normotensives (2.28 +/- 45 ng.liter-1.min-1 in hypertensives and 0.80 +/- 0.27 ng.liter-1 in normals; P less than 0.01). Forearm glucose uptake rose to 5.1 +/- .7 mg.liter-1.min-1 in response to insulin in hypertensives and to 7.9 +/- 1.3 mg.liter-1.min-1 in normotensives (P less than 0.05). To clarify whether insulin action was due to a direct effect on muscle NE metabolism, in another set of experiments insulin was infused locally into the brachial artery to expose only the forearm tissues to the same insulin levels as in the systemic studies. During local hyperinsulinemia, forearm NE release remained virtually unchanged both in hypertensive and in normal subjects. Furthermore, forearm glucose disposal was activated to a similar extent in both groups (5.0 +/- 0.6 and 5.2 +/- 1.1 mg.liter-1.min-1 in hypertensives and in normals, respectively). These data demonstrate that: (a) insulin evokes an abnormal muscle sympathetic overactivity in essential hypertension which is mediated by mechanisms involving the central nervous system; and (b) insulin resistance associated with hypertension is demonstrable in the skeletal muscle tissue only with systemic insulin administration which produces muscle sympathetic overactivity. The data fit the hypothesis that the sympathetic system mediates the pathophysiologic link between hyperinsulinemia and essential hypertension.

Pattern of recurrence of illness after recovery from an episode of major depression: a prospective study.

Abstract: OBJECTIVE This study assessed prospectively the pattern of recurrence of illness after recovery from an episode of major depression. METHOD Seventy-two patients who had recovered from an episode of primary, nonbipolar, nonpsychotic major depression were evaluated bimonthly with the Comprehensive Psychopathological Rating Scale for a period ranging from 20 to 108 months (median = 66 months). New ("prospective") episodes were ascertained with a structured diagnostic interview. The probabilities of remaining well after the index episode and after the first prospective episode were assessed by the life-table method. The severity and duration of prospective episodes and the index episode were compared by linear regression analysis. RESULTS The probability of remaining well after recovery from the index episode was 76% at 6 months, 63% at 1 year, and 25% at 5 years. The risk of recurrence was lower among patients receiving prophylactic treatment with antidepressants and/or lithium and among those with histories of fewer than three previous episodes. The probability of remaining well was significantly lower 2 years after the first prospective episode than 2 years after the index episode. A pattern of increasing severity from the index episode to the first, second, and third prospective episodes was observed and was not affected by treatment. CONCLUSIONS Major depression has a high rate of recurrence, even when bipolar and psychotic cases are excluded. The highest rate is observed during the first months after recovery from an episode. Prophylactic drug treatment reduces the risk of recurrence but apparently does not affect the trend toward increasing severity of subsequent episodes.

Papillary cystic tumor of the pancreas. A clinicopathologic study of 20 cases with cytologic, immunohistochemical, ultrastructural, and flow cytometric observations, and a review of the literature.

Abstract: Twenty cases of papillary cystic tumor of the pancreas were studied (19 female patients, one male patient; median age, 195 years) Most tumors developed in the head or body of the pancreas as well-circumscribed, large masses Gross examination showed that they were solid, cystic, and hemorrhagic Preoperative fine-needle aspiration biopsy anticipated the diagnosis in four cases Histologic examination showed that uniform cells formed solid sheets, and loss of cohesion produced pseudopapillae Hemorrhage, foam cells, cholesterol granulomas, and entrapped nests of pancreatic parenchyma were often found Fifteen cases studied immunohistochemically were reactive for vimentin and alpha-1-antitrypsin, 13 expressed neuron-specific enolase, 2 expressed cytokeratin, and 1 expressed S-100 protein None were reactive for pancreatic hormones, opioid peptides, hormonal receptors, or neuroendocrine markers Electron microscopic examination in five cases showed oval nuclei, moderate amounts of rough endoplasmic reticulum, and many mitochondria; it also showed that annulate lamellae were common No diagnostic secretory granules were found DNA study in nine cases revealed a diploid GO/1 peak in eight and hyperdiploid (diploid index = 11) DNA content in one case Fourteen patients with follow-up were free of disease (mean, 26 years) Papillary cystic tumor of the pancreas possibly originates from primordial pancreatic cells and lacks definite evidence of endocrine or exocrine differentiation

Identification of viable myocardium in patients with chronic coronary artery disease: Comparison of thallium-201 scintigraphy with reinjection and technetium-99m-methoxyisobutyl isonitrile

Abstract: We compared the results of 201Tl reinjection and those of 99mTc-methoxyisobutyl isonitrile (MIBI) in identifying viable myocardium in 20 male patients with angiographically proven coronary artery disease (CAD) and left ventricular dysfunction (ejection fraction 30% +/- 8%). All patients had irreversible defects on standard exercise-redistribution thallium imaging. Thallium was reinjected immediately after the redistribution study, and images were reacquired. The patients also underwent stress and rest 99mTc-MIBI myocardial scintigraphy (2-day protocol). A total of 300 myocardial regions were analyzed, of which 122 (41%) had irreversible thallium defects on redistribution images before reinjection. Of the 122 myocardial regions with irreversible defects on standard stress-redistribution thallium cardiac imaging, 65 (53%) did not change at reinjection and 57 (47%) demonstrated enhanced uptake of thallium after reinjection. Of the same 122 irreversible defects on stress-redistribution thallium, 100 (82%) appeared as fixed defects and 22 (18%) were reversible on 99mTc-MIBI myocardial scintigraphy. These data indicate that 201Tl cardiac imaging with rest reinjection is superior to 99mTc-MIBI myocardial scintigraphy in identifying viable myocardium in patients with chronic CAD, suggesting that regions with severe reduction of 99mTc-MIBI uptake both on stress and rest images may contain viable myocardium.

Hematocrit, blood pressure, and hypertension. The Gubbio Population Study.

Abstract: Baseline data from the Gubbio Population Study in north central Italy were used to investigate the relation of hematocrit to blood pressure and hypertension among 2,809 men and women aged 25-74 years. Independent of gender, age, and other confounders, the hypertensive group had a higher hematocrit than the nonhypertensive group (p less than 0.001). In comparison with the untreated hypertensive group, the hypertensive group being treated with diuretics or with other drugs only had similar mean hematocrit levels despite significantly lower blood pressures. Hematocrit was positively correlated with systolic pressure (r = 0.085, p less than 0.01 and r = 0.264, p less than 0.001 for men and women, respectively) and diastolic pressure (r = 0.214, p less than 0.001 and r = 0.266, p less than 0.001). In both sexes, whether or not the treated hypertensive group was included, age-adjusted prevalence of hypertension and average blood pressure were higher for persons in higher quintiles of hematocrit (p less than 0.001). The association of hematocrit with blood pressure and hypertension was significant and independent of several confounders. The regression coefficient of blood pressure on hematocrit ranged between 0.410 and 0.620 mm Hg per unit of hematocrit for systolic pressure and between 0.371 and 0.581 for diastolic pressure, depending on gender and whether the treated hypertensive group was included in multiple regression analysis. Based on exponentiation of the multiple logistic coefficient, prevalence of hypertension was at least two times greater for persons whose hematocrit levels were higher by 10 units.

Modulation of the induction of nitric oxide synthase by eicosanoids in the murine macrophage cell line J774.

Abstract: The effect of eicosanoids on the induction of nitric oxide synthase in the murine macrophage cell line J774 has been studied. We found that prostaglandin E2 (PGE2) and iloprost (a stable analogue of prostacyclin) both at nanomolar concentrations inhibited the lipopolysaccharide stimulated induction of NO synthase. In contrast PGF2 alpha, U46619, a stable analogue of thromboxane A2, leukotrienes B4 and C4 had no effect. These data demonstrate that the L-arginine: NO pathway in macrophages may be modulated by prostanoids.

Differential immunohistochemical detection of amphiregulin and cripto in human normal colon and colorectal tumors.

Abstract: Thirty-six primary human colorectal tumors, 43 noninvolved colon samples that were adjacent to either carcinomas of adenomas, 22 adenomas, and nine normal colon specimens were immunohistochemically examined for the presence and localization of two epidermal growth factor-related peptides, amphiregulin (AR) and cripto. Within the primary tumors, 18 (50%) showed moderate levels of AR expression. Approximately 60% of the tubular and tubulovillous adenomas were positive for AR expression, whereas only 15% of the adjacent, noninvolved colon mucosa expressed AR. A greater proportion of well-differentiated tumors (71%) were positive for AR expression than were poorly differentiated tumors (18%). All of the nine normal colon specimens were positive. Consequently, AR expression appeared to be associated with both normal and malignant epithelial cells that were more differentiated. The distribution of cripto expression was different. Seventy-nine % of the colon tumors expressed cripto with a frequency of expression that was approximately equivalent between well-differentiated and poorly differentiated tumors. Approximately 86% of the tubulovillous adenomas, but only 43% of the tubular adenomas, were positive for cripto expression. In contrast, whereas AR was expressed in normal colon specimens, none of these tissues expressed cripto, and only 12% of the noninvolved normal colon samples adjacent to tumors or adenomas were positive for cripto. Cripto expression therefore appeared related to neoplasia. These data suggest that AR and cripto may be functioning as potential autocrine and/or paracrine growth factors in the colon and that the differential expression of cripto may serve as a potential tumor marker for colonic carcinogenesis.

ACE inhibition improves insulin-sensitivity in aged insulin-resistant hypertensive patients.

Abstract: We have compared the cardiovascular and metabolic responses to five different ACE inhibitors in 86 patients matched for age, body mass index, blood pressure, fasting plasma glucose and insulin levels in a placebo-controlled, double-blind, crossover, randomised trial. In the active drug treatment phase the patients were randomly assigned to one of five ACE inhibitors: captopril (75 mg/day; n = 16); enalapril (20 mg/day; n = 14); quinapril (20 mg/day; n = 17); ramipril (5 mg/day; n = 21) and lisinopril (20 mg/day; n = 18). Placebo and ACE inhibition phases lasted two weeks and were separated by a one week wash-out period. At the end of each treatment period blood pressure and heart rate were recorded and a fasting sample intravenous glucose tolerance test was conducted. Our study demonstrated that ACE inhibition significantly reduces blood pressure and improves insulin sensitivity. All the ACE inhibitors studied had similar cardiovascular responses but lisinopril displayed the larger metabolic response.

The dual-mode quaternary structure of seminal RNase.

Abstract: Bovine seminal ribonuclease, the only dimeric ribonuclease described thus far, is found to exist in two different quaternary structure forms. In one, the N-terminal segment (residues 1-17) of each subunit is interchanged with the remaining segment of the other subunit, whereas in the second, such interchange does not occur. Functionally, they differ in that the catalytic activity of the form with interchange can be modulated by the substrate, whereas the noninterchange form exhibits no cooperativity. Each form can convert into the other, up to an equilibrium ratio, which is that found for the isolated protein. The results of refolding experiments of unfolded protein chains suggest that also in vivo the form lacking interchange may be produced first and is then partially transformed into the other dimeric form until equilibrium is reached. Although the implications of these findings may not be immediately apparent, they are intriguing and may have an impact on the unusual noncatalytic actions of the protein, such as its selective cytotoxicity toward tumor cells, activated T cells, and differentiated male germ cells.

Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.

Abstract: Transforming growth factor beta (TGF-beta) is the name of a group of closely related polypeptides characterized by a multiplicity of effects, including regulation of extracellular proteolysis and turnover of the extracellular matrix. Its cellular mechanism of action is largely unknown. TGF-beta 1 is a strong and fast inducer of type 1 plasminogen activator inhibitor gene transcription. We have identified a TGF-beta 1-responsive element in the 5'-flanking region of the human type 1 plasminogen activator inhibitor gene and shown that it is functional both in its natural context and when fused to a heterologous nonresponsive promoter. Footprinting and gel retardation experiments showed that two different nuclear factors, present in extracts from both TGF-beta 1-treated and nontreated cells, bind to adjacent sequences contained in the responsive unit. A palindromic sequence binds a trans-acting factor(s) of the CCAAT-binding transcription factor-nuclear factor I family. A partially overlapping dyad symmetry interacts with a second protein that much evidence indicates to be USF. USF is a transactivator belonging to the basic helix-loop-helix family of transcription factors. Mutations which abolish the binding of either CCAAT-binding transcription factor-nuclear factor I or USF result in reduction of transcriptional activation upon exposure to TGF-beta 1, thus showing that both elements of the unit are necessary for the TGF-beta 1 response. We discuss the possible relationship of these findings to the complexity of the TGF-beta action.

Consensus in distributed soft environments

Abstract: This paper studies the problem of formalizing consensus reaching within a set of decision makers trying to find and agree upon a mutual decision. Decision makers produce their individual rankings, using their own pet decision schemas. Thus consensus reaching relies only on the aggregation of individual decisions rather than on individual decision procedures. The aggregation of the individual rankings is supported by an advising monitor which tries to contract the decision makers into a mutual decision through soft enforcement. Convergence to consensus then depends upon the decision makers' willingness to compromise. We use a topological approach to consensus where we can measure distances between decision makers. Within the approach we can also model the trade-off between a degree of consensus and a strength of majority.

Cerebrospinal fluid cytokines in AIDS dementia complex.

Abstract: We evaluated cerebrospinal fluid (CSF) and serum concentrations of interleukin-1-alpha (IL-1 alpha), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) in 30 patients with AIDS dementia complex (ADC), and in 20 HIV-seronegative subjects with other neurological diseases (OND) CSF TNF alpha, IL-1-alpha and IL-6 were more frequently detectable in ADC patients than in OND subjects These cytokines were also detectable in CSF of ADC patients with minimal symptoms In contrast, the majority of both ADC and OND patients did not contain detectable serum levels of cytokines Our data support the notion of intrathecal synthesis of cytokines in ADC patients and raise the possibility that activated macrophages may play a significant role in the pathogenesis of ADC

Prevalence of hereditary ataxias and spastic paraplegias in Molise, a region of Italy.

Abstract: An epidemiological survey of hereditary ataxias and paraplegias was conducted in Molise, a region of Italy (335, 211 inhabitants on 1 January 1989). Total prevalence was 7.5 x 10−5 inhabitants (95% confidence limits 4.8–11.1). There were 7 patients with Friedreich's disease, 5 with early onset cerebellar ataxia with retained tendon reflexes, 4 with ataxia-telangiectasia, 9 with hereditary spastic paraplegias (2 autosomal dominant and 7 autosomal recessive cases). There was no patient with autosomal dominant cerebellar ataxia.

Plasma GSH/GSSG affects glucose homeostasis in healthy subjects and non-insulin-dependent diabetics.

Abstract: In healthy subjects (n = 10) and non-insulin-dependent (type II) diabetics (n = 10) matched for age [43.1 +/- 2.2 vs. 41 +/- 4.4 yr, P = not significant (NS)], body mass index (25.1 +/- 1.1 vs. 26 +/- 0.8 kg/m2, P = NS), gender ratio [5 males (M)/5 females (F) vs. 5M/5F], and mean arterial blood pressure (105 +/- 7 vs. 106 +/- 9 mmHg, P = NS), we determined the changes in insulin secretion and action after glutathione infusion (15 mg/min) and the relative increase in the plasma reduced (GSH)/oxidized (GSSG) glutathione ratio. The rise in the plasma GSH/GSSG ratio significantly improved total body glucose disposal in healthy subjects and in diabetic patients. In this latter group, GSH infusion potentiated the beta-cell response to glucose slightly. In controls and diabetics, insulin infusion with a simultaneous increase in the plasma GSH/GSSG ratio significantly enhanced nonoxidative glucose disposal without affecting oxidative glucose metabolism. After glutathione infusion, all metabolic and hormonal changes correlated with a significant decline in plasma membrane microviscosity. In conclusion, the plasma GSH/GSSG ratio seems to play a major role in the modulation of glucose homeostasis mainly in diabetics.

Constituents of Eriobotrya japonica. A study of their antiviral properties.

Abstract: The CHCl3 extract of Eriobotrya japonica from an Italian source was shown to contain four new triterpene esters, namely, 23-trans-p-coumaroyltormentic acid [1], 23-cis-p-coumaroyltormentic acid [2], 3-O-trans-caffeoyltormentic acid [3], and 3-O-trans-p-coumaroylrotundic acid [4], in addition to three common ursolic acid derivatives 5, 6, and 7. An investigation of the antiviral properties of compounds 1-7 revealed that only 3 significantly reduced rhinovirus infection. The compounds were ineffective towards human immunodeficiency virus type 1 (HIV-1) and Sindbis virus replication.

Electrogastrography in non-ulcer dyspepsia.

Abstract: Fasting and fed gastric electrical activity was recorded by cutaneous electrodes (electrogastrography) in 14 children with unexplained recurrent symptoms of upper intestinal dysfunction, and in 10 controls. The unexplained symptoms included vomiting, epigastric pain, fullness, and early satiety. Mean (SD) age was 7.0 (3) and 7.5 (2) years, respectively. Gastric emptying time of a solid-liquid meal was also measured by real time ultrasonography in all subjects (patients and controls). In all patients radiography and endoscopy excluded structural and focal abnormalities of the gastrointestinal tract. Gastric emptying time was significantly more prolonged in patients than in controls. It was also found that there were appreciable irregularities of gastric electrical rhythm (tachygastria, bradygastria, flat line pattern, and mixed arrhythmia) in 12 fasting and 10 fed patients, whereas controls showed short and rare episodes of arrhythmia during both fasting and fed recording periods. The percentage distribution of the total electrogastrographic energy power across three frequency bands of electrical activity (low, normal, and high) showed that patients were different from controls both for reduced activity of normal frequency and for increased incidence of high and low abnormal frequencies. It is concluded that gastric electrical abnormalities are found in a high proportion of children with recurrent unexplained upper gastrointestinal symptoms. Electrogastrography can be a valuable tool in the assessment of these patients.

The expression of proliferating cell nuclear antigen in paraffin sections of peripheral, node-negative non-small cell lung cancer.

Abstract: Cell proliferation of 40 peripheral, node-negative non-small cell lung cancers (NSCLC) treated with surgery alone was investigated by immunohistochemical analysis with the monoclonal antibody (MoAb) PC10, which recognizes a proliferating cell nuclear antigen (PCNA) in formalin-fixed and paraffin-embedded material. Results were correlated with DNA ploidy and S-phase fraction (SPF) analyzed by DNA flow cytometric study. Mitotic count (MC) was analyzed by light microscopic study and histopathologic features. PCNA immunoreactivity was seen in all samples and confined to the nuclei of cancer, but not to the surrounding, tumor-negative cells; its frequency ranged from 0-70% (median, 15%), and tumors expressed either a low (0-25%, n = 25) or intermediate (26-75%, n = 15) proliferative activity. There was no relationship between PCNA immunoreactivity and tumor stage or among size, histologic type, and mitotic count (MC). Tumors with intratumoral blood vessel invasion (BVI) showed a significantly higher (P less than 0.005) PCNA immunoreactivity than BVI-negative tumors. PCNA scores were significantly higher (P less than 0.005) in DNA aneuploid (n = 22) than in DNA diploid (n = 18) tumors and correlated significantly with the SPF of DNA aneuploid tumors (r = 0.825, P less than 0.0001), but not with diploid tumors (r = 0.002, P = 0.9). Intermediate proliferating tumors had a significantly higher (P less than 0.01) MC than their counterparts. In univariate analysis, significant predictors of survival were tumor classification (T1 versus T2), tumor size (less than or equal to 2.6 cm versus more than 2.6 cm), BVI (BVI-negative versus BVI-positive), MC (less than or equal to 8 versus more than 8), and PCNA immunoreactivity (low versus intermediate). DNA ploidy and SPF did not influence survival significantly. Only PCNA immunoreactivity retained its independent level of significance (P = 0.02) by multivariate analysis. It was concluded that PCNA immunostaining is a simple and clinically useful method for estimating cell proliferation in formalin-fixed, paraffin-embedded tissue of resected peripheral, node-negative NSCLC.

Superiority of L-propionylcarnitine vs L-carnitine in improving walking capacity in patients with peripheral vascular disease: an acute, intravenous, double-blind, cross-over study.

Abstract: The effects of L-propionylcarnitine on walking capacity were assessed in a group of patients with peripheral vascular disease. In 12 patients, 300 mg of L-propionylcarnitine, given intravenously as a single bolus did not affect walking capacity, while 600 mg increased both initial claudication distance from the placebo value of 179 +/- 114 to 245 +/- 129 m (P less than 0.05), and maximal walking distance from 245 +/- 124 to 349 +/- 155 m (P less than 0.05). Once the efficacious dose of L-propionylcarnitine was assessed, its effect was compared to that of an equimolar dose of L-carnitine (500 mg i.v.) according to a double-blind, double-dummy, cross-over design. In 14 patients, both treatments improved walking capacity; however, the analysis of variance showed that the increase in maximal walking distance with L-propionylcarnitine was greater than that with L-carnitine (P less than 0.05). Finally, in seven additional patients, the effects of L-propionylcarnitine and L-carnitine on the haemodynamics of the affected limb were assessed by an ultrasonic duplex system. Results indicated that both drugs did not affect the blood velocity and the blood flow rate in the ischaemic leg, thus suggesting that the beneficial effect on walking capacity was dependent on a metabolic effect. In conclusion, L-propionylcarnitine improves walking capacity in patients with peripheral vascular disease, probably acting through a metabolic mechanism. On a molar basis, this beneficial effect is greater than that observed with L-carnitine and, thus, the findings of the present study may have clinical relevance in terms of treatment cost and patient compliance.

Endothelium-derived relaxing factor modulates platelet aggregation in an in vivo model of recurrent platelet activation.

Abstract: It has been shown that endothelium-derived relaxing factor (EDRF) may inhibit platelet aggregation in vitro through activation of platelet-soluble guanylate cyclase. To assess whether EDRF may also affect platelet function in vivo, intravascular platelet aggregation was initiated by placing an external constrictor around endothelially injured rabbit carotid arteries. Carotid blood flow velocity was measured continuously by a Doppler flow probe placed proximal to the constrictor. After placement of the constrictor, cyclic flow reductions (CFRs), due to recurrent platelet aggregation, developed at the site of the stenosis. After CFRs were observed for 30 minutes, a solution of authentic nitric oxide (NO, n = 10) was infused into the carotid artery via a small catheter placed proximally to the stenosis. Before infusion of NO, CFR frequency averaged 18.3 +/- 2.9 cycles per hour, and CFR severity (lowest carotid blood flow as percentage of baseline values) was 6 +/- 1%. NO completely inhibited CFRs in all animals, as shown by the normal and constant pattern of carotid blood flow (CFR frequency, 0 cycles per hour, p < 0.001; carotid blood flow, 92 +/- 5%, p = NS versus baseline). These effects were transient; CFRs were restored spontaneously within 10 minutes after cessation of NO infusion. After CFRs returned, S-nitroso-cysteine (S-NO-cys), a proposed form of EDRF, was infused into the carotid artery. S-NO-cys also abolished CFRs in all animals but at a significantly lower dose than NO (0.3 +/- 0.1 versus 12 +/- 4 nmol/min). The role of endogenously released EDRF in modulating in vivo platelet function was then tested in additional experiments. In 10 animals, endogenous release of EDRF was stimulated by infusing acetylcholine into the aortic root during CFRs. Infusion of acetylcholine was also associated with a complete inhibition of CFRs, similar to that observed during exogenous infusion of NO or S-NO-cys. These antithrombotic effects of acetylcholine were completely lost when EDRF synthesis was prevented by administration of the L-arginine analogue NG-monomethyl L-arginine (L-NMMA). Furthermore, in six additional rabbits the basal release of EDRF was blocked by L-NMMA after CFRs had been previously abolished with aspirin or the combination of aspirin and ketanserin, a serotonin S2 receptor antagonist. L-NMMA caused restoration of CFRs in all animals, indicating that even the basal release of EDRF is important in modulating platelet reactivity in vivo. Taken together, the data of the present study demonstrate that endogenous EDRF might importantly contribute to the modulation of platelet function in vivo.

Glutathione Infusion Potentiates Glucose-Induced Insulin Secretion in Aged Patients With Impaired Glucose Tolerance

Abstract: Objective –To evaluate the effect of glutathione infusion on β-cell response to glucose in elderly people with impaired glucose tolerance (IGT). Research Desigh and Methods –Ten patients with normal glucose tol-erance and 10 patients with IGT were matched for age (mean ± SE, 72.1 ± 2.8 vs. 71.0 ± 3.4 yr), body mass index (23.1 ± 1.1 vs. 22 ± 2.1 kg/m 2 ), and sex (6/4 vs. 5/5, men/women) underwent glutathione infusion (10 mg/min) under basal conditions and during 75-g oral glucose tolerance tests and intravenous glucose tolerance tests (0.33 g.kg body wt −1 .3 min −1 ). Patients with IGT were also submitted to euglycemic-hyperinsulemic and hyperglycemic glucose clamps. Results –In subjects with normal glucose tolerance, glutathione infusion failed to affect β-cell response to glucose. In contrast, glutathione significantly potentiated glucose-induced insulin secretion in patients with IGT. Furthermore, in the latter group studied by hyperglycemic clamps, glutathione infusion significantly potentiated the beta-cell response to glucose when plasma glucose levels varied between 10 and 15 mM. This effect disappeared at plasma glucose levels Conclusios –Glutathione infusion enhances insulin secretion in elderly people with IGT.