Biomedical subjects

Gianluigi Vendemiale

Publications and source records attributed to Gianluigi Vendemiale.

11 recordsLinked to original sources

PubMed2007

Mitochondrial function in liver disease.

Oxidative stress is involved in the pathogenesis and progression of different liver diseases, such as alcoholic liver disease and biliary cirrhosis. The increased mitochondrial production of O2(-) at complexes I and III, and consequently of H2O2 and other reactive oxygen species (ROS), triggered by NADH overproduction seems the major cause of mitochondrial and cellular oxidative stress and damage in chronic alcoholism. The mitochondrial oxidative stress renders hepatocytes susceptible to ethanol- or acetaldehyde-induced mitochondrial membrane permeability transition (MMPT) and apoptosis. Nitrosative stress contributes to cell death by peroxynitrite formation. The expression of the death receptor ligand CD95 is also up-regulated by acetaldehyde metabolism. Consequently, a dual mechanism, NADH-driven MMPT and CD95-mediated apoptosis, involving in both cases acetaldehyde metabolism and ROS production, operates in ethanol-induced apoptosis. In the biliary cirrhosis induced by chronic cholestasis, liver mitochondria show increased H2O2 production and GSH depletion and oxidation. Dysfunctional hepatocytes, with a loss in mitochondrial cardiolipin and decreased mitochondrial membrane potential evolve during cholestasis to apoptosis. Ursodeoxycholic acid prevents enlargement of this population as well as mitochondrial oxidative stress. Mitochondrial oxidative stress precedes the initiation and execution of hepatocyte apoptosis in chronic alcoholism and biliary cirrhosis. We suggest that overproduction of mitochondrial NADH is the primary cause for the development of alcoholic and non-alcoholic liver disease by a situation of chronic mitochondrial oxidative stress, which should be considered the second hit that renders hepatocytes susceptible to cell injury and apoptosis.

Animals↗

PubMed2006

Contrast-enhanced ultrasound (CEUS) for the study of peripheral lung lesions: a preliminary study.

The use of contrast-enhanced ultrasound (CEUS) for the study of peripheral lung lesions has never been systematically investigated. We evaluated the CEUS patterns of 98 peripheral lung lesions before performing US-guided fine-needle biopsies (FNB). The examinations were done with an Esaote Technos MPX scanner in the harmonic mode with a mechanical index of 0.04 or less. Contrast enhancement was achieved with a 4.8 mL bolus of SonoVue (Bracco) administered via an antecubital vein. All FNBs performed under CEUS guidance were adequate for pathologic diagnosis. Seventy-eight lesions were malignant: 33 (41.9%) were adenocarcinomas, 29 (36.5%) were squamous-cell carcinomas, 13 (17.6%) were undifferentiated large-cell carcinomas and the remaining three (4.1%) were small-cell carcinomas. All presented intralesional enhancement consistent with tumor neovascularization. In some cases, there were unenhanced areas consistent with zones of necrosis and these areas were avoided during FNB. The other 20 lesions were benign (four lipomas, two fibrous lung tumor, two noncaseous granulomas, six abscesses, one rheumatoid nodule, one histiocytosis X, one chondroid hamartoma, one sclerosing hemangioma, two sarcoid nodules) and none presented intralesional enhancement. This initial and admittedly limited experience suggests that CEUS may provide diagnostically useful information on peripheral lung lesions and increase the diagnostic yield of transthoracic FNB by reducing the risk of inadequate tissue sampling.

Adenocarcinoma↗

PubMed2005

Melatonin and cortisol serum levels in lung cancer patients at different stages of disease.

BACKGROUND: Numerous interactions exist among the nervous, endocrine, and immune systems, mediated by neurotransmitters, hormones, and cytokines. Melatonin may modulate the integrated functions of a unique neuro-immune-endocrine system. Neoplastic diseases may be linked to progressive loss of integration among these systems. We investigated whether there are differences among healthy elderly people and elderly people suffering from lung cancer at different stages of disease in 24-hour melatonin and cortisol secretory profiles. MATERIAL/METHODS: In seventeen healthy subjects (mean age +/-S.E.: 68.8+/-1.92 years), seventeen patients with stage I and II lung cancer (mean age: 67.2+/-0.80), seventeen patients with stage III and IV lung cancer (mean age: 69.5+/-2.26), melatonin and cortisol serum levels were measured in blood samples collected every four hours for 24 hours. The area under the curve (AUC) and the presence of circadian rhythmicity were evaluated. RESULTS: The circadian rhythm of melatonin was present in all the groups, but serum levels were decreased in the subjects suffering from lung cancer (P<0.05). In these patients, cortisol serum levels were increased (not in a significant way), with a loss of the circadian rhythm of secretion. The melatonin/cortisol ratio was decreased in stage III and IV cancer patients (P<0.05). CONCLUSIONS: The progressive decrease of melatonin secretion and altered cortisol secretion pattern with advancing stage of neoplastic disease may be an expression of a gradual alteration of the integrated function of the neuro-endocrine system in lung cancer patients.

Aged↗

PubMed2005

The reduced tolerance of rat fatty liver to ischemia reperfusion is associated with mitochondrial oxidative injury.

BACKGROUND: Oxidative stress contributes to the pathogenesis of hepatic ischemia-reperfusion injury. This study aimed to determine whether fatty degeneration affects the oxidative damage during warm ischemia reperfusion and whether mitochondria, the major intracellular site of energy synthesis, represent a preferential target of this injury. MATERIALS AND METHODS: Fed rats with control or fatty liver induced by choline deficiency underwent 60' lobar ischemia and reperfusion. Oxidative damage was assessed by measuring in whole liver tissue and in isolated mitochondria the thiobarbituric acid-reactive substances (TBARs), protein carbonyls (PC), and total and oxidized glutathione (GSH and GSSG) concentrations. The mitochondrial F0-F1-ATPase content and the oxidative phosphorylation activity were also determined. Rat survival and ALT release were assessed as parameters of liver injury. RESULTS: In the whole liver tissue, with the exception of TBARs, no differences were observed for GSH, GSSG, and PC between the two groups throughout all of the experiment. In contrast, in isolated mitochondria, fatty infiltration was associated with a mild oxidative imbalance already under basal conditions. The preischemic differences in the mitochondrial TBARs, PC, and GSSG levels were significantly amplified by reperfusion in the presence of steatosis. The enhanced oxidative damage was associated to a reduced F0-F1-ATPase content and oxidative phosphorylation activity in fatty liver mitochondria. Finally, serum ALT levels were significantly greater and survival significantly lower in rats with steatotic liver. CONCLUSIONS: Fatty infiltration exacerbates mitochondrial oxidative injury during warm ischemia reperfusion. The increased oxidative stress can alter mitochondrial functions, including key processes for ATP synthesis, thus, contributing to the reduced tolerance to reperfusion injury.

Animals↗

PubMed2005

Oxygen therapy at low flow causes oxidative stress in chronic obstructive pulmonary disease: Prevention by N-acetyl cysteine.

UNLABELLED: Exposure to high oxygen concentration produces toxicity by free radical release. We aimed to study: whether stable chronic obstructive pulmonary disease (COPD) patients present an unbalance in the blood redox status; the effect of oxygen administration on blood redox balance; the efficacy of N-acetyl-cysteine (NAC) treatment against the oxidative stress-induced by oxygen administration and whether it is dose-related. To this, 45 stable state III COPD patients were recruited and reduced glutathione (GSH) and oxidised glutathione (GSSG) in erythrocytes and thiol proteins (P-SH) and carbonyl proteins (PC) in both erythrocytes and plasma were evaluated. All COPD patients underwent 2 l/m oxygen for 18 h and NAC at 1200 or 1800 mg/day or placebo for 48 h starting with oxygen administration. Blood samples were collected at basal conditions, after 8 and 18 h of oxygen administration and 24 h after oxygen withdrawal. RESULTS: COPD patients present an unstable redox equilibrium mainly due to plasma sulphydryl protein depletion. Oxygen administration oxidize erythrocyte GSH, decrease P-SH and increase PC levels in both plasma and erythrocytes. NAC administration counteract the oxidative stress and at the highest dose completely prevent protein oxidation. In conclusion, stable state III COPD patients present an unstable redox balance; long term low flow oxygen administration induces systemic oxidative stress, which is prevented by NAC treatment.

Acetylcysteine↗

PubMed2005

The cathepsin D gene exon 2 (C224T) polymorphism and sporadic Alzheimer's disease in European populations.

The cathepsin D gene (CTSD) exon 2 (C224T) polymorphism has been associated with an increased risk for sporadic Alzheimer's disease (AD), but with controversial findings. We studied CTSD exon 2 (C224T) and apolipoprotein E (APOE) genotype frequencies in 168 AD patients and 218 age-matched healthy controls from Southern Italy. No statistically significant differences were found in CTSD allele or genotype frequencies between AD patients and controls, and there were no interactions with sex or APOE genotype. Furthermore, comparing our results with the findings from other European populations, the CTSD*T allele frequency showed a statistically significant increasing trend from Northern to Southern regions of Europe in AD patients and controls (z=2.51, p<.01; z=4.02, p<.001, respectively), with a concomitant inverse trend for CTSD*C allele frequency. The regional differences in CTSD allele frequencies could be related to the different patterns of association between this polymorphism and AD in various European studies.

Aged↗

PubMed2005

Brief hypoxia before normoxic reperfusion (postconditioning) protects the heart against ischemia-reperfusion injury by preventing mitochondria peroxyde production and glutathione depletion.

Several recent works have shown that a brief ischemia applied during the onset of reperfusion (postconditioning) is cardioprotective in different animal models and that the early minutes of reperfusion are critical to its cardioprotection. This effect has been related to prevention of oxidative stress, but mechanisms have not been clearly demonstrated. The present study tested the hypothesis that mitochondria play a central role in peroxide production and oxidative stress during reperfusion and are responsible for the protective effect of postconditioning. Isolated perfused rat hearts were subjected to complete global ischemia for 45 min and reperfused for 40 min. Normoxic group was reperfused with a Krebs-Henseleit solution with the preischemic pO2 level (600 mmHg); in the "hypoxic group," normoxic reperfusion was preceded by 3 min with 150 mmHg pO2. Reperfusion was stopped at 3 and 40 min. The rate of hydroperoxide production, GSH, GSSG, and carbonyl protein levels were measured in mitochondria at 3 min and at the end of reperfusion. GSH and GSSG were also measured in tissue. Hemodinamic function was monitored during the experiment. LVEDp increased and LVDp decreased in the normoxic group but not in the hypoxic group. The rate of mitochondrial peroxide production was higher in normoxic than in the hypoxic group 3 min after reperfusion and at its conclusion. Accordingly, GSH was oxidized in normoxic but not in hypoxic hearts. Mitochondria carbonyl proteins were significantly higher in normoxic than in the hypoxic group at the end of reperfusion. In this model, 1) hypoxic reperfusion at the onset of reperfusion reduces myocardial injury; 2) the major rate of mitochondrial peroxide production is 3 min after the onset of reperfusion; 3) cardioprotection of postconditioning correlates with reduced mitochondria peroxide production and prevention of GSH oxidation.

Animals↗

PubMed2004

Ursodeoxycholic acid protects against secondary biliary cirrhosis in rats by preventing mitochondrial oxidative stress.

Ursodeoxycholic acid (UDCA) improves clinical and biochemical indices in primary biliary cirrhosis and prolongs survival free of liver transplantation. Recently, it was suggested that the cytoprotective mechanisms of UDCA may be mediated by protection against oxidative stress, which is involved in the development of cirrhosis induced by chronic cholestasis. The aims of the current study were 1) to identify the mechanisms involved in glutathione depletion, oxidative stress, and mitochondrial impairment during biliary cirrhosis induced by chronic cholestasis in rats; and 2) to determine the mechanisms associated with the protective effects of UDCA against secondary biliary cirrhosis. The findings of the current study indicate that UDCA partially prevents hepatic and mitochondrial glutathione depletion and oxidation resulting from chronic cholestasis. Impairment of biliary excretion was accompanied by decreased steady-state hepatic levels of gamma-glutamyl cysteine synthetase and gamma-cystathionase messenger RNAs. UDCA treatment led to up-regulation of gamma-glutamyl cysteine synthetase in animals with secondary biliary cirrhosis and prevented the marked increases in mitochondrial peroxide production and hydroxynonenal-protein adduct production that are observed during chronic cholestasis. A population of damaged and primarily apoptotic hepatocytes characterized by dramatic decreases in mitochondrial cardiolipin levels and membrane potential as well as phosphatidylserine exposure evolves in secondary biliary cirrhosis. UDCA treatment prevents the growth of this population along with the decreases in mitochondrial cardiolipin levels and membrane potential that are induced by chronic cholestasis. In conclusion, UDCA treatment enhances the antioxidant defense mediated by glutathione; in doing so, this treatment prevents cardiolipin depletion and cell injury in animals with secondary biliary cirrhosis.

Animals↗

PubMed2004

Seborrhoeic dermatitis in the elderly: inferences on the possible role of disability and loss of self-sufficiency.

The constant increase of life expectancy in countries with high standards of living raises growing concern about many aspects of skin morbidity in the elderly. As regards seborrhoeic dermatitis, literature yields prevalence estimates for elderly people that are consistently higher than those reported from the general population. This prompts speculations on whether factors inherently involved in senescence might have some role in the course of seborrhoeic dermatitis. In a series of 186 subjects, aged > or =65, strength of association of the skin disorder with age, sex, coexisting non-cutaneous conditions, and degree of loss of self-sufficiency in activities of daily living (ADL index) was evaluated by univariate and multivariate analysis. We found that age (OR: 1.14; p<0.001) and, more importantly, dependency in more than one ADL (OR: 30.2; p<0.0001) were independent explanatory variables of seborrhoeic dermatitis. These findings suggest that senescence per se might have some significance in the natural history of this type of eczema.

Activities of Daily Living↗

PubMed2003

Mitochondrial glutathione content determines the rate of liver regeneration after partial hepatectomy in eu- and hypothyroid rats.

BACKGROUND/AIMS: Mitochondrial glutathione has been postulated to affect mitochondrial function and liver regeneration. METHODS: Mitochondrial respiration, total and oxidized glutathione, and liver regeneration were assessed after partial hepatectomy in glutathione-depleted and in hypothyroid rats with/without supplementation of glutathione ester. RESULTS: Mitochondrial, cytosolic and circulating glutathione levels were lower in glutathione-depleted rats. Hepatectomy was followed by significant changes of intra- and extracellular glutathione and of mitochondrial respiration. In glutathione-deficient rats, the recovery of mitochondrial function and the liver regeneration were delayed. Administration of glutathione ester partially corrected the fall of cytosolic and mitochondrial glutathione following hepatectomy, reduced mitochondrial oxidative damage, and accelerated the restoration of mitochondrial respiration and the rate of liver regeneration. In hypothyroid rats, intracellular glutathione homeostasis and mitochondrial respiration were impaired already at baseline; slower regeneration and mitochondrial oxidative alterations were observed after hepatectomy. Glutathione ester ameliorated the regenerative response in hypothyroid rats by providing higher concentrations of cytosolic and mitochondrial glutathione. CONCLUSIONS: Glutathione depletion and hypothyroidism affect the mitochondrial function during liver regeneration. Liver regenerates more slowly in glutathione-depleted and in hypothyroid rats. The earlier restoration of mitochondrial function and the higher rate of proliferation in glutathione ester treated rats suggest that the maintenance of intracellular glutathione facilitates liver regeneration.

Animals↗

PubMed2002

Hepatic oxidative alterations in patients with extra-hepatic cholestasis. Effect of surgical drainage.

BACKGROUND/AIMS: The mechanisms of liver injury in conditions of biliary obstruction are poorly understood. Hepatic oxidative injury has been observed in experimental models of cholestasis. Little is known in humans. This study aimed to gain more insights into the hepatic redox status in human cholestasis. METHODS: Liver concentrations of total glutathione, protein sulfhydryls and malondialdehyde (end-product of lipid peroxidation) were measured in hepatic specimens of 12 patients with obstructive jaundice before and after the application of an external biliary drainage and in six control subjects. RESULTS: Compared to control subjects, biliary obstructed patients showed significantly (P < 0.001) lower concentrations of hepatic glutathione and protein sulfhydryls, and higher (P < 0.001) levels of malondialdehyde, in the presence of comparable protein concentrations. Two-weeks after the application of external biliary drainage, cholestatic indices were significantly improved and the observed changes in glutathione, protein sulfhydryls and malondialdehyde levels, significantly decreased. CONCLUSIONS: This study shows that cholestasis is associated with a decreased protein and non-protein sulfhydryl content in the liver and with an increased lipid peroxidation. These alterations reversed almost completely after biliary drainage, indicating the cholestasis itself as the determining factor for the redox status impairment observed in the liver of patients with extra-hepatic biliary obstruction.

Adult↗