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F Cardellach

Publications and source records attributed to F Cardellach.

At least 19 recordsLinked to original sources
PubMed2004

Reversible inhibition of mitochondrial complex IV activity in PBMC following acute smoking.

Smoking causes a decrease of mitochondrial complex IV activity in chronic smokers. However, it is not known if this toxic effect is due to the acute effect of cigarette smoke itself or is a secondary phenomenon related to other smoking factors. The study assessed mitochondrial respiratory chain function in peripheral blood mononuclear cells of 15 healthy nonsmoker individuals before smoking (t0), immediately after smoking five cigarettes in 45 min (t1) and 24 h later (t2). Blood carboxyhaemoglobin (COHb) and carbon monoxide concentrations in exhaled air (COEA) were determined to ascertain smoke inhalation status. After acute smoking, COHb increased from 0.5 +/- 0.3% to 3.3 +/- 1.5%, and COEA from 2.9 +/- 2.5 to 26.1 +/- 9.9 ppm. Complex II and III enzyme activities did not change along the study. Complex IV activity showed a 23% inhibition at t1 but returned to initial (to) levels at t2. A decay in oxygen consumption was observed after the correction for mitochondrial content. Lipid peroxidation of cell membranes remained unchanged. Short-time smoking causes an acute and reversible mitochondrial complex IV inhibition in human mononuclear cells. These results suggest that smoke itself is one of the causes for the decrease of complex IV activity observed in chronic smokers.

Adult↗
PubMed2003

A high carbohydrate diet does not induce hyperglycaemia in a mitochondrial glycerol-3-phosphate dehydrogenase-deficient mouse.

AIMS/HYPOTHESIS: The electrons of the glycolysis-derived reduced form of NADH are transferred to mitochondria through the NADH shuttle system. There are two NADH shuttles: the glycerol phosphate and malate-aspartate shuttle. Mice with a targeted disruption of mitochondrial glycerol-3-phosphate dehydrogenase, a rate-limiting enzyme of the glycerol phosphate shuttle, are not diabetic and have normal islet glucose-induced secretion. In this study, we analyzed if environmental factors, such as a high carbohydrate diet could contribute to the development of Type 2 diabetes mellitus in mice with a specific defective genetic background. METHODS: The mice were fed with a high carbohydrate diet for 1 and 6 months, and several biochemical parameters were analysed. The mitochondrial respiratory activity was assayed by polarography; and the islet function was studied by islet perifusion and pancreas perfusion. RESULTS: The high carbohydrate diet induced hyperglycaemia, hyperinsulinaemia, and islet hyperplasia in the wild-type and heterozygote mice. Activity of the respiratory chain complex I also increased in these mice. In contrast, these effects were not observed in the null mice fed with the diet; in addition, these null mice had an increased insulin sensitivity compared to wild-type mice. CONCLUSION/INTERPRETATION: The phenotype of the mice with an impairment of NADH shuttles does not worsen when fed a high carbohydrate diet; moreover, the diet does not compromise islet function.

Animals↗
PubMed2003

Cholinesterase inhibitor rivastigmine enhance the mitochondrial electron transport chain in lymphocytes of patients with Alzheimer's disease.

Electron transport chain (ETC) dysfunction has been claimed to contribute to the expression of neurodegenerative disorders. We have investigated the effects of the treatment with rivastigmine, a commonly used cholinesterase inhibitor, on lymphocyte mitochondria of patients with Alzheimer's disease (AD). Increased enzymatic activities of diverse complexes and oxidative capacity of the ETC were found. Enhanced mitochondrial ETC function may contribute to the beneficial effects of rivastigmine on clinical manifestations of AD.

Aged↗
PubMed2001

Mitochondrial involvement in antiretroviral therapy-related lipodystrophy.

OBJECTIVES: The management of HIV infection has greatly improved during recent years essentially because of the appearance of new antiretroviral drugs. Highly active antiretroviral therapy (HAART) has achieved important reductions of viraemia and significant recoveries of CD4(+) cell counts in HIV-infected patients. Nonetheless, cases of HIV-infected individuals experiencing lipodystrophy (LD) are being increasingly reported. The purpose of this work was to analyse whether the presence of mitochondrial abnormalities is a frequent feature in LD, since we previously detected mitochondrial abnormalities in an HIV-patient. The second main objective was to study whether LD could be associated with a specific drug. DESIGN: Seven HIV patients presenting LD and five HIV non-LD controls participated in the study. LD patients met the following criteria: (1) LD was their only clinical abnormality, (2) LD was clinically relevant, (3) compliance with antiretroviral treatment was higher than 90% and (4) patients did not have personal or familial history suggestive of mitochondrial disease or neuromuscular disorder. METHODS: Histological stainings, histo-enzymatic reactions, enzymatic and respiratory activities of mitochondrial respiratory chain complexes, and mitochondrial DNA (mtDNA) depletion and rearrangements were examined on muscle mitochondria. RESULTS: Structural muscle abnormalities, mitochondrial respiratory chain dysfunction or mtDNA deletions were detected in all HIV lipodystrophic patients. CONCLUSIONS: The mitochondrial abnormalities found suggest that mitochondrial dysfunction could play a role in the development of antiretroviral therapy-related lipodystrophy.

Adult↗
PubMed2001

Small-vessel vasculitis surrounding a spared temporal artery: clinical and pathological findings in a series of twenty-eight patients.

OBJECTIVE: Occasionally, a temporal artery biopsy reveals small-vessel vasculitis (SVV) surrounding a spared temporal artery, the significance of which is unclear. We analyzed the final diagnosis in a series of patients with this condition and tried to identify histopathologic features with potential usefulness in predicting the ultimate diagnosis. METHODS: We performed a clinical and histopathologic review of 28 patients in whom SVV surrounding a spared temporal artery was the first histologic finding that led to the diagnosis of vasculitis. For comparison purposes, we analyzed the pattern of small vessel involvement in 30 patients with biopsy-proven giant cell arteritis (GCA). RESULTS: GCA was considered the most likely diagnosis in 12 patients, based on the absence of clinical evidence of additional organ involvement and normal findings on muscle biopsy and electrophysiologic study. Three patients had systemic necrotizing vasculitis (SNV), based on the demonstration of typical lesions on subsequent muscle, nerve, or kidney biopsy. After extensive evaluation, 4 patients remained unclassifiable. Nine patients were incompletely studied. Fibrinoid necrosis was significantly more frequent in patients with SNV (P = 0.0022), whereas involvement of vasa vasorum was more frequent in patients classified as having GCA (P = 0.022). No differences in the pattern of small vessel involvement were found in patients with SVV surrounding a spared temporal artery who were classified as having GCA compared with patients with biopsy-proven GCA. Granulocytes were observed at similar frequency in all conditions. CONCLUSION: SVV may be the only abnormal feature in a temporal artery biopsy and the only histologic evidence of vasculitis. The diagnosis of GCA can be reasonably established in most of these patients when there is no apparent evidence of additional organ involvement. However, when fibrinoid necrosis is observed or the temporal artery vasa vasorum are not involved, SNV must be extensively excluded.

Adult↗
PubMed2000

Aging is associated with increased lipid peroxidation in human hearts, but not with mitochondrial respiratory chain enzyme defects.

BACKGROUND: Aging is associated with increased oxidative damage at multiple cellular and tissular levels. A decrease in mitochondrial function has repeatedly been advocated as a primary key event, especially on the basis of analysis of skeletal muscle mitochondria. However, some doubts on this issue have arisen when confounding variables (such as physical activity or smoking habit) have been taken into account in the analysis of mitochondrial respiratory chain (MRC) enzyme activities or when additional analytical parameters such as enzyme ratios have been considered. OBJECTIVE: To determine whether oxidative damage and enzyme activities of the MRC are influenced by the aging process in human hearts. PATIENTS AND METHODS: We studied cardiac muscle obtained from 59 organ donors (age: 56+/-12 years, 75% men). Oxidative membrane damage was evaluated through the assessment of lipid peroxidation. Absolute and relative enzyme activities (AEA and REA, respectively) of complex I, II, III and IV of the MRC were spectrophotometrically measured. Stoichiometric relationships among MRC complexes were also assessed through calculating MRC ratios. Linear regression analyses were employed to disclose any potential correlation between mitochondrial dysfunction and aging. RESULTS: We found a progressive, significant increase of heart membrane lipid peroxidation with aging (P<0.05). Conversely, neither AEA nor REA decreased with age (P=n.s. for all complexes). Similarly to observations in other tissues, we found that stoichiometry of the MRC enzymes is maintained within a narrow range in human hearts. When the effects of aging on MRC ratios were explored, we failed again in demonstrating any subtle disarray. CONCLUSION: MRC enzymes remain preserved in heart with aging, and thus they cannot be considered the main cause of the increased oxidative damage associated with aging.

Adolescent↗
PubMed2000

Mitochondrial function in heart muscle from patients with idiopathic dilated cardiomyopathy.

OBJECTIVE: To study the mitochondrial respiratory chain enzyme activities in patients with idiopathic dilated cardiomyopathy (IDC). METHODS: Mitochondrial respiratory chain enzyme activities were assessed spectrophotometrically in left ventricular tissue of 17 patients with IDC undergoing cardiac transplantation, as well as in two groups of controls: a group of six patients suffering from ischemic dilated cardiomyopathy (IC) also undergoing cardiac transplantation, and a group of 17 organ donors considered normal from a cardiac point of view. Cytochrome b gene from three IDC patients whose complex III activity was particularly low and from three controls was also sequenced. RESULTS: We found that complex III enzymatic activity was lower not only in IDC but also in IC patients when compared with normal controls. When analysing cytochrome b gene we only found neutral polymorphisms previously described. CONCLUSIONS: In view of such results, we believe that the decrease of respiratory chain complex III activity found in some cases of IDC is a secondary phenomenon, and not due to a primary mitochondrial disease.

Adult↗
PubMed2000

Heart mitochondrial respiratory chain complexes are functionally unaffected in heavy ethanol drinkers without cardiomyopathy.

BACKGROUND: Harmful effects of chronic ethanol intake on liver mitochondria have been clearly demonstrated; however, mitochondria from skeletal muscle are preserved, and the effect of ethanol on heart mitochondria remains controversial. We assessed individual enzyme activity of mitochondrial respiratory chain (MRC) complexes and membrane oxidative damage of heart mitochondria in active ethanol drinkers before the development of dilated cardiomyopathy. PATIENTS AND METHODS: Heart samples were obtained from otherwise healthy organ donor individuals with a sudden death of traumatic or neurological cause in whom hearts could not be used because of absence of matched receptors or size inadequacy. Detailed history of alcohol intake was achieved from the relatives. Citrate synthase activity was spectrophotometrically assayed, as well as absolute (nmol x min(-1) x mg protein(-1)) and relative (corrected by citrate synthase) activities of complex I, II, III, and IV of the MRC. Oxidative damage of myocardium membranes was assessed measuring the degree of lipid peroxidation by fluorescence using cis-parinaric acid as probe. RESULTS: We included 10 ethanol drinkers (age 53 +/- 13 years, 100% males, mean lifetime intake of 15.6 +/- 7.9 kg ethanol kg body weight(-1)) and 12 controls (age 60 +/- 10 years, 75% males). Mitochondrial content did not differ between the two groups. Absolute enzyme activities for ethanol drinkers and controls were, respectively, 145 +/- 75 and 130 +/- 50 for complex I (p = NS); 399 +/- 193 and 376 +/- 100 for complex II (p = NS); 719 +/- 288 and 714 +/- 308 for complex III (p = NS); and 475 +/- 139 and 570 +/- 160 for complex IV (p = NS). After correcting such activities by citrate synthase activity, we failed again to demonstrate differences between ethanol drinkers and controls. Lipid peroxidation of myocardium membranes was similar in both groups. CONCLUSIONS: Chronic ethanol drinkers without cardiomyopathy exhibit normal MRC activity in the heart and do not show increased oxidative damage in myocardial membranes.

Adult↗
PubMed1999

Oxidative damage on lymphocyte membranes is increased in patients suffering from acute carbon monoxide poisoning.

Increased oxidative damage seems to be a relevant mechanism in the pathophysiology of patients with an acute carbon monoxide (CO) poisoning. We have investigated the degree of membrane oxidative damage through the assessment of lipid peroxidation in circulating lymphocytes from five patients acutely intoxicated by CO. Since mitochondria are a major source of reactive oxygen species and mitochondrial cytochrome c oxidase (COX) has been reported to be inhibited after acute CO poisoning, we have also assessed the lymphocyte COX activity and its relationship with the degree of lipid peroxidation. Data were compared with those from 32 non-smoker healthy controls comparable in terms of age, gender and physical activity. In intoxicated patients, we have found a significant increase of lipid peroxidation compared to control individuals (P < 0.05), as well as a marked COX inhibition (P < 0.001). Both parameters showed a positive, nearly significant correlation (r = 0.81, P = 0.09). We conclude that oxidative damage of lymphocyte membranes is increased after acute CO poisoning, and suggest that such increase could be partially mediated by mitochondrial COX inhibition caused by CO.

Acute Disease↗
PubMed1999

Interferon-alpha may exacerbate cryoblobulinemia-related ischemic manifestations: an adverse effect potentially related to its anti-angiogenic activity.

The discovery of the strong association between hepatitis C virus (HCV) infection and the development of mixed cryoglobulinemia has motivated active testing of antiviral-directed alternative therapies. Several trials have demonstrated that classic cryoglobulinemia-associated manifestations improve with interferon-alpha (IFNalpha) treatment. Herein we report on 3 HCV-infected patients with severe cryoglobulinemia-related ischemic manifestations who were closely followed up during IFNalpha therapy. Clinical evaluations with special attention to ischemic lesions, liver function tests, and cryocrit determinations were serially performed. In addition to prednisone and immunosuppressive agents, the patients received IFNalpha at 3 x 10(6) units, 3 times per week for 2 months, 3 months, and 4 months, respectively. In all 3 patients, systemic features improved, liver function results returned to normal, and cryocrit values decreased. However, ischemic lesions became less vascularized and ischemia progressed, leading to transmetatarsal and subcondylar amputation, respectively, in 2 of the patients and fingertip necrosis and ulcer enlargement in the third. Skin biopsies performed before IFNalpha therapy and after 2 months of IFNalpha therapy in the third patient showed a significant decrease in subepidermal microvessels. When IFNalpha was discontinued, the lesions finally healed. Cryoglobulinemia-related ischemic lesions may worsen during IFNalpha treatment, presumably through a decrease in inflammation-induced angiogenesis. The anti-angiogenic activity of IFNalpha may delay the appropriate healing of ischemic lesions.

Cryoglobulinemia↗
PubMed1999

Effects of general anaesthetic procedures on mitochondrial function of human skeletal muscle.

BACKGROUND: General anaesthetics inhibit mitochondrial function in animal models. However, very few studies have been performed in humans, and the results have not been conclusive. METHODS: We prospectively studied the oxygen consumption and the individual enzyme activity of each complex of the mitochondrial respiratory chain of skeletal muscle mitochondria in 54 healthy individuals who underwent general anaesthesia for orthopaedic surgery. The control group (n = 54) was made up of individuals submitted to the same orthopaedic procedure under regional anaesthesia (n = 31), and patients who underwent muscle biopsies for diagnostic purposes by local anaesthesia (n = 23). RESULTS: We found a significant decrease in the oxidation of glutamate (-36%), succinate (-25%) and ascorbate (-29%) in the general anaesthetic group compared with the controls (P < 0.001 for all substrates). The level of such inhibition was similar for volatile anaesthetics with strong (halothane) or weak (isoflurane) negative inotropic effect. By contrast, the enzymatic activity of all individual complexes and the coupling of oxidative phosphorylation did not differ between the two groups. CONCLUSION: We conclude that during general anaesthetic procedures there is an extensive inhibition of substrate oxidation in human muscle mitochondria, and that it is not caused by a direct effect on complexes of the mitochondrial respiratory chain or through uncoupling oxidative phosphorylation.

Anesthesia, Conduction↗
PubMed1999

Absence of mitochondrial dysfunction in polymyalgia rheumatica. Evidence based on a simultaneous molecular and biochemical approach.

OBJECTIVE: To investigate the molecular and biochemical profile of skeletal muscle mitochondria of patients with isolated polymyalgia rheumatica (PMR). PATIENTS AND METHODS: We included patients with a recent diagnosis of PMR and as control healthy individuals submitted to orthopedic surgery. Skeletal muscle was obtained from quadriceps, thus was mitochondria immediately isolated. Long polymerase chain reaction and Southern blot transference were performed to detect deleted mtDNA molecules. Mitochondrial oxidative activity using different substrates and individual enzyme activity of respiratory chain complexes were assessed to search for any biochemical dysfunction. RESULTS: Fifty-one individuals (PMR=25, controls=26) were included. Mean age was 72 (11) years; 45% were females. We found no significant increase of deleted mtDNA molecules in PMR patients compared to controls. Both groups differed neither on oxygen consumption (p=NS for all substrates) nor enzymatic activity (p=NS for all complexes). CONCLUSIONS: Skeletal muscle mitochondria are molecularly and biochemically unaffected in PMR.

Adenosine Triphosphatases↗
PubMed1999

Smoking disturbs mitochondrial respiratory chain function and enhances lipid peroxidation on human circulating lymphocytes.

Mitochondria constitute a source of reactive oxygen species. We tested whether mitochondrial function from human circulating lymphocytes is affected by smoking habit and if this could be associated with an increase in oxidative damage of biological membranes. We prospectively studied 35 smokers and 35 non-smoking healthy individuals matched by age and sex, with a similar physical activity. Individual enzyme activity of complexes II, III and IV of the mitochondrial respiratory chain (MRC) and of glycerol-3-phosphate dehydrogenase activity were measured spectrophotometrically. Intact cell respiration and oxidative rates after addition of pyruvate, succinate and glycerol-3-phosphate were assessed polarographically. Lipid peroxidation of biological membranes was assessed measuring the loss of cis-parinaric acid fluorescence. Results are expressed as means (+/-SD). Smokers showed a significant decrease in complex IV activity compared with non-smokers (112.8 +/- 40.9 versus 146.4 +/- 62.5 nmol/min/mg protein, respectively; 23% of inhibition; P = 0.01), while the rest of the complexes of MRC were unaffected. Conversely, oxidative rate with succinate, but not with the other substrates, was enhanced in smokers compared with non-smokers (16.7 +/- 10.4 versus 11.4 +/- 4.7 nmol oxygen/min/mg protein, respectively; 46% of activation; P = 0. 01). Lipid peroxidation of lymphocyte membranes was increased in smokers with respect to non-smokers (3.49 +/- 1.27 versus 4.39 +/- 1. 76 units of fluorescence/mg protein, respectively; 21% of increase; P = 0.03) and this increase correlated positively with succinate oxidation activation (R = 0.34, P = 0.02) and, to a lesser extent, with complex IV inhibition, although it did not reach statistical significance (R = 0.19, P = 0.18). In smokers, the MRC function of lymphocytes is disturbed and correlates with the degree of oxidative damage of membranes. This mitochondrial dysfunction could contribute to increased endogenous production of reactive oxygen species and could play a role in tobacco carcinogenicity.

Adult↗
PubMed1999

Skeletal muscle mitochondrial function in polymyalgia rheumatica and in giant cell arteritis.

OBJECTIVE: To ascertain whether mitochondrial function is impaired in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). PATIENTS AND METHODS: Thirteen patients suffering from isolated PMR, 19 from GCA (eight with and 11 without PMR) and 25 healthy people submitted to orthopaedic surgery were included. Skeletal muscle was obtained from the quadriceps by open biopsy. Mitochondrial histological abnormalities were assessed on Gomori's trichrome staining and on cytochrome c oxidase and succinic dehydrogenase reactions. Biochemical studies consisted of polarographic measurement of oxidative activity using complex I, II, III and IV substrates, and spectrophotometric determination of individual enzymatic activity of such complexes. RESULTS: We did not find differences among groups either with respect to the percentage of histological or histochemical abnormalities [P = not significant (NS) for all stainings and reactions], oxidative capacity (P = NS for all substrates) or individual enzymatic activities (P = NS for all complexes). CONCLUSION: Skeletal muscle mitochondria remain histologically and functionally unaffected in PMR and in GCA.

Aged↗