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O Beloqui

Publications and source records attributed to O Beloqui.

32 records · Page 2Linked to original sources

Iron uptake from transferrin and asialotransferrin by hepatocytes from chronically alcohol-fed rats.

Chronic alcohol intake is often associated with alterations to iron homeostasis and an increase in the serum levels of carbohydrate-deficient transferrin. As the liver is a major iron storage site and also synthesizes transferrin, the normal serum iron transport protein, the aim of this study was to test the hypothesis that these disturbances in iron homeostasis were caused by altered hepatocyte iron uptake from the abnormal transferrin. To achieve this, we have investigated iron uptake from both transferrin and asialotransferrin by hepatocytes from male Sprague-Dawley rats fed the De Carli and Lieber alcohol diet. Iron uptake from transferrin by hepatocytes from alcoholic rats was less than 60% that of control values, and in the presence of 50 mM ethanol decreased still further to 35% of the uptake by the corresponding control cells. Iron uptake from rat asialotransferrin was reduced in both groups when compared to that observed from normal transferrin; 13% by control cells and 39% by hepatocytes from alcohol-fed rats. Alcohol, however, had no further effect on asialotransferrin uptake by either hepatocytes from alcohol-fed rats, or their pair-fed controls. Transferrin binding to hepatocytes was also influenced by the alcohol diet. Although there was no difference in binding at 37 degrees C, cells from alcohol-fed rats bound 85% of this total at 4 degrees C, compared to 44% by control hepatocytes. Similar values were also obtained for hepatocyte binding of asialotransferrin; alcohol feeding resulted in an increase in binding at 4 degrees C to 73% from 58% with control cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

Effects of endotoxin on iron uptake by the hepatocyte.

Administration of endotoxins is often followed within 12-24 h by marked hypoferremia. Because the hepatocyte is the major site of both iron storage and transferrin synthesis, we have investigated the effects of an Escherichia coli endotoxin (lipopolysaccharide, LPS) on these parameters on isolated hepatocytes from normal Wistar rats (ND), rats previously treated intraperitoneally with 2.5 mg/kg (LD) or 25 mg/kg (HD) LPS, and control rats injected intraperitoneally with sterile saline (CD). No effects were observed on iron uptake from transferrin by ND cells incubated in vitro with up to 350 micrograms LPS/10(7) hepatocytes. There was also no significant difference in iron uptake between CD, HD, and LD hepatocytes 1 h after LPS injection. However, hepatocytes isolated 24 h after LPS administration took up iron significantly faster than controls. The uptake of non-transferrin-bound iron was also increased in HD and LD hepatocytes at 24 h but only in HD cells at 1 h. Transferrin binding was not altered in LPS-treated cells from ND rats but was depressed in cells from LPS-treated rats both at 1 h and at 24 h after injection. Transferrin receptor recycling was significantly increased at 24 h in cells from both LD and HD rats. Transferrin and total protein synthesis were also depressed at 1 h in LPS-treated rats, returning to normal values at 24 h. Direct preincubation of ND cells, however, failed to increase synthesis except at the highest concentrations of LPS. We conclude that LPS has an immediate (although indirect) effect on protein synthesis by the hepatocyte but not on iron uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Prevention of microsomal production of hydroxyl radicals, but not lipid peroxidation, by the glutathione-glutathione peroxidase system.

The glutathione-glutathione peroxidase system is an important defense against oxidative stress. The ability of this system to protect against iron-catalyzed microsomal production of hydroxyl radicals [oxidation of 4-methylmercapto-2-oxo-butyrate (KMBA)] and lipid peroxidation was evaluated. When rat liver cytosol was added to microsomes, strong inhibition against KMBA oxidation was observed. No protection was found when the cytosol was boiled or dialyzed. In the latter case, the addition of 0.5 mM glutathione restored almost complete protection, whereas in the former case protection could be restored by the addition of both glutathione and glutathione peroxidase. Cysteine could not replace glutathione, nor could glutathione S-transferase replace glutathione peroxidase. The glutathione-glutathione peroxidase system was also very effective in decreasing production of hydroxyl radicals stimulated by the addition of menadione or paraquat to microsomes. In the absence of cytosol, the addition of glutathione plus glutathione peroxidase was also effective; however, 5 mM glutathione was necessary to protect against KMBA oxidation. The effective concentration of glutathione required for protection was lowered when glutathione reductase was added to the system, to regenerate reduced glutathione. These results indicate that low concentrations of glutathione in conjunction with glutathione peroxidase plus reductase can be very effective in preventing microsomal formation of hydroxyl radicals catalyzed by iron and other toxic compounds. Microsomal lipid peroxidation was decreased 40% by glutathione alone, and this decrease was potentiated in the presence of glutathione reductase. In contrast to KMBA oxidation, the combination of glutathione plus glutathione peroxidase was not any more effective than glutathione alone in preventing lipid peroxidation. The differences in sensitivities of microsomal lipid peroxidation and KMBA oxidation to glutathione peroxidase suggest that these two processes can be distinguished from each other, and that free H2O2 and hydroxyl radicals are involved in KMBA oxidation, but not lipid peroxidation.

Animals↗

Depression of iron uptake from transferrin by isolated hepatocytes in the presence of ethanol is a pH-dependent consequence of ethanol metabolism.

Incubation of freshly isolated rat hepatocytes with highly purified radiolabeled rat transferrin in weakly buffered medium in the presence of 10 mM ethanol resulted in a marked diminution of iron uptake by these cells, associated with a greater pH depression than in ethanol-free control studies. This effect on iron uptake persisted, even when the cells were preincubated for 90 min with ethanol before the addition of transferrin. Increasing the buffering capacity of the system or the addition of a metabolic inhibitor of alcohol dehydrogenase (4-methylpyrazole) returned iron uptake to control values. Acetaldehyde, acetate, lactate (products of ethanol metabolism), and 3-butanol (an alcohol not metabolized by alcohol dehydrogenase) had no influence on iron uptake. Further investigation of iron uptake over the pH range 6-8.5 revealed a marked dependency of iron uptake on the extracellular pH. Leucine incorporation into cell protein was also found to be pH dependent. It is suggested that, in the light of current understanding of transferrin recycling by other cell types, the disturbances of iron homeostasis observed in alcoholics can be partially accounted for by alterations in their acid-base metabolism.

Acetaldehyde↗

Microsomal interactions between iron, paraquat, and menadione: effect on hydroxyl radical production and alcohol oxidation.

The addition of menadione or paraquat to rat liver microsomes resulted in about a threefold increase in the production of hydroxyl radical (.OH) as reflected by the increased oxidation of 2-keto-4-thiomethylbutyric acid (KMBA) to ethylene. This increase was not sensitive to superoxide dismutase but was blocked by catalase. The increase occurred in the absence of added iron and was not affected by the potent iron chelating agent, desferrioxamine, which suggests the possibility that .OH was produced from an interaction between H2O2 and the paraquat or menadione radical. Menadione and paraquat were especially effective in stimulating the oxidation of KMBA in the presence of certain iron chelates such as ferric-ADP, -ATP, or -EDTA, but not ferric-desferrioxamine, -citrate, or -histidine, or unchelated iron. In fact, ferric-ADP or -ATP only stimulated .OH production in the presence of menadione or paraquat. In the presence of ferric-EDTA, the greater than additive increase of .OH production was sensitive to catalase, but not to superoxide dismutase, suggesting the possibility of reduction of ferric-EDTA by paraquat or menadione radical. The interactions with ferric adenine nucleotides may increase the catalytic effectiveness of menadione or paraquat in producing potent oxidants such as the hydroxyl radical, and thus play a role in the toxicity associated with these agents. Paraquat and menadione had little effect on the overall oxidation of ethanol by microsomes. Microsomal drug metabolism was decreased by menadione or paraquat. As a consequence, the effect of these agents on the microsomal oxidation of ethanol was complex since it appeared that paraquat and menadione stimulated the oxidation of ethanol by a .OH-dependent mechanism, but inhibited the oxidation of ethanol by a cytochrome P-450-dependent oxidation pathway. Experiments with carbon monoxide, ferric-EDTA, and 2-butanol plus catalase tended to verify that microsomal oxidation of alcohols was increased by a .OH-dependent pathway when menadione or paraquat were added to microsomes.

Aminopyrine↗

Iron uptake from transferrin by isolated hepatocytes: effect of ethanol.

Freshly isolated rat hepatocytes incubated with highly purified 59Fe-labelled diferric 125I-rat transferrin for 90 minutes in the presence of 10 mM ethanol took up significantly less 59Fe than did cells incubated without ethanol, while producing a significantly greater reduction of the pH of the incubation medium. Total transferrin binding was equivalent in both groups, but the molecular ratio of iron:transferrin on cell membranes isolated after 90 minutes was markedly reduced in the presence of ethanol, suggesting increased retention of apotransferrin. These data are compatible with the hypothesis that iron uptake from transferrin by hepatocytes is mediated by a pH dependent transferrin receptor mechanism similar to that in reticulocytes.

Animals↗

Percutaneous transgastric cystoduodenostomy in the treatment of a pancreatic pseudocyst: a new approach.

A case of an infected pseudocyst in the head of the pancreas is presented. Due to its small size and fistulization to the duodenum, a drainage catheter was placed through the fistulous tract from a distant transgastric approach. The fistula was balloon dilated to improve its emptying. Sixteen months later the patient remains asymptomatic with no recurrence of the pseudocyst.

Adult↗

[Antiphospholipid syndrome].

Antiphospholipid syndrome is a well-defined clinical and serological entity characterized by arterial and/or venous thrombosis, recurrent abortion and thrombocytopenia. Anticardiolipin antibodies and lupus anticoagulant are autoantibodies directed against negatively charged phospholipids, which represent the serologic criteria for the diagnosis of the antiphospholipid syndrome. In this review the pathogenic mechanisms of anticardiolipin antibodies, their clinical findings and the current therapeutical strategies are discussed.

Abortion, Habitual↗

[McArdle's disease. Apropos of a case].

McArdle's disease (glycogenosis type V) is a metabolic disorder of hydrocarbons, inherited with autosomic recessive pattern. Biochemically is defined by a myophosphorylase deficiency; clinically it is characterized by exercise intolerance, due to the impossibility of providing energetic substrate to the muscle, myalgias and stiffness. We present a case report of a patient with McArdle's disease and we comment the diagnostic procedures and current therapeutic options.

Adult↗

[Idiopathic hemochromatosis. Review of the literature and study of 17 patients].

Idiopathic hemochromatosis is an inherited and primary disease. Its definition requires: a) a family history of abnormalities of iron storage; b) an association with HLA; c) inadequate iron absorption in relation to iron stores in liver and other territories; d) the absence of any other known causes of iron overload. The recent evidence of its high family related frequency and the existence of an effective treatment, demand the understanding of this entity and the strongest medical effort towards the diagnosis in the pre-cirrhotic stages. We present here the results from the study of 17 patients diagnosed of idiopathic hemochromatosis over a seven year period in the University Clinic of Navarra. Our aim is to review this subject and to compare our findings with those described in the current literature.

Adult↗

[Upper digestive hemorrhage in a patient with von Recklinghausen neurofibromatosis].

Neurofibromatosis (Von Recklinghausen's disease) is uninherited as an autosomal dominant trait. It is characterised by the development of tumors in diverse sites, which may be benign or malignant. The case of a 39 year old woman with Von Recklinghausen's disease is discussed. She presented with a 3 year history of episodes of melaena and iron deficient anaemia. Mesenteric angiography demonstrated a hypervascular tumour in the jejunum. It was surgically excised with an anatomopathological diagnosis of neurofibroma.

Adult↗

[Acalculous cholecystitis in Schöenlein-Henoch syndrome. Apropos of a case].

We describe the case of a 51 year-old man affected of relapsing bouts of abdominal pain and hematuria, who began acutely with pain in the right upper quadrant, fever, hematuria, arthralgias and purpura on the lower extremities; ultrasonography revealed the existence of acalculous cholecystitis. The lack of response to intravenous antibiotherapy and the clinical association of cholecystitis to the renal, cutaneous and articular manifestations, oriented to the diagnosis of Schöenlein-Henoch vasculitis; thereafter, the response to steroids was successful and immediate. The etiologic diagnosis of this case of acalculous cholecystitis based on clinical aspects, avoid the surgical therapy and the possible morbidity that this procedure can produce.

Arthralgia↗