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Biomedical subjects

R Corrocher

Publications and source records attributed to R Corrocher.

At least 91 records · Page 5Linked to original sources

Low selenium status in the elderly influences thyroid hormones.

1. Iodothyronine 5'-deiodinase, which is mainly responsible for peripheral triiodothyronine (T3) production, has recently been demonstrated to be a selenium-containing enzyme. In the elderly, reduced peripheral conversion of thyroxine (T4) to T3 and overt hypothyroidism are frequently observed. 2. We measured serum selenium and erythrocyte glutathione peroxidase (as indices of selenium status), thyroid hormones and thyroid-stimulating hormone in 109 healthy euthyroid subjects (52 women, 57 men), carefully selected to exclude abnormally low thyroid hormone levels induced by acute or chronic diseases or calorie restriction. The subjects were subdivided into three age groups. To avoid conditions of under-nutrition or malnutrition, dietary records were obtained for a sample of 24 subjects, randomly selected and representative of the whole population for age and sex. 3. In order to properly assess the influence of selenium status on iodothyronine 5'-deiodinase type I activity, a double-blind placebo-controlled trial was also carried out on 36 elderly subjects, resident at a privately owned nursing home. 4. In the free-living population, a progressive reduction of the T3/T4 ratio (due to increased T4 levels) and of selenium and erythrocyte glutathione peroxidase activity was observed with advancing age. A highly significant linear correlation between T4, T3/T4 and selenium was observed in the population as a whole (for T4, R = -0.312, P < 0.002; for T3/T4 ratio, R = 0.32, P < 0.01) and in older subjects (for T4, R = -0.40, P < 0.05; for T3/T4 ratio, R = 0.54, P < 0.002). 5. The main result of the double-blind placebo-controlled trial was a significant improvement of selenium indices and a decrease in the T4 level in selenium-treated subjects; serum selenium, erythrocyte glutathione peroxidase activity and thyroid hormones did not change in placebo-treated subjects. 6. We concluded that selenium status influences thyroid hormones in the elderly, mainly modulating T4 levels.

Adult↗

Correlations between the intensity of fMLP-dependent respiratory burst and cellular fatty acid composition in human neutrophils.

The peripheral blood neutrophils were isolated from a group of normal subjects and their fatty acid composition determined by capillary gas-chromatography. The superoxide (O2-) release by the same cell preparation in response to formyl-methionyl-leucyl-phenylalanine was also determined following cytochrome c reduction in a microplate assay. A strong negative correlation was found between C18:2 (linoleic acid) (r = 0.703, P = 0.001) and C:16:0 (palmitic acid) (r = 0.569, P = 0.009) and fMLP-stimulated O2- release, whereas C20:4 (arachidonic acid) correlated positively (r = 0.448, P = 0.048). Other fatty acids, namely C12:0, C14:0, C16:1, C18:1, C18:3, C18:4, C20:0, C20:1, C20:2, C20:5, C22:0, C22:1, C22:6, C24:0 and C26:0, were not correlated with O2-. No correlations were found between fatty acid composition and O2- release from resting cells and from cells stimulated by phorbol-myristate acetate. These results suggest that the fatty acid composition of blood neutrophils may be a critical factor determining the capability of releasing free radicals in response to formylpeptides. Moreover, since a concomitant increase of arachidonic acid and decrease of its precursor linoleic acid has been found in high-responsive neutrophils, the rate of the enzymes of the arachidonic acid biosynthetic pathway (elongases and desaturases) appear to play an important role.

Arachidonic Acid↗

A linkage between hereditary hyperferritinaemia not related to iron overload and autosomal dominant congenital cataract.

The only genetic disorder with elevated serum ferritin levels so far described is hereditary HLA-related haemochromatosis. On the other hand, hereditary cataract is both genotypically as well as phenotypically heterogenous, and no specific locus or any useful marker has been yet identified. We studied two Italian families in whom a combination of elevated serum ferritin not related to iron overload and congenital nuclear cataract is transmitted as an autosomal dominant trait. Affected individuals have normal serum iron and transferrin saturation, but high serum ferritin. Red cell counts are normal and venesection therapy rapidly produces iron-deficiency anaemia. This genetic disorder, which is characterized by hyperferritinaemia, differs from hereditary HLA-related haemochromatosis mostly for the absence of iron overload. A gene responsible for the congenital nuclear cataract likely maps on chromosome 19q close to the ferritin L-subunit gene. Within families with autosomal dominant congenital cataract, serum ferritin might be an early marker of disease.

Adult↗

Red blood cell cation transports in uraemic anaemia: evidence for an increased K/Cl co-transport activity. Effects of dialysis and erythropoietin treatment.

This study examines the role of uraemia and the effect of different dialysis treatments on red cell cation transport. We evaluated the main cation transport systems in erythrocytes of non-dialysed end-stage renal disease (ESRD) subjects, of patients undergoing haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD), as well as the changes induced by human recombinant erythropoietin (r-HuEPO) administration. In uraemic undialysed and dialysed patients, we observed an increase in K/Cl co-transport activity and in shrinkage-induced amiloride-sensitive (HMA-sensitive) Na efflux (Na/H exchange) and a decrease in Na/K pump and Na/K/Cl co-transport activity, while Na/Li exchange was increased only in dialysed patients. In uraemic erythrocytes, we showed for the first time an increased K/Cl co-transport activity, which was cell age independent. Generally, the different method of dialysis (CAPD or HD) did not modify the cation transport abnormalities observed. During the treatment with r-HuEPO, all the systems, with the exception of the Na/K pump and Na/K/Cl co-transport, increased their activities following the increase of circulating young red cells. The changes produced under r-HuEPO administration were transient and cation transports returned to the baseline values within 100 days of treatment, indicating a primary and prominent pathogenetic role of uraemia in modulating the red cell membrane cation transport activities.

Anemia↗

Fatty acids and antioxidant micronutrients in psoriatic arthritis.

OBJECTIVE: Red blood cell (RBC) fatty acid composition and micronutrient status were investigated in patients with psoriatic arthritis (PsA), with special regard to their relationship to clinical variables. METHODS: RBC fatty acid composition, selenium status--serum selenium and RBC glutathione-peroxidase activity (GSH-Px)--plasma copper, plasma and RBC zinc, plasma vitamins A and E, and RBC thiobarbiturate reactive substances (TBARS) after H2O2 exposure as an index of susceptibility to lipoperoxidation were measured in 25 patients with PsA and in 25 sex and age matched controls. RESULTS: A significant increase in C16:0 (p < 0.01) and in total saturated fatty acids (SFA) (p < 0.05), a significant decrease in C18:2 (p < 0.05), C20:4 (p < 0.001) and omega-6 polyunsaturated fatty acids (PUFA) (p < 0.001), a lower level of serum selenium (p < 0.01) and an increased level of plasma copper (p < 0.05) were observed in patients with PsA in comparison with controls. Significant direct correlations were observed between RBC SFA and erythrocyte sedimentation rate (ESR) (r = 0.445), duration of disease (r = 0.403) and morning stiffness (r = 0.434). CONCLUSION: As in other reports for rheumatoid arthritis (RA), our results support the view that an abnormal fatty acid pattern might be a particular metabolic modification involved or associated with the pathogenesis of rheumatic diseases.

Adult↗

Omega-3 polyunsaturated fatty acid supplements and ambulatory blood pressure monitoring parameters in patients with mild essential hypertension.

OBJECTIVE: To evaluate the effects of low doses of omega-3 polyunsaturated fatty acids on ambulatory blood pressure monitoring parameters in a group of mild essential hypertensives. PATIENTS: We studied 24 consecutive essential hypertensive patients from our outpatient clinic with mild hypertension (diastolic blood pressure < or = 105 mmHg), no previous treatment for 4 weeks at least and no other disease. METHODS: After a 3-month run-in period, the patients entered an intervention phase and were given 3 g omega-3 polyunsaturated fatty acids (85% eicosapentaenoic and docosahexaenoic acid concentrate) daily for 4 months; this phase was followed by a 4-month washout period. Ambulatory blood pressure monitoring was performed at the end of each phase; erythrocyte membrane fatty acids were assessed to check compliance. RESULTS: After 4 months of treatment, erythrocyte omega-3 polyunsaturated fatty acids significantly increased but average systolic and diastolic blood pressure and the heart rate did not significantly change; no significant variations were recorded in blood pressure or heart rate variability (assessed as blood pressure and heart rate SD) nor in the diurnal blood pressure rhythm. After washout, a significant decrease was observed in erythrocyte omega-3 polyunsaturated fatty acids but the ambulatory blood pressure monitoring parameters were not substantially modified. CONCLUSIONS: The present data show that low doses of omega-3 polyunsaturated fatty acids as a single treatment are not effective in lowering blood pressure or the heart rate in mild essential hypertensive patients, despite a significant change in fatty acid cell membrane composition. Nor does this treatment seem likely to affect blood pressure variability or the diurnal rhythm.

Blood Pressure↗

Oxidative damage and erythrocyte membrane transport abnormalities in thalassemias.

Oxidative damage induced by free globin chains has been implicated in the pathogenesis of the membrane abnormalities observed in alpha and beta thalassemia. We have evaluated transport of Na+ and K+ in erythrocytes of patients with thalassemias as well as in two experimental models that use normal human red blood cells, one for alpha thalassemia (methylhydrazine treatment, alpha thalassemia like) and one for beta thalassemia (phenylhydrazine treatment, beta thalassemia like). With the exception of the Na-K pump, similar alterations in membrane transport were observed in thalassemia and thalassemia-like erythrocytes. These were: increased K-Cl cotransport, Na-Li countertransport and reduced Na-K-Cl cotransport. The Na-K pump was reduced in thalassemia-like cells, whereas it was increased in severe alpha thalassemia and in beta thalassemia cells. The increased K-Cl cotransport activity could be observed in light and dense fractions of beta-thalassemic cells. K-Cl cotransport in thalassemic and thalassemia-like erythrocytes was partially inhibited by [(dihydro-indenyl) oxy] alkanoic acid and completely abolished by dithiothreitol. Thus, oxidative damage represents an important factor in the increased activity of the K-Cl cotransport observed in thalassemias, and of the K+ loss observed in beta-thalassemia erythrocytes.

Chlorides↗

Decreased activity of scavenger enzymes in human hepatocellular carcinoma, but not in liver metastases.

To investigate the role of oxygen free radicals in hepatocellular carcinoma we assayed tissue scavenger enzymes (superoxide dismutase and selenium-dependent glutathione peroxidase) in liver homogenate, plasma concentrations of vitamins A and E and the serum selenium level from 19 control patients, 23 cases of hepatocellular carcinoma and 18 cases of metastases to liver from different carcinomas. In hepatocellular carcinoma tissue the enzyme activities were all significantly lower than in control liver and in metastases-bearing liver; the enzyme activities of the latter tissues were not different from control liver. In contrast, normal liver adjacent to the hepatocellular carcinoma had decreased activity of superoxide dismutase. Serum selenium concentrations were significantly decreased in patients with hepatocellular carcinoma and those with liver metastases, while vitamin A was significantly decreased only in the former. These findings suggest that hepatocellular carcinoma develops in liver with severe impairment of cellular antioxidant systems, since, in patients with liver metastases from different cancers, despite low selenium concentrations, cellular scavenger enzymes have normal activities.

Adult↗

Factors affecting the thiobarbituric acid test as index of red blood cell susceptibility to lipid peroxidation: a multivariate analysis.

The relationship between formation of thiobarbituric acid reactive substances (TBARS) in red blood cells (RBC) after exposure to H2O2 and factors potentially able to modulate it was investigated by a multivariate analysis in 92 healthy volunteers. The independent covariates considered were: RBC membrane fatty acids and cholesterol, RBC antioxidant enzymes and zinc, plasma vitamins A and E and serum selenium, zinc and copper. The stepwise multiple-linear-regression analysis revealed RBC membrane fatty acids and cholesterol as predictors of a consistent proportion of the RBC-TBARS variability whereas none of the antioxidants entered the equation. The unsaturation index was the most important individual predictor; RBC-TBARS increased with increasing concentrations of total omega-3 polyunsaturated fatty acids, C 20:5 omega-3 and cholesterol, whereas they decreased with increasing concentrations of total monounsaturated fatty acids, saturated fatty acids, C 16:0 and C 18:0. It is suggested that formation of TBARS, at least in currently used conditions, reflects mainly the lipid composition of the tissue under investigation, without giving sufficient information about the status of the antioxidant defences.

Adult↗

Activation of K+/Cl- cotransport in human erythrocytes exposed to oxidative agents.

Activation of K+/Cl- cotransport was studied after exposure of normal human erythrocytes to the oxidative action of acetylphenylhydrazine (APH), menadione sodium bisulfite (MSB), hydrogen peroxide (H2O2) or phenazine metasulfate (PMS). In order to better define the relative contributions of K+/Cl- cotransport on ouabain and bumetanide-resistant (OBR) K+ efflux induced by oxidation, we used (dihydroindenyl)oxyalkanoic acid (DIOA) and carbocyanine as specific inhibitors, respectively, of cotransport system and Ca(2+)-activated K+ channel. APH, MSB and - to much less extent - H2O2 promoted a K+ efflux pathway with features corresponding to those of K+/Cl- cotransport. This pathway showed: (i) kinetics of efflux compatible with a specific cation transport system; (ii) requirement for chloride anion; (iii) resistance to ouabain, bumetanide and carbocyanine inhibition; (iv) stimulation by hypotonic challenge; (v) susceptibility to inhibition by DIOA. Dithiothreitol (DTT) or 2-mercaptoethanol (2-ME) decreased K+/Cl- cotransport activation, suggesting that oxidative mechanisms affected crucial SH groups of the transporter. These data suggest that oxidation represents a factor capable of modulating activation of K+/Cl- cotransport. Its possible contribution in situations with high oxidative risk, such as sickle-cell anaemia or beta thalassemia, is discussed.

Biological Transport↗

alpha-Interferon in the treatment of chronic viral hepatitis: effects on fibrogenesis serum markers.

Forty patients with chronic viral hepatitis or active cirrhosis (33 anti-HCV positive) entered a recombinant human alpha 2A interferon randomized trial. Twenty-one subjects were treated with 6 million units (MU) three times per week for 6 months. Nineteen were not treated. Six months later in 12 patients of the treated group (60% of the evaluable 20) with normalized serum aminotransferases levels (responders), fibrogenesis serum markers (NPIIIP and laminin) were significantly lower than baseline. In the untreated patients and in non-responders NPIIIP and laminin were unchanged. Semi quantitative histological evaluation (allotting scores for inflammation, necrosis and fibrosis) confirmed a significant improvement of necro-inflammation in the responders. These data suggest that alpha-IFN treatment may decrease stimuli for fibrogenesis by reducing liver inflammation and necrosis, thus preventing evolution to cirrhosis.

Adult↗

Low platelet glutathione peroxidase activity and serum selenium concentration in patients with chronic renal failure: relations to dialysis treatments, diet and cardiovascular complications.

1. Selenium status was investigated in patients with chronic renal failure, with special regard to its relations to the dialysis treatments, dietary habits and clinical signs of atherosclerosis. 2. Serum selenium concentration and platelet glutathione peroxidase activity were measured in 45 patients with chronic renal failure subdivided into three groups according to the type of treatment: 15 non-dialysed, 15 on haemodialysis, 15 on continuous ambulatory peritoneal dialysis. A 7-day diet history was carried out in all patients. Seventeen of the patients with chronic renal failure had clinically overt cardiovascular disease. Forty-five age-matched healthy subjects were considered as controls. 3. Both serum selenium concentration and platelet glutathione peroxidase were significantly reduced in all patients with chronic renal failure compared with control subjects; a direct and significant correlation was found between the two parameters. No differences in selenium status were observed among the non-dialysed, haemodialysis and continuous ambulatory peritoneal dialysis groups. No correlation between total calorie or protein intakes and selenium indices were observed. The chronic renal failure patients with cardiovascular complications showed a further significant reduction in both serum selenium concentration and platelet glutathione peroxidase activity as compared with the patients without cardiovascular complications; these two groups were similar with respect to the other well-known cardiovascular risk factors (age, smoking, plasma lipids, hypertension, body mass index). 4. It is concluded that a low selenium concentration is present in chronic renal failure, which is independent of dialysis and is accompanied by biological repercussion in terms of reduced platelet glutathione peroxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Potassium loss and cellular dehydration of stored erythrocytes following incubation in autologous plasma: role of the KCl cotransport system.

We studied the regulation of cell volume and cation content in erythrocytes stored at 4 degrees C under blood bank conditions for various lengths of time and subsequently incubated in autologous plasma at 37 degrees C for 4 or 24 h. Cell swelled during storage at 4 degrees C whereas marked K+ loss and cell shrinkage were observed when erythrocytes were incubated at 37 degrees C in autologous plasma. The cell shrinkage was inhibited only by the K+ Cl- cotransport-specific inhibitor, [(dihydroindenyl)oxy] alkanoic acid, and not by other specific inhibitors of cation transport systems such as ouabain (Na(+)-K+ ATPase pump), bumetanide (Na(+)-K(+)-Cl- cotransport) or carbocyanine (Ca+(+)-activated K+ channel). Acidification and swelling of the erythrocytes are well known to be able to activate the K+ Cl cotransport; such conditions, which were demonstrated to occur during the storage, could lead to activation of the K+ Cl- cotransport in reinfused cells. These data strongly support the evidence that K+ Cl- cotransport plays a role in K+ loss and dehydration of stored erythrocytes, when incubated in autologous plasma.

Adult↗

[Effectiveness of loratadine vs. placebo in the treatment of urticaria-angioedema syndrome in patients with food allergy].

Loratadine is a new, highly selective, non sedating, H 1-receptor antagonist, without central nervous system activity. In a randomized double-blind, crossover study, we evaluated the effects of loratadine and placebo administered once daily in 184 food intolerant patients affected by urticaria-angioedema. The difference between loratadine and placebo treatment was significant in relieving symptoms. Adverse reactions reported in the treatment were mild, in fact somnolence was reported by 3.4%, dry mouth by 2.2% of patients.

Adult↗

Red blood cells and platelet membrane fatty acids in non-dialyzed and dialyzed uremics.

Three groups of patients with chronic renal failure (CRF), 16 non-dialyzed, 16 undergoing haemodialysis (HD), 16 undergoing continuous ambulatory peritoneal dialysis (CAPD), and 48 controls were examined. We analyzed the fatty acid composition in membranes from erythrocytes and platelets and the platelet malondialdehyde (MDA) production as an index of thromboxane metabolism. Marked differences in erythrocytes fatty acid composition were observed between patients with CRF and controls and, particularly, among the three groups of patients with CRF. Patients on CAPD were characterized by an increase in oleic acid, while haemodialyzed had a marked increase in arachidonic acid. Platelet fatty acid composition showed similar differences, suggesting a 'systemic' membrane abnormality. Platelet MDA was increased in haemodialyzed and positively correlated with the platelet arachidonate content.

Adult↗