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D Girelli

Publications and source records attributed to D Girelli.

At least 55 records · Page 3Linked to original sources
PubMed1996

Influences of lipid and non-lipid nutritional parameters on factor VII coagulant activity in normal subjects: the Nove study.

Community-based studies have suggested that the dietary intake of total fat influences factor VII coagulant activity (FVIIc), a predictor of fatal events from coronary heart disease (CHD). Nevertheless, the question whether the quality of dietary fats, with special reference to fatty acids (FAs), influences FVIIc is unsolved. The authors investigated in 90 healthy volunteers living in Nove, a village near Vicenza (northern Italy), the relationships between FVIIc and the plasma concentration of individual FAs. Several indices of other nutritional factors that have recently received increasing attention as determinants of CHD risk (antioxidant vitamins A and E, oligoelements) were also included in the multivariate analysis. The stepwise multiple linear regression analysis revealed body mass index (BMI), and the concentrations of plasma stearic acid (C18:0) and serum copper as significant independent predictors of a substantial proportion of FVIIc variability (R = 0 center dot 52; R2 = 0 center dot 27; P < 0 center dot 001). This study substantially supports the role of the plasma concentration of stearic acid as an important factor in modulating FVIIc.

Adult↗
PubMed1996

The ancestral hemochromatosis haplotype is associated with a severe phenotype expression in Italian patients.

We evaluate the relation between genotype and phenotype in 47 Italian male patients with homozygous genetic hemochromatosis (GH). Phenotype evaluation was based on the ratio of amount of iron removed (IR) by phlebotomy and age (IR/age). Patients were divided in two classes of phenotype expression: class I included 26 patients with less severe iron overload (IR/age <0.33) and class II included 21 patients with a more marked one (IR/age >0.33). Genetic variability was assessed by haplotype analysis combining alleles at HLA-B, D6S265, HLA-A, and D6S105 loci. A common ancestral haplotype carrying D6S265-1, HLA-A3, and D6S105-8 alleles was present in 13 of 52 (25%) chromosomes in class I and in 24 of 42 (57%) chromosomes in class II (P = .0027). Homozygotes and heterozygotes for the ancestral haplotype had higher iron indices than patients carrying two haplotypes other than the ancestral one. Seven of the eight patients homozygous for the ancestral haplotype were in class II, heterozygotes were equally distributed between the two classes, whereas 14 of 18 carriers of other haplotype combinations were in class I. Our results suggests that the gene defect linked to the ancestral haplotype is the result of a single, severe mutation. The high variability of phenotype expression in heterozygotes for the ancestral haplotype could be accounted for the contribution of the mutation carried by the second haplotype. Combination of different mutations could be responsible for the variable degrees of iron overload found in patients with GH.

Adult↗
PubMed1995

Molecular basis for the recently described hereditary hyperferritinemia-cataract syndrome: a mutation in the iron-responsive element of ferritin L-subunit gene (the "Verona mutation")

Recently, we described a new genetic disorder (the "hereditary hyperferritinemia-cataract syndrome") clinically characterized by the combination of elevated serum ferritin and congenital bilateral nuclear cataract, both cotransmitted as an autosomal dominant trait. In affected subjects, hyperferritinemia (ranging from 950 to 2,259 micrograms/L) is typically not related to iron overload. Differently from subjects with hereditary hemochromatosis, they have normal to low levels of serum iron and percent of transferrin saturation and absence of iron overload in parenchymal organs. When unnecessary phlebotomies are performed, they rapidly develop iron-deficient anemia, with persistently elevated levels of serum ferritin. By RNA-single-strand conformation polymorphism screening of the L-subunit ferritin gene on chromosome 19, we were able to identify in affected subjects a mutation in the 5' untranslated region. This mutation involves the five nucleotides sequence [CAGUG] of the iron-responsive element (IRE), which is critical for the posttranscriptional regulation of ferritin synthesis by means of IRE-binding protein (IRE-BP). Thus, it is very likely to provide the molecular basis for the iron-insensitive upregulation of ferritin synthesis in affected subjects.

Adult↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

Resistance to activated protein C in healthy women taking oral contraceptives.

Resistance to activated protein C (APC) is at present considered the most frequent laboratory abnormality in patients with deep-vein thrombosis. An increased risk for venous thrombosis is associated to the use of oral contraceptives (OC). We studied APC sensitivity in 50 healthy women taking OC and in 50 healthy controls, matched for age, smoking habit, educational and social levels, and the main biochemical routinary parameters. Subjects with a personal or familial history of thrombosis and also with chronic or acute diseases were excluded. Protein C, protein S, antithrombin III and lupus anticoagulant activity (LAC) were also evaluated. Increased fibrinogen and protein C levels, decreased protein S. and shortened PT and APTT were also observed in women taking OC. APC sensitivity ratio (APC-SR) was significantly lower in the OC group than in a control group (2.6 +/- 0.38 v 2.81 +/- 0.35, P < 0.01). Seven of eight women with APC ratio < or = 2 (APC resistant) were OC users: the difference of prevalence was statistically significant (chi-squared test, P < 0.05). Only two out of eight women were found heterozygous for the Leiden factor V mutation. Two APC-resistant women without the Leiden mutation subsequently discontinued OC and both then normalized their APC-SR. We conclude that acquired factors, i.e. oral contraceptives, may play an important role in determining plasma APC resistance.

Adult↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

Cyclosporin in Behçet's disease: results in 16 patients after 24 months of therapy.

The aim of this study was to evaluate the usefulness of cyclosporin in Behçet's disease. Sixteen subjects (10 males and 6 females; mean age 25.2 years) affected by the complete type of Behçet's syndrome received 5 mg/kg/day of cyclosporin for 24 months. A marked improvement of the symptoms was observed after three months of therapy. Within 6 to 12 months of treatment 14 of the 16 patients obtained a complete clinical remission. Biochemical and immunological parameters were controlled periodically to evaluate the clinical response and the possible side-effects. Two patients dropped out of the study because of anaemia and renal dysfunction, which returned to normal when cyclosporin was withdrawn. Our results confirm the efficacy of cyclosporin in the treatment of Behçet's disease.

Adult↗
PubMed1994

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↗
PubMed1994

Selenium status, fatty acids, vitamins A and E, and aging: the Nove Study.

To investigate the relationships between aging and selenium status, vitamins A and E, and plasma and erythrocyte fatty acids, we studied 105 healthy subjects (53 women, 52 men) living in Nove, a village near Vicenza (Veneto Region, northern Italy). The subjects were distributed equally for age and sex into four groups: group 1, 20-39 y; group 2, 40-59 y; group 3, 60-75 y; and group 4, > 75 y. A careful selection of subjects to exclude those with chronic or acute diseases was obtained with the collaboration of the three general practitioners operating in Nove. Aging was associated with a progressive decrease in selenium status and in the ratio of plasma and erythrocyte polyunsaturated to saturated fatty acids (P:S). Stepwise multiple linear analysis revealed age, vitamin A, and n-6 polyunsaturated fatty acids (PUFAs) as useful predictors of a substantial proportion of the selenium variability (R = 0.618, R2 = 0.382; P < 0.001) and age and erythrocyte oleic acid as predictors of erythrocyte glutathione peroxidase variability (R = 0.413, R2 = 0.17; P < 0.001).

Adult↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

Linkage analysis of 6p21 polymorphic markers and the hereditary hemochromatosis: localization of the gene centromeric to HLA-F.

Hereditary Hemochromatosis (HFE) is one of the most common inherited disorders with an estimated frequency of homozygous patients of 0.002-0.0045. The disease is characterized by increased intestinal iron absorption and progressive iron overload. Affected subjects show clinical symptoms of parenchymal organ damage after the third-fourth decade of life and have a 200 fold increased risk of developing hepatocellular carcinoma. Early diagnosis and treatment prevent complications and may normalize life expectancy of patients. The biochemical and genetic defects leading to progressive iron accumulation are still unknown, but the HFE gene is tightly linked to HLA complex on the short arm of chromosome 6. Utilizing HLA serotypes and the study of several polymorphic markers of 6p21, a linkage analysis of the disease locus was performed in a series of Italian hemochromatosis families. The data obtained by linkage analysis and the study of a family with a double recombinant allowed us to better define the HFE gene location with respect to HLA-class I A and F loci.

Chromosome Mapping↗
PubMed1993

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↗