ALTERAZIONI TISSUTALI INDOTTE DAL 2-ETIL-EXIL-FTALATO IN UN "SISTEMA COLTURALE IN VIVO". POSSIBILI IMPLICAZIONI SULLA TOSSICITA' DEL PLASTIFICANTE NEI PAZIENTI IN TRATTAMENTO DIALITICO

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EFFECTS OF THE RECOMBINANT-HUMAN-ERYTHROPOIETIN (RHUEPO) ADMINISTRATION ON HEMATOLOGIC PARAMETERS, RED-CELL CREATINE AND 2,3-DIPHOSPHOGLYCERATE CONTENTS, IN PATIENTS AFFECTED BY END-STAGE RENAL-DISEASE

Twenty patients with renal failure and severe anemia (hemoglobin range 6.6-8.7 g/dl) on thrice-weekly maintenance hemodialysis were treated with recombinant human erythropoietin (rHuEPO). After three months of intravenous (iv) therapy the hemoglobin increase averaged 2 g/dl, and was steadily maintained even after two months of subcutaneous (sc) therapy. The significant increase of macrocyte counts, determined by an automated red blood cell counter after both steps of therapy, suggested the release of young red cells (large cells) into blood circulation. This assumption may be supported by the significant increase of the red cell creatine contents. 2,3-diphosphoglycerate (2,3-DPG) levels of the erythrocytes did not significantly change after rHuEPO administration

Favorable clinical effects of Iloprost infusion in 4 uremic patients with critical limb ischemia

Four uremic patients with advanced peripheral arterial occlusive disease (PAOD) of lower limbs causing rest pain and ischemic-necrotic lesions were treated with a four-hour intravenous infusion of Iloprost at doses of 0.75- 2.5 ng/kg/min for twenty-eight days. After a week of the therapy all patients experienced disappearance of rest pain and prolonged walking distance. At the end of the trial a diabetic patient showed a complete regression of the necrotic areas of two toes while the other patients still showed ischemic- necrotic foot lesions that were well demarcated. Iloprost therapy can be effective in uremic patients with severe PAOD

Detection of urinary abnormalities in a community from northern Italy based on the World Kidney Day screening program

BACKGROUND: Chronic kidney disease (CKD) is a worldwide health problem, and promotion of the World Kidney Day has improved general population education and awareness of renal illnesses aimed at ameliorating disease prevention. The Kidney Day was also an opportunity for us to investigate risk factors for CKD in an Italian population. PATIENTS AND METHODS: A total of 1,341 subjects from the general population living in the area of Ferrara, a town in the northeast of Italy, aged 50-70 years, were investigated. From each participant age, sex, smoking status, current antihypertensive medications, hypercholesterolemic and diabetic status, body mass index (BMI), waist circumference and blood pressure (BP) were obtained. All subjects underwent dipstick urinalysis for the evaluation of proteinuria, hematuria and leukocyturia. RESULTS: Fifteen percent of patients were diabetics, and 20% were smokers. Mean BMI was 26.9 ± 4.3 kg/m(2), mean systolic BP was 133.7 ± 18.7 mmHg and mean diastolic BP 78.1 ± 9.9 mmHg. A total of 828 participants were not taking any antihypertensive drugs. In 24% of subjects, we found proteinuria, in 18% hematuria and in 16% leukocyturia. Proteinuria was significantly associated with age and diabetes, hematuria was associated with age, female sex and smoking status, and leukocyturia was associated with age and female sex. CONCLUSIONS: Urinary abnormalities are common in general population, and in many cases, various abnormalities overlap. These abnormalities could be associated with cardiovascular risk factors. We believe that our initiative, based on the experience of the World Kidney Day, could increase the awareness of general practitioners and general population of the risks of renal conditions

The effect of polyamines and dialysate fluid on extracellular matrix synthesis in VERO cell cultures

Background: Polyamines are involved in normal and pathological cell proliferation and differentiation. Like acid radicals, they play an important role in remodelling the extracellular matrix and are considered "uremic toxins". Proteins and glycosaminoglycans are essential components of the extracellular matrix, and contribute to normal mature organ functions. The aim of this study was to analyse the effects of free polyamines, dialysate fluid components and dialysis fluid on protein and extracellular glycosaminoglycan synthesis in VERO cell cultures. Methods: The dialysate fluid components were separated with a Sephadex G15 column and the cultures were analysed after incorporation of 3H-leucine and 3H-glucosamine. Cultures were run at pH 7.0 and pH 7.4. The glycosaminoglycan classes were separated with a DEAE column, and polyamines were determined by high-performance liquid chromatography. Proteins and single glycosaminoglycan classes were quantified by a scintillator. DNA gel electrophoresis was done to detect chromatin fragmentation. Results: Dialysate contained putrescine, spermidine and spermine, chromatography showing four peaks; only peaks I and II indicated polyamines at respectively Da 5000 and 1500. Polyamines are therefore linked to different carriers. There was an increase of protein and glycosaminoglycan synthesis with dialysis fluid and polyamines, but inhibition with peak II or dialysate. DNA gel electrophoresis showed no chromatin fragmentation. Findings at pH 7.0 and 7.4 were similar. Conclusions: It would appear that in uremic patients polyamines are conjugated to protein carriers of different molecular weights with different biological actions. As polyamines and dialysis fluid affect changes in extracellular matrix, they could be related to physiological organ functions. However, these in vitro data must be considered with the appropriate limitations when we try to extrapolate them to the in vivo situation

Cyclosporin A and transforming growth factor beta modify the pattern of extracellular glycosaminoglycans without causing cytoskeletal changes in human gingival fibroblasts1

Cyclosporin A is a powerful immunosuppressive drug that has had a major impact on transplant therapy. It apparently links to different enzymatic pathways, and affects multiple enzymatic systems. Transforming growth factor beta induces the deposition of glycosaminoglycans, proteoglycans, and collagen fibers in the extracellular matrix. The aim of this study of normal and hypertrophic human gingival fibroblast cultures was to evaluate the cytoskeletal and extracellular changes in glycosaminoglycan secretion due to the presence of cyclosporin A and transforming growth factor beta. The results showed that there is an increase in total and individual classes of extracellular glycosaminoglycans in the presence of cyclosporin A and transforming growth factor beta, but the action of the latter was significantly greater. Immunohistochemical analysis of the cytoskeleton did not reveal any morphological differences between treated and control cells. Our data suggest that the biochemical changes in the extracellular matrix are caused more by cytokine, and that cyclosporin A does not induce any morphological changes in fibroblast cultures derived from hypertrophic and normal gingiva

Cyclosporin A and transforming growth factor beta modify the pattern of extracellular glycosaminoglycans without causing cytoskeletal changes in human gingival fibroblasts

Cyclosporin A is a powerful immunosuppressive drug that has had a major impact on transplant therapy. It apparently links to different enzymatic pathways, and affects multiple enzymatic systems. Transforming growth factor beta induces the deposition of glycosaminoglycans, proteoglycans, and collagen fibers in the extracellular matrix. The aim of this study of normal and hypertrophic human gingival fibroblast cultures was to evaluate the cytoskeletal and extracellular changes in glycosaminoglycan secretion due to the presence of cyclosporin A and transforming growth factor beta. The results showed that there is an increase in total and individual classes of extracellular glycosaminoglycans in the presence of cyclosporin A and transforming growth factor beta, but the action of the latter was significantly greater. Immunohistochemical analysis of the cytoskeleton did not reveal any morphological differences between treated and control cells. Our data suggest that the biochemical changes in the extracellular matrix are caused more by cytokine, and that cyclosporin A does not induce any morphological changes in fibroblast cultures derived from hypertrophic and normal gingiva

Chick embryo back skin organ and fibroblast cultures. Extracellular matrix change induced by dialysate fluid and uraemic toxins in relation to proliferation and differentiation processes

Aim: During uraemia, an increase of middle molecules and acetylpolyamines occurs. In vitro the middle molecules produce cell toxicity, while the acetylpolyamines stimulate cell proliferation and differentiation. These phenomena are related to protein and extracellular glycosaminoglycan production. The aim of the present study was to evaluate the activity of dialysate, dialysate fluid and the chromatographic peaks of dialysate fractionated by G-15 Sephadex column on chick embryo skin development. Methods: We evaluated the effects of protein and glycosaminoglycan synthesis using monolayer and organotypic cultures. Results: Our data show that dialysate, chromatographic peak II, and 261028M N1-acetylspermine cause inhibition of chick embryo skin culture development. On the contrary, 1028M N-acetylornithine and dialysate fluid increase protein and extracellular glycosaminoglycan synthesis, whereas chromatographic peak I does not reveal differences when compared to controls. Conclusions: These extracelluar changes are related to cell proliferation and feather formation in chick embryo organotypic culture. Moreover, the pH changes of culture medium do not influence the biological action of acetylpolyamines and dialysate fluid on protein and extracellular glycosaminoglycan synthesis. Cell death in the presence of N1acetylspermine, dialysate and peak II appears unrelated to the apoptotic process. The data show that acetylpolyamines, dialysis fluid, dialysate and chromatographic peaks act on fibroblasts, and are able to modify glycosaminoglycan synthesis. The organotypic cultures of chick embryo back skin could represent a model for studying the modifications of the extracellular matrix induced by these substances