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Biomedical subjects

G Gambaro

Publications and source records attributed to G Gambaro.

At least 19 recordsLinked to original sources

Risk for renal failure in nephrolithiasis.

Evaluation of the risk for developing renal insufficiency is generally not considered during the clinical metabolic workup of the stone-forming patient. This review approaches the problem of the severity of nephrolithiasis by addressing the renal risk. Although renal stones are an infrequent cause of renal failure, some lithiasic forms present a greater risk, such as in hereditary stone diseases (eg, cystinuria, primary hyperoxaluria, Dent's disease), primary struvite stones, and infection-related urolithiasis associated with anatomic and functional urinary tract anomalies and spinal cord injury. Recurrent bouts of obstruction and/or crystal-specific biological effects on tubular epithelial cells and interstitial renal cells may activate the fibrogenic cascade responsible for the loss of renal parenchyma. In clinical terms, frequent stone relapses, episodes of urinary tract infection and obstruction, number of urological interventions, and size of the gravel are all significantly associated with the risk for renal failure. Percutaneous and extracorporeal urological methods for the treatment of renal stones may also lead to some chronic deterioration of renal function, particularly in recurrent stone formers treated with multiple therapeutic sessions. Although still speculative, concerns exist about the effect of extracorporeal shock wave lithotripsy on small or pathological kidneys. Without doubt, the medical prevention of stones would be more sensible.

Humans↗

Dietary manipulation of delta-6-desaturase modifies phospholipid arachidonic acid levels and the urinary excretion of calcium and oxalate in the rat: insight in calcium lithogenesis.

An anomalous n-6 polyunsaturated fatty acid composition in plasma and erythrocyte membrane phospholipids, namely increased levels of arachidonic acid (AA), has been reported in calcium nephrolithiasis and has been proposed to play an important role in its pathogenesis. To confirm this, in rats we modified phospholipid AA levels by dietary manipulation of the delta-6-desaturase, the rate-limiting enzyme of the fatty acid biosynthetic pathway, and evaluated the effect on cellular and renal functions predisposing to lithogenesis. Increased AA levels led to conditions at risk for nephrolithiasis: higher oxalate flux and lower sodium cotransport in erythrocytes and a rise in urinary prostaglandin E2, calcium, sodium, and oxalate levels; reduced AA levels reversed these changes. In vitro, in human erythrocytes the incorporation of exogenous AA into membranes increased band 3 protein phosphorylation directly activating the Ser/Thr protein kinase CK1 and induced a parallel raise in band 3-mediated oxalate transport. These findings demonstrate the pivotal role of phospholipid AA in modulating erythrocyte and renal transport of calcium and oxalate.

Animals↗

Direct effect of chronic cyclosporine treatment on collagen III mRNA expression and deposition in rat kidneys.

BACKGROUND: It is hypothesized that in acute and chronic CsA nephrotoxicity, in vivo models CsA side-effects are mediated by Renin-Angiotensin II (RAS)-TGF-beta-1 pathway. However, to induce chronic nephrotoxicity, CsA administration has to be combined with a low salt diet, which causes hemodynamic changes and RAS up-regulation. MATERIALS AND METHODS: In order to define any direct correlation between CsA and nephrotoxicity, we studied in normal sodium fed rats, the chronic effects of CsA administration (group-1 treated with 12.5 mg/Kg/day of CsA subcutaneously; group 2 received daily placebo; group 3 interrupted CsA injection after 60 days), on renal TGF-beta-1 and collagen III expression, and on TGF-beta-1, collagen III and IV deposition. Sacrifices were performed after 2, 4, 8 and 12 weeks (wks) and kidneys were harvested for immunohistological studies and RT/PCR analysis. RESULTS: No difference of TGF-beta-1 expression and deposition was found among groups. Starting from the 2nd week of treatment, an increased collagen III deposition was evident in vessels and in outer medulla with subsequent extension at the 4th week to medullary rays and to cortex interstitium. The deposition paralleled the renal collagen III mRNA up-regulation: it was significantly higher in group 1 than in group 2 (p < 0.009 at 2nd wk; p < 0.016 at 4th wk). Collagen IV deposition did not differ between groups at any point. CONCLUSIONS: Our results suggest that chronic CsA administration can induce, in normal fed rats, the process of interstitial fibrogenesis through TGF-beta non-related mechanisms.

Animals↗

Liver-kidney-transplantation in type 1 primary hyperoxaluria: description and comments on a case.

BACKGROUND: Primary hyperoxaluria leads to oxalosis, a systemic illness with fatal prognosis in uremic youngsters because of systemic complications. CASE REPORT: A 14-year old boy with primary type 1 hyperoxaluria who had a long-lasting history of nephrolithiasis and passed from normal renal function to end-stage renal disease within 7 months. MEASUREMENT of alanine: glyoxylate aminotransferase (AGT) catalytic activity in the liver biopsy disclosed very low activity which was not. responsive to pyridoxin., thus the patient entered onto a priority national waiting list for liver-kidney transplantation and a week later received a combined transplant. In order to increase body clearance of oxalate, the patient underwent medical treatment to increase urine oxalate solubility (sodium and potassium citrate oral therapy, magnesium supplementation and increase of diuresis) and intensive dialysis both before and after transplantation. COMMENT: The medical approach to the treatment of this rare illness is discussed. Since the major risk for the grafted kidney is related to the oxalate burden, i.e. oxalate deposition from the body deposits to the kidney that becomes irreversibly damaged, treatment consists of increasing the body clearance of oxalate both by increasing oxalate solubility in the urine and with intensive dialysis performed both before and after combined transplantation. To the same extent (by limiting body oxalate deposits), a relatively early (native GFR 20-25 ml/minute) transplantation is advisable.

Adolescent↗

Predictive markers of pre-eclampsia in hypertensive disorders of pregnancy.

OBJECTIVE: The aim of this work is to assess the most widespread methods currently proposed and two new markers for predicting the development of pre-eclampsia in pregnant women with hypertension. METHODS: The study involved 212 pregnant Caucasian women: 104 normotensive, 68 pregnancy-induced hypertensive and 40 chronic hypertensive. Blood and urine were sampled between 28 and 30 weeks gestation. All 108 hypertensive pregnant women, at the time of sampling, demonstrated proteinuria below 0.3 g/24 h. The following laboratory tests were performed: fibronectin, antithrombin-III, alpha-1-microglobulin, U-N-acetyl-beta-glucosaminidase, uric acid and albumin excretion rate. Student's t-test, discriminant analysis and chi2 (chi-square) test were used as statistical methods. A P value less than 0.05 was considered significant. RESULTS: After discriminating analysis, only three of the six variables analyzed were able to discriminate patients who would develop pre-eclampsia from the remaining hypertensive pregnant women: microalbuminuria, uric acid and fibronectin (chi2 = 29.122, P < 0.01). CONCLUSIONS: In agreement with previous studies, albumin excretion rate appeared to be the best predictive test for pre-eclampsia in hypertensive pregnant women, giving a higher positive predictive value and specificity (87.5 and 98.9%, respectively).

Adult↗

Glycosaminoglycans prevent the functional and morphological peritoneal derangement in an experimental model of peritoneal fibrosis.

Chronic peritoneal dialysis results in fibrosis of the peritoneal membrane, which leads to progressive reduction in dialytic efficacy. It was recently shown that the intraperitoneal administration of glycosaminoglycans (GAGs) improves the efficiency of peritoneal dialysis in CAPD patients. To verify whether the favorable effects of GAGs are purely functional or involve a morphological amelioration of the peritoneal membrane structure, a study was carried out in an animal model of plasticizer-induced peritoneal fibrosis. Rats, in which chronic renal failure had been induced by subtotal nephrectomy, received either placebo, plasticizers (i.p.), or GAGs (s.c.), or plasticizers (i.p.) and GAGs (s.c.). Urea dialysate-to-plasma equilibrium, urea and albumin peritoneal clearance, and glucose reabsorption were determined. The peritoneal membrane was evaluated morphometrically and histologically. In plasticizer-treated animals, peritoneal function tests and morphology were dramatically deranged. On the contrary, the subcutaneous administration of GAGs in plasticizer-treated rats maintained the peritoneal physiology and normal structure. The subcutaneous administration of GAGs protects peritoneal functions by affecting the remodeling of the peritoneum, rather than by a purely functional or simple mechanical effect.

Analysis of Variance↗

Mesangial cell proliferation in long-term streptozotocin-induced diabetes mellitus in the rat and the renoprotective activity of heparin.

At present, it is not clear whether mesangial proliferation underlies mesangial expansion in diabetic nephropathy. To address this issue and the relationship between heparin's renoprotective and antimitogenic activities, we studied three streptozotocin-induced diabetic rat groups 5 and 12 months after diabetes induction: two groups were administered a modified heparin, each with a different protocol, and two healthy rat groups, one of which was treated with the same heparin, served as controls. Untreated diabetic animals developed clear evidence of nephropathy, namely expansion of the glomerular extracellular matrix, as expressed by glomerular basement membrane thickening, and increased mesangial deposition of type IV collagen. These alterations were prevented/cured by heparin treatment. Kidney sections were processed immunohistochemically for proliferating cell nuclear antigen and smooth muscle alpha-actin which is expressed only by proliferating mesangial cells. The number of proliferating cell nuclear antigen positive nuclei and alpha-actin-positive cells per glomerulus did not differ between groups at both 5 and 12 months. In conclusion, there is no evidence that mesangial proliferation is increased in late experimental diabetic nephropathy, and heparin seems to be renoprotective through mechanisms other than antiproliferation.

Actins↗

Urinary galactosyl-hydroxylysine in postmenopausal osteoporotic women: A potential marker of bone fragility.

Alterations of the collagen matrix, e.g., increased hydroxylation and glycosylation of lysyl residues in collagen I, were found in human osteoporotic bone, and it was suggested that they could alter the mechanical properties of skeleton. To test this hypothesis, we evaluated the content of galactosyl-hydroxylysine (GHYL) in bone collagen, as assessed by its urinary excretion, and related it to the occurrence of fracture. Two hundred and fifteen unselected postmenopausal women with osteoporosis were divided in two subgroups (comparable for age, age of menopause, bone mineral density, and biochemical parameters of bone turnover) on the basis of the history of fragility fracture; 115 patients had suffered no fracture and 100 patients had suffered one or more fractures 3 or more years before. Four urinary markers of bone turnover (hydroxyproline, cross-linked N-telopeptide, free deoxypyridoline, and GHYL) were evaluated in all patients. There was no difference between the two groups with regard to all the parameters studied except for GHYL, which was significantly higher in the group with a history of fracture (1.35 +/- 0.82 mmol/mol of creatinine [Cr] versus 1.03 +/- <0.48 mmol/mol Cr, p < 0.001); this marker did not correlate with other markers of bone remodeling in the fracture group, indicating a possible defect in bone collagen. In conclusion, provided that increased levels of urinary GHYL do reflect overglycosylation of hydroxylysine in bone collagen, the GHYL may be considered a marker of bone collagen quality. Our results, showing higher urinary GHYL in osteoporosis patients with fracture, seem to confirm this suggestion.

Aged↗

Advances in reverse transcription polymerase chain reaction analysis of cellular mRNA levels of transforming growth factor-beta1 by capillary electrophoresis with laser-induced fluorescence detection.

The prosclerotic transforming growth factor beta1 (TGF-beta1) is a key factor in the induction and maintenance of fibrosis in different organs. To assess relative changes in TGF-beta1 mRNA levels, the comparative kinetic reverse transcription-polymerase chain reaction strategy was used. In this method, cellular mRNA levels of the target and a house-keeping gene are reverse transcribed, amplified by the polymerase chain reaction (PCR) and the kinetics of PCR amplification are compared. Since the current determination of the PCR products, using electrophoretic separation in polyacrylamide gel, staining and scanning of the gel, is time-consuming (> or = 5 hours) and inaccurate, we have developed a method using capillary gel electrophoresis (CGE) in combination with laser-induced fluorescence (LIF) detection for quantification of PCR-products. Using the CGE-LIF method, a minute aliquot of the PCR reaction mixture is separated and quantified within 10 min. Comparison of the values with those obtained by polyacrylamide gel electrophoresis demonstrates the improved sensitivity (> 1000 fold) and accuracy of the proposed method. The CGE-LIF procedure offers a convenient way of automated, comparative analysis of low levels of mRNA via reverse transcription PCR in low cell numbers or small amounts of tissue samples.

Electrophoresis, Capillary↗

[Non-Hodgkin's lymphoma of the larynx: clinical cases].

Non-Hodgkin Lymphoma (NHL) is a relatively frequent lymphatic system tumor in the head and neck region with both nodal and extranodal localizations. The larynx is one of the least frequent extranodal sites. The present study reports three cases of NHL with extranodal laryngeal localization that had recently come under observation. In these cases, the symptoms reported by the patients were aspecific and not particularly significant. Indirect macroscopic laryngoscopy and direct microlaryngoscopy did not prove pathognomonic while definitive histology clearly diagnosed lymphoma. The treatment of choice for primary laryngeal lymphoma is radiotherapy; combined chemo-radiotherapy is indicated in cases of high malignancy and in multifocal cases.

Aged↗