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Biomedical subjects

B Baggio

Publications and source records attributed to B Baggio.

At least 19 recordsLinked to original sources
PubMed2000

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↗
PubMed2000

Plasma phospholipid arachidonic acid content and calcium metabolism in idiopathic calcium nephrolithiasis.

BACKGROUND: Reports of an increase in plasma and erythrocyte phospholipid arachidonic acid content and in urinary prostaglandin E2 (PGE2) excretion in patients with idiopathic calcium nephrolithiasis suggested their crucial role in the pathogenesis of hypercalciuria, a well-known risk factor for lithogenesis. METHODS: To confirm this hypothesis, 15 healthy subjects and 20 nephrolithiasis patients were evaluated for plasma phospholipid polyunsaturated fatty acid content and PGE2 concentration, serum parathyroid hormone, 25 hydroxyvitamin D3, 1, 25-dihydroxyvitamin D3, and bone-specific alkaline phosphatase levels, as well as urinary excretion of calcium, biochemical markers of bone resorption (hydroxyproline and crossLaps), and intestinal calcium absorption. Furthermore, the effect of a 30-day fish-oil diet supplementation on the previously mentioned parameters was investigated in the patients. RESULTS: At baseline, patients compared with controls showed higher levels of plasma phospholipid arachidonic acid content (P = 0.002), PGE2 (P = 0.0004), serum 25-vitamin D3 (P = 0.001), and 1,25-vitamin D3 (P = 0.001), urinary excretion of calcium (P = 0.001), hydroxyproline (P = 0.007), and crossLaps (P = 0.019), as well as intestinal calcium absorption (P = 0.03 at 60 min). Fish oil supplementation induced a reduction in the plasma phospholipid arachidonic acid level (P < 0.0001), and except for serum concentrations of 25-vitamin D3, normalized baseline blood and urinary parameters, including intestinal calcium absorption. A close correlation between plasma PGE2 and serum 1,25-vitamin D3 (P = 0.004) and between phospholipid arachidonic acid and intestinal calcium absorption (P = 0.0002) and calciuria (P = 0.007) was observed, as well as between urine excretion of crossLaps and hydroxyproline (P < 0.0001), crossLaps and calcium (P < 0.0001), and hydroxyproline and calcium (P < 0.0001). CONCLUSIONS: These findings indicate that the phospholipid arachidonic acid content anomaly could represent the primary event responsible for the mosaic of metabolic and clinical alterations that are distinctive features of renal stone formers, and suggest that a common pathogenetic mechanism might account for the several forms of hypercalciuria detected in idiopathic calcium nephrolithiasis.

Adult↗
PubMed2000

Course of renal function in type 2 diabetic patients with abnormalities of albumin excretion rate.

Heterogeneity in renal structure has been described in type 2 diabetic patients with both microalbuminuria and proteinuria; in fact, only a subset of type 2 diabetic patients have the typical diabetic glomerulopathy. However, it is currently unknown whether abnormalities in albumin excretion rate (AER) have a different renal prognostic value depending on the underlying renal structure. Aims of this study were: 1) to study the course of renal function in type 2 diabetic patients with altered AER; 2) to evaluate the relationship between the course of glomerular filtration rate (GFR) and renal structure; and 3) to evaluate the relationship between the course of GFR and baseline AER levels, metabolic control, and blood pressure levels during a follow-up period of 4 years. A total of 108 type 2 diabetic patients, 74 with microalbuminuria (MA) and 34 with proteinuria (P), were recruited into a prospective study that encompassed: 1) a baseline kidney biopsy with morphometric measurements of glomerular parameters; 2) intensified antihypertensive treatment for an average 4-year period (blood pressure target <140/90 mmHg); and 3) determinations of GFR at baseline and every 6 months. Mean (+/- SD) GFR significantly decreased from baseline in both MA (-1.3+/-9.4 [95% CI -3.51 to +0.86], P < 0.05) and P (-3.0+/-13.0 ml x min(-1) x 1.73 m(-2) per year [-7.71 to +1.61], P < 0.01). However, the changes in GFR were quite heterogeneous. Thus, on the basis of percent GFR change per year from baseline (delta%GFR), both MA and P patients were defined as progressors or nonprogressors when they were below or above the median, respectively. Baseline parameters of glomerular structure had a strong influence on the course of GFR. Indeed, the odds ratios of being progressors significantly increased across the quartiles of baseline glomerular basement membrane (GBM) width and mesangial fractional volume [Vv(mes/glom)], being 2.71 and 2.85 higher, respectively, in the fourth quartile than in the first quartile (P < 0.01 for both). Conversely, nonprogressors outnumbered progressors in the first quartile of GBM width (odds ratio: 2.14, P < 0.05) and in the first quartile of Vv(mes/glom) (odds ratio: 2.28, P < 0.01). Baseline albumin excretion rate (AER) did not influence delta%GFR; in fact, the number of progressors did not increase across quartiles of baseline AER among either MA or P. Similarly, mean blood pressure levels during follow-up (and intensified antihypertensive therapy) did not affect the course of GFR: the number of progressors and nonprogressors did not change across quartiles of mean blood pressure. In contrast, HbA1c during follow-up had an impact on delta%GFR: the odds ratio for being a progressor increased across quartiles of HbA1c, particularly for the highest quartile (HbA1c >9.0%). In conclusion, the course of renal function is heterogeneous in type 2 diabetic patients with microalbuminuria or proteinuria. In fact, a subset of patients has a rapid decline in GFR over a 4-year follow-up period; these patients have more advanced diabetic glomerulopathy and worse metabolic control than the remaining patients, whose GFR remains stable. These two cohorts are otherwise undistinguishable as regards the degree of AER at baseline and tight blood pressure control. Kidney biopsy has an important prognostic role in these patients. Thus, tight blood pressure control, when not associated with satisfactory glycemic control, is unable to prevent rapid GFR decline in type 2 diabetic patients with typical diabetic glomerulopathy.

Adult↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

Specific modulatory effect of arachidonic acid on human red blood cell oxalate transport: clinical implications in calcium oxalate nephrolithiasis.

Greater arachidonic acid (AA) contents, which were correlated with erythrocyte transmembrane oxalate (Ox) transport, were observed in plasma and erythrocyte membrane phospholipids of patients with idiopathic calcium renal stones, suggesting a link between membrane phospholipid fatty acid composition and cellular Ox transport. To confirm this hypothesis, the effects of exogenous red blood cell incorporation of three different fatty acids (i.e., oleic acid, AA, and eicosapentaenoic acid) on Ox transport and the phosphorylation status of band 3 protein, which has been shown to mediate red blood cell Ox flux, were investigated. Preincubation of erythrocytes with AA induced a dose-dependent increase in the phosphorylation level of band 3 protein and an increase in transmembrane Ox self-exchange. In contrast, inhibitory effects on both parameters were observed after the incorporation of oleic and eicosapentaenoic acids. These data, together with previous observations of dietary effects on erythrocyte Ox transport and urinary Ox excretion, indicate that genetic and/or nutritional changes in membrane phospholipid fatty acid composition play a crucial role in modulating cellular Ox transport in idiopathic calcium Ox nephrolithiasis.

Adult↗
PubMed1998

Growth factors and the kidney in diabetes mellitus.

Nephromegaly and mesangial matrix expansion observed in the diabetic kidney are all clues of a role of growth factors in the pathogenesis of these lesions. A growing body of evidence shows that changes in (1) insulin-like growth factor I regulation, and (2) the transforming growth factor beta loop exist in the kidney in the diabetic hypertrophic kidney and in diabetic glomerulosclerosis. However, other growth factors may be involved in some diabetic renal changes. The abnormalities in growth factor content and regulation, the role of growth factors in the diabetic kidney, and the effect of hyperglycemia and advanced glycosylation end products on growth factors in the kidney are reviewed.

Animals↗
PubMed1998

Pathogenesis of idiopathic calcium nephrolithiasis: update 1997.

Idiopathic calcium nephrolithiasis (ICN) is a frequent disease in Western countries. The physicochemical theory of lithogenesis, which explains stone formation by the precipitation, growth, and crystalline aggregation of lithogenic salts in the urine, has contributed greatly to the understanding of the pathogenesis of calcium urolithiasis. However, several aspects are still unexplained; the co-existence of familial occurrence, primary tubular dysfunctions with ICN, and anomalies in the systemic handling of oxalate and calcium led to the development of a cellular hypothesis of ICN. A number of cellular defects in the handling of ions has been reported that involves both anion and cation transport. These anomalies are probably the expression of a still unknown cellular defect in idiopathic calcium stone formers. We suggested that an anomaly in the cell membrane composition might be responsible for the complex array of cell ion flux abnormalities observed in ICN. Recently, a disorder in the n-6 polyunsaturated fatty acid series has been described; it is characterized by a lower linoleic acid content and a higher arachidonic acid concentration in both plasma and erythrocyte membrane phospholipids of renal calcium stone patients. This anomaly could cause an increased activity of ion carriers; furthermore, it may lead to increased prostaglandin synthesis and to secondary phenomena at the kidney, skeletal, and intestinal level. As a consequence, critical conditions for lithogenesis in the kidney may ensue. The data suggest a common pathogenesis for hypercalciuria and hyperoxaluria. The systemic defect in the phospholipid arachidonic acid level may be both of dietary or genetic origin; experimental data suggest that the increase in delta-6 desaturase activity, the limiting enzyme in the metabolic pathway of polyunsaturated fatty acids, might be relevant to the pathogenesis of lipid abnormalities observed in nephrolithiasis and to the pathogenesis of ICN and its related problems (at the kidney, intestinal, and bone level).

Calcium↗
PubMed1998

Molecular biology of diabetic glomerulosclerosis.

Diabetic nephropathy is one of the leading causes of renal failure in Western countries, where diabetic patients account for nearly half of all patients on haemodialysis. Progressive expansion of the mesangial matrix, and thickening of the glomerular and tubular basement membranes without signs of major cell proliferation are hallmarks of human and experimental diabetic nephropathy. These lesions eventually lead to glomerular fibrosis, a central pathological feature in many human acute and chronic kidney diseases, which progressively destroys the renal filtration unit, and may finally cause renal failure. Indeed, structure function relationship studies have shown that mesangial matrix expansion is strongly related to the clinical manifestation of diabetic nephropathy.

Diabetic Nephropathies↗
PubMed1998

Renal impairment in chronic cigarette smokers.

To determine the effect of chronic cigarette smoking on renal function, a cross-sectional study was carried out with 30 subjects who had no known vascular disease risk factor other than cigarette smoking, and 24 age- and sex-matched controls without any vascular risk factor including cigarette smoking. Renal function by radionuclide studies of renal plasma flow, GFR, and plasma endothelin-1 concentration was determined. Compared with nonsmokers, smokers had a renal function impairment characterized by a normal GFR and a significant reduction in renal plasma flow as reflected by MAG3 clearance (199.20 +/- 58.85 ml/min per 1.73 m2 versus 256.54 +/- 60.14 ml/min per 1.73 m2; t = 3.52, P < 0.001). MAG3 clearance was significantly correlated with age and smoking. The renal dysfunction was associated with an increase in plasma endothelin-1 concentration (21.56 +/- 1.15 pmol/L versus 25.01 +/- 3.21 pmol/L; t = 5.00, P < 0.001). Former smokers as well had similar, although milder, abnormalities. In conclusion, cigarette smokers manifest an impairment of renal function, suggesting that smoke may have a detrimental effect on renal function.

Aged↗
PubMed1998

Intracellular processing of transforming growth factor-beta in mesangial cells.

Transforming growth factor beta 1 (TGF-beta 1) is a multifunctional regulator of cell-growth, differentiation and extracellular matrix formation in several physiological conditions. It plays a crucial role in the process of glomerulosclerosis. Mature TGF-beta 1 is secreted as a latent form associated with the latency associated peptide (LAP), and its activation occurs through the LAP cleavage. The intracellular localization and the mechanisms of activation of TGF-beta 1 protein have not been elucidated in the mesangial cell. In the present report we examined the intracellular processing from TGF-beta 1 precursor to the latent-TGF-beta 1 in cultured mesangial cells by immunocytochemistry, using three rabbit polyclonal antibodies directed against different epitopes of human TGF-beta 1. The anti-LAP-TGF-beta 1 precursor Ab stained mesangial cells in the perinuclear region and in the cytoplasm in the area corresponding to the rough endoplasmic reticulum; the anti-COOH-terminal fragment of TGF-beta 1 Ab reacted in the same area, in vesicular structures located in the cytoplasm and furthermore, in the mesangial cell clusters, so-called hillocks, with an extracellular pattern; the anti-NH2-terminal fragment of TGF-beta 1 Ab stained only large exocytotic vesicles at the periphery of the cytoplasma. Our investigations suggest a conformational rearrangement of pro-TGF-beta 1 molecule occurring between the rough endoplasmic reticulum and the TGF-beta 1 secretion and support the idea that in mesangial cells the activation of TGF-beta 1 occurs during the secretion process. In conclusion, the processing of TGF-beta 1 in mesangial cells seems to be similar to that one observed in other mesenchymal cells.

Animals↗
PubMed1997

Down-regulation of glomerular matrix metalloproteinase-2 gene in human NIDDM.

Regulation of mesangial matrix deposition is a dynamic phenomenon involving synthetic and degradative processes. The latter involve a number of matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinases (TIMP). Experimental studies suggest that mesangial matrix degradation is inhibited in diabetic nephropathy, and that this phenomenon has a pathogenic role. The expression of genes for MMP2 and TIMP2 in human diabetic nephropathy was investigated. Reverse transcription polymerase chain reaction was carried out in microdissected glomeruli and tubulo-interstitium obtained from kidney biopsies. We studied 16 NIDDM patients, 5 patients with glomerulonephritis or chronic kidney transplant rejection, and 5 normal control subjects. Albumin excretion rate and renal histology for NIDDM patients were available. Contrary to TIMP2 which was expressed both in tubulo-interstitium and glomeruli in almost all renal biopsies, MMP2 gene down-regulation was observed in glomeruli from all NIDDM patients, irrespective of the albumin excretion rate, and of renal histology. In contrast, this gene was expressed in biopsies from other subjects (chi(2) = 20.6; p = 0.000). In conclusion, this study demonstrates that: 1) in glomeruli of NIDDM patients the MMP2 gene is down-regulated; 2) in biopsies of NIDDM patients the MMP2/TIMP2 pattern is peculiar for NIDDM; 3) the MMP2 gene down-regulation is observed in all NIDDM patients, irrespective of the level of albuminuria and of renal histology. MMP2 gene down-regulation seems to be a molecular epiphenomenon of diabetes, rather than a marker of diabetic nephropathy.

Adult↗
PubMed1997

Effect of glucose and heparin on mesangial alpha 1(IV)COLL and MMP-2/TIMP-2 mRNA expression.

Mesangial cells are responsible for the synthesis of mesangial matrix as well as its degradation, which is mediated by a number of proteolytic activities, including metalloproteinases (MMPs). Imbalanced matrix protein metabolism may be responsible for mesangial expansion and glomerulosclerosis in diabetic nephropathy. Heparin prevents this complication. In human and murine mesangial cell cultures, RT-PCR was able to detect mRNA expression for a number of molecules involved in the mesangial extracellular matrix turnover: type IV collagen [alpha 1(IV)COLL], MMP-1, MMP-2, MMP-3, MMP-9 and MMP-10, and the tissue inhibitors TIMP-1 and TIMP-2. The expression of mRNA for alpha 1(IV)COLL and MMP-2/TIMP-2 balance was studied in human cells in the presence of high glucose and heparin. mRNAs for all the studied molecules were expressed at different levels. Interestingly, a shift in the balance of alpha 1(IV)COLL, MMP-2 and TIMP-2 was observed in high glucose, which was partially reversed by heparin supplementation. The new equilibrium was mostly due to the down-regulation of type IV collagen expression, rather than further reduction of potential proteolysis. Our data, while extending the list of potential mediators of mesangial matrix catabolism, highlight a molecular mechanism by which the pathogenesis of diabetic nephropathy may be sustained, and at the same time suggest that heparin may have the potential to correct this abnormality.

Anticoagulants↗