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Biomedical subjects

R T Barros

Publications and source records attributed to R T Barros.

10 recordsLinked to original sources

Decreased in vitro osteoblast proliferation and low turnover bone disease in nonuremic proteinuric patients.

Patients with proteinuria, even those with normal glomerular filtration rate, often present abnormal bone histology. We evaluated bone histology and the in vitro proliferation of osteoblasts in samples obtained from 17 proteinuric patients with primary glomerulopathies. Histomorphometric analysis of bone biopsies was performed, and bone fragments were obtained for osteoblast culture, in which we evaluated cell proliferation. In comparison to controls, patients presented lower trabecular bone volume (20.9+/-14.5% vs 26.8+/-5.9%; P=0.0008); lower trabecular number (1.7+/-0.2/mm vs 2.0+/-0.3/mm; P=0.004); and greater trabecular separation (475.5+/-96.4 microm vs 368.3+/-86.2 microm, P=0.0002). We also found alterations in bone formation and resorption: lower osteoid volume (0.9+/-0.7% vs 2.0+/-1.4%; P=0.0022); lower osteoid thickness (6.4+/-2.8 microm vs 11.5+/-3.2 microm; P<0.0001); less mineralizing surface (4.6+/-3.1% vs 13.5+/-6.0%; P<0.0001); lower bone formation rate (0.03+/-0.04 microm(3)/microm(2)/day vs 0.09+/-0.05 microm(3)/microm(2)/day; P<0.0001); and greater osteoclast surface (0.35+/-0.6 vs 0.05+/-0.1%, P=0.0016). Mean in vitro osteoblast proliferation was lower in patients than in controls (910.2+/-437.1 vs 2261.0+/-1121.0 d.p.m./well, P=0.0016). Serum concentrations of 25-hydroxyvitamin-D(3) correlated negatively with proteinuria and positively with in vitro osteoblast proliferation. Our results demonstrate that nonuremic proteinuric glomerulonephritic patients present bone structure disorder, low bone formation and high bone resorption, as well as low osteoblast proliferation.

Adult↗

Genetic potential for an acute inflammatory response in IgA glomerulonephritis in mice.

Mice selected on the basis of an acute inflammatory response (AIR) can provide information about the immunopathological mechanisms of glomerulonephritis. We studied the differences between mice selected for a maximal AIR (AIRmax that attract more polymorphonuclear cells to the site of injury) or a minimal AIR (AIRmin that attract more mononuclear cells) in an experimental model of IgA nephropathy in order to investigate the effect of genetic background on glomerular disease progression and the participation of the monocyte chemoattractant protein-1 (MCP-1) chemokine. IgA nephropathy was induced by intraperitoneal ovalbumin injection and bile duct ligation in AIRmax and AIRmin mice. Histological changes, urinary protein/creatinine ratio, serum IgA levels, immunofluorescence for IgA, IgG and complement C3 fraction, immunohistochemistry for macrophages and MCP-1, and MCP-1 levels in macerated kidney were determined. Mesangial IgA deposition was seen only in AIRmin mice, which presented more renal lesions. Increased serum IgA levels (1.5 +/- 0.4 vs 0.3 +/- 0.1 mg/mL, P < 0.001), high glomerular MCP-1 expression and decreased monocyte/macrophage infiltration in the interstitial area (0.3 +/- 0.3 vs 1.1 +/- 0.9 macrophages/field, P < 0.05) were detected in AIRmin mice compared to AIRmax mice. No glomerular monocyte/macrophage infiltration was detected in either strain. In spite of the absence of IgA deposition, AIRmax mice presented discrete or absent mesangial proliferation. The study showed that there are differences between mice selected for AIRmax and AIRmin with respect to serum IgA levels, histological damage and MCP-1 chemokine production after ovalbumin injection in combination with bile duct ligation.

Acute Disease↗

Comparative study of IgA nephropathy with and without crescents.

Glomerular crescents were analyzed as a prognostic factor in retrospectively reviewed data from 144 patients with biopsy-proven IgA nephropathy. Crescents were found in 26 (18%) patients, and detected in 2 to 100% of glomeruli in each specimen. In 5% of the patients more than 50% of the glomeruli were affected. Thirty patients with IgA nephropathy without crescents were studied as a control group. Mean age was 30.3 +/- 9.4 and 30.2 +/- 12.0 years for the patients with and without crescents, respectively, and males prevailed in both groups. The length of follow-up was 23.2 +/- 41.6 months for patients with crescents and 29.3 +/- 35.3 months for patients without crescents. Eighty percent of the patients with crescents were hypertensive, compared to 27% of the non-crescent control group (P < 0.05). Mean serum creatinine at the time of diagnosis was 3.9 +/- 2.9 and 1.9 +/- 2.1 mg/dl for the patients with and without crescents, respectively. Initial urinary protein excretion was higher in patients with crescents (4.6 +/- 3.5 vs 1.2 +/- 0.9 g/day; P < 0.05). At the end of follow-up 17 patients (77.3%) from the crescent group and 3 (11.1%) from the non-crescent group had end-stage renal disease (P < 0.0001). The presence of crescents was associated with higher levels of initial serum creatinine and urinary protein excretion, and a higher frequency of hypertension and progression to end-stage renal disease.

Biomarkers↗

The renal and hepatic distribution of Bence Jones proteins depends on glycosylation: a scintigraphic study in rats.

The aim of the present study was to evaluate renal and liver distribution of two monoclonal immunoglobulin light chains. The chains were purified individually from the urine of patients with multiple myeloma and characterized as lambda light chains with a molecular mass of 28 kDa. They were named BJg (high amount of galactose residues exposed) and BJs (sialic acid residues exposed) on the basis of carbohydrate content. A scintigraphic study was performed on male Wistar rats weighing 250 g for 60 min after i.v. administration of 1 mg of each protein (7.4 MBq), as the intact proteins and also after carbohydrate oxidation. Images were obtained with a Siemens gamma camera with a high-resolution collimator and processed with a MicroDelta system. Hepatic and renal distribution were established and are reported as percent of injected dose. Liver uptake of BJg was significantly higher than liver uptake of BJs (94.3 vs 81.4%) (P < 0.05). This contributed to its greater removal from the intravascular compartment, and consequently lower kidney accumulation of BJg in comparison to BJs (5.7 vs 18.6%) (P < 0.05). After carbohydrate oxidation, there was a decrease in hepatic accumulation of both proteins and consequently a higher renal overload. The tissue distribution of periodate-treated BJg was similar to that of native BJs: 82.7 vs 81.4% in the liver and 17.3 vs 18.6% in the kidneys. These observations indicate the important role of sugar residues of Bence Jones proteins for their recognition by specific membrane receptors, which leads to differential tissue accumulation and possible toxicity.

Animals↗

Nodular diabetic glomerulosclerosis without diabetes mellitus.

A 66-year-old white man presented with severe chronic renal failure. He had no past or present symptomatic glucose intolerance nor a family history of diabetes mellitus. Several fasting plasma glucose determinations, hemoglobin Alc and an oral glucose tolerance test were normal. Funduscopic ophthalmoscopy and retinal fluorescein angiography did not demonstrate diabetic retinopathy. The kidney biopsy showed nodular diabetic nephropathy, with increased mesangial matrix, thickened glomerular basement membrane, and afferent and efferent glomerular arteriolar hyalinization. The diagnosis of nodular diabetic nephropathy was made in this patient in the absence of past or present or familial evidence of diabetes mellitus.

Aged↗

Nephrotic syndrome associated with hepatointestinal schistosomiasis.

Schistosomal nephropathy has long been related to the hepatosplenic form of schistosomiasis. In the last few years, 24 patients with hepatointestinal schistosomiasis and the nephrotic syndrome were studied. Aiming at evaluating a possible etiologic participation of schistosomiasis in the development of the nephropathy, this group was comparatively studied with a group of 37 patients with idiopathic nephrotic syndrome. Both groups had a different distribution of the histologic lesions. In the group with schistosomiasis there was a statistically significant prevalence of proliferative mesangial glomerulonephritis (33.3%), whereas in the control group there was prevalence of membranous glomerulonephritis (32.4%). On immunofluorescence, IgM was positive in 94.4% of the patients with schistosomiasis versus 55.0% in the control group (P < 0.01). In the group with schistosomiasis, 8 patients evidenced mesangial proliferative glomerulonephritis and 5, membranoproliferative glomerulonephritis. In both histological types immunofluorescence showed IgM and C3 granular deposits in the glomeruli. The data in this study suggests that mesangial proliferative and membranoproliferative glomerulonephritis, with glomerular granular IgM and C3 deposits, represent the renal lesions of the schistosomiasis associated nephropathy.

Adolescent↗

[Protein/creatinine index in isolated samples of urine for evaluation of 24-hour proteinuria].

The correct determination of the 24 hours proteinuria (PU24) in the non-hospitalized patients is frequently subject to collection errors. To overcome this problem it has been proposed the use of the proteinuria ratio (PR), obtained by dividing the concentrations of protein/creatinine in random urine samples. In the present investigation PR and PU24 were correlated in 42 patients (22 male and 20 female), aged between 14 and 63 years. Each patient was submitted to a 2 hours creatinine clearance (Ccr), to determination of PU24 and to evaluation of PR in the urine samples. The measures of PU24 were correlated with the values of PR. On linear regression analysis the equation y = 0,517 + 0,759x was obtained, with r = 0,914, suggesting good correlation between PU24 and PR. Values of r greater than 0,9 were always obtained, independently of the values of Ccr and PU24. The results indicate that PR in random urine samples may be practical and reliable in the follow-up of nephrological patients.

Adolescent↗