Biomedical subjects

E B Prado

Publications and source records attributed to E B Prado.

9 recordsLinked to original sources

PubMed1997

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↗

PubMed1995

Reduced humoral immunity in uremic mice genetically selected for high antibody response.

Biozzi's Selection IV-A mice, genetically selected for 25 generations for high and low antibody response to sheep red blood cells (SRBC), 2-3 months old, were made uremic by subtotal nephrectomy and characterized for antibody production against the selection antigen. T cell activity was evaluated in vitro by lymphocyte proliferation and interleukin 2 (IL 2) production in response to the super antigen staphylococcal enterotoxin B (SEB). Total and IgM antibody titers (log2) were similar in uremic and non-uremic low responder mice (total antibody: 4.0 +/- 0.6 vs 3.6 +/- 0.6; IgG: 3.0 +/- 0.7 vs 2.4 +/- 0.4), while uremic high responders presented with non-uremic animals (total antibody: 10.8 +/- 1.6 vs 13.0 +/- 0.2; IgG: 10.3 +/- 1.5 vs 11.7 +/- 0.3). T cell proliferation and IL 2 production were similar in uremic and non-uremic groups after SEB stimulation. The results indicate a genetic effect on sensitivity to humoral immune response modulation by uremic status, with deficient antibody production despite a normal T cell proliferative response to mitogen stimulation in short-duration renal failure in high responder mice.

Animals↗

PubMed1993

Snakebite-induced acute renal failure: an experimental model.

Acute renal failure (ARF) has been frequently reported after bites from the Viperidae snake family. The lack of a reproducible animal model has hampered the study of renal damage mechanisms. Intravenous injection of rats with 0.4 mg/kg of Bothrops jararaca venom produced functional and morphologic changes similar to those observed in human snakebite-induced ARF. There was an acute and significant decrease in the glomerular filtration rate, diuresis, and renal plasma flow. Serum fibrinogen levels decreased significantly. There was intravascular hemolysis, as shown by a significant decrease in hematocrit, and an increase in plasma lactate dehydrogenase levels and free hemoglobin. Blood pressure and serum creatine phosphokinase levels were not affected. Light and electron microscopy showed massive fibrin deposition in glomerular capillaries, proximal and distal tubular necrosis, and hemolyzed red blood cell casts in renal tubules. Based on these findings, a model of snakebite-induced ARF was achieved. Ischemia related to glomerular coagulation and intravascular hemolysis were the most important pathogenic factors causing a decrease in the glomerular filtration rate, although a direct venom nephrotoxicity cannot be excluded.

Acute Kidney Injury↗

PubMed1993

Influence of the hydrostatic intraperitoneal pressure and the cardiac function on the lymphatic absorption rate of the peritoneal cavity in CAPD.

The purpose of this study was to determine the influence of hydrostatic intraperitoneal pressure (IPP) and cardiac function (CF) on the lymphatic absorption rate (LAR) in 9 patients on continuous ambulatory peritoneal dialysis (CAPD). The LAR was measured by estimation of the intraperitoneal disappearance of dextran 70 added to 2 L of 2.5% dextrose dialysis solution. The patients remained in the supine position during the 4-hour dwell. The IPP was obtained by measuring a column of dialysate in the peritoneal dialysis line, immediately before the drainage of the peritoneal cavity. The pressure was measured at the level of the umbilical cicatrix with point zero located on the mid axillary line of the patient. IPP was measured at inspiration and expiration, and the average of these two measurements was taken. These patients also underwent an echocardiographic examination. The LAR was 0.46 +/- 0.25 mL/minute, and the IPP was 13.07 +/- 2.61 cm H2O. The IPP correlated positively with the LAR (r = 0.80, p < 0.05). The intraperitoneal volume at the 4-hour dwell correlated inversely with the IPP (r = -0.68, p < 0.05). The left ventricular circumferential shortened fraction was 36 +/- 6% (27%-43%) and did not correlate with the LAR. These data suggest that the LAR is higher in patients with more elevated IPP. In addition, the CF, in the range studied, does not affect the lymphatic absorption rate.

Absorption↗

PubMed1993

Influence of spontaneous contractions of the lymphatic vessels on the lymphatic absorption rate of the peritoneal cavity in CAPD.

The lymphatic vessels have sympathetic innervation. Noradrenaline increases the number of spontaneous contractions of the lymphatic vessels, whereas isoprenaline slows these contractions. The purpose of this study was to analyze the influence of the blockade of spontaneous contractions of the lymphatic vessels on the lymphatic absorption rate (LAR) in 6 patients on continuous ambulatory peritoneal dialysis (CAPD) by using 0.12 mg of isoprenaline added to 2 L of 2.5% dextrose dialysis solution. This dose of isoprenaline has been shown to inhibit bovine mesenteric lymphatic contractions. The LAR was measured by the quantification of the intraperitoneal disappearance of dextran 70 added to this same dialysis solution during a 4-hour dwell. All patients were submitted to a control test without isoprenaline. The LAR was 0.57 +/- 0.19 and 0.65 +/- 0.38 mL/minute (p > 0.05), with and without isoprenaline, respectively. We conclude that spontaneous contractions of the lymphatic vessels do not play an important role in the lymphatic drainage mechanism of the peritoneal cavity. The diaphragmatic contractions seem to be more important, since drugs that interfere with such diaphragmatic mechanisms alter the LAR.

Absorption↗

PubMed1993

Nephrotoxicity of human Bence Jones protein in rats: proteinuria and enzymuria profile.

The effect of intravenous administration of 80 mg purified human Bence Jones protein twice weekly for 5 weeks was investigated in male Wistar rats (N = 7; 2 months old). A state of immunological tolerance was demonstrated by the absence of a B-cell response (plaque-forming cells and hemagglutination titers) and by the absence of detectable antigen or antibody deposition in glomeruli, as indicated by light and electron microscopy. No rise in blood urea level was detected (33.9 +/- 4.3 vs 32.8 +/- 1.3 mg%). There was an increase in proteinuria (5.3 +/- 0.9 vs 32.8 +/- 4.0 mg/day), mainly due to Bence Jones protein excretion (0 vs 29.2 +/- 5.2 mg/day), with a slight but significant increase in albuminuria (0.2 +/- 0.1 vs 1.0 +/- 0.2 mg/day). There was a significant increase of lysosomal N-acetyl-beta-D-glucosaminidase in the urine (6.1 +/- 1.3 vs 72.7 +/- 18.8 mU/mg in creatinine). Lysosomal accumulation of Bence Jones protein in proximal tubular cells was evidenced by immunoelectronmicroscopy with protein A-gold. These results clearly showed proximal tubular dysfunction induced by chronic Bence Jones protein administration, without interference of autologous immune response as demonstrated by immunological state of tolerance.

Animals↗

PubMed1992

Use of dextran 70 to estimate peritoneal lymphatic absorption rate in CAPD.

Peritoneal lymphatic absorption rate (LAR) in 15 patients on a CAPD program was measured by estimation of the disappearance of dextran 70 from the peritoneal cavity. The LAR was 1.03 +/- 0.45 ml/min. The cumulative lymphatic absorption, cumulative net transcapillary ultrafiltration, calculated net ultrafiltration (CUF) and measured net ultrafiltration (MUF) at 4 h exchange were respectively: 261 +/- 127 ml, 694 +/- 134 ml, 446 +/- 135 ml and 409 +/- 136 ml. Calculated and measured net ultrafiltration didn't differ significantly. An inverse correlation between MUF and LAR and a positive correlation between MUF and the ratio for dialysate glucose concentration at 4 hand dialysate glucose at 0 h (G4/G0) were observed (r = -0.522 and 0.547, respectively, p < 0.05). The multiple correlation coefficient between the MUF and LAR plus G4/G0 was higher (r = 0.617, p < 0.05). Peritonitis and the presence of diabetes didn't interfere with LAR. We have concluded that lymphatic absorption plus peritoneal transfer rate of glucose are important determinants of intraperitoneal volumes and that dextran 70 is a useful marker to measure lymphatic absorption.

Absorption↗

PubMed1988

Nephritis blunts urinary kallikrein excretion and aggravates DOCA/NaCl hypertension in rats.

1. Normal rats and passive Heymann membranous glomerulonephritic rats were chronically treated with DOCA/NaCl for 9 weeks. Normal and untreated nephritic rats were used as controls. Urinary kallikrein excretion (UKE), proteinuria and tail blood pressure (BP) were determined in awake rats. Glomerular filtration rate (GFR), plasma renin activity (PRA), and plasma potassium (PK) concentration were measured at the end of the experiment. 2. Comparison between basal and 9th-week measurements indicated that DOCA/NaCl administration significantly increased (P less than 0.05) UKE (3.96 +/- 0.30 vs 7.60 +/- 1.51 U/24 h) and BP (118 +/- 2 vs 135 +/- 6 mmHg) in normal rats, whereas in nephritic DOCA/NaCl-treated rats, UKE was unaltered (3.80 +/- 0.50 vs 3.40 +/- 0.30 U/24 h) and BP increased to higher levels (117 +/- 2 vs 152 +/- 3 mmHg) than in the normal DOCA/NaCl group (P less than 0.05). Passive Heymann nephritis alone did not affect UKE (3.56 +/- 0.40 vs 3.60 +/- 0.80 U/24 h) or BP (124 +/- 2 vs 125 +/- 2 mmHg). 3. At the end of the study, PK was decreased and PRA totally suppressed in both normal and nephritic DOCA/NaCl-treated rats. Proteinuria was more pronounced in nephritic DOCA/NaCl-treated rats (44.8 +/- 5.2 mg/day) than in control nephritic animals (15.1 +/- 2.4 mg/day) and GFR was increased equally in both DOCA/NaCl-treated groups. 4. The failure of nephritic rats to respond to DOCA/NaCl by increasing UKE was not associated with any significant derangement of renal function or structure and may have been related to the aggravation of arterial hypertension in this group.

Animals↗

PubMed1987

Potentiation of immune complex injury in rats by pretreatment with subnephrotoxic doses of guinea pig anti-glomerular basement membrane IgG1.

1. Female Wistar rats received a single subnephrotoxic dose of guinea pig anti-glomerular basement membrane (GBM) IgG1, 2.5 mg, followed by infusion of preformed immune complexes (BSA, 5.0 mg/rabbit anti-BSA, 6 mg), 10 X antigen excess. Control groups received guinea-pig IgG1 anti-GBM, or preformed immune complexes alone, or isotonic saline. Systemic reactions were observed clinically during the first 24 h, and 24 h urine was collected for the measurement of proteinuria and hematuria. 2. Blood was collected before and 2 h after the above treatment for the determination of complement (50% hemolytic assay), kininogen (isolated guinea pig assay of released bradykinin-like spasmogenic activity) and activated partial thromboplastin time (APTT). Kidney and lung tissue was examined by light microscopy, immunofluorescence and electron microscopy. 3. Rats treated with guinea pig anti-GBM IgG1 followed by BSA immune complex presented a severe systemic picture, with macroscopic hematuria (9/14), several deaths (8/14), slight proteinuria (24.6 +/- 5.2 mg/day), marked complement consumption (delta = 49.4 +/- 2.4 UCH50/ml), intravascular coagulation and severe diffuse interstitial pneumonia, obliteration of glomerular capillary walls by edema of endothelial cells, without deposition of immune complexes in kidneys or lungs. The control groups showed no signs of systemic reaction (isotonic saline alone) or slight dyspnea (guinea pig anti-GBM IgG1 or immune complexes alone), without proteinuria or macroscopic hematuria, and with foci of interstitial pneumonia. 4. Complement consumption was significant in rats receiving immune complexes alone (delta = 31.1 +/- 1.3 UCH50/ml) and even higher when associated with infusion of guinea pig anti-GBM IgG1 (delta = 49.3 +/- 2.4 UCH50/ml). APTT was significantly lengthened only for the group treated with guinea pig anti-GBM IgG1 plus immune complexes (delta = 18.5 +/- 1.9 s), with no alterations in the other groups. Kininogen consumption was demonstrable for all groups except the saline control and was more extensive in rats which received immune complexes alone or preceded by guinea pig IgG1. 5. These data show that previous infusion of a subnephrotoxic dose of guinea pig IgG1 anti-GBM aggravated the pathological effects of preformed immune complexes by promoting marked complement consumption and activation of the coagulation system, rather than by enhancing tissue deposition.

Animals↗