Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current medical management programs for established joint diseases in hemophiliacs are unsatisfactory and do not modify the eventual outcome. D-penicillamine, a drug effective in the proliferative synovitis of rheumatoid arthritis, was evaluated in a rabbit model of hemarthroses-induced arthritis and in four hemophiliacs with chronic synovitis. The animals had intra-articular injections of citrate (left knees) and autologous citrated whole blood (right knees). Eight weeks later, the rabbits were divided into two groups: no treatment and D-penicillamine (50 mg/kg/day, IM) until sacrificed at 6 months. The saline-injected joints showed no inflammation and no iron deposition. The blood-injected knees showed iron deposition in both groups, the D-penicillamine animals had marked suppression of chronic inflammation. Of the four patients treated, three had clinical responses (reduction in synovial thickness, reduction in number of bleeds in the affected joint). One patient, who did not respond, developed mild-moderate proteinuria. Those patients who responded received between 5.3 and 7.1 mg/kg/day of the drug. Mild abnormalities in platelet aggregation were seen in the responders. This preliminary study suggests that D-penicillamine is beneficial in the chronic synovitis/arthritis induced by hemarthroses. Further trials are recommended.
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PMID:Treatment of hemophilic arthritis with D-penicillamine: a preliminary report. 401 26

Previously we have demonstrated that systemic activation of the complement system after intravenous injection of cobra venom factor (CVF) results in acute lung injury as reflected by increases in the vascular permeability of the lung as well as by morphologic evidence of damage to lung vascular endothelial cells. In using the vascular permeability of the lung as the reference, the current studies show a quantitative correlation between lung injury and the appearance in plasma of lipid peroxidation products (conjugated dienes) as well as increased concentrations of lactic dehydrogenase (LDH) and one of its isoenzymes (LDH-4). After injection of CVF, extracts of lungs also showed elevated levels of conjugated dienes, whereas no elevations were found in extracts of liver, kidney, and spleen. There was no evidence in CVF-injected rats of renal or hepatic injury as reflected by the lack of development of proteinuria and the failure to detect increased serum levels of liver-related enzymes. Other peroxidation products identified in plasma of CVF-injected rats involved hydroperoxides and fluorescent compounds with features of Schiff bases. Not surprisingly, malondialdehyde was not found to be a reliable plasma indicator of lipid peroxidation associated with oxygen radical-mediated lung vascular injury. In using a model of oxygen radical-independent lung injury induced by oleic acid, although large amounts of LDH and LDH-4 were found in the plasma, no increases in plasma levels of conjugated dienes were detected. In CVF-injected animals treated with interventions protective against lung injury (neutrophil depletion, catalase, hydroxyl radical scavengers, or iron chelators), there were striking reductions in the plasma levels of conjugated dienes, hydroperoxides, and fluorochromic products. Morphometric analysis of lung sections revealed that the protective interventions did not interfere with the accumulation of neutrophils in lung interstitial capillaries after systemic activation of complement. In vitro studies with phorbol-stimulated neutrophils failed to demonstrate appearance of conjugated dienes, suggesting that the dienes appearing in plasma of CVF-injected animals are not the result of autotoxic changes in neutrophils. The data presented in this paper suggest that acute lung injury mediated by oxygen radicals derived from phagocytic cells can be monitored by the appearance in plasma of products of lipid peroxidation.
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PMID:Systemic complement activation, lung injury, and products of lipid peroxidation. 403 Oct 60

7 of 16 patients with rheumatoid arthritis in whom penicillamine glomerulonephritis had developed had been taking oral iron, usually without the knowledge of their hospital clinician, while the dose of penicillamine was being gradually increased to an effective level. In 4 patients glomerulonephritis had appeared after the patients had stopped iron, with proteinuria developing with 2-5 months of discontinuation. Chelation of penicillamine by iron in the gut reduces its absorption, and in these 4 patients toxicity only became apparent after iron was stopped and there was a sudden increase in penicillamine absorption.
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PMID:Penicillamine nephropathy and iron. 612 65

To investigate the mechanism of proteinuria in minimal change nephropathy, the renal handling of dextrans was studied in seven nephrotic patients with this disorder. Although the urinary excretion of albumin was greatly increased, the urinary excretion and fractional clearance of dextrans (Einstein-Stokes radius (ESR), range 20 to 48 A) were depressed relative to those in nonproteinuric healthy volunteers. This suggests that mean glomerular pore size or pore density was reduced. Uptake of colloidal iron by glomeruli obtained from these patients by needle biopsy was diminished, suggesting loss of glomerular polyanion. Since the fractional clearance of dextrans similar in size to albumin was depressed, not increased, it is proposed that the lack of electrostatic interaction between the glomerular capillaries and polyanionic plasma albumin (ESR = 36 A) accounts for the selective albuminuria which characterizes minimal change nephropathy.
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PMID:Minimal change nephropathy: an electrochemical disorder of the glomerular membrane. 616 82

It is widely believed that polyanionic plasma proteins, such as albumin, are normally prevented from penetrating the glomerular capillary wall by the presence of intrinsic fixed negative charges in the wall. There is also strong support for the corollary that proteinuria occurs in glomerular disease as a result of loss of such charges. Morphologic studies using cationic 'stains' have indicated that anionic groups can be detected in normal glomeruli and that, in proteinuric states, there is an apparent reduction in such staining. Because most of the latter claims are based largely upon light microscopic studies, critical reassessment at the electron microscopic level is necessary, particularly using the recently developed technique of in situ drip-fixation of superficial glomeruli during good blood flow. In normal rats, this technique results in heavy cationic colloidal iron staining of podocytic epithelial surfaces but little or no staining in the basement membrane or within endothelial fenestrae. In two experimental proteinuric models, rat nephrotoxic nephritis and aminonucleoside nephrosis, there was no loss of colloidal iron staining on podocytic epithelial surfaces at any stage. There was, however, a striking alteration in glomerular architecture in each model, particularly affecting podocytic epithelium. Thus, there was extensive replacement of foot processes by flattened expanses of epithelial cytoplasm, associated with scattered focal gaps in the epithelial covering of the basement membrane. It therefore appears that the reduction of glomerular polyanion seen by light microscopy in glomerular disease results simply from a decrease in visceral epithelial surface area rather than a loss of intrinsic polyanion from the filtering portion of the glomerular capillary wall.
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PMID:Distribution of anionic groups in the glomerular capillary wall in rat nephrotoxic nephritis and aminonucleoside nephrosis. 616 35

The purpose of this study was to determine if exercise was associated with alterations in renal cortical sialic acid content or glomerular capillary anionic character. These factors have been shown to be important, insofar as they contribute to an electrostatic barrier which prevents the filtration of negatively charged macromolecules. In unilaterally nephrectomized dogs (n=7), exercised kidneys tended to have increased amounts of sialic acids and a decrease in glomerular anionic character, as evaluated by the intensity of colloidal iron staining, however, nephrectomy alone also caused similar changes. Additional experiments were conducted using rat litter mates assigned to control or treadmill-exercise groups. Exercised animals were run for 60-80 min. Renal cortical sialic acids were 2.74 +/- 0.07 mumol/g for controls (n=12) and 3.03 + 0.09 mumol/g for the exercised animals (n=10) (P less than 0.05). Colloidal iron staining, rated on a 0-3 scale (0=no uptake, 3=maximum staining) was 2.5 +/- 0.1 and 1.3 +/- 0.3 for the controls and exercised animals, respectively (P less than 0.05). Colloidal iron staining remained below control levels for 24 h post-exercise. These data suggest that exercise increases glomerular sialic acid content and decreases colloidal iron staining. This latter effect may decrease the glomerular capillary electrostatic barrier and thereby may be an important factor in causing exercise proteinuria.
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PMID:Changes in renal cortical sialic acids and colloidal iron staining associated with exercise. 616 85

Adriamycin has been suspected of causing experimental nephrotoxicity. We report here that adriamycin induces a nephrotic syndrome in rats, proteinuria beginning 4 to 5 days after a single intravenous injection (7.5 mg. per kg. of body weight). The full expression of the syndrome develops 13 to 15 days later. Minimal alterations at light microscopy, negative immunofluorescence, and only some focal "fusion" of foot processes can be observed by electron microscopy in the early phase after injection (28 hours). At 13 days, loss of foot process architecture, and replacement by flattened epithelial cytoplasm, was invariably found. These ultrastructural findings became extensive at 28 days follow-up. Colloidal iron staining of kidney biopsies revealed loss of glomerular polyanions as early as 3 hours and very marked loss at 28 hours after adriamycin injection. Polyanions were totally absent at 13 days and were still undetectable at 28 days. Thus, the loss of polyanionic charges associated with the sialic acid coat precedes the ultrastructural changes and the onset of proteinuria. These changes appeared similar to those reported in rats treated with daunomycin or puromycin animonucleoside. The present study supports in a different animal model the concept that both morphologic changes and proteinuria are the consequence of a common primary event that is the loss of glomerular fixed negative charges.
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PMID:Adriamycin-induced nephrotic syndrome in rats: sequence of pathologic events. 617 62

Renal biopsies from 23 patients with the nephrotic syndrome and five patients with slight or no proteinuria were examined for the presence of cell coat of podocytes by light and electron microscopy. Of those with nephrotic syndrome, five had minimal change disease, nine focal glomerular sclerosis, six membraneous nephropathy and three amyloidosis. Colloidal iron and phosphotungstic acid stains were used for the demonstration of anionic and neutral polysaccharide components of the cell coat. On light microscopy, the colloidal iron reaction showed a reduction in intensity of the stain in glomeruli of patients with massive proteinuria, as compared to those with slight or no proteinuria. On electron microscopy, only the cell coat lining the surface of the foot processes disappeared parallel to the loss of these structures, while the coat covering the surface facing the urinary space remained unchanged with both stains.
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PMID:Cell coat of podocytes in patients with nephrotic syndrome. 617 75

Alterations in glomerular permeability were studied in Adriamycin-induced proteinuria in rats by measuring fractional clearances (C/GFR) of uncharged labeled dextrans of varying molecular radii (ae) and of anionic, native, and cationic horseradish peroxidases (HRP) in experimental and control animals. Experimental animals were studied between days 14 and 55 after a single intravenous dose of Adriamycin (doxorubicin), 7.5 mg/kg. Mean proteinuria in the experimental animals was 98 mg/24 hr. Glomerular morphology showed few changes except for epithelial cell swelling, vacuolization, and foot process obliteration, and a significant reduction of glomerular colloidal iron staining. Polyethyleneimine staining revealed a similar distribution of anionic sites in the laminae rarae interna and externa in proteinuric rats as compared with controls. Inulin clearances revealed reduction in GFR and RPF of 20 and 15%, respectively. Dextran C/GFR values showed in experimental animals a size defect for molecules with an ae exceeding 40 A, with a four- to fivefold increase over the values found in control animals for dextrans with ae of 58 and 60 A. The peroxidase clearances showed a slight increase in C/GFR of anionic HRP in experimental animals, as could be expected on the basis of the sieving defect, whereas the C/GFR values for native and cationic HRP were virtually unchanged, indicating an intact functional charge barrier in the proteinuric animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glomerular permeability and polyanion in adriamycin nephrosis in the rat. 619 86

Immunologic mechanisms of proteinuria and ultrastructural alterations of the slit pore complex and glomerular charge barrier were investigated in Munich Wistar (MW) rats with nephrotoxic serum nephritis. Prior to disease induction, normal MW sera demonstrated 50% of the complement hemolytic activity compared with sera obtained from Sprague-Dawley rats. MW rats were sacrificed prior to, at onset (5 to 6 hours), and during maximal proteinuria (heterologous phase). Immunofluorescence revealed binding of rabbit antirat IgG antibodies in a linear pattern to the glomerular basement membrane (GBM) within 15 minutes postinjection. Complement deposition was not demonstrable in vivo in this model. Immediately after injection of nephrotoxic serum a decreased penetration of the GBM occurred, restricting ferritin to the level of the endothelium in in situ fixed glomeruli. GBM permeability to native ferritin did not increase despite areas of epithelial cell detachment, endothelial cell sloughing, and proteinuria between 2 and 24 hours postnephrotoxic serum injection. Colloidal iron initially decreased staining intensity between 6 and 8 hours, with a major decrease at 24 hours, indicating a loss in glomerular sialoprotein coincident with the onset of proteinuria. Polyethyleneimine (PEI) localization revealed an initial loss of anionic binding sites by 2 hours postinjection. At 6 hours peripheral capillary loops demonstrated only scattered, random polyethyleneimine-binding sites. Splitting of the lamina densa occurred at 24 hours with the exposure of previously undetected anionic binding sites within the lamina densa. Ultrastructurally, as early as 2 hours postnephrotoxic serum injection tissue perfused with tannic acid-glutaraldehyde showed epithelial membranes forming numerous pinocytotic vesicles. Blunting and retraction of foot processes caused displacement and stacking of slit diaphragms prior to the onset of proteinuria. Between 6 and 24 hours postinjection, slit diaphragms appeared to stretch and contract to compensate for epithelial cell retraction. Tangential sections showed neither alterations nor condensation products disrupting the isoporous substructure of the slit diaphragm 24 hours postnephrotoxic serum injection. Polymorphonuclear leukocytes were not found within capillary loops during the heterologous phase of nephrotoxic serum nephritis in MW rats. The absence of complement and polymorphonuclear leukocytes accompanying anti-GBM antibody deposition suggests that early epithelial cell injury and GBM charge alterations in MW rats are mediated by heterologous antibody via a complement-independent mechanism. The lower complement hemolytic activity in normal MW sera may explain the lack of complement involvement in renal lesions in this model of nephrotoxic serum nephritis. Loss of characteristic staining for both glomerular sialoprotein and discrete anionic sites in the GBM coincided with early epithelial cell alterations and occurred prior to the onset of measurable proteinuria.
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PMID:Complement-independent nephrotoxic serum nephritis in Munich Wistar rats. Immunologic and ultrastructural studies. 634 11


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