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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The suppressive effect of dipyridamole on the proteinuria of aminonucleoside nephrosis and protamine-induced proteinuria, was investigated. Male Wistar rats were given puromycin aminonucleoside (80 mg/kg s.c.) or protamine sulfate (20 mg/kg i.v.), and the urine was collected in metabolic cages. The content of proteins in the urine was determined by using a continuous gradient microgel electrophoresis procedure. Dipyridamole (20 mg/kg p.o.) suppressed the excretion of albumin and proteins larger than albumin (HMP) in aminonucleoside nephrosis. But the excertion of proteins smaller than albumin (LMP) was not affected by dipyridamole. Dipyridamole also suppressed the excertion of HMP in protamine-induced proteinuria, though the excretion of albumin and LMP was not affected. Puromycin aminonucleoside and protamine sulfate were known to cause renal glomerular epithelial changes referred to as "fusion" of foot processes. Since dipyridamole was effective in suppressing the both types of proteinuria, this drug was considered to improve the damaged renal glomerular barrier for plasma proteins.
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PMID:Suppressive effect of dipyridamole on the proteinuria of aminonucleoside nephrosis in rat. 48 Apr 1

The purpose of these experiments was to determine whether reported changes in substrate metabolism by isolated glomeruli from rats with aminonucleoside nephrosis could be explained by the glomerular changes associated with proteinuria or, alternatively, whether these metabolic changes and proteinuria were synchronous but causally unrelated events. Aminonucleoside of puromycin produced proteinuria within 7 days when injected intraperitoneally or subcutaneously. However, when aminonucleoside of puromycin as well as adenine were given, the onset of proteinuria was delayed until after day 7. A significant reduction in U-14C-glucose oxidation to CO2 was found at day 7 by glomeruli from rats given aminonucleoside of puromycin intraperitoneally but no significant changes were found with aminonucleoside of puromycin given subcutaneously on days 7 and 9 and aminonucleoside of puromycin + adenine given subcutaneously on days 7 and 9. Rats given daunomycin or adriamycin had developed proteinuria by day 14. U-14C-glucose oxidation to CO2 was significantly reduced on day 14 in glomeruli from rats given daunomycin but no significant changes were found on day 21 with daunomycin, or on days 14 and 21 with adriamycin. There was a reduction in pyruvic-acid carbon metabolism but not in glutamine-carbon oxidation 14 days after treatment with daunomycin. These results suggest that the observed changes in glomerular metabolism occur independently of, albeit synchronous with, the development of proteinuria. A causal relationship between these metabolic alterations and proteinuria therefore may be unlikely.
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PMID:Effects of aminonucleoside, daunomycin, and adriamycin on carbon oxidation by glomeruli. 124 18

Puromycin aminonucleoside (PA)-nephrotic rats have a high plasma renin activity (PRA) and low angiotensinogen levels. We measured proteinuria, urine renin, and urine angiotensinogen daily, for 11 days after PA injection. Proteinuria and urine angiotensinogen were evident on day 5, and urine renin on day 6. Peak levels of urine renin and angiotensinogen were attained on day 8. These data suggest that angiotensinogen urine excretion may contribute to its low plasma levels, and urine renin loss may limit a further increase in PRA.
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PMID:Urinary excretion of renin and angiotensinogen in nephrotic rats. 204 2

Puromycin aminonucleoside (PAN)-nephrotic rats have high serum angiotensin I-converting enzyme (ACE) activity. We studied ACE activity in serum, urine, and tissues from PAN-nephrotic rats on days 2, 6, 11, and 16 after PAN injection. Proteinuria and hypoproteinemia were evident on days 6 and 11. Though significantly decreased, proteinuria was still evident on day 16. Serum ACE activity increased on days 2, 6, and 11. Urinary ACE activity became evident on days 6, 11, and 16 and correlated positively with proteinuria, suggesting that the source of urine ACE is the blood serum. ACE activity increased in testis on days 2 and 6, in lungs and aorta on days 6 and 11, in adrenal glands and small intestine on day 11, and in kidney on days 11 and 16. Heart ACE activity decreased on days 2 and 6, and increased on day 16; brain ACE activity decreased on day 6 and increased on day 11. These data implicate that changes in tissue ACE content may contribute to elevate serum ACE in PAN-nephrotic rats.
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PMID:Angiotensin I-converting enzyme activity in puromycin aminonucleoside-nephrotic syndrome. 217 83

Puromycin aminonucleoside (PA) nephrosis is associated with a significant increase in the glomerular macrophage number during peak proteinuria. The significance of this observation remains uncertain. An essential fatty acid-deficient (EFAD) diet depletes normal rat glomeruli of resident macrophages and alters glomerular eicosanoid metabolism. In this study, we found that an EFAD diet, administered only for the duration of the acute nephrotic phase, significantly ameliorated the recurrent albuminuria, renal dysfunction, and morphological injury characteristic of the late, recurrent phase of chronic aminonucleoside nephrosis. Glomerular macrophage number, isolated glomerular thromboxane B2 production, and circulating leukocyte and monocyte counts were significantly reduced in nephrotic rats on the EFAD diet 2 wk after PA injection, which temporally corresponds to peak albuminuria. The exact mechanism(s) by which the EFAD diet conferred protection in the late phase of chronic aminonucleoside nephrosis and lowered glomerular macrophage number during the acute nephrotic phase remain to be elucidated.
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PMID:Essential fatty acid deficiency during acute puromycin nephrosis ameliorates late renal injury. 258 83

Puromycin aminonucleoside nephropathy with heavy proteinuria and oedema was induced in rats by 10 consecutive daily subcutaneous injections of aminonucleoside (1.67 mg/100 g of body weight). The main ultrastructural lesions were vacuolation of podocytes and total fusion of foot processes with loss of colloidal iron-reactive polyanion layer on the epithelial surface adjacent to the basement membrane. On the other hand the outer surface of podocytes and intravacuolar granular substance stained with colloidal iron. In scanning electron microscopy of freeze-fractured tissue the swollen podocytes and the urinary spaces displayed granular and filamentous precipitates. Seven cell surface antigens were examined by indirect enzyme immunohistochemistry with a series of MRC OX monoclonal antibodies. Glomeruli of control rats exhibited rare isolated Ia- positive endocapillary cells, possibly monocytes; these elements were significantly reduced in puromycin aminonucleoside nephropathy but there was an increase in Ia- positive cells in the cortical interstitium. Control kidneys harboured scanty interstitial T lymphocytes. These latter, especially the T8- positive cytotoxic/suppressor subpopulation, were markedly augmented in puromycin aminonucleoside nephropathy. The expression of class I histocompatibility antigens and of differentiation antigens (Thy 1) was not altered by aminonucleoside.
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PMID:Puromycin aminonucleoside nephropathy: ultrastructure, glomerular polyanion, and cell surface markers. 351 67

Several lines of evidence suggest that increased neuraminidase activity may be responsible for the loss of glomerular N-acetylneuraminic acid (AcNeu) observed in various glomerular diseases. However, virtually no information is available on the activity of neuraminidase in glomeruli or the potential role of this enzyme in glomerular pathophysiology. Utilizing 2'-(4-methylumbelliferyl)-alpha-D-N-acetylneuraminic acid (4MU-AcNeu) as substrate, we defined optimal assay conditions and characterized neuraminidase activity in glomeruli and, for comparison, in other renal fractions and liver. Neuraminidase activity in glomeruli, cortex and tubules was maximal at pH 4.4. The Km for 4MU-AcNeu was estimated to be 195 microM for glomeruli and 226 microM for cortex. Glomerular neuraminidase was inhibited by AcNeu (90% at 25 mM) and high concentrations of Triton X-100 (26% at 0.5%), but unaffected by CaCl2, EDTA or N-ethylmaleimide (each 1 mM). Neuraminidase activity (nmol/h per mg of protein; mean +/- S.E.M.) in normal rat kidney was: cortex, 14.47 +/- 0.76; medulla, 7.85 +/- 0.64; papilla, 2.64 +/- 0.11; tubules, 13.79 +/- 0.70; glomeruli, 5.57 +/- 0.28. In comparison, neuraminidase activity in rat liver was 2.58 +/- 0.14. Puromycin aminonucleoside (PAN)-induced nephrotic syndrome is a model of glomerular disease in which the loss of glomerular AcNeu is well documented. In two separate studies, we observed no change in the specific activity of neuraminidase in either glomeruli or cortex isolated from rats treated with PAN (15 mg/100 g, intraperitoneally) and killed at either the onset or the peak of proteinuria. Results were similar whether neuraminidase activity was expressed per mg of protein or per microgram of DNA.
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PMID:Renal neuraminidase. Characterization in normal rat kidney and measurement in experimentally induced nephrotic syndrome. 382 21

Puromycin aminonucleoside (PA), injected intravenously into rats in a single dose, causes proteinuria and ultrastructural pathology reminiscent of human lipoid nephrosis (puromycin aminonucleoside nephrosis (PAN]. Glomerular epithelial cell (GEC) endocytosis was studied in this model and in rats with protein-overload proteinuria using ultrastructural morphometry. Disappearance curves were constructed for protamine-heparin aggregates (PHA), which localized in the subepithelial region of the glomerular basal lamina following intravenous injection of protamine followed by heparin. Five groups were studied: (a) preproteinuric PAN, 4 days after PA (mean 4.5 +/- 1.5 mg of urinary protein/24 hours); (b) proteinuric PAN, 10 days after PA (mean 128 +/- 9.6 mg/24 hours); (c) recovery from PAN (mean 12.5 +/- 1.5 mg/24 hours); (d) protein-overload proteinuria, induced by injecting albumin intraperitoneally (mean 211 +/- 15.9 mg/24 hours); and (e) saline-injected controls (mean 1.2 +/- 0.2 mg/24 hours). Only the proteinuric PAN animals (group 2) had altered GEC endocytosis with a PHA half-disappearance time different from the group 5 saline controls (143.2 versus 72.6 minutes, p less than 0.05). The half-disappearance times in groups 1, 3, and 4 were 74.6, 80.7 and 86.5 minutes, respectively. Altered GEC function was further characterized by comparing PHA disappearance with the abundance of albumin-filled vacuoles in the GEC. Prolongation of PHA disappearance in group 2 correlated with the virtual absence of vacuoles; they were abundant in nonproteinuric phases of PAN and in animals with overload proteinuria. We conclude (a) GEC endocytosis is reduced only during the proteinuric phase of PAN, (b) GEC endocytosis is active during the preproteinuric phase of PAN and is a factor that may account for the absence of protein in the urine despite abnormal GBM permeability, (c) decreased GEC endocytosis during proteinuric PAN reflects abnormal cell metabolism due to PA and is not simply a consequence of albuminuria, as overload proteinuria did not produce diminished PHA or albumin uptake.
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PMID:Inhibition of glomerular visceral epithelial cell endocytosis during nephrosis induced by puromycin aminonucleoside. 638 77

The aminonucleoside of puromycin induces proteinuria and renal damage when given to rats. Aminonucleoside of puromycin was administered to male Wistar-Furth rats as a single intravenous injection in a dose of 15 mg. per 100 gm. of body weight. The animals were studied 9 days later when the mean urinary protein was 175 mg. per 24 hours. Evidence of glomerular epithelial cell injury included massive obliteration of foot processes, appearance of microvilli, protein reabsorption droplets, extreme attenuation of cytoplasm with formation of blebs, and focal detachment of epithelial cells from glomerular basement membrane. An increase in both the amount of mesangial matrix and the number of mesangial cells was also observed. The fractional clearance (C/GFR) of anionic horseradish peroxidase had increased 18.5 times as compared to control values and was nearly equal to the C/GFR of neutral horseradish peroxidase in the experimental rats. The C/GFR of cationic horseradish peroxidase was decreased by one-third so that it approximated the C/GFRs of both anionic and neutral horseradish peroxidase. These findings indicate a nearly complete loss of the charge-selective barrier to filtration. In addition, C/GFRs of tritiated uncharged dextrans with a range of molecular radii from 18 to 58 Angstrom (A) were determined. The C/GFRs of dextrans (alpha e less than 30 A) were decreased in the experimental rats as compared to C/GFRs of dextrans of corresponding molecular size in control rats. However, the C/GFRs of dextrans (alpha e greater than 38A) were increased in experimental as compared to control rats. Further, both anionic and cationic ferritin (alpha e = 61 A) were observed in the urinary space near denuded areas of glomerular basement membrane. These results indicate that the size-selective properties of the glomerular barrier to filtration have been modified with decreased C/GFR of small molecules and increased C/GFR of large molecules. Thus, the proteinuria of aminonucleoside nephrosis in rats occurs secondary to alterations in both the charge- and size-selective barriers to glomerular filtration.
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PMID:Alterations in the charge and size selectivity barrier of the glomerular filter in aminonucleoside nephrosis in rats. 746 51

Puromycin aminonucleoside (PAN)-induced proteinuria in rats may be mediated by reactive oxygen metabolites (ROM), which are injurious to several cell components including membrane lipids. Increased malondialdehyde (MDA) production is indicative of lipid peroxidation. We examined if MDA content of glomeruli and its urinary excretion were increased in rats administered PAN. Of three groups of 8 Sprague-Dawley rats each, group 1 served a control, group 2 animals received a single intravenous injection of PAN (5 mg/100 g body weight) and group 3 animals PAN with intraperitoneal injections of dimethylthiourea (DMTU), a free radical scavenger of oxidants such as hydroxyl radicals, for 4 days. The rats were sacrificed on day 8 after PAN injection. Increasing proteinuria, starting on day 4, developed in animals in group 2 but not in the others. The glomerular MDA (nmol/mg protein) in group 2 animals was 2.93 +/- 1.91, significantly higher than 0.87 +/- 0.63 and 1.26 +/- 0.76 in groups 1 and 3, respectively. Urinary levels of MDA markedly increased in group 2 rats on day 3 and remained high thereafter, but no such increase occurred in the control animals and those administered PAN with DMTU; the latter was thus protective against PAN toxicity. Our observations support the view that ROM are involved in PAN-induced glomerular injury and that increased urinary MDA excretion can be a marker of ROM-mediated lipid peroxidation.
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PMID:Increased glomerular and urinary malondialdehyde in puromycin aminonucleoside-induced proteinuria in rats. 774 22


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