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)

1-(2-Chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU) and chlorozotocin (CZ; 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose) are structurally related anticancer agents which differ by virtue of the increased water solubility, and comparatively low carbamylating activity, of CZ relative to MeCCNU. In the present study, a single sc injection of either of these chloroethylnitrosoureas was nephrotoxic to male Fischer 344 rats. However, at equimolar doses, CZ was shown to be a much more potent nephrotoxicant. A lethal 40-mg/kg dose of CZ (127 microM) initially resulted in acute tubular necrosis of the proximal tubules of the cortex, followed later by a necrosis of papillary collecting ducts. In contrast, lethal doses of MeCCNU (100-180 mg/kg; 400-730 microM) produced only minimal proximal tubule injury. A 250-mg/kg (1 mM) dose of MeCCNU resulted in massive papillary necrosis within 7 days, with only limited necrosis to the proximal tubules. Sublethal doses of either drug, resulted in a similar, chronic, progressive nephropathy which was delayed in onset and was characterized by polyuria, enzymuria, a decrease in urine concentrating ability, and in renal slice organic ion accumulation. Alterations in less sensitive indicators of renal toxicity (i.e., proteinuria, glucosuria, and elevated blood urea nitrogen) were observed no earlier than 3 to 7 days after administration of only the highest tested doses of CZ (40 mg/kg) or MeCCNU (250 mg/kg). At sublethal doses, administration of either drug resulted in karyomegaly to the collecting ducts in the renal medulla within 2 to 4 weeks. These studies demonstrate that carbamylation-mediated reactions may not be necessary for nephrotoxicity to develop following administration of this class of antitumor agent.
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PMID:Comparative nephrotoxicity of 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea (MeCCNU) and chlorozotocin: functional-structural correlations in the Fischer 344 rat. 293 79

The effect of the antiplatelet agents ticlopidine and dipyridamole on immune complex glomerulonephritis in rats was evaluated. Bovine serum albumin (BSA) nephritis was induced in rats with subcutaneous immunization and intravenous dosage of BSA. Ticlopidine and dipyridamole were administered for 4 weeks before and for 7 days after onset of proteinuria. It was shown that both ticlopidine and dipyridamole could reduce the development of proteinuria when administered before the onset of proteinuria. Ticlopidine also reduced the amount of urinary protein after onset of proteinuria, and may thus be more effective against urinary protein excretion. When the antiplatelet agents were administered before onset of glomerulonephritis, blood urea nitrogen and serum creatinine levels were significantly lower, and glomerular hypercellularity and mesangial widening were milder in animals treated with ticlopidine than in controls. Glomerular deposition of BSA was less intense in treated animals than in nontreated controls. Thus, ticlopidine as well as dipyridamole was found to inhibit the development of proteinuria and glomerular alteration. It is suggested that ticlopidine could be more effective than dipyridamole against the development of immune complex glomerulonephritis in rats.
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PMID:Effect of the antiplatelet agents ticlopidine and dipyridamole on experimental immune complex glomerulonephritis in rats. 293 58

Clinical effects of dipyridamole and carbazochrome sodium sulfonate in patients with IgA nephropathy are described. Oral administration of 300 mg of dipyridamole and 180 mg of carbazochrome sodium sulfonate per day was employed in the present study. Urinalysis and renal function tests, i.e. serum creatinine (s-Cr), blood urea nitrogen (BUN), glomerular filtration rate (GFR) and phenolsulfonphtalein (PSP) tests, were performed before and after the administration of dipyridamole. It was demonstrated that the administration of dipyridamole was effective in reducing the level of proteinuria in the patients. The administration of carbazochrome sodium sulfonate was not effective in reducing the proteinuria level. It was concluded that the administration of dipyridamole may be useful for treatment of patients with IgA nephropathy.
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PMID:Clinical effect of dipyridamole in patients with IgA nephropathy. 296 35

The acute phase of glomerular injury in a model of antiglomerular basement membrane, antibody-induced glomerulonephritis (antiGBM-GN) in rabbits was shown to be neutrophil-dependent using nitrogen mustard depletion studies. Administration of desferrioxamine (DFX) prevented the development of proteinuria in this model of renal injury [24 hr protein excretion (mean +/- SEM): antiGBM-GN/DFX = 16.2 +/- 2.9 mg compared with antiGBM-GN control = 271.5 +/- 92.2 mg, P less than 0.01]. Antibody binding levels, glomerular filtration rates, circulating complement and neutrophil counts, glomerular C3 deposition, and neutrophil infiltration did not differ between DFX treated and antiGBM-GN groups. In vitro assay systems to assess oxygen radical production [superoxide anion (O2-) and hydroxyl radical (OH.)] by neutrophils activated via the interaction of antiGBM antibody, GBM and complement were established. In these assays, DFX inhibited OH. production by immunologically-stimulated neutrophils (ISN) [nM diphenol/hr/10(6) cells, mean +/- SEM, ISN/DFX = 8 +/- 2 compared with ISN = 191 +/- 22, P less than 0.01] while production of O2- was not affected [nM O2-/hr/10(6) cells, mean +/- SEM, ISN/DFX = 29.1 +/- 4.3 compared with ISN = 32.6 +/- 2.5, P greater than 0.05]. These studies demonstrate that the iron chelator desferrioxamine can prevent neutrophil-dependent immune renal injury by interfering with neutrophil function. Treatment with the hydroxyl radical scavenger dimethylthiourea also significantly attenuated renal injury in antiGBM-GN. Together, the in vivo and in vitro data strongly suggest that neutrophil-dependent immunological renal injury is mediated via hydroxyl radical production by activated neutrophils within glomeruli.
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PMID:Hydroxyl radical mediation of immune renal injury by desferrioxamine. 302 99

Mediation of the glomerular lesion and proteinuria produced by sheep antirabbit F x 1A globulin (SAFG) in rabbits was examined by prior treatment with cobra venom factor and nitrogen mustard. SAFG binding and proteinuria at 24 h were independent of complement or leucocytes but dose dependent. SAFG reacted by immunoblot with a wide range of antigens in deoxycholate extracts of rabbit glomeruli and autologous F x 1A including eight prominent shared bands of 29-128 kd. Immunogold electron microscopy has revealed the in vivo glomerular binding of SAFG as discrete, nonlinear and predominantly within the laminae rarae, in association with epithelial and particularly endothelial components of the glomerular capillary wall. In vitro binding was prominent on the endothelium. Proteinuria in this model is mediated by antibody without requirement for complement or leucocytes. The putative antigen(s) is/are associated with components of the glomerular capillary wall which share epitopes with autologous tubular F x 1A. This model is an example of an in situ immune complex glomerular nephritis and is distinct from the classical anti-F x 1A model, passive Heymann's nephritis in the rat.
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PMID:Tubular antigen-associated renal disease in New Zealand white rabbits. II. Investigation of mediators of glomerular injury: localization and characterization of the glomerular capillary wall antigen. 307 Apr 16

2-Bromo-(diglutathion-S-yl)hydroquinone [2-Br-(diGSyl)HQ] causes severe necrosis of the proximal renal tubules in the rat, elevations in blood urea nitrogen (BUN) and increased urinary excretion of protein, glucose, and lactate dehydrogenase. In contrast, 2-Br-3-(GSyl)HQ, 2-Br-5-(GSyl)HQ, and 2-Br-6-(GSyl)HQ caused differentially less toxicity than the diglutathionyl conjugate. None of these conjugates had any apparent effect on liver pathology and serum glutamate-pyruvate transaminase remained within the normal range. Pretreatment of rats with probenecid, an organic anion transport inhibitor, offered only slight protection against 2-Br-(diGSyl)HQ-mediated elevations in BUN, proteinuria, or glucosuria. In contrast, quinine, an organic cation transport inhibitor, potentiated the nephrotoxicity of 2-Br-(di-GSyl)HQ. Thus, in contrast to other nephrotoxic sulfur conjugates, probenecid-sensitive organic ion transport systems do not contribute to the kidney-specific toxicity of 2-Br-(diGSyl)HQ. However, inhibition of renal gamma-glutamyl transpeptidase by AT-125 completely protected rats from the nephrotoxic effects of 2-Br-(diGSyl)HQ. Aminooxyacetic acid, an inhibitor of cysteine conjugate beta-lyase, caused a 20-25% decrease in 2-Br-(diGSyl)HQ-mediated elevations in BUN and urinary excretion parameters. The isomeric 35S conjugates covalently bound to rat kidney 10,000 x g homogenate in the order 2-Br-6-(GSyl)HQ greater than 2-Br-5-(GSyl)HQ greater than 2-Br-3-(GSyl)HQ greater than 2-Br-(diGSyl)HQ. AT-125 (0.4 mM) decreased covalent binding by 25%, 17%, 33%, and 28%, respectively. Aminooxyacetic acid (0.1 mM) inhibited covalent binding by 26%, 10%, 17%, and 17% respectively. Ascorbic acid (1.0 mM) inhibited covalent binding by 63%, 87%, 62%, and 28%, respectively, and this inhibition correlated, inversely, with the redox potential of the conjugates. Thus, the covalent binding is mediated preferentially by oxidation of the quinol moiety, although the formation of reactive thiols cannot be excluded. In addition, the initial conjugation of 2-BrHQ with GSH does not result in the formation of a less redox-active species. However, the subsequent addition of a second molecule of GSH results in the formation of a more redox-stable compound, which, paradoxically, enhances toxicity. The metabolism of 2-Br-(diGSyl)HQ by renal proximal tubular gamma-glutamyl transpeptidase and trans-membrane transport of the cysteine conjugate(s) followed by oxidation of the quinol moiety is probably responsible for the target organ toxicity of this compound.
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PMID:2-Bromo-(diglutathion-S-yl)hydroquinone nephrotoxicity: physiological, biochemical, and electrochemical determinants. 317 33

The prevalence of diabetic retinopathy and the evaluation of its risk factors is poorly known in Italian population. Therefore, we have studied 894 diabetic outpatients (420 males, 474 females, 27.6% IDDs, 38.1% insulin-treated) in order to investigate the effect of clinical and metabolic characteristics on the frequency of diabetic retinopathy, classified into six different classes. In univariate analyses age, duration of disease, systolic and diastolic blood pressure, blood urea nitrogen, 24 hr proteinuria and fasting glycemia significantly correlated (p less than 0.001) with severity of retinopathy. The significance was confirmed in multivariate analysis for duration, age and systolic blood pressure (p less than 0.001). Stratification by type of diabetes showed that undefined onset of diabetes probably reduced in NID patients the power of duration as an associated factor of retinopathy. Worsening of this complication in three clinical classes of therapy (diet, oral and insulin-treatment) is evident too. Finally, our 11 variables in the step-wise multiple-regression analysis explain only 16.8% of diabetic retinopathy in all patients, but 36.6% in selected ID subjects.
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PMID:Univariate and multivariate analysis of associated factors of retinopathy in 894 Italian adult diabetics. 324 87

A toxicology study of cis-diamminedichloroplatinum (II) (CDDP), aqua(1,1-bis-(aminomethyl)cyclohexane)sulfatoplatinum(II) (TNO-6), diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA), cis-dichloro-trans-dihydroxo-cis-bis(isopropylamine)platinum-(IV) (CHIP) and ethylenediaminemalonatoplatinum(II) (JM-40) was carried out in dogs. The main purpose of the study was to compare the results with those obtained earlier in mice and rats and with the toxicology data in humans. Each platinum compound was tested in three dogs. Each dog received three intravenous bolus injections at intervals of 3 weeks. The compounds were administered in dosages of 1.2, 1.0, 12, 10 (or 6) and 10 mg/kg, respectively. Toxic death occurred for two dogs (both on day 54) from haematotoxicity (10 mg/kg CHIP) and renal toxicity (TNO-6), respectively. Serum urea nitrogen and creatinine concentrations were variable after TNO-6 and remained within normal values after treatment with the other compounds. Severe proteinuria was observed in all three dogs treated with TNO-6. Values returned to normal within 16 days. JM-40 did not cause significant proteinuria. CDDP, CBDCA and CHIP caused short-lasting and slight proteinuria. CHIP caused a severe reduction in the number of leukocytes and platelets, while the other drugs caused acceptable reductions. Except after the high dose CHIP regimen, haematotoxicity was of a transient nature. Vomiting in order of severity occurred after TNO-6, CHIP, CDDP and JM-40, while CBDCA did not cause any vomiting. The dogs were sacrificed 6 weeks after the last drug dose. Organs were fixed for histopathology to complete and support clinical-toxicological parameters. On the basis of the results from the single-dose study in dogs and those obtained earlier in mice and rats it can be concluded that the gain from the use of the dog as a prognosticator for organ toxicity in man was disappointing and limited to the prediction of vomiting.
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PMID:Preclinical toxicology of platinum analogues in dogs. 330 82

Hepatic dysfunction is one of the frequent manifestations of multisystemic involvement in preeclampsia. This study was conducted to establish the impact of liver dysfunction on maternal and neonatal outcome in women with pregnancy-induced hypertension (PIH). The prevalence of liver dysfunction as determined by an elevated serum glutamic oxalacetic transaminase (SGOT) concentration was 21% in a population of 355 patients with PIH. Liver dysfunction was associated with the presence of severe hypertension, proteinuria, a lower platelet count, and renal compromise (elevated blood urea nitrogen, creatinine, and uric acid serum concentrations). Abdominal pain was also associated with an SGOT elevation. Liver dysfunction was associated with intrauterine growth retardation and prematurity. Furthermore, the association with these neonatal complications was independent from the severity of the hypertension and the presence of proteinuria. Thus, we conclude that liver dysfunction is a frequent complication of PIH and that it is an independent risk factor for maternal and perinatal complications.
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PMID:Clinical significance of liver dysfunction in pregnancy-induced hypertension. 334 61

The role of the major histocompatibility complex in the development of apoferritin induced immune complex glomerulonephritis was studied in H-2 congenic B10 mice. The glomerular lesions varied strikingly among the three different strains studied. The B10 (H-2b) mice had minimal mesangial expansion or no lesions at all. The B10.BR (H-2k) mice had mesangial expansion and proliferative glomerulonephritis without crescents or interstitial mononuclear cell infiltration. In contrast, the B10.D2 (H-2d) mice had necrotizing glomerulonephritis with crescents and an interstitial mononuclear cell infiltrate. Immunofluorescence and electron microscopy demonstrated only minimal mesangial deposits in B10 (H-2b) mice, predominantly mesangial deposition in the B10.BR (H-2k) mice, and mesangial and subepithelial immune complex deposits in B10.D2 (H-2d) mice. These morphologic differences correlated with functional abnormalities. Only the B10.D2 (H-2d) mice developed proteinuria, hematuria, and elevated blood urea nitrogen. They also had the most elevated antiapoferritin IgG levels. These experiments demonstrate that differences in the pathologic lesions and susceptibility to immune complex glomerulonephritis can be seen in animals that differ only at the H-2 locus. This model will lend itself to the study of the mechanisms by which the major histocompatibility complex influences the development of immune complex glomerulonephritis.
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PMID:The role of H-2 in apoferritin-induced murine immune complex glomerulonephritis. 337 15


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