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)

We optimized the electrophoretic separation using sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE) and silver staining to detect small peptides in serum, without extraction of major proteins and applied this method to the search for specific peptides that may be used as early markers of preeclampsia during pregnancy. Appropriate separation of peptides was possible by modifying several parameters: increasing total proportion of monomers (%T) from 3 to 5% in the stacking gel; decreasing total proportion of crosslinker (%C) from 2.7 to 1.5% in the separating gel; selecting alkaline stacking gel buffer (pH 8.8) and alkaline sample buffer (pH 8.0); adding glycerol to both gels; and processing with weak current (15 mA). Silver nitrate staining was improved by using glutaraldehyde as the fixing agent, by reducing cross-linker concentration and by eliminating oxidizing and reducing agents. Sensitivity of the improved silver nitrate staining was 50 ng. We compared the electrophoretic pattern of serum peptides in the range of 2-14 kDa of 20 preeclamptic women with and without proteinuria and of 25 women in their third trimester who later developed preeclampsia to that of 24 normal pregnant women at term. No differences were found in the electrophoretic patterns among the groups and there was no correlation between the intensity of the bands and the severity of preeclampsia. We conclude that there is no characteristic electrophoretic pattern associated with preeclampsia.
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PMID:Electrophoretic method for separating small peptides in serum without extraction of macromolecules: application to the detection of preeclampsia. 807 74

Preautoimmune New Zealand Black/White (NZB/NZW) mice immunized with Escherichia coli (EC) double standard (ds) DNA produce antibodies that bind mammalian dsDNA and display specificities similar to spontaneous lupus anti-DNA. Since calf thymus (CT) dsDNA fails to induce these antibodies, these results suggest a special potency of foreign DNA in inducing serological manifestations of lupus in a susceptible host. To assess the effects of DNA immunization on clinical manifestations in NZB/NZW mice, we measured renal disease and survival of mice immunized with either (a) EC dsDNA as complexes with methylated bovine serum albumin (mBSA) in adjuvant; (b) CT dsDNA with mBSA in adjuvant; (c)mBSA alone in adjuvant; or (d) unimmunized. After immunization with EC dsDNA, NZB/NZW mice developed significant levels of anti-dsDNA antibodies. Nevertheless, these mice had less proteinuria, nitrate/nitrite excretion, and glomerular pathology than mice immunized with either mBSA alone, CT dsDNA/mBSA complexes, or unimmunized mice. Survival of the EC dsDNA immunized mice was significantly increased compared with the other mice. Furthermore, immunization of mice after the onset of anti-DNA production and proteinuria stabilized nephritis and prolonged survival. The improvement in renal disease occurred despite the expression of autoantibodies that bound mammalian dsDNA as well as glomerular antigens. These results suggest that bacterial DNA has immunological properties that attenuate murine lupus despite the induction of pathogenic antibodies.
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PMID:Modulation of renal disease in autoimmune NZB/NZW mice by immunization with bacterial DNA. 866 97

The present study was undertaken to investigate whether the development of proteinuria in the borderline hypertensive rat (BHR) is influenced by the Y chromosome and to determine if the onset of proteinuria in the BHR is delayed when blood pressure is lowered with enalapril, an angiotensin I converting enzyme inhibitor. Male F1, rats were the first-generation offspring of the mating of spontaneously hypertensive (SHR) females and Wistar-Kyoto (WKY) males and the mating of SHR males and WKY females. At 20 weeks of age, enalapril (125 mg/l) was added to the drinking water. Untreated BHR and enalapril-treated BHR (BHRE) were followed to 90-100 weeks of age. Urine was collected every 10-20 weeks for determination of protein, albumin, and nitric oxide (NO2/NO3) metabolite excretion. Indirect blood pressure in BHR from both crosses was approximately 175 mm Hg from 20 to 90-100 weeks of age. Enalapril lowered blood pressure by about 30 mm Hg, but was ineffective in reducing urinary protein or albumin excretion rates at any age. Urinary excretion of nitric oxide metabolites was similar in all groups at all time periods. There were significant differences in the percent of glomerulosclerosis between the two matings. Based on these results, renal injury in the BHR is not associated with the Y chromosome and can be dissociated from hypertension. Further studies using congenic and transgenic technology will be necessary to identify functions of genes and associations with hypertension in order to understand the kidney disease in this model of hypertension.
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PMID:Sex chromosomes do not influence renal injury in borderline hypertensive rats. 885 66

This study was designed to determine whether the diabetic BioBreeding rat develops significant renal injury following long-term moderate to severe hyperglycaemia. Diabetic and control rats were followed from the onset of diabetes (2-4 months) to 18 months of age. Frank proteinuria and/or albuminuria were always absent. Glomerular filtration rate, measured by inulin clearance (ml min-1 (100 g body weight)-1), was significantly higher in diabetic rats than in controls at 10, 12 and 18 months of age. Advanced glycosylation end-product cross-links assessed by percentage solubility of tail tendon collagen were moderately increased in diabetic compared with control animals. Urinary excretion of advanced glycosylation end-products in unfractionated urine and in urine fractionated for low molecular mass peptides (< 10 kDa) was 11-fold greater in the diabetic rats than in the control group. Urinary excretion of nitric oxide metabolites (nmol NO2- and NO3- (24 h)-1) were significantly (P < 0.05) greater in diabetic rats than in controls after 8 months of age. Mild histopathology resembling human diabetic nephropathy, including increased mesangial volume and glomerular basement membrane thickness, was detected at 18 months of age. The findings of hyperfiltration and mild glomerular morphological changes in diabetic BioBreeding rats are similar to the abnormalities seen in stage 2 human diabetic nephropathy. We hypothesize that two factors which may contribute to the resistance or tolerance to renal injury in the BioBreeding diabetic rat are increased nitric oxide production and the decreased accumulation of advanced glycosylation end-products.
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PMID:Resistance to glomerular injury in the diabetic biobreeding rat. 896 13

The purpose of the present study was to examine renal functional changes caused by chronic blockade of nitric oxide (NO) synthesis in young rats. Two types of NO synthase inhibitor were used: NG-nitro-L-arginine methyl ester (L-NAME) as a non-selective inhibitor and aminoguanidine (AG) as a selective inhibitor of the inducible isoform. Oral administration of L-NAME (20-80 mg/dL of drinking water), not AG (400 mg/dL), for 4 weeks induced systemic hypertension in the treated rats. Both inhibitors caused a significant reduction in urinary excretion of NO2-/NO3-. Rats treated with L-NAME developed proteinuria and tubular enzymuria (high excretion of N-acetyl-beta-D-glucosaminidase) in a dose-dependent fashion, with normal serum levels of creatinine, albumin and cholesterol. Chronic AG administration did not alter the urinary levels of protein and N-acetyl-beta-D-glucosaminidase or serum laboratory values. Overall, these observations highlight the importance of the continuous generation of NO by the constitutive isoform in the control of vascular tone and the maintenance of renal glomerular and tubular function. Oral administration of L-NAME may serve as a model of chronic NO-deficient hypertension with renal injury in young rats.
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PMID:Renal functional measurements in young rats with chronic inhibition of nitric oxide synthase. 900 96

Patients with any of four different types of chronic renal failure (CRF) (glomerular disease, interstitial nephritis, diabetic nephropathy, or polycystic disease) were observed using sequential determinations of glomerular filtration rate (GFR). Those whose GFR showed progression were either given ketoconazole 200 to 600 mg/d (to suppress cortisol production) plus prednisone 2.5 mg/d (to prevent anterior pituitary escape) and observed with the use of more GFRs, or were observed while four additional GFRs were determined before starting these drugs; some patients were subsequently withdrawn from these drugs and were observed using more GFRs. The effect of these drugs on rate of progression was estimated by a linear spline technique, using observations before, during, and (when available) after treatment. In 20 patients, sufficient data were obtained to estimate the magnitude of this effect. In seven patients with chronic glomerular disease, progressing at -0.62 +/- 0.12 mL/min/mo, progression slowed by 66% +/- 12% (P < 0.01). In five patients with interstitial nephritis of various etiologies, progressing at -1.19 +/- 0.34 mL/min/mo, progression slowed by 55% +/- 27% (P < 0.05). In five diabetic patients progressing at -1.22 +/- 0.14 mL/min/mo, progression slowed by an average of 77% +/- 14% (P < 0.01). In contrast, in four patients with polycystic kidney disease, progression accelerated by 99% +/- 63%. Mean urinary steroid excretion decreased significantly; plasma corticotropin did not increase. Neither proteinuria nor serum lipid levels changed. Urinary nitrate excretion decreased significantly, but serum nitrate did not change. Blood pressure decreased slightly (4.3 mm Hg). Three patients developed transiently elevated serum transaminase levels; two others withdrew because of side effects. We conclude that in chronic glomerular disease, diabetic nephropathy, and interstitial nephritis, this combination of drugs is as safe as ketoconazole in the absence of renal disease and shows promise of slowing progression. In polycystic kidney disease, it is apparently ineffective or harmful.
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PMID:Effect of ketoconazole plus low-dose prednisone on progression of chronic renal failure. 910 38

1. To investigate the role of nitric oxide (NO) in diabetic nephropathy the effect of nitric oxide synthase (NOS) inhibition by NG-nitro-L-arginine methyl ester (L-NAME) was observed in a streptozotocin diabetic spontaneously hypertensive rat (SHR) model. 2. Two groups of SHR (n = 8) with streptozotocin-induced diabetes were studied. One group was given L-NAME 5 mg/kg bodyweight per day in the drinking water for 8 weeks while both groups received daily subcutaneous injections of Ultratard insulin. Creatinine clearance, urinary protein excretion, urinary nitrate concentration and systolic blood pressure were measured at fortnightly intervals. Rats were killed at 8 weeks and plasma angiotensin II (AngII) was measured by radioimmunoassay. 3. Renal function (endogenous creatinine clearance) remained stable in both groups. In the L-NAME group, however, there was a progressive increase in proteinuria that was highly significant at 6 weeks (22.1 +/- 2.9 compared with 6.5 +/- 0.7 mg/ 24 h per 100 g in control SHR diabetic rats P < 0.001). 4. Systolic blood pressure was significantly elevated in the L-NAME group throughout the study compared with the control group. 5. Plasma AngII was significantly elevated in the L-NAME group compared with controls (42.8 +/- 10.3 vs 15.1 +/- 1.9 pmol/L, respectively; P < 0.05). 6. Activation of the renin-angiotensin system may account, at least in part, for the resulting vasoconstrictor activity with chronic nitric oxide depletion.
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PMID:Nitric oxide synthase inhibition in a spontaneously hypertensive rat model of diabetic nephropathy. 917 57

Nitric oxide (NO) is an important factor in tissue trauma, but its detailed role in the pathogenesis remains unknown. In autoimmune vasculitis, it is possible that NO in one of the factors underlying tissue trauma and induction of autoimmune antibodies. To study its role on an animal model using mercury chloride (HgCl2), Brown Norway rats (BN rats) were given five injections of] HgCl2, each 1 mg/kg, over 10 days. Vasculitis and production of some autoimmune antibodies developed after HgCl2 injections. Urine nitrate/nitrite, metabolic production of NO, was produced in advance of the production of other autoimmune antibodies. To elucidate the role of NO, NG-nitro-L-arginine methyl ester (L-NAME), which is a nitric oxide synthase (NOS) inhibitor, was given in addition to HgCl2, at the daily dose of 30 mg/kg. There was no difference in production of autoimmune antibodies between this group and the control group, but urine protein excretion was suppressed in the HgCl2 + L-NAME group (p < 0.001). By immunohistochemical study, inducible NOS was positive in small vessels and mesangial cells in rat kidney. We conclude that in this animal model, over-production of NO leads to the production of autoimmune antibodies and inhibition of NOS production ameliorates proteinuria. These results suggest that NO plays an important role in the induction of renal injury in the rat model of autoimmune vasculitis.
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PMID:[The role of nitric oxide in mercury chloride-induced vasculitis in the brown Norway rat]. 928 9

Cationic colloid gold, a polycationic histochemical probe, was used to analyze the distribution of glomerular basement membrane (GBM) polyanions, including heparan sulfate protoglycan in genetic salt-sensitive (SBH/Y) and resistant (SBN/Y) hypertensive rats, with or without high dietary salt intake. GBM morphology, renal function and nitric oxide, as measured by plasma and urine nitrite (NO2) and nitrate (NO3) were also determined. In the salt-sensitive rats the high-salt dietary intake resulted in severe hypertension, proteinuria and decreased glomerular filtration rate. After 1 month of high-salt intake, the average width of the GBM of salt-sensitive rats was higher by 27% than that of salt-resistant rats. The number of GBM anionic sites (lamina rata externa and interna) was much lower in both salt-sensitive and salt-resistant groups after 1 month of salt loading, 8.04+/-0.36 and 7.8+/-0.25 counts/cm, respectively, compared to the respective values of non-salt-loaded animals, 20.58+/-1.08 counts/cm in the SBH/Y (p < 0.001) and 21+/-1.86 counts/cm in the SBN/Y (p < 0.001). A decreased nitric oxide production was found in the salt-sensitive rats before and after salt loading compared with the salt-resistant group. No correlation was found between the nitric oxide changes and the GBM modifications. It is concluded that high-salt intake may be deleterious to the permselectivity of the GBM. It is suggested that salt restriction in hypertension may have a beneficial effect in preventing GBM permselectivity changes and proteinuria.
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PMID:Glomerular basement membrane polyanionic sites and nitric oxide in genetically salt-sensitive and resistant hypertensive rats. 939 26

We conducted longitudinal measurements of blood pressure and renal function in the conscious, chronically catheterized rat before and during acute nitric oxide synthase inhibition (N-nitro-L-arginine methylester [L-NAME], 37 micromol/kg IV) and then chronic administration of oral L-NAME (approximately 37 micromol/kg per 24 hours). These studies specifically investigate the impact on plasma and renal renin as well as volume status during the evolution of this hypertension in rats not subjected to acute experimental stress. Blood pressure progressively increased with chronic administration of L-NAME and reached values greatly above those seen with acute administration of L-NAME. There were parallel increases in renal vascular resistance and development of proteinuria, and glomerular filtration rate began to decline at day 21, coincident with the appearance of renal damage. Twenty-four-hour urinary nitrite and nitrate excretion remained depressed, reflecting reduced nitric oxide synthesis. The plasma renin activity was variable and only increased transiently at 21 days, thus the angiotensin II dependence of this hypertension is not caused by stimulated plasma renin activity. Despite severe hypertension, sodium intake and excretion were unchanged over the 21 days of L-NAME administration. Plasma volume was significantly reduced at days 2 and 12 of L-NAME administration; thus the prolonged plasma volume contraction must result from the acute natriuretic response to the initial acute L-NAME administration.
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PMID:Evolution of chronic nitric oxide inhibition hypertension: relationship to renal function. 944 85


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