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)

Pharmacologic quantities of prostaglandin alter the immune complex nephritis of NZB/W mice. To study the mechanism of this change, NZB/W mice received 200 micrograms. of prostaglandin E1 or E2 twice daily starting at 2, 4, or 6 months of age. Mice were sacrificed at bimonthy intervals, renal function and serologic parameters were evaluated, and renal tissue was examined by light, fluorescence, and electron microscopy. Therapy decreased the incidence of proteinuria, lessened renal pathology, and prolonged survival. Maximal beneficial effects occurred when treatment began at 2 months of age. The most striking change was a decrease in the rate of immune complexes depositing in the mesangium and their absence from peripheral loops. Accompanying this change was a reduction in glomerular hypercellularity and a decrease in renal perivascular and interstitial mononuclear infiltrates. By contrast, treatment did not alter serum levels of immunoglobulins, antinuclear antibodies, and antisingle or double-stranded DNA. These results indicate that prostaglandin E is capable of prolonging survival in NZB/W mice by decreasing the rate of immune complexes depositing in glomeruli.
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PMID:Effect of prostaglandin E on immune complex nephritis in NZB/W mice. 15 78

NZB/NZW F1 hybrid mice were treated with pharmacologic doses of prostaglandin E1 (PGE1) (200 microng subcutaneously either once or twice daily) from 6 through 52 weeks of age. PGE1-treated mice were protected against development anemia, clinical nephritis, and death. At 52 weeks 18 of 19 treated mice were alive, wherase only 2 of 19 untretreated control mice were alive. None of the 10 mice treated with PGE1 twice daily exhibited significant (greater than 2+) proteinuria at 1 year of age. PGE1 treatment did not prevent development of antibodies to nuclear antigens. The data also suggest that survival of NZB/NZW mice is prolonged when treatment with PGE1 is begun at 24 weeks, an age at which mice already show evidence of nephritis. Thus all 6 mice treated with PGE1 (200 microng sc twice daily) from 24 weeks were alive at 52 weeks, whereas only 2 of 6 untreated control mice were alive. The mechanisms whereby PGE1 treatment influences the course of disease in NZB/NZW mice are not known.
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PMID:Prostaglandin E treatment of NZB/NZW mice. 30 Jun 26

In an investigation into the effect of prostaglandin E1 on proteinuria in nephrotic diabetic nephropathy, five patients were treated with 40 micrograms prostaglandin E1 administered intravenously over 2 h twice daily for 4 weeks. The following parameters were compared before and after treatment: protein excretion in urine; total serum protein concentration; serum albumin concentration; creatinine clearance; blood urea nitrogen; and serum creatinine content. A further five patients with nephropathy resulting from non-insulin-dependent diabetes mellitus were selected as controls. Analysis of the results using Student's t-test showed no significant change in any of the parameters before and after treatment.
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PMID:Influence of prostaglandin E1 on slight proteinuria in non-azotaemic diabetics. 156 24

The present study was designed to examine the suppressive action of Lipo PGE1 on the development of accelerated passive Heymann nephritis in rats. Lipo PGE1, given i.v. twice a day at 20, 40 and 80 micrograms/kg from the day after immunization with rabbit gamma-globulin (gamma-G) (the 1st day), remarkably inhibited the urinary protein excretion as well as glomerular histopathological changes such as thickening of basement membrane and spike formation. Lipo PGE1 at doses which the development of nephritis was suppressed, significantly inhibited the elevation of plasma antibody titer against rabbit gamma-G from the day before the appearance of the heavy proteinuria and apparently reduced the deposition of rat IgG in glomeruli. In addition, a single i. v. administration of Lipo PGE1 remarkably recovered the diminished renal blood flow induced by nephritis. These results suggest that intravenous Lipo PGE1 is effective in suppressing the development of the experimental membranous nephropathy. This agent may mainly prevent the development of nephritis by reducing the deposition of rat IgG in glomeruli via the suppression of host antibody formation. Furthermore, the increasing action of Lipo PGE1 on renal blood flow may be also in part related to a beneficial effect of this agent.
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PMID:[Studies on antinephritic effect of Lipo PGE1 (2). The suppressive action of Lipo PGE1 on the development of accelerated passive Heymann nephritis in rats]. 172 34

Prostaglandin E1 (PGE1) suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage dependent glomerulonephritis. Macrophages are mediators of glomerular injury in models of proliferative glomerulonephritis. We have recently shown that macrophages in glomerulonephritis have low prostaglandin E2 (PGE) generation, and other evidence implicates eicosanoids as regulators of macrophage activation. Here we have studied in rats the effect of 15(s)-15-methyl PGE1 (M-PGE1) on accelerated nephrotoxic nephritis, a model of acute macrophage-dependent glomerular injury. M-PGE1 ameliorated proteinuria (day 4; 61 +/- 13 mg/24 h, n = 9; vehicle treated, 164 +/- 17 mg/24 h, n = 11; P less than 0.002) and glomerular hypercellularity; quantification of infiltrating macrophages by isolating glomerular cells showed reduction in the numbers of macrophages (44 +/- 9/glomerulus; vehicle treated, 119 +/- 15/glomerulus; P less than 0.02) with inhibition of Ia antigen expression on infiltrating macrophages (8 +/- 5%; vehicle treated 25 +/- 4% P less than 0.05). Glomerular binding of nephrotoxic globulin and levels of autologous antibodies were not affected by M-PGE1. Thus the mechanism of suppression involves inhibition of macrophage accumulation and activation. M-PGE1 administered to normal rats did not affect numbers of resident leucocytes (12.6 +/- 1.5/glomerulus; vehicle treated, 13.2 +/- 1.3/glomerulus) or alter Ia antigen expression (4.1 +/- 0.2 Ia + cells/glomerulus; vehicle treated, 3.9 +/- 0.6/glomerulus). This study suggests a therapeutic role for PGE1 in this type of glomerulonephritis, and has implications for the pathophysiology of macrophage-mediated inflammation.
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PMID:Prostaglandin E1 suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage-dependent glomerulonephritis. 231 3

From January 1986 to December 1988, 8 patients with lupus nephritis did not respond to the administration of two courses of methylprednisolone pulse therapy and cyclophosphamide treatment for 56 days. These cases then received intravenous prostaglandin E1 (PGE1) for 3 weeks. All of them had a good response with decreased proteinuria and azotemia; serum C3 and C4 levels and creatinine clearance also increased. Both OKT4+ and OKT8+ cells increased, and the OKT4/OKT8 ratio was almost normal. The macrophage functions included increased production of interleukin 1 and gamma-interferon. The capacity to synthesize immunoglobulin after pokeweed mitogen stimulation was reduced, the circulating immune complexes lowered, and glomerular IgG deposits decreased in the two class IV follow-up biopsy cases after PGE1 therapy. These clinical improvements after PGE1 therapy are probably related to the modulation of macrophage T-B cell interaction, enhancement of reticuloendothelial system function, and increased glomerular capillary flow.
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PMID:Improvement in steroid and immunosuppressive drug resistant lupus nephritis by intravenous prostaglandin E1 therapy. 237 Sep 25

One hundred NZB/W F1 female mice were studied to compare the effects of a thromboxane synthase inhibitor (TSI), a stable prostacyclin analog (iloprost) and prostaglandin E1 (PGE1) in the evolution of the nephritis. At 10 weeks of age mice were randomly assigned to cohorts of 20 to receive either no treatment, vehicle control, PGE1, iloprost or TSI. Proteinuria, mortality, systemic blood pressure, renal immune complex deposition, urinary TX B2 and 6 keto PGF1 alpha levels were measured. Mice receiving PGE1 and iloprost had a significant delay in the onset of proteinuria and reduction in mortality at 40 weeks. The TSI treatment had no apparent effect on proteinuria or mortality. The amelioration of the nephritis was not associated with an alteration in immune complex deposition in survivors at 40 weeks. Although PGE1 and iloprost lessened the age related increase in urinary TX B2, increased the urinary 6 keto PGF1 alpha levels and the ratio of 6 keto PGF1 alpha to TX B2; so did the TSI. The PGE1 treated mice did experience a marked and persistent reduction in blood pressure but this was not observed in the iloprost- or the TSI-treated mice. All drugs tested reduced the age-related increase in thromboxane B2 but only the PGE1 and iloprost had a significant effect on the evolution of the nephritis.
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PMID:The effects of a thromboxane synthase inhibitor, a prostacyclin analog and PGE1 on the nephritis of the NZB/W F1 mouse. 245 Jul 13

Prostaglandin E1 was intravenously injected daily for 4 weeks to three patients with lupus nephritis accompanied by severe nephrotic syndrome. Histologic examination revealed diffuse proliferative or membranous glomerulonephritis. Proteinuria decreased markedly 1 year after the treatment with improvement in hypoproteinemia in all three patients. Five years later, the conditions of three cases ameliorated further.
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PMID:Beneficial effect of prostaglandin E1 in three cases of lupus nephritis with nephrotic syndrome. 305 87

Repeated subcutaneous (SC) injections of mercuric chloride (MC) in Brown Norway (BN) rats induce an autoimmune glomerulonephritis (GN) due to antiglomerular basement membrane (BM) antibody deposition in the glomeruli. The aim of this study was to investigate the effects on MC-induced autoimmune GN of OKY-046, a selective TXA-synthetase inhibitor herring oil (HO), which is rich in eicosapentaenoic acid (EPA) (5.6%) precursor of the three series of prostaglandins (PGs) and of (inactive) thromboxane (TXA3), and evening primrose oil (EPO), which is rich in linoleic acid (LA) (72%) and gamma-linolenic acid (GLNA) (9%), precursors of the one series of PGs, mainly PGE1, and of (inactive) TXA1. The administration of OKY-046 significantly inhibited proteinuria, partially prevented fibrin thrombi (FT) formation in the glomeruli, decreased urinary TXB, enhanced 6ketoPGF excretion and, increased survival rate of the animals from 60% (group receiving only MC) to 86%. However, OKY-046 did not prevent body weight (BW) loss or the development and deposition of IgG in the glomeruli. Increased intake of HO (80 days prior and throughout the experiment) and avoidance of arachidonic acid (AA) intake produced an effect comparable to that of OKY-046 in the rats. Furthermore, HO significantly inhibited the deposition of IgG in the glomeruli, increased the survival rate of the animals to 100% and further enhanced the increased urinary PGE excretion induced by MC. However, HO did not prevent BW loss in the animals. Increased intake of EPO and avoidance of AA intake produced an effect comparable to that of HO. Additionally, EPO completely prevented BW loss induced by MC in these animals. These findings suggest that the metabolites of AA, EPA and GLNA play an important role either in the development or in the modulation of this model of MC induced GN.
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PMID:Alteration of mercuric chloride-induced autoimmune glomerulonephritis in brown-Norway rats by herring oil, evening primrose oil and OKY-046 a selective TXA-synthetase inhibitor. 347 24

Prostaglandins have been implicated by previous investigators in the pathogenesis of the nephrotic syndrome. A single subcutaneous injection of 1 mg/kg of stable analogs of prostaglandins E1 or F2 alpha (15[S]-15-methyl -PGE1 [M-PGE1] and -PGF2 alpha [M-PGF2 alpha]) was found in the present study to dramatically decrease proteinuria on Day 10 of puromycin aminonucleoside (PAN) nephrosis in Lewis rats. The decrease in proteinuria was mediated at least in part by a decrease in glomerular filtration rate (GFR), as quantitated by inulin clearances in nephrotic control and prostaglandin-treated rats. M-PGE1, moderately, and M-PGF2 alpha, to a lesser degree, also decreased the GFR in normal rats. Interestingly, the GFR was dramatically decreased in nephrotic as compared with nonnephrotic control rats, which suggests that PAN nephrosis may not be an ideal experimental model for human minimal change nephrosis in which the GFR is usually not severely compromised. The prostaglandin-induced decrease in GFR in both nephrotic and normal rats was coincident with a drop in systemic blood pressure. Nephrotic rats, however, had a slightly higher baseline blood pressure than normals, and the hypotensive effects of both prostaglandins were much less in nephrotic than in normal rats. The decrease in proteinuria was not related to a cytoprotective effect, as indicated by the failure of daily doses of 5 micrograms/kg M-PGE1 to reduce proteinuria 6, 8, or 10 days after injection of puromycin aminonucleoside. The similar antiproteinuric effects of prostaglandin synthesis inhibitors and of pharmacologic doses of prostaglandins are somewhat paradoxical but are reminiscent of the similarly paradoxical mutual antiinflammatory effects of these agents. The high doses of prostaglandins required to reduce proteinuria as well as their reduction of blood pressure and GFR will limit their clinical usefulness in the nephrotic syndrome.
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PMID:Stable analogs of prostaglandins E1 and F2 alpha ameliorate the proteinuria of aminonucleoside-of-puromycin nephrosis in Lewis rats. 349 82


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