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)

Accelerated anti-glomerular basement membrane nephritis was induced in rabbits, and the immunological, clinical and histological evolution studied in relation to urinary immunoreactive thromboxane B2 (i-TXB2) and immunoreactive prostaglandin E2 (i-PGE2) excretion. In control nephritic animals, urinary i-TXB2 increased 5-fold on day +1, but was normal again by day +5. The urinary i-TXB2 showed a positive correlation with creatinine clearance (CCr), proteinuria and anti-sheep immunoglobulin antibody. Urinary i-PGE2 excretion increased by 50% on day +1, but was indistinguishable later from controls. The effects of the specific thromboxane synthetase inhibitor OKY-046 on this model was studied. In non-nephritic control animals, OKY-046 did not affect the CCr, the urinary protein excretion or the number of monocytes in glomeruli but reduced the excretion of i-TXB2. Although OKY-046 markedly inhibited the i-TXB2 excretion throughout the experiment in nephritic animals, the creatinine clearances were significantly worse, the proteinuria greater, and the number of infiltrating monocytes greater at day +5; by day +10 there was no difference from controls. There was no evidence that TXB2 is involved in the induction of proteinuria, and increased PGE2 synthesis did not protect against later proteinuria and fall in creatinine clearance. Inhibition of thromboxane synthetase appears to make this model of nephritis worse, rather than better.
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PMID:Rabbit nephrotoxic nephritis: effect of a thromboxane synthetase inhibitor on evolution and prostaglandin excretion. 331 92

Urinary PGE2 levels in urine collected over 24 hours were measured by radioimmunoassay after chloroform extraction. In normal pregnancy, urinary PGE2 levels did not change during pregnancy. After 36 gestational weeks, urinary PGE2 levels in severe hypertensive pregnancy (616 +/- 91 ng/day (mean +/- S.E., n = 18)) were significantly decreased compared to those of normal pregnancy (1,039 +/- 85 ng/day, n = 13, p less than 0.005) and mild hypertensive pregnancy (1,025 +/- 140 ng/day, n = 8, p less than 0.03). We then analyzed the urinary PGE2 levels by noting clinical symptoms and their severity. Urinary PGE2 levels in the severe blood pressure group were significantly decreased compared to those of the mild group. There was a significant negative correlation between urinary PGE2 and mean blood pressure, systolic pressure and diastolic pressure. Diastolic pressure in particular had the most significant negative correlation with the urinary PGE2 level (n = 33, r = -0.593, p less than 0.001). Urinary PGE2 levels in the severe proteinuria and edema groups were significantly decreased compared to those in the mild group. These results suggested that renal synthesis of PGE2 may be decreased in severe hypertensive pregnancy and closely related to blood pressure, especially to diastolic pressure, and also related to the occurrence of edema.
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PMID:[Urinary PGE2 levels in toxemia of pregnancy]. 346 58

Immediate and longer-term (five-day) effects of indomethacin on proteinuria and renal function were examined in a group of nephrotic subjects with glomerular filtration rates (GFR) that ranged from near normal to moderately impaired. The modifying role of the patients' sodium/volume (S/V) status on renal prostaglandin inhibition was systematically evaluated by renal clearance and balance studies. After patients were S/V-depleted for five days, indomethacin (75 mg/d) decreased protein excretion by 45%. The decrement in proteinuria was greater than 2 times greater than the fall in creatinine clearance and was unrelated to baseline clearance. In acute clearance studies, 75 mg indomethacin administered orally immediately reduced protein excretion, effective renal plasma flow (CPAH), GFR (C inulin), Na, K, and free water excretion. Indomethacin responsiveness (reduced proteinuria) correlated with the change in PGE2 excretion. The effect of indomethacin on protein excretion and renal hemodynamics was apparent, but blunted, when dietary Na intake was increased to 200 mEq/d. Mean BP increased during indomethacin therapy only when patients were S/V-expanded.
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PMID:Reduction of proteinuria by indomethacin in patients with nephrotic syndrome. 346 3

Reduction of renal mass in the rat results in an increased glomerular prostaglandin (PG) and thromboxane (TX) formation that modulates renal hemodynamics. To evaluate whether dietary protein intake could exert effects on renal PG and TX formation after reduction of approximately 70% of renal mass, rats with remnant kidneys were placed on either a high-protein (HP) or a low-protein (LP) diet. After 2 wk on the diet, proteinuria, glomerular filtration rate (GFR), urinary PGE2 excretion, and glomerular PGE2, 6-keto PGF1 alpha, and TxB2 biosynthesis were significantly greater in the rats on HP diets. Two-wk administration of the thromboxane synthesis inhibitor UK 38485 reduced renal TxB2 formation by approximately 70%. In addition, chronic UK 38485 treatment significantly inhibited papillary PGE2 production. Neither chronic nor bolus administration of UK 38485 had an effect on proteinuria or GFR in rats on HP diets. Chronic UK 38485 treatment, however, reduced GFR and proteinuria in rats on LP diets. The bolus administration of UK 38485 did not alter GFR in animals receiving a LP diet. The cyclooxygenase inhibitor indomethacin reduced GFR only in rats on HP diets. The data demonstrate that HP intake stimulates renal prostanoid formation. The increased prostaglandin formation on HP intake modulates GFR in these rats.
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PMID:High protein intake stimulates glomerular prostaglandin formation in remnant kidneys. 347 40

We studied the effects of fish oil on the progression of renal insufficiency in rats with subtotal nephrectomy. Five weeks after a 1-2/3 nephrectomy, sixteen rats were fed two different diets which differed only in fat composition. Lipid in the control diet was primarily beef tallow; that of the experimental diet, menhaden oil. Fish oil-fed rats had significant increases in plasma creatinines, decreases in urinary PGE2 and accelerated death rates. An additional twelve rats underwent 1-1/3 nephrectomies, and the same dietary manipulations, followed by renal clearance, histologic and biochemical studies after 12 weeks on the diets. Fish oil-fed rats again did worse, with decreased glomerular filtration rates and filtration fractions, more proteinuria and more glomerular sclerosis. Glomeruli and slices of cortex, medulla and papillae from rats fed fish oil produced much less PGE2 and TXB2 than dietary controls. Fish oil-induced suppression of renal PGE2 may be deleterious in this model and may outweigh the beneficial effect derived from TXA2 suppression. In contrast to fish oil's potentially therapeutic role in cardiovascular and immune-mediated renal disease, this diet is detrimental in rat renoprival nephropathy. This illustrates the importance of examining the effects of fatty acid manipulation individually for each disease entity.
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PMID:Effects of dietary fish oil on renal insufficiency in rats with subtotal nephrectomy. 348 Sep 73

S and R female rats were raised on a 1% NaCl diet, and excretion rates of urinary protein, kallikrein esterase activity, and PGE2 were measured (1) at 1 1/2 months of age, when both S and R rats were normotensive, (2) at 3 months of age, when S rats were mildly hypertensive and R controls remained normotensive, and (3) at 6 months of age, when S rats were markedly hypertensive relative to the still normotensive R rats. Urinary protein excretion rate in S compared to R rats was slightly elevated at 1 1/2 months of age and greatly elevated at 3 and 6 months of age. Urinary kallikrein was measured by hydrolysis of TAME after separation of kallikrein from nonkallikrein TAME esterases on DEAE-Sephadex minicolumns. Kallikrein TAME esterase activity was the same in 1 1/2-month-old S and R rats but became reduced in S relative to R rats at 3 and 6 months of age, concomitant with the development of hypertension and marked proteinuria. Urinary PGE2 was decreased in S rats as compared to R rats at all ages, and therefore the strain difference in urinary PGE2 preceded the development of strain differences in blood pressure and urinary kallikrein activity. We conclude that (1) reduced excretion of urinary kallikrein TAME esterase activity in S rats is probably secondary to hypertension and severe proteinuria and (2) decreased urinary PGE2 excretion in prehypertensive S rats is compatible with, but does not prove, the presence of a primary defect in intrarenal PGE2 production that could be involved in initiating hypertension.
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PMID:Developmental patterns of blood pressure and urinary protein, kallikrein, and prostaglandin E2 in Dahl salt-hypertension-susceptible rats. 691 75

Labor was induced with oral prostaglandin (PGE2) without amniotomy in 20 patients (10 nulliparae and 10 multiparae) with hypertension, whether or not associated with edema and/or proteinuria. An average dose of 8 mg was required to achieve effective uterine contractility in both nulliparae and multiparae. Multiparae required only a mean dose of 12 mg but nulliparae a dose of 18 mg to achieve delivery. The mean duration of labor was slightly longer in both nulliparae and multiparae than that achieved with fast escalating doses of i.v. oxytocin. The need for analgesia was greater in oxytocin-induced patients than in the prostaglandin-induced patients. Otherwise no differences were found between the two groups.
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PMID:Comparison of oral prostaglandin E2 and intravenous oxytocin for induction of labor in hypertensive pregnancies. 718 29

Hypertension in pregnancy probably has many causes. Increasing blood pressure carries an increasing risk to mother and fetus, particularly when associated with proteinuria and hyperuricaemia. Insufficient attention has been paid to a normal fall in diastolic blood pressure during early and mid-pregnancy; hence standards of normality need to be set. Antihypertensive treatment may reduce perinatal mortality and improve fetal and placental growth. Alpha- and beta-adrenergic blockers may be better than alpha-methyldopa. Pregnancy should be terminated as soon as risk from hypertension is greater than risk of fetal prematurity. Successful management depends upon a careful clinical, biochemical, and biophysical assessment of maternal and fetal condition and fetal maturity. Examination of amniotic fluid for surfactant, the use of dexamethasone to accelerate pulmonary maturity, and intravaginal PGE2 for cervical ripening and induction of labour are significant advances. With critical observation, timely intervention and sympathetic care a successful and happy outcome can be achieved in most pregnancies.
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PMID:The management of hypertension in pregnancy. 742 92

Vasoactive agents alter proteinuria by modulating glomerular hemodynamics. The authors hypothesized that vasoactive agents may be altering degradation of the collagen component of glomerular basement membrane, which also may be contributing to proteinuria. Mesangial cells treated with 10(-6) M angiotensin II had higher (P < 0.01) metalloproteinase activity (MA) when compared with control cells. This effect of angiotensin II was dose dependent. Amlodipine (10(-6) M), a calcium channel blocker, inhibited MA (control, 5.86 +/- 0.08 microgram versus 4.13 +/- 0.06 microgram gelatin degraded/mg protein, P < 0.001). The decrease in mesangial MA caused by amlodipine also occurred in a dose dependent manner. Amlodipine attenuated (P < 0.05) angiotensin II-stimulated MA (control, 6.69 +/- 0.30 micrograms, angiotensin II, 10.68 +/- 0.49 micrograms, angiotensin II+amlodipine 8.29 +/- 0.30 micrograms gelatin degraded/mg protein). Prostaglandin E2 increased (P < 0.001) MA (control, 10.22 +/- 0.9 micrograms versus prostaglandin E2, 17.9 +/- 0.9 micrograms gelatin degraded/mg protein), whereas indomethacin, a prostaglandin inhibitor, attenuated the metalloproteinase activity (control, 9.67 +/- 0.32 micrograms vs. 10(-6) M indomethacin, 4.22 +/- 0.31 micrograms gelatin degraded/mg protein, P < 0.001). Indomethacin also inhibited angiotensin II-stimulated MA (angiotensin II, 18.66 +/- 0.46 vs. angiotensin II+indomethacin, 11.86 +/- 0.56 micrograms degraded/mg protein, P < 0.001). Similarly, meclofenamate, another prostaglandin inhibitor, attenuated (P < 0.001) angiotensin II-induced MA. Because angiotensin II increases prostaglandin E2 synthesis by mesangial cells, it appears that increased MA, induced by angiotensin II, may be mediated partly through the generation of prostaglandin E2.
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PMID:Vasoactive agents modulate matrix metalloproteinase-2 activity by mesangial cells. 750 3

1. Endotoxin E. Coli lipopolysaccharide (LPS)-treatment in conscious, restrained rats increased plasma and urinary prostaglandin (PG) and nitric oxide (NO) production. Inducible cyclo-oxygenase (COX-2) and nitric oxide synthase (iNOS) expression accounted for the LPS-induced PG and NO release since the glucocorticoid, dexamethasone inhibited both effects. Thus, LPS (4 mg kg-1) increased the plasma levels of nitrite/nitrate from 14 +/- 1 to 84 +/- 7 microM within 3 h and this rise was inhibited to 35 +/- 1 microM by dexamethasone. Levels of 6-keto PGF1 alpha in the plasma were below the detection limit of the assay (< 0.2 ng ml-1). However, 3 h after the injection of LPS these levels rose to 2.6 +/- 0.2 ng ml-1 and to 0.7 +/- 0.01 ng ml-1 after LPS in rats that received dexamethasone. 2. The induced enzymes were inhibited in vivo with selective COX and NOS inhibitors. Furthermore, NOS inhibitors, that did not affect COX activity in vitro markedly suppressed PG production in the LPS-treated animals. For instance, the LPS-induced increased in plasma nitrite/nitrate and 6-keto PGF1 alpha at 3 h was decreased to 18 +/- 2 microM and 0.5 +/- 0.02 ng ml-1, 23 +/- 1 microM and 0.7 +/- 0.01 ng ml-1, 29 +/- 2 microM and 1 +/- 0.01 ng ml-1 in rats treated with LPS in the presence of the NOS inhibitors NG-monomethyl-L-arginine, NG-nitro arginine methyl ester and aminoguanidine, respectively. 3. The intravenous infusion of the NO donors sodium nitroprusside (SNP) or glyceryl trinitrate (GTN)increased prostaglandin production in normal animals (for instance urinary PGE2 excretion was increased from 96 +/- 10 to 576 +/- 12 pg min-1 and 400 +/- 24 pg min-1 in the presence of GTN or SNP respectively).4. Proteinuria was measured in order to evaluate the roles of NO and PG in renal damage associated with the in vivo injection of LPS. Interestingly, dexamethasone and the NOS inhibitors attenuated proteinuria in the LPS-treated rats. The COX inhibitors had no effect. It therefore appears that NO and not PG contributes to the LPS-induced renal damage; these findings support the potential use of NOS inhibitors in the treatment of renal inflammation.5. This study demonstrates the regulatory contribution of NO on the in vivo production of prostanoids and suggests that in inflammatory diseases that are driven by both NO and the prostaglandins, NOS inhibitors may act to reduce inflammation by the dual inhibition of cytotoxic NO and pro-inflammatory PG.
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PMID:Regulation of prostaglandin production by nitric oxide; an in vivo analysis. 754 31


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