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)

The oral gold salt auranofin, 6 mg per day, was compared with oral d-penicillamine, 500 mg per day, in a single-blind trial in 40 patients suffering with definite or classic rheumatoid arthritis. The patients were randomly allocated into the two therapeutic regimens (19 patients auranofin; 21 patients d-penicillamine) and monitored at a minimum of four-week intervals during the first year of treatment. Significant diminution in rheumatoid disease activity, as assessed by numerous clinical and laboratory parameters, was observed in both the auranofin- and penicillamine-treated groups. No significant differences existed for these parameters between the two groups, either initially or at the end of the trial period. Ten patients were lost from the trial over the 52-week period. Three subjects were withdrawn from the auranofin-treated group (increasing severity of rheumatoid arthritis at four weeks; severe diarrhea at four weeks; probable drug-related erosive gastritis at 40 weeks). Seven subjects were permanently withdrawn from the penicillamine-treated group (four, skin rashes four to eight weeks; one, heavy proteinuria at 24 weeks; one, therapeutic failure at 32 weeks; one, compliance failure at eight weeks), and treatment was temporarily withheld in three further patients because of thrombocytopenia (two) and proteinuria (one). We conclude that both drugs are effective in rheumatoid arthritis and that the lesser toxicity with auranofin will make it a valuable addition to our therapeutic armamentarium.
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PMID:A 12-month comparative trial of auranofin and D-penicillamine in rheumatoid arthritis. 641 96

Numerous open and placebo-controlled trials have shown Auranofin, an oral gold salt, to be effective in the base-line treatment of rheumatoid arthritis. In comparative trials the drug was found to be somewhat less potent than sodium aurothiomalate. Whether it is equal or superior to other base-line antirheumatoids like D-penicillamine or antimalarials, can as yet not be established because of the small patient groups involved in the published trials. While adequately effective clinically, oral gold salts, like their parenteral counterparts, do not halt the radiological progression of rheumatoid lesions. Overall, Auranofin is much better tolerated than the parenteral gold salts, although soft feces are more commonly seen and diarrhea may occur occasionally. Skin rashes as well as proteinuria and thrombocytopenia have been reported in some instances so that, as during parenteral treatment, laboratory studies at regular intervals are mandatory. On account of its oral dosage form and its low side-effect rate Auranofin is a true alternative to conventional parenteral gold salt therapy.
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PMID:[Comparison of oral and parenteral gold therapy--review of the literature]. 644 57

The effects of a novel compound, 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone, CV-2619), on cerebral and renal vascular changes were examined in stroke-prone spontaneously hypertensive rats (SHRSP) and in rats with experimentally induced hypertension. CV-2619 (35 mg/kg/day, p.o.) significantly inhibited the onset of cerebrovascular lesions (stroke) and the elevation of blood pressure in SHRSP with mild hypertension. A higher dose (2 X 50 mg/kg/day, p.o.) clearly delayed the onset of both stroke and proteinuria without any effect on the blood pressure in SHRSP with severe hypertension. In DOCA-salt hypertensive rats, CV-2619 (2 X 5 or 2 X 25 mg/kg/day, p.o.) dose-dependently inhibited decreases in body weight and water balance and the development of cerebral and renal vascular changes. These results suggest that CV-2619 inhibits the development of stroke and renal vascular lesions in hypertensive rats.
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PMID:Inhibitory effect of idebenone (CV-2619), a novel compound, on vascular lesions in hypertensive rats. 652 Oct 74

The effect of hypertension on the anatomy, physiology, and course of glomerulonephritis in rats was investigated by inducing deoxycorticosterone acetate-salt hypertension in animals with heterologous immune complex glomerulonephritis and vice versa. The effect of hypertension on glomerulonephritis with different degrees of intensity was also studied. Hypertension increased the proteinuria in the glomerulonephritic rat substantially (p less than 0.01), reduced the creatinine clearance (p less than 0.05), and induced an enormous thickening of the glomerular basement membrane. Furthermore, the life span was shortened (p less than 0.01) when hypertension was induced in nephritic rats, possibly due to insufficient cerebral vascular activity secondary to malnutrition. Glomerulonephritis did not influence the blood pressure in animals with severe protein loss; in rats with minor proteinuria the presence of glomerulonephritis increased the blood pressure. Hypertension lowered the antiserum dose needed to produce pathologic proteinuria (p less than 0.02). Hypertension seemed to increase the amount of glomerular immune deposits in early glomerulonephritis but lowered the amounts of glomerular rat IgG during the course of nephritis. In conclusion, hypertension increases the glomerular damage substantially in rats with heterologous immune complex glomerulonephritis, influences the glomerular deposition of immunoglobulins, and shortens the life span.
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PMID:Effect of hypertension on experimental glomerulonephritis in rats. 669 57

Of 521 children with a previously untreated nephrotic syndrome, as defined by proteinuria greater than or equal to 40 mg/h/m2 and serum albumin less than or equal to 2.5 g/dL, entering the International Study of Kidney Disease in Children between January 1967 and April 1976, 389 showed minimal changes on renal biopsy. Of these, seven boys and three girls died, all before July 1972. Infection was the cause of death in six patients. One child died of dural sinus thrombosis, one died as a result of cardiorespiratory failure following salt-poor albumin infusion, and another died from chronic renal failure due to focal and segmental glomerulosclerosis not apparent on initial biopsy. The mode of death in the remaining child was uncertain. Analysis according to histopathologic subgroups of minimal change disease showed no statistically significant differences in the incidence of deaths, although mesangial abnormalities and tubular atrophy were associated with higher mortality than nil disease or focal glomerular obsolescence. Nine of the ten children who died had either failed to respond to initial prednisone therapy (initial nonresponders, n = 5), or responded but relapsed during the initial 8 weeks of treatment (early relapser, n = 4), even though only one quarter of the total sample were nonresponders or early relapsers (P less than .0005). Nearly one fifth of all initial nonresponders with minimal change nephrotic syndrome died. Thus the pattern of response to initial steroid therapy in patients with minimal change nephrotic syndrome may have prognostic significance.
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PMID:Minimal change nephrotic syndrome in children: deaths during the first 5 to 15 years' observation. Report of the International Study of Kidney Disease in Children. 670 28

Micropuncture and/or morphologic studies were performed in seven groups of uninephrectomized (UNX) adult male Munich-Wistar rats. Control groups 1, 3, and 6 received standard (24% protein) chow and tap water. Groups 2, 4, and 5 received weekly injections of desoxycorticosterone pivilate (DOC) and 1% saline for drinking, groups 2 and 4 were fed standard chow, and Group 5 a diet containing 6% protein. Group 7 received DOC, salt, and standard chow for 3 wk followed by withdrawal of DOC and salt for an additional 6 wk. 10-14 d after UNX, groups 1 and 2 exhibited similar single nephron glomerular filtration rates (SNGFR) and initial glomerular plasma flow rates (QA). Group 2 had higher mean arterial pressure (AP) and glomerular capillary hydraulic pressure (PGC) than group 1. 3-4 wk after UNX, group 4 exhibited further elevations in AP and PGC as compared with groups 2 and 3. SNGFR and QA were similar in groups 3 and 4, but these average values were greater than typical for normal rats. Group 4 also demonstrated increased urinary protein excretion. Morphologic evaluation of glomeruli in groups 2 and 4 revealed mesangial expansion and focal intraglomerular hemorrhage whereas glomeruli of groups 1 and 3 were essentially normal. Values for AP and PGC in group 5 were not different than group 3 but significantly lower than group 4. QA and SNGFR were lower in group 5 (low protein) than in groups 3 and 4. Furthermore, proteinuria and glomerular structural lesions were abolished in group 5. Morphologic studies performed in groups 6 and 7 showed that early DOC-SALT lesions progress to focal glomerular sclerosis. These studies suggest that continued elevations in glomerular capillary flows and pressures predispose to glomerular injury in this model of systemic arterial hypertension.
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PMID:Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension. 671 46

Iodine-labeled ([125I]) rat urinary kallikrein and rat urinary TAME esterase A2 were used as probes to look for urinary and plasma proteins that bind to these enzymes. Such proteins are presumptive enzyme inhibitors. Complexes formed with labeled enzymes were identified by polyacrylamide gel electrophoresis followed by autoradiography. Urine from young (6 weeks old) Dahl salt-sensitive (S) rats showed no, or only traces, of protein binding to kallikrein. Concomitant with the slow development of hypertension and proteinuria in S rats fed normal rat chow, one of the six kallikrein-binding proteins demonstrable in plasma was readily found in S-rat urine. This kallikrein-binding protein was called "KBP-1." R rats showed either no or much less KBP-1 in the urine, compared to S rats up to 5 months of age. A partly purified preparation of KBP-1 was shown to inhibit the TAME esterase activity of rat urinary kallikrein in the radiometric TAME assay. Urine of proteinuric S rats also contained two TAME esterase-binding proteins, TEBP-1 and TEBP-2, detected with the [125I]-esterase A2 probe. As S rats aged from 3 to 8 months, free KBP-1 disappeared from the urine in spite of increased and marked proteinuria and the continued presence of KBP-1 in plasma. Concomitant with this age-related loss of urinary KBP-1 there was a marked shift in S urinary proteins binding to [125I]-esterase A2 from TEBP-1 to TEBP-2. It was speculated that KBP-1 and TEBP-1 were the same protein detectable with either labeled kallikrein or labeled esterase A2. The concomitant disappearance of free KBP-1 (TEBP-1) and the appearance of free TEBP-2 in the urine of old, hypertensive, proteinuric S rats suggests that: 1) most of the KBP-1 (TEBP-1) is bound to enzyme(s) in old rats; or 2) KBP-1 (TEBP-1) is largely converted to TEBP-2 in old rats; or 3) both are true and that binding of KBP-1 (TEBP-1) to enzymes is associated with the generation of TEBP-2.
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PMID:Proteins binding to kallikrein and esterase A2 in the urine of salt-sensitive and salt-resistant rats. 675 95

Previous evidence shows that salt-sensitive (S) rats have a net increase in plasma mineralocorticoid activity due to 18-hydroxy-11-deoxycorticosterone and decreased urinary kallikrein excretion compared to salt-resistant (R) rats. Since mineralocorticoids stimulate urinary kallikrein excretion, these results are inconsistent. This inconsistency was explained by the fact that, while R rats responded normally to treatment with deoxycorticosterone (DOC) by an increase in urinary kallikrein excretion, S rats showed no change in urinary kallikrein even when treated with 10 mg of DOC/day for 24 days. S and R rats responded identically to DOC with changes muscle electrolytes and relative hypertrophy of the renal distal tubule. Other measures of chronic mineralocorticoid response in S rats beside kallikrein were, therefore, intact. It was found that S rats were capable of responding to Na deficient diet with an increase in urinary kallikrein comparable to R rats. It was argued, therefore, that mineralocorticoid receptor mechanisms and distal-tubular cell responsiveness are intact in S rats. Mild glomerular and tubular scarring was found in S rats and the severity of renal lesions was increased by DOC treatment in S rats. These lesions correlated well with blood pressure and proteinuria. No such lesions were present in control or DOC treated R rats. It was suggested that failure of urinary kallikrein to respond to DOC in S rats may be a secondary phenomenon resulting from renal damage.
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PMID:Anomalous response of urinary kallikrein to deoxycorticosterone in Dahl salt-sensitive rats. 691 11

Urinary enzymes that hydrolyze the artificial substrate alpha-N-p-tosyl-L-arginine methyl ester (TAME) were studied in Dahl salt-sensitive (S) and salt-resistant (R) rats. Total urinary TAME esterase activity (kallikrein and non-kallikrein) showed a marked increase with dialysis against water, but only in hypertensive S rats with proteinuria. This phenomenon suggests the presence of dialyzable TAME esterase inhibitor(s) in urine following renal damage, but these data do not define what urinary esterases might be affected. Partially purified urinary kallikrein exhibited a ratio of kininogenase to esterase activity which was equal for S and R rats. Thus, the marked discrepancy between kininogenase and esterase activities reported by Carretero et al. with S and R whole urine is not a function of the S and R kallikrein molecules but is probably related to interfering substances in the whole urine. Urinary kallikrein excretion was measured on individual rat samples by TAME esterase activity following dialysis and separation from non-kallikrein TAME esterase(s) using DEAE-Sephadex minicolumns. S rats had lower urinary kallikrein excretion that R when the S rats were hypertensive and showed marked proteinuria. Young S and R rats raised on low salt showed similar blood pressures and similar kallikrein excretion. High salt (8% NaCl) diet decreased kallikrein excretion in both S and R, but the decrease was greater in the S rats which became hypertensive and had increased urine protein excretion. These data suggest that the lower urinary kallikrein excretion in S rats relative to R rats is probably a consequence of hypertension and renal damage rather than a primary cause of hypertension.
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PMID:Total and kallikrein arginine esterase activities in the urine of salt-hypertensive susceptible and resistant rats. 700 38

Of 58 patients treated with captopril, 3 have now received the drug for more than 2 years and 22 for more than one year. This study concerns 38 patients treated for 6 months, captopril having been given alone during the first 2 months. They all had severe hypertension (diastolic BP Greater Than 110 mmHg) which had resisted previous treatments in normally effective doses, including at least one beta-blocker, dihydralazine and a diuretic. After 6 months blood pressure levels were normal in 53% of the patients, reduced in 31% and unchanged in 16%. Clinical improvement was habitual with, in particular, disappearance or decrease of tiredness and dyspnoea. Since some side-effects of the drug, such as granulopenia, proteinuria and ageusia, are mainly observed with high dosage, captopril is usually administered in doses lower or equal to 400 mg/day. In resistant or malignant hypertension it must be used in combination with salt-free diet, a beta-blocker and/or prazosin. Clinical, haematological and renal surveillance is necessary during treatment. When these precautions are observed, captopril constitutes a very useful drug for the treatment of patients with severe resistant hypertension.
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PMID:[Treatment of severe resistant arterial hypertension with captopril. 58 patients, including 38 treated for more than 6 months (author's transl)]. 702 47


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