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)

Angiotensin II (Ang II) is the primary mediator of the renin-angiotensin system (RAS). Inappropriate control of the RAS is critically involved in the development and maintenance of hypertension and congestive heart failure. The actions of Ang II are thought to be mediated by specific surface receptors on the various target organs. At present, two receptors for Ang II have been firmly established in mammals, including man. According to current nomenclature, losartan represents the prototype antagonist of the Ang II type 1 (AT1) receptor and does not possess significant affinity for the so-called AT2 receptor. Losartan is the first of a new class of orally active, nonpeptide Ang II receptor antagonists able to very specifically and selectively inhibit the RAS while lacking the agonistic effects of the peptide receptor antagonists, e.g. sarlasin, or the bradykinin potentiating effects of the angiotensin converting enzyme (ACE) inhibitors. Virtually all of the known actions of Ang II, e.g. those defined by Ang II itself, saralasin, ACE or renin-inhibitors are blocked by losartan, emphasizing the major role of this distinct Ang II receptor subtype in mediating the responses of Ang II. The functional correlate of the AT2 receptor remains poorly understood. In several models of experimental and genetic hypertension, AT1 receptor antagonists are effective antihypertensive agents with similar efficacy to that of ACE and renin-inhibitors. In animal models of renal disease, AT1 receptor antagonists significantly decrease proteinuria, protect against diabetic glomerulopathy and increase survival in stroke-prone spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A new class of therapeutic agents: the angiotensin II receptor antagonists. 763 3

The effects of long-term oral administration of losartan on the occurrence of stroke and on mortality were investigated in young salt-loaded stroke-prone spontaneously hypertensive rats (SHR-SPs) during the treatment period (5-20 weeks of age) and up to 8 weeks thereafter. Two doses of losartan, 1 and 10 mg/kg/day, were investigated, which afforded no and only moderate antihypertensive effects, respectively. During the treatment period, losartan at both doses completely suppressed stroke and mortality and strongly opposed (low dose) or abolished (high dose) the increases in saline intake, diuresis, and proteinuria observed in controls. It markedly limited (low dose) or abolished (high dose) vascular fibrinoid necrosis formation in the brain, kidneys, and heart. Finally, losartan, especially at the high dose, reduced arterial thickening and glomerular and tubulo-interstitial lesions in the kidneys, as well as arterial thickening, infarction, and fibrosis in the heart. Eight weeks after treatment discontinuation, all animals but one (low dose) were still alive. Vascular fibrinoid necrosis development remained strongly prevented (low dose) or fully suppressed (high dose) in all investigated organs. Finally, cardiac and renal lesions tended to worsen, and proteinuria was noted only in the low-dose group. We conclude that in SHR-SPs, angiotensin II, through AT1 receptor stimulation, most likely plays a major role in fibrinoid necrosis formation, vascular proliferative changes, and stroke occurrence and that losartan, most likely independently of its effect on blood pressure, affords a full and long-lasting protection against stroke and mortality both during and after the treatment period.
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PMID:Losartan's protective effects in stroke-prone spontaneously hypertensive rats persist durably after treatment withdrawal. 769 74

In 179 patients subjected to 186 renal transplants, 30 renal biopsies were performed due to the presence of a proteinuria over 3.5 g/24 h or due to a reduction in glomerular filtration rate. Six of these biopsies, coming from 5 patients, disclosed morphological alterations compatible with focal segmental glomeruloesclerosis. Five of these were due to recurrence of the primary disease (in four patients) and in all, massive proteinuria appeared from 1 to 23 days after transplantation. Two patients with three transplants, evolved to renal failure and required dialysis in a period 12 months as a mean. The third patient, developed a nephrotic syndrome without renal failure and died 14 months after the renal transplant due to a stroke. In the fourth patient, the nephrotic syndrome disappeared 38 days after the transplant and remained with minimal proteinuria until his last follow up visit two years later. The primary disease of the fifth patient is unknown; the nephrotic syndrome appeared 68 months after the transplant and remitted spontaneously in 2 months. The renal biopsy showed focal and segmental lesions with partial effacement of epithelial foot processes. It is concluded that focal segmental glomerulosclerosis recurrence in renal transplant occurs with early massive proteinuria and frequently leads to renal failure and graft loss in no more than two years.
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PMID:[Focal and segmental glomerulosclerosis in renal transplantation]. 773 12

In 1979, all the known diabetic subjects (849) were identified from a community (population 81851), of whom 717 (85%) were reviewed by a single observer. Using the NHS Central Register, follow-up was completed for 98% of subjects. After 11 years, 306 (42.7%) diabetic subjects had died, of whom 65 were insulin treated and 241 were non-insulin treated. Circulatory disease accounted for 168 (54.9%) deaths, of which 124 (73.8%) were due to ischaemic heart disease. The standardized mortality ratio (SMR) for all causes of death, based on data from England and Wales, was significantly raised for both insulin-treated and non-insulin-treated patients (1.75, 95% CI 1.35 to 2.24 and 1.32, 95% CI 1.15 to 1.50, respectively). SMRs for all cause mortality were significantly greater for diabetic subjects in the 45-64 (SMR, 1.97, 95% CI 1.34 to 2.80), 65-74 (SMR 1.59, 95% CI 1.27 to 1.97 and 75 years and over (SMR 1.26, 95% CI 1.08 to 1.45) age ranges. Using a proportional hazards model, after adjusting for age and gender, systolic blood pressure and vibration threshold were significant predictors of all cause mortality in insulin-treated subjects. For non-insulin-treated subjects, blood glucose, systolic blood pressure, glycated haemoglobin, retinopathy, proteinuria, coronary artery disease, and stroke were significant baseline predictors of mortality. No association was found for serum cholesterol, body mass index, diastolic pressure or cigarette smoking in either treatment group.
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PMID:Mortality in diabetic subjects: an eleven-year follow-up of a community-based population. 789 62

We investigated the rate of decline in GFR and the changing prevalences of micro- and macrovascular complications in 20 type II diabetic patients [mean age 58 (46-71) years, female:male = 7:13, duration of diabetes 16 (12-30) years] from the stage of macroproteinuria with GFRs which were still normal until the beginning of dialysis or the time of death. Controls of renal function, proteinuria, HbAlc, serum lipids, and blood pressure were performed every 6 months at the beginning of the study and later on at 3-month intervals. Fundoscopy, electrocardiogram at rest and in case of need a symptom-limited treadmill ECG, a Duplex ultrasound examination of the carotid vessels, and a Doppler sonographic examination of the femoral arteries were repeated each year. The creatinine clearance (mean +/- SD) of the patients was 81 +/- 6 mL/min/1.73 m2 at the beginning of the study. The rate of decline in creatinine clearance was 1.01 +/- 0.38 mL/min/month during the whole period of observation. Twelve patients (group A) required dialysis after a mean time of 74 (40-119) months; their creatinine clearance was 7 +/- 2 mL/min/month at the beginning of renal replacement therapy. Eight patients (group B) died a short time before the beginning of dialysis treatment; their creatinine clearance was 13 +/- 5 mL/min/1.73 m2. The causes of death were sudden death (n = 4), cardiac failure (n = 1), and stroke (n = 2); in one case it was unknown. The two patient groups did not differ in respect to the mean age, duration of diabetes, HbAlc values, serum cholesterol levels, and blood pressure. The decline in the creatinine clearance was also similar in both patient groups, with 1.07 +/- 0.35 versus 0.98 +/- 0.41 mL/min/month. Only the mean serum triglyceride concentration was significantly higher in the patients who died before dialysis. At the start of the study, cerebrovascular disturbances (including plaques in the carotid vessels) were found in 30%, cardiovascular disturbances (including pathologic ECG findings) in 45%, a peripheral vascular disease in 15%, and diabetic retinopathy (grade I and II) in 75%. At the beginning of dialysis treatment or the time of death, respectively, the prevalence of cerebrovascular diseases was increased to 70% and the prevalence of cardiovascular diseases to 90%; peripheral vascular disease was present in 50% and diabetic retinopathy in all of the cases. We conclude that type II diabetic patients show high mortality (40%) and poor quality of life, not only when they require dialysis treatment, but also in the predialysis phase.
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PMID:High mortality and poor quality of life during predialysis period in type II diabetic patients with diabetic nephropathy. 804 65

The prophylactic and therapeutic effects of S-312-d (S-(+)-methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)thieno[2, 3- b]pyridine-5-carboxylate, CAS 120056-57-7) were compared with those of nimodipine or nicardipine using male stroke-prone spontaneously hypertensive rats (SHRSP). The survival rate of SHRSP was dose-dependently increased by once a day oral administration of S-312-d (0.3, 1, and 3 mg/kg) or nimodipine (10 mg/kg), while all non-treated SHRSP fed with high Na+ diet died within 40 days after the start of the experiment. All SHRSP treated with 3 mg/kg S-312-d survived during the 60-day experiment periods. Marked decreases of body weights and various neurological symptoms were also inhibited with S-312-d or nimodipine. Moderate diuretic effects were observed with S-312-d at doses of 1 and 3 mg/kg. The appearance of urinary occult blood in control SHRSP was markedly inhibited with S-312-d at 1 mg/kg and nimodipine at 10 mg/kg. Histological examination of the brain of SHRSP showed that cerebral stroke lesion including edema, hemorrhage, and/or softening was dose-dependently inhibited with S-312-d. Once a day oral administration of S-312-d (1, 3, or 10 mg/kg) dose-dependently increased the body weights and improved the neurological symptoms of diseased SHRSP. The appearance of proteinuria and of occult blood in the urine of SHRSP were also markedly inhibited with S-312-d or nicardipine. Histological examination of the brain of SHRSP showed that the arbitrary neurotoxic index (ANI) for stroke lesion dose-dependently decreased with S-312-d at 1, 3, and 10 mg/kg as follows: 4.8, 3.0, 2.3. The ANI for non-treated SHRSP was 7.6. The therapeutic effects of nicardipine (ANI 3.9) at 10 mg/kg corresponded to those of S-312-d at 3 mg/kg. Thus, S-312-d can be recommended for the treatment of cerebral insufficiency or vasospasm following stroke as well as in essential hypertension.
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PMID:Pharmacological studies on a new dihydrothienopyridine calcium antagonist. 4th communication: prophylactic and therapeutic effects of S-(+)-methyl-4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)thieno[2, 3- b]pyridine-5-carboxylate in stroke-prone spontaneously hypertensive rats. 814 16

A case of systemic lupus erythematosus (SLE) complicated with hypopituitarism after steroid pulse therapy is reported. A 46-years-old-female with a history of SLE starting in 1975 was admitted to our hospital in February 1991 for lupus nephritis. Steroid pulse therapy, 1000 mg methyl-prednisolone for 3 successive days as one therapy unit, was administered. Proteinuria improved remarkably, however, general fatigue and headache appeared 2 weeks after initiation of therapy. Endocrinological examination revealed hypopituitarism including the levels of TSH, FSH, GH and ACTH. The secretion of FSH and LH gradually improved after replacement therapy of dried thyroid. MRI examination of the brain revealed an empty sella. It is known that pituitary tumor, cerebrovascular accident and autoimmune lymphocytic hypophysitis cause hypopituitarism. In this case, it is unlikely that the pulse therapy may be responsible for the infarction of the anterior pituitary artery furthermore, there has been no articles describing such incidence after steroid pulse therapy. This case may be indicative of a very rare case in which the empty sella might have been exacerbated by the pulse therapy in the causation of hypopituitarism.
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PMID:[Hypopituitarism associated with empty sella after steroid pulse therapy in a patient with SLE]. 814 29

The effects of long-term oral administration of the angiotensin-converting enzyme (ACE) inhibitor trandolapril (0.01 mg/kg [T0.01] and 1 mg/kg [T1]) on the occurrence of stroke and on mortality were investigated in young salt-loaded stroke-prone spontaneously hypertensive rats during the treatment period (5-20 weeks of age) and up to 8 weeks thereafter. During the treatment period T1, but not T0.01, limited the increase in blood pressure. However, both doses of trandolapril prevented stroke and mortality and strongly opposed (T0.01) or abolished (T1) the increases in saline intake, diuresis, and proteinuria observed in control animals. Simultaneously, trandolapril markedly prevented (T0.01) or abolished (T1) vascular fibrinoid necrosis formation in the brain, kidney, and heart. Finally, trandolapril dose-dependently reduced arterial thickening and glomerular and tubulointerstitial lesions in the kidney, as well as arterial thickening, infarction, and fibrosis in the myocardium. At 8 weeks after treatment withdrawal, the antihypertensive effect of T1 had disappeared, but stroke-related mortality and fibrinoid necrosis remained completely suppressed. Further, no additional cerebral, renal, or cardiac lesions developed, and no increase in proteinuria occurred. In the T0.01 group, 17% of the animals died, fibrinoid necrosis tended to develop, organ lesions worsened, and proteinuria strongly increased. We conclude that (1) early ACE inhibition with trandolapril affords a long-lasting protection versus stroke and mortality both during and after the treatment period; and (2) that this beneficial effect is due to the suppression of fibrinoid necrosis formation and not to the drug's antihypertensive action. In contrast, both properties appear to contribute to trandolapril's renal and cardiac protective effects.
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PMID:Trandolapril's protective effects in stroke-prone spontaneously hypertensive rats persist long after treatment withdrawal. 816 51

Patients with mild to moderate hypertension require only a simple schedule of investigations, especially if there is a history of stroke or hypertension in first degree relatives. Tests are necessary to profile other cardiovascular risk factors and to detect target organ damage with only limited screening for secondary hypertension. Careful history, physical examination, repeated blood pressure measurements over months and measurements of body mass index, random cholesterol, routine blood chemistry and urinalysis using impregnated paper strips are all that are required. More detailed investigations can be reserved for special groups such as those with peripheral vascular disease or abnormal renal function before or after treatment with angiotensin converting enzyme inhibitors or significant proteinuria or hypokalaemia. Patients with essential hypertension who are smokers with lipid abnormalities may go on to develop superimposed renovascular disease. Severe hypertension at any age and especially if there is a reliable negative family history also merits special consideration. Resistance to antihypertensive treatment is more often due to non-compliance or non-steroidal anti-inflammatory drug use or alcohol abuse than to underlying secondary causes.
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PMID:Hypertension: investigation, assessment and diagnosis. 820 68

The effects of long-term oral administration of quinapril on the occurrence of stroke and on mortality were investigated in young salt-loaded stroke-prone spontaneously hypertensive rats (SHR-SPs) during the treatment period (8th-34th week of age) and up to 6 weeks thereafter. Simultaneously, blood pressure, saline intake, diuresis, and proteinuria were investigated at regular intervals, and cerebrovascular, renal, and cardiac lesions were assessed after death. Untreated SHR-SPs served as controls. Quinapril completely suppressed stroke and mortality, afforded only limited protection v blood pressure rise, and prevented any increase in saline intake, diuresis, and proteinuria both during and after the treatment period. Quinapril long-lastingly prevented vascular fibrinoid necrosis development at the cerebral, but also at the renal and cardiac levels. In the kidneys, vascular intimal and medial hyperplasia were strongly reduced, as were the glomerular and tubulo-interstitial lesions. At the cardiac level, intimal and medial hyperplasia were slightly reduced but infarction and fibrosis were hardly affected. As the renin-angiotensin system is highly stimulated in SHR-SPs and as angiotensin II (AII) is responsible for fibrinoid necrosis formation, vessel obstruction, and stroke in these animals, we conclude that the long-lasting protection afforded by quinapril v stroke and mortality in SHR-SPs both during and after the treatment period is mostly due to the drug-induced interruption of the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quinapril prevents stroke both during and after the treatment period in stroke-prone spontaneously hypertensive rats. 830 70


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