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 effectiveness of insulin therapy on early diabetic nephropathy has not been established. In this study we examined the influence of continuous subcutaneous insulin on the progression of established nephropathy in streptozocin-induced diabetic rats. Normal controls and diabetic rats were studied for 11 mo. During the first 6 mo, all the diabetic rats received 2 U protamine zinc insulin s.c. twice weekly. During the last 5 mo of study, diabetic rats either continued on the occasional subcutaneous insulin regimen or received regular insulin by continuous subcutaneous infusion. Six months after the initiation of the study, the diabetic rats were severely hyperglycemic, and their relative mesangial areas had increased. Continued poor glycemic control in the rats receiving occasional insulin was associated with relative increased mesangial area (25.2 +/- 1.0% of glomerular area) and significant proteinuria (148 +/- 17 mg/24 h) compared with normal controls. In contrast, the use of continuous subcutaneous insulin therapy with improved glycemic control arrested mesangial changes (19.5 +/- 1.4% of glomerular area) and prevented the excessive proteinuria (71 +/- 13 mg/24 h). Indeed, these parameters did not differ from age-matched controls. We conclude that in the rat, continuous subcutaneous insulin therapy instituted after the development of early glomerular pathology is effective in arresting the disease process.
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PMID:Effect of insulin therapy on established diabetic nephropathy in rats. 297 Sep 81

Since their introduction in clinical practice in 1980, ACE inhibitors have been found useful in the treatment of hypertension and CHF. In hypertension, they are effective as monotherapy in 40% to 50% of the patients, and in combination with diuretics or calcium antagonists, they are effective in up to 85% of the patients. They are well tolerated, are not associated with depression, impotence, bronchospasm or metabolic derangements such as hypokalemia, hyperuricemia or hyperglycemia, and do not have adverse effects on the quality of life. As a result, they are preferred in hypertensive patients with CHF, left ventricular dysfunction, mental depression, older age, coronary artery disease, metabolic disorders, chronic destructive pulmonary disease, and peripheral vascular disease. In CHF they cause long-lasting hemodynamic and symptomatic improvement, improve exercise tolerance, and may lower mortality in certain patient subsets. Evolving new indications for ACE inhibitors include the diagnosis of renovascular hypertension, the prediction of surgical success, the treatment of scleroderma renal crisis, the reduction of proteinuria, renal protection, cardioprotection, the improvement of arterial compliance, in Bartter's syndrome and idiopathic edema, etc. ACE inhibitors are usually well tolerated but in some instances they may cause class-specific side effects such as hypotension; usually reversible azotemia or renal failure, especially in patients with renal artery stenosis or with CHF with low blood pressure; cough; angioedema; and hyperkalemia. Differences among ACE inhibitors are emerging and include chemical class (e.g., zinc ligand), biotransformation, potency, pharmacokinetics, prodrugs, tissue effects, additional pharmacologic properties, and drug interactions.
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PMID:Angiotensin converting enzyme inhibitors. II. Clinical use. 305 46

To delineate the urinary excretion of prostaglandins E2 (PGE), F2 alpha (PGF), and thromboxane B2 (TxB) in diabetic rats, we treated male Sprague-Dawley rats with streptozocin 60 mg/kg or with vehicle. Plasma glucose and creatinine concentration and 24-hour urine collections for determination of TxB, PGE, PGF, creatinine, and protein excretion were measured at 2, 8, and 14 weeks after streptozocin. Creatinine clearance was significantly decreased in diabetic rats at 2 and 8 weeks, whereas the urinary protein excretion was three to five times that of control animals at all times. The 24-hour excretion of TxB was elevated twofold to threefold in diabetic rats, whereas PGE and PGF excretion were both significantly decreased. This alteration in excretion was not caused by increased urine flow rate, inasmuch as mannitol-induced osmotic diuresis caused an increase in PGE and PGF excretion. Eight weeks after streptozocin, a group of diabetic and control rats were sacrificed, and the production of PGE, PGF, and TxB by the renal papillae and glomeruli determined. An additional five diabetic rats were treated with protamine zinc insulin for 1 week before sacrifice to determine the effect of insulin treatment on the production of PGE, PGF, and TxB by the glomeruli and renal papillae. Papillary production of PGE, PGF, and TxB was decreased in diabetic rats, as was glomerular production of PGE and PGF. Insulin treatment increased PGF production by the renal papillae and increased PGE, PGF, and TxB production by glomeruli. These results indicate that changes in prostaglandin excretion accompany the development of marked proteinuria and a decrease in creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Urinary excretion and renal production of prostaglandins E2, F2 alpha, and thromboxane B2 in experimental diabetes mellitus. 309 17

Sodium aurothiomalate was given to male Wistar rats (initial body weights: 150 g) by subcutaneous (s.c.) injection at doses of up to 7.5 mg/kg (corresponding to 4.27 mg gold/kg), twice a week, for 4-5 weeks. The concentrations of Ca, Mg, Fe, Cu and Zn were measured in serum, urine, faeces and in the liver, kidney, spleen, heart, lung, testis, bone and muscle. Kidney cytosol was separated by gel chromatography and the fractions analysed for protein, copper, zinc, iron and gold concentrations. The concentration of copper was increased 5-fold in kidney while smaller increases of zinc in kidney, copper in muscle, iron in muscle and testis and calcium in spleen were found. There was a significant reduction in the concentration of copper in serum. Kidney cytosol from gold-treated but not from control animals contained a low molecular weight protein which was associated with copper, zinc and gold. The rats developed proteinuria and microscopic changes to renal tubular cell structure were also observed. It is suggested that the gold-induced accumulation of copper may follow from an increased rate of synthesis of metallothionein and could be responsible for the renal dysfunction which develops in a proportion of rheumatoid arthritis patients who are treated with gold.
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PMID:The effect of sodium aurothiomalate (myochrysin) on the distribution of calcium, magnesium, copper, zinc and iron in the rat. 312 69

The concentration of cadmium in the New Zealand dredge oyster Tiostrea lutaria (commonly known as a Bluff oyster) is sufficiently high so that the ingestion of just one oyster can more than double a normal daily dietary intake of cadmium for a New Zealand adult. A survey of 75 adults (18-76 years old) associated with the oyster fishing industry in Bluff, Southland, New Zealand, was carried out before and at the end of the oyster season. Preseason intakes (from dietary history questionnaires and from 3-day fecal collections) of cadmium, selenium, zinc, copper, and manganese were normal for a New Zealand adult not consuming Bluff oysters. The subjects were classified according to their reported average oyster consumption during the 6 months of the oyster fishing season; the subjects who consumed more oysters were more likely to smoke cigarettes. The end-season fecal output of cadmium confirmed the reported average oyster intakes: Category I (0-5 oysters/week): 15 +/- 8 (mean +/- SD) micrograms Cd/day; Category II (6-23 oysters/week): 84 +/- 134 micrograms Cd/day; Category III (24-71 oysters/week): 129 +/- 144 micrograms Cd/day; Category IV (72+ oysters/week): 233 +/- 185 micrograms Cd/day. The fecal output of selenium as well was increased by the consumption of many oysters but the fecal outputs of zinc, copper, and manganese were not. Using fecal cadmium excretion to predict dietary cadmium intake, 8-15% of the subjects in this study were identified as having an intake of cadmium which has been associated with an increased prevalence of tubular proteinuria. The highest individual daily fecal excretion of cadmium at the end of the season was 580 micrograms Cd/day, i.e., a daily excretion equivalent to more than 10 times above the weekly intake provisionally considered tolerable (400-500 micrograms Cd/week; WHO, 1972). Continued investigations on this population group will determine whether there are any health consequences of these extremely high cadmium intakes.
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PMID:Unusually high intake and fecal output of cadmium, and fecal output of other trace elements in New Zealand adults consuming dredge oysters. 337 Dec 88

Female mice were given nutrient-sufficient, purified diets containing cadmium at either 0.25, 5, or 50 ppm, as described in the accompanying publication. One-half of the females were bred for 6 consecutive 42-day rounds of pregnancy/lactation (PL mice); remaining females were non-pregnant controls (NP mice). PL mice and NP controls were sacrificed after 1, 2, 4, or 6 consecutive rounds of pregnancy/lactation. At all levels of dietary cadmium and after all reproductive rounds, kidney cadmium concentrations were 2-5-fold higher in PL than NP mice. After 6 rounds of reproduction, the mean concentration of cadmium in the kidneys of PL mice exposed to dietary cadmium at 50 ppm was 115 micrograms Cd/g kidney, close to the critical concentration for cadmium-induced renal damage (200 micrograms/g). No consistent increases in the concentrations of amino acids, protein, or cadmium in urine were observed in the NP or PL mice in our study, indicating that cadmium-induced renal dysfunction had not yet appeared. Very small increases in kidney concentrations of zinc and copper were observed with large increases in kidney cadmium concentrations. Threshold cadmium concentrations below which the concentrations of zinc and copper were relatively constant and independent of cadmium concentration were identified; they were 7.2 micrograms Cd/g kidney for zinc and 13 micrograms Cd/g kidney for copper. In this study, cadmium-induced decreases in bone-mineral content occurred in the PL mice exposed to cadmium at 5 and 50 ppm (see accompanying publication). Data presented here indicate that the latter bone changes occurred in the absence of cadmium-induced renal dysfunction of the type that results in increased aminoaciduria/proteinuria. They suggest that the bone disease of Itai-Ital patients may also have started prior to the onset of this type of renal dysfunction.
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PMID:Kidney changes in multiparous mice fed a nutrient-sufficient diet containing cadmium. 338 40

Cadmium, a toxic heavy metal, has been incriminated in the etiology of essential hypertension. Zinc, an essential micronutrient necessary for growth, competes with cadmium for binding sites in biochemical processes; zinc deficiency states (i.e. pregnancy and low protein diet) might expose an individual to increased risk of cadmium toxicity. The increased sensitivity to cadmium during pregnancy could also be related to the effect of progesterone on zinc and cadmium metabolism through the actions of metallothionein (MT). MT is a low molecular weight protein believed to function in cadmium detoxification. Several studies in lab animals have documented a late gestation drop of maternal MT levels. This was thought to be due to rising progesterone levels. If there is also a late gestation drop in human maternal MT, then the propensity toward maternal cadmium toxicity would be enhanced. Therefore, we propose that when a zinc deficient woman becomes pregnant and is exposed to both the nutritional demands of the fetus and to the influence of progesterone, she will be likely to develop the manifestations of cadmium toxicity (i.e. hypertension, proteinuria, edema, etc.).
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PMID:Zinc, cadmium, metallothionein, and progesterone: do they participate in the etiology of pregnancy induced hypertension? 390 Jun 51

Recently Brewer et al. reported the possibility of an oral zinc therapy in Wilson's Disease. We treated a 19 years old patient with decompensated liver cirrhosis due to Wilson's disease with zinc-sulphate. D-Penicillamine had to be withdrawn since proteinuria occurred under treatment. After the discontinuation of D-Penicillamine an increase of serum copper almost up to normal range was observed; concomitantly urinary copper elimination decreased. Under oral zinc sulphate therapy (145 mg/day) a drop of serum copper level was achieved and liver function improved: serum albumin, gamma globulins and prothrombin time reached normal values. The patient did not complain any side effects during oral zinc sulphate therapy. Oral zinc therapy in Wilson's Disease may be regarded as an alternative to D-Penicillamine treatment when this drug has to be discontinued because of side effects.
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PMID:[Oral zinc in Wilson disease--an alternative to D-penicillamine]. 406 Jul 99

Cadmium has been shown to manifest its toxicity in human and animals by mainly accumulating in almost all of the organs and kidney is the main target organ where it is concentrated mainly in cortex. Environmental exposure of cadmium occurs via food, occupational industries, terrestrial and aquatic ecosystem. At molecular level, cadmium interferes with the utilization of essential metals e.g. Ca, Zn, Se, Cr and Fe and deficiencies of these essential metals including protein and vitamins, exaggerate cadmium toxicity, due to its increased absorption through the gut and greater retention in different organs as metallothionein (Cd-Mt). Cadmium transport, across the intestinal and renal brush border membrane vesicles, is carrier mediated and it competes with zinc and calcium. It has been postulated that cadmium shares the same transport system. Cadmium inhibits protein synthesis, carbohydrate metabolism and drug metabolizing enzymes in liver of animals. Chronic environmental exposure of cadmium produces hypertension in experimental animals. Functional changes accompanying cadmium nephropathy include low molecular weight proteinuria which is of tubular origin associated with excess excretion of proteins such as beta 2 microglobulin, metallothionein and high molecular weight proteinuria of glomerular origin (excretion of proteins such as albumin IgG, transferrin etc.). Recent data has shown that metallothionein is more nephrotoxic to animals. Cadmium is also toxic to central nervous system. It causes an alterations of cellular functions in lungs. Cadmium affects both humoral and cell mediated immune response in animals. Cadmium induces metallothionein in liver and kidney but under certain nutritional deficiencies like protein-calorie malnutrition and calcium deficiency, enhanced induction and greater accumulation of cadmium metallothionein has been observed.
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PMID:Molecular basis of cadmium toxicity. 638 35

Cadmium metallothionein (CdMT) nephrotoxicity was studied in rats injected i.p. with a single nonlethal dose of CdMT (0.6 mg of Cd per kg). Within 8 hr of CdMT injection, urine volume and urine sodium excretion were increased and sodium dodecyl sulfate gel electrophoresis of urine proteins showed that elevated levels of low molecular weight proteins were present in the urines of CdMT-treated rats. Urine RNAase activity was also elevated, approximately 7-fold, by CdMT but not by zinc metallothionein (ZnMT) or lysozyme at equivalent protein doses, demonstrating that a proteinuria indicative of proximal tubule cell dysfunction develops as an early response to CdMT exposure. Ultrastructural alterations were also present in animals injected with CdMT but not ZnMT or lysozyme. The earliest alterations occurred in the lysosome compartment of the cell. By 1 hr, the number of small lysosomes in renal proximal convoluted tubule cells increased significantly with no changes in other organelle compartments. By 4 and 8 hr, there was a further increase in lysosome number with a concomitant decrease in size and a marked increase in the number of small clear apical vacuoles. Lysosomal cathepsin D activity was decreased at 4 and 8 hr after CdMT injection, and in vitro studies indicated that this effect was not due to a direct inhibition of the enzyme by Cd++ or CdMT. Thus, both lysosome size and protease activity were rapidly altered by CdMT exposure. Studies of Cd binding in the kidney suggest that non-MT-bound Cd is an important factor in CdMT-associated toxicity. Approximately 97% of the Cd present in the cytoplasm at 1 hr was non-MT-bound. Prior induction of renal MT by treatment with zinc (20 mg of Zn per kg as ZnSO4, i.p. 16 hr before CdMT injection) markedly reduced non-MT binding of Cd++ in kidneys of treated animals and inhibited the alterations in urine volume and low molecular weight protein reabsorption induced by CdMT. These data suggest that acute CdMT exposure provides an excellent system for studying the mechanism of cadmium tubular proteinuria and that the intracellular renal MT pool plays a key role in regulating this process.
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PMID:Cadmium-Metallothionein nephropathy: relationships between ultrastructural/biochemical alterations and intracellular cadmium binding. 670 45


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