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)

Zinc metabolism in 20 patients with stable type II diabetes mellitus was investigated. Twenty-five percent of these patients had depressed serum zinc concentrations, and all demonstrated hyperzincuria. Urinary zinc loss was greater when proteinuria was present and correlated with the mean serum glucose concentration. Studies of gastrointestinal zinc absorption suggested zinc malabsorption in patients with type II diabetes mellitus. Glucose infusion in normal dogs produced hyperzincuria without a diminution in serum zinc. It is concluded that hyperzincuria, resulting from a glucose-mediated process that is not osmotic, interacts with impaired zinc absorption to produce zinc deficiency in patients with type II diabetes mellitus.
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PMID:Abnormal zinc metabolism in type II diabetes mellitus. 688 Nov 79

In order to elucidate some pathogenic factors of diabetic hyperzincuria we studied 60 adult insulin treated diabetic out-patients (40 males and 20 females), all with normal serum creatinine concentrations and absence of proteinuria during a 24-h period. Diabetic males and females both had significantly (p less than 0.01) increased zinc excretion rates (1.14 +/- 0.06 (S.E.M.) mumol/mmol creatinine and 1.37 +/- 0.10 mumol/mmol creatinine) compared with normal males and females (0.55 +/- 0.06 and 0.48 +/- 0.08, respectively). The urinary zinc excretion rate correlated positively with the degree of glycosuria (r = 0.36, p less than 0.01), but was not associated with the duration of the disease. However, serum zinc levels gave no evidence of a state of zinc depletion in these patients. It was calculated that zinc originating from a diabetic bone loss and the exogenous insulin administration accounted for only a small part of the hyperzincuria. Compensatory hyperabsorption and/or increased zinc content in the diabetic diet may therefore serve to explain the lack of zinc depletion in the presence of hyperzincuria.
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PMID:Hyperzincuria in insulin treated diabetes mellitus--its relation to glucose homeostasis and insulin administration. 701 79

Copper (Cu) and zinc (Zn) were measured in urine, serum and tissues from rats with nephrotic syndrome (NS) induced with a single subcutaneous dose of puromycin aminonucleoside (PAN; 15 mg/100 g BW). Control animals were pair-fed. Urine was collected daily, and the rats were sacrificed on day 10. PAN-nephrotic rats had proteinuria (days 3-10), high urinary Cu (days 1, 2, 4-10) and Zn (days 3-10) excretion. On day 10, nephrotic rats had: (a) albuminuria, hypoalbuminemia, hypoproteinemia, high urine and low serum levels of ceruloplasmin; (b) low Cu and Zn serum levels; (c) high clearance and fractional excretion of Cu and Zn, and (d) low kidney and liver Cu content and essentially normal tissue Zn levels. The alterations in Cu metabolism were more intense than those in Zn metabolism. Urine Cu and Zn showed a positive correlation with urine total protein on days 3-10 which suggests that high urinary excretion of Cu and Zn may be due to the excretion of its carrier proteins. In conclusion, these rats did not show a typical Zn deficiency but a clear decrease in Cu in the liver and kidney.
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PMID:Copper and zinc metabolism in aminonucleoside-induced nephrotic syndrome. 810 60

Protection against the development of nephrotoxicity following the administration of cadmium-metallothionein (CdMT) at a dose of 0.4 mg Cd per kg body weights was studied in streptozotocin (STZ)-induced diabetic rats. Six groups of Wistar male rats were used (Groups A and B, Groups A1 and C, and Groups A2 and D were injected intraperitoneally with STZ at doses of 0, 50 and 100 mg/kg, respectively, and then 6 days later, Groups B, C and D were injected subcutaneously with CdMT). Proteinuria, albuminuria and transferrinuria were observed after the administration of CdMT, and a dose-related decrease following the increased STZ dose was seen in Groups B, C and D. The concentrations of metallothionein (MT) and zinc (Zn) in liver and kidney were dose-dependently increased in Groups B, C and D. Induction of increased MT synthesis in liver and kidney as the result of the STZ treatment was observed in this study. In particular, a remarkable increase in liver MT concentration was induced by STZ, and transport to the kidney of MT synthesized in liver may perhaps explain the protection against cadmium nephrotoxicity in STZ-induced diabetic rats.
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PMID:Protection against cadmium-metallothionein nephrotoxicity in streptozotocin-induced diabetic rats: role of increased metallothionein synthesis induced by streptozotocin. 857 2

The role of the glomerular visceral epithelial cell in the physiologic turnover and pathologic breakdown of the glomerular extracellular matrix has remained largely unexplored. In this study a 98-kD neutral proteinase secreted by cultured rat visceral glomerular epithelial cells was shown to be a calcium, zinc-dependent enzyme secreted in latent form. In addition, the protein was heavily glycosylated and demonstrated proteolytic activity against Type I gelatin, Type IV collagen gelatin, and fibronectin. The similarity in molecular mass and substrate specificities to the 92-kD human matrix metalloproteinase-9 (MMP-9, or gelatinase B) suggested the identity of this activity, which was confirmed by immunoprecipitation and Northern blot analysis. The differences in molecular mass (98 vs. 92 kD) were not due to species-specific differences in glycosylation patterns, since cultured rat peritoneal macrophages secreted MMP-9 as a 92-kD enzyme. Furthermore, transfection of the human MMP-9 cDNA into rat glomerular epithelial cells yielded the 98-kD product. Using a specific monoclonal anti-MMP-9 antibody and in situ reverse transcription (ISRT) analysis of MMP-9 mRNA, the expression of this enzyme was evaluated in vivo. Normal rat glomeruli expressed little immunohistochemical or ISRT staining for MMP-9, while in rats with passive Heymann nephritis there was a major increase in MMP-9 protein and mRNA staining within the visceral epithelial cells. The temporal patterns of MMP-9 expression correlated with the period of proteinuria associated with this model, suggesting that a causal relationship may exist between GEC MMP-9 expression and changes in glomerular capillary permeability.
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PMID:Characterization of a glomerular epithelial cell metalloproteinase as matrix metalloproteinase-9 with enhanced expression in a model of membranous nephropathy. 861 33

Cadmium-metallothionein, mobilized from the liver, might be the toxic serum factor associated with pre-eclampsia. We base this on four documented concepts. First, during pregnancy, maternal physiology adjusts to assure the fetus of the proper amounts of nutrients necessary for growth. Our focus is on zinc and progesterone. Second, because zinc and cadmium are similar, they compete for binding sites. Our focus is on the storage protein metallothionein. Third, the manifestations of cadmium toxicity closely mimic the manifestations of toxemia (i.e. hypertension, proteinuria, edema). Our focus is on cadmium-induced endovasculitis. Fourth is the concept that metallothionein-bound cadmium can be mobilized from the liver into the serum during pregnancy as it follows the mobilization of metallothionein-bound zinc. Our focus is on the extreme toxicity of extracellular cadmium-metallothionein. We correlate these four concepts into a rational theory on the etiology of toxemia, and we suggest a method of proof.
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PMID:Further observations on the etiology of pre-eclampsia: mobilization of toxic cadmium-metallothionein into the serum during pregnancy. 886 28

Preeclampsia and eclampsia are very important health problems because they are the main contributors to maternal and perinatal morbidity and mortality. These disorders are unique in pregnancy and are characterized by oedema, proteinuria and hypertension. they occur in 0.5% to 30% of all pregnancies, primarily in primigravidas, after the 20-th week of gestation. Preeclampsia and eclampsia are diseases of undetermined cause. Many different factors might play an important role in the development of these diseases. One of them is nutrition. Recent studies have emphasized the possible role of general nutritional deficiency or imbalance of several specific nutrients in the aetiology of the disease. Deficiency of a variety of nutrients has been reported in patients with preeclampsia. The obtained results are contradictory and further study is necessary. Nevertheless, some evidence is highly suggestive of a relationship between nutritional status and the onset or progress of the disease. The article reviews the study that correlates the role of several nutritional elements with the pathophysiology of preeclampsia and eclampsia: proteins, lipids, calcium, vitamin D, sodium, magnesium and zinc. The evidence that supports or rejects the role of each of these nutrients is presented. In this way a guideline for general nutritional counseling in the prenatal period that will promote a healthier pregnancy, is offered.
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PMID:[The role of nutritional factors in pre-eclampsia and eclampsia]. 910 38

Frasier syndrome (FS) is a rare disease defined by male pseudo-hermaphroditism and progressive glomerulopathy. Patients present with normal female external genitalia, streak gonads and XY karyotype and frequently develop gonadoblastoma. Glomerular symptoms consist of childhood proteinuria and nephrotic syndrome, characterized by unspecific focal and segmental glomerular sclerosis, progressing to end-stage renal failure in adolescence or early adulthood. No case of Wilms' tumour has been reported, even in patients with extended follow-up. In contrast with FS patients, most individuals with Denys-Drash syndrome (DDS; refs 6,7) have ambiguous genitalia or a female phenotype, an XY karyotype and dysgenetic gonads. Renal symptoms are characterized by diffuse mesangial sclerosis, usually before the age of one year, and patients frequently develop Wilms' tumour. Mutations of the Wilms'-tumour gene, WT1, cause different pathologies of the urogenital system, including DDS. WT1 is composed of ten exons and encodes a protein with four zinc-finger motifs and transcriptional and tumour-suppressor activities. Alternative splicing generates four isoforms: the fifth exon may or may not be present, and an alternative splice site in intron 9 allows the addition of three amino acids (KTS) between the third and fourth zinc fingers of WT1 (ref. 17). Here we demonstrate that FS is caused by mutations in the donor splice site in intron 9 of WT1, with the predicted loss of the +KTS isoform. Examination of WT1 transcripts indeed showed a diminution of the +KTS/-KTS isoform ratio in patients with FS.
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PMID:Donor splice-site mutations in WT1 are responsible for Frasier syndrome. 939 52

Fractional dextran clearances have been extensively used to study glomerular size selectivity. We report on an analysis of different laboratory procedures involved in measuring fractional dextran clearances. The deproteinization of plasma samples by 20% trichloroacetic acid (TCA) revealed a protein contamination of 0.2% +/- 0.3%, whereas both 5% TCA and zinc sulfate deproteinization revealed a significantly higher remaining sample protein content (2.5% +/- 0.4% and 3.4% +/- 0.1%, respectively). Only zinc sulfate revealed incomplete deproteinization of urine samples (0.6% +/- 0.2%). Dextran recovery in plasma and urine supernatants was significantly lower after 5% TCA and zinc sulfate deproteinization when compared with 20% TCA deproteinization. Gel permeation chromatography (GPC) and high-performance liquid chromatography (HPLC) showed a variance of calibration smaller than 5% over 1 year. The use of 3 different sets of standard dextrans revealed significant differences in calibration. GPC and HPLC followed by anthrone assay showed a comparable variance in dextran concentration in plasma, from 3 to 6 nm (14% to 25%), whereas the variance in urine was lower for the GPC and anthrone assay, especially from 5.4 to 6 nm (23% to 43% versus 50% to 78%). HPLC and online refractometry showed the lowest variance of dextran concentration in plasma, from 3 to 6 nm (<4%), and in urine, from 3 to 5.2 nm (<7%), whereas it showed a higher variance in urine, from 5.4 to 6 nm, in comparison with GPC and HPLC with the anthrone assay. The GPC and anthrone assay revealed higher fractional dextran clearances in comparison with the HPLC and anthrone assay in healthy subjects (3 to 5.4 nm) as well as in patients with nondiabetic proteinuria (4.2 to 5.8 nm), and lower clearances in patients from 3 to 3.4 nm. The HPLC and anthrone assay revealed higher clearances in comparison with HPLC and online refractometry in healthy subjects (3.6 to 5.4 nm) and in patients (3.6 to 5.2 nm). The GPC and anthrone assay revealed characteristic differences in fractional dextran clearances between healthy subjects and patients. The HPLC and anthrone assay showed no significant differences between both groups, whereas HPLC and online refractometry showed only an increased clearance of dextrans from 4.6 to 5.2 nm in patients. Fractional clearances of dextran 5.6 nm as estimated by all 3 dextran assays were not significantly related to the fractional immunoglobulin G clearance or the immunoglobulin-to-albumin clearance index in our patients. Quantitative and qualitative differences in fractional dextran clearances may be induced by differences in laboratory procedures. We recommend sample preparation by 20% TCA deproteinization, frequent calibration with 1 set of dextran standards with low polydispersity, size-exclusion chromatography by GPC, and dextran detection by anthrone assay for optimal measurement of fractional dextran clearances. Even with such an approach, however, the variability in the measurement remains extremely high in the important range of dextrans greater than 5 nm.
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PMID:A comparison of analytic procedures for measurement of fractional dextran clearances. 982 28

Both Type I and Type II diabetes mellitus (DM) have been associated with unusually aggressive periodontitis. Accordingly, rat models of both types of DM were used to study (i) mechanisms mediating this systemic/local interaction and (ii) new pharmacologic approaches involving a series of chemically modified tetracyclines (CMTs) that have lost their antimicrobial but retained their host-modulating (e.g., MMP-inhibitory) properties. In vitro experiments on tissues from Type I DM rats demonstrated that several of these CMTs were better matrix metalloproteinase (MMP) inhibitors than was antibacterial doxycycline (doxy), except for CMT-5, which, unlike the other MMP inhibitors, was found not to react with zinc. Data from in vivo studies on the same rat model generally supported the relative efficacy of these compounds: the CMTs and doxy were found to inhibit MMP activity, enzyme expression, and alveolar bone loss. To examine other long-term complications such as nephropathy and retinopathy, a Type II (ZDF) model of DM was studied. Treatment of these DM rats with CMT-8 produced a 37% (p < 0.05), 93% (p < 0.001), and 50% (p < 0.01) reduction in the incidence of cataract development, proteinuria, and tooth loss, respectively; whereas the doxy-treated ZDF rats showed little or no effect on these parameters. CMT treatment decreased mortality of the Type II ZDF diabetic animals, clearly indicating that CMTs, but not commercially available antibiotic tetracyclines (TCs), may have therapeutic applications for the long-term management of diabetes.
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PMID:MMP-mediated events in diabetes. 1041 38


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