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)

In this study, we investigated the regulation and physiological role of heme oxygenase-1 (HO-1) in the kidney of rats with hypertension. Rats were continuously administered either angiotensin II (Ang II) or norepinephrine with an osmotic minipump for up to 7 days. Ang II infusion decreased the glomerular filtration rate (GFR) as determined through creatinine clearance (3.2+/-0.2 versus 1.2+/-0.2 mL/min with Ang II infusion, P<0.01) and increased proteinuria (9. 7+/-1.3 versus 28.1+/-7.2 mg/d with Ang II infusion, P<0.01). In contrast, norepinephrine did not alter these laboratory values. Ang II infusion significantly increased HO-1 expression in mRNA (442+/-98% of control at day 5, P<0.01) and protein levels (314+/-49% of control at day 5, P<0.01). Immunohistochemistry showed that in the kidney of normotensive rats, HO-1 was expressed mainly in the basal side in the renal tubules. After Ang II infusion, HO-1 staining was more extensively dispersed in the tubular epithelial cells. The intraperitoneal administration of zinc protoporphyrin, an HO inhibitor, to Ang II-infused rats further decreased GFR (0.8+/-0. 1 mL/min) and increased proteinuria (52.5+/-13.0 mg/d). In contrast, the administration of hemin, an HO inducer, ameliorated the Ang II-induced decrease in GFR (2.4+/-0.2 mL/min) and increase in proteinuria (9.3+/-4.5 mg/d). These data suggest that HO-1 upregulation in the kidney of Ang II-induced hypertensive rats may exert a renoprotective effect against Ang II-induced renal injury.
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PMID:Heme oxygenase-1 is upregulated in the kidney of angiotensin II-induced hypertensive rats : possible role in renoprotection. 1072 May 98

Renal remodelling in hyperinsulinic/insulinopenic states is mediated by glucotoxicity, endothelial dysfunction and vascular and nephron collagen turnover. Hypertensive and renal links are renewed by renoprotective interventions of renin-angiotensin. Vasoactive peptide processing and vascular collagen deposition are under the tight control of two zinc metalloproteinase families that regulate vascular tone and trophicity: gluzincins (or vasopeptidases) are convertases of angiotensins, endothelins or atrial natriuretic factors; and metzincins or matrix metalloproteases (MMP, matrixins)] regulate vascular type IV collagen basement membrane proteolysis. Association of natural tissue inhibitors of MMPs, pharmacological inhibitors of vasopeptidases [either conventional (angiotensin-converting enzyme inhibitors) or innovative (omapatrilat)], together with synthetic MMP inhibitors, are currently screened to counteract vascular remodelling and renal scarring. Our studies focused on the 72 kDa (MMP-2) and 92 kDa (MMP-9) matrixin gelatinases and tissue inhibitors involved in basement membrane degradation and rebuilding. Three complementary settings were developed, allowing evaluations from basic to clinical stages. A leucocyte-endothelial transmigration model was designed for transcription and addressing of enzymes and inhibitors, in situ matrix degradation, and blockading by metalloprotease inhibitors (captopril). Insulin-resistant fructose-fed rats showed heavy proteinuria and glomerulosclerosis involving angiotensin II-dependent changes in renal gelatinases and inhibitors. Urinary gelatinolytic profiles from Type 2 diabetic patients with overt nephropathy were compared with those of normal first-degree relatives and age-matched healthy controls. Physiologically, MMP-9 was the primary urinary gelatinolytic enzyme. In Type 2 diabetic proteinuric patients, MMP-9 and MMP-2 releases were significantly increased in the absence of renin-angiotensin blockade, while first-degree relatives showed reduced gelatinase levels suggestive of a genetic control of renal matrix regulation prior to potential glycaemic dysregulation. These preliminary data suggest that local MMP/TIMP imbalance is involved in diabetic renal remodelling. Further studies are needed to define the redundancies and specificities of vasopeptidase and MMP inhibitors, differentiate the antihypertensive effect from target-organ protection, screen for innovative pharmacological compounds, and validate simple, efficient biological markers of renal fibrosis progression and the effect of anti-fibrotic therapeutic interventions.
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PMID:Role of metalloproteases and inhibitors in the occurrence and progression of diabetic renal lesions. 1092 70

A study of acute and subacute toxicity of cadmium ions [Cd(II)] was carried out on male Swiss mice and Sprague-Dawley rats with and without previous administration of zinc chloride. The LD50 of Cd(II) as cadmium sulfate (ip) was lower in animals previously given 10 mg/kg of zinc(II) chloride (sc). Factors such as animal weight variations, biochemical parameters, and accumulation patterns of Cd(II) and Zn(II) were taken into consideration when the subacute toxicity was evaluated. Alteration of the activities of glutamic pyruvic transaminase (GPT) and of glutamic oxaloacetic transaminase (GOT) was observed in short-term-exposure (<6 h) cases. These alterations reverted to normal after 1 wk. The activity of alkaline phosphatase (ALP) and the concentrations of cholesterol and triglycerides in serum are also changed, especially so in the groups given CdSO4 alone. In the experimental groups treated with ZnCl2 prior to administration of cadmium, proteinuria was detected 5 wk after the treatment. Also at 5 wk, both Zn-treated and nontreated groups showed an abnormally low liver mass with respect to total body mass. Both Cd and Zn are retained preferentially in the liver but show also in the kidneys. If CdSO4 and ZnCl2 are given simultaneously, especially after 1 wk of treatment, Cd is accumulated in greater amounts in these organs when compared to the groups given only cadmium sulfate.
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PMID:Protective effects of zinc on cadmium toxicity in rodents. 1105 91

A 44-year-old patient died from amyotrophic lateral sclerosis (ALS) after nine years of heavy exposure to cadmium (Cd) in a nickel cadmium (Ni-Cd) battery factory. Two years after starting work he and co-workers had experienced pruritus, loss of smell, nasal congestion, nosebleeds, cough, shortness of breath, severe headaches, bone pain, and proteinuria. Upper back pain and muscle weakness progressed to flaccid paralysis. EMG findings were consistent with motor neuron disease. Cd impairs the blood-brain barrier, reduces levels of brain copper-zinc (Cu-Zn) superoxide dismutase (SOD), and enhances excitoxicity of glutamate via up-regulation of glutamate dehydrogenase and down-regulation of glutamate uptake in glial cells. High levels of methallothionein, a sign of exposure to heavy metals, have been found in brain tissue of deceased ALS patients. The effects of Cd on enzyme systems that mediate neurotoxicity and motor neuron disease suggest a cause effect relationship between Cd and ALS in this worker.
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PMID:Amyotrophic lateral sclerosis in a battery-factory worker exposed to cadmium. 1137 40

Focal segmental glomerulosclerosis (FSGS) is responsible for intractable proteinuria and has become the leading cause of renal insufficiency in children. Protenuria in FSGS is probably due to the effect of one or more permeability plasma factors which increase the glomerular permeability to proteins. We fractioned serum from children with FSGS using two mixed chromatographic-electrophoretic approaches and have purified ten proteins among several hundreds which maintained the original permeability activity after renaturation, utilizing an isolated rat glomeruli assay. Six proteins were successfully characterized by mass spectometry as fibulin, apolipoprotein J, vitronectin, albumin isoforms, gamma chain fibrinogen and mannan-binding lectin-associated serine protease. Both procedures utilized for purification were based on affinity chromatography with Protein A-Sepharose and ended with two-dimensional electrophoresis, whereas the intermediate steps were different. Cross inhibition with zinc and aprotinin of purified factors and whole FSGS serum indicate strong homology. These are the first data demonstrating permeability activity for serum proteins, an observation with important implications in pathogenesis of proteinuria. Determination of the serum levels of each protein and a careful differentiation of FSGS from normal serum could provide the basis for clarifying the mechanism of proteinuria.
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PMID:Characterization of plasma factors that alter the permeability to albumin within isolated glomeruli. 1184 May 65

Studies suggest that cadmium is associated with several clinical complications, primarily renal dysfunction and bone disease, but also some cancers. Cadmium toxicity has been associated with clinical manifestations at exposure levels that are well below the limits set by the World Health Organization. Here I review the OSCAR study, which demonstrates an association between environmental and occupational cadmium exposure and renal tubular damage, as well as the Cadmibel study, a cross-sectional population study demonstrating an association of cadmium exposure with renal dysfunction. The paper also reviews the association of end-stage renal disease prevalence with occupational and environmental exposure to cadmium in the Swedish population of Kalmar County. Renal tubular damage was shown to develop at levels of exposure much lower than previously thought. Cadmium-induced tubular proteinuria is irreversible, and continued exposure may lead to glomerular damage with decreased glomerular filtration rate. Itai-itai disease in the Jinzu river basin is discussed, as are the implications of low-level cadmium exposure in the PheeCad project. Cadmium accumulates in bone and is associated with osteomalacia and osteoporosis. Other bone-seeking trace elements, such as chromium, lanthanum, strontium and zinc, are of concern because of low level environmental, occupational or clinical exposure. As techniques are perfected for detecting smaller amounts of trace elements in various tissues in the body, investigators are finding that the threshold for toxicity from trace elements is much lower than expected. Further research on cadmium is necessary to reveal the mechanisms of toxicity and true environmental and occupational exposure limits.
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PMID:Cadmium overload and toxicity. 1190 57

Hypertension is the most common medical complication of pregnancy in South Africa and a major cause of maternal and perinatal morbidity and mortality worldwide. At King Edward VIII Hospital in Durban, 18% of all admissions to the obstetric unit have some degree of high blood pressure. Hypertension in its most severe form produces convulsions, proteinuria, and edema and may lead to fetal and maternal death. High-risk groups for preeclampsia are teenage mothers, primigravidas, and women with a history of elevated blood pressure, previous preeclampsia, molar pregnancies, multiple pregnancies, or hydrops fetalis. Methods used to prevent preeclampsia include a low-salt diet supplemented with calcium, magnesium, zinc, fish, and pharmacological manipulation. In developing countries, prevention and detection of preeclampsia is difficult since women seek antenatal care late in their pregnancies. In Durban, the average gestational age at first antenatal attendance is 28 weeks, and 80% of patients presenting with eclampsia have defaulted antenatal care. Treatment includes admission to hospital to establish the etiology of the hypertension and maternal renal function tests . Fetal condition is a sensitive index of hypertension and is judged by 1) clinical evidence of fetal growth, 2) weekly antepartum cardiotocography, and 3) ultrasonographic screening. Patients are managed according to three clinical groups: 1) those identified before 36 weeks, 2) those identified after 36 weeks, and 3) patients in hypertensive crisis. Dihydralazine is the drug of choice for imminent eclampsia. If the patients has a ripe cervix, delivery is induced with 6-8 hours. Steroid contraception use in the older hypertensive patient should be avoided because of possible development of atherosclerosis and stroke. Puerperal tubal ligations in the hypertensive patient ought to be avoided because of the risks of thromboembolic phenomena and pulmonary embolism. Methyldopa is the treatment of choice in cases of moderate to severe hypertension. Intravenous dihydralazine is relatively safe for the rapid reduction of high blood pressure.
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PMID:Coping with hypertension in pregnancy. 1234 38

A 28-year-old female presented for evaluation of left flank pain and polyuria after having been exposed to cadmium in the jewelry manufacturing industry for approximately 3 years. This patient possessed both elevated 24-hr urinary ss2-microglobulin and elevated blood cadmium levels. Approximately 6 months after initial presentation, the patient resigned from her job due to shortness of breath, chest pain, and anxiety. Exposure to cadmium in the jewelry industry is a significant source of occupational cadmium exposure. Other occupational sources include the manufacture of nickel-cadmium batteries, metal plating, zinc and lead refining, smelting of cadmium and lead, and production of plastics. Cadmium is also an environmental pollutant that accumulates in leafy vegetables and plants, including tobacco. Major toxicities anticipated from cadmium exposure involve the renal, pulmonary, and, to a lesser extent, gastrointestinal systems. These include the development of renal proximal tubular dysfunction, glomerular damage with progressive renal disease, and respiratory symptoms including pneumonitis and emphysema. Low-level cadmium exposure has also been associated with increased urinary calcium excretion and direct bone toxicity, effects that recent research suggests may result in the development of osteoporosis. The body burden of cadmium, over half of which may reside in the kidneys, is most often measured through the use of urinary cadmium levels. Blood cadmium measurements generally reflect current or recent exposure and are especially useful in cases with a short exposure period and only minimal accumulation of cadmium in the kidneys. Both ss2-microglobulin and alpha1-microglobulin serve as organ-specific, early-effect biomarkers of tubular proteinuria and thus play a role in identifying early signs of cadmium-induced renal damage in those with potential exposures. In addition to ensuring workplace compliance with Occupational Safety and Health Administration-mandated monitoring and screening measures, it is prudent for those with cadmium exposure to maintain adequate intake of both iron and calcium, appropriate measures even in the absence of exposure.
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PMID:Cadmium exposure and nephropathy in a 28-year-old female metals worker. 1246 Aug 7

Proteinuria is an independent risk factor for progression of renal diseases. Glia maturation factor-beta (GMF-beta), a 17-kDa brain-specific protein originally purified as a neurotrophic factor from brain, was induced in renal proximal tubular (PT) cells by proteinuria. To examine the role of GMF-beta in PT cells, we constructed PT cell lines continuously expressing GMF-beta. The PT cells overexpressing GMF-beta acquired susceptibility to cell death upon stimulation with tumor necrosis factor-alpha and angiotensin II, both of which are reported to cause oxidative stress. GMF-beta overexpression also promoted oxidative insults by H2O2, leading to the reorganization of F-actin as well as apoptosis in non-brain cells (not only PT cells, but also NIH 3T3 cells). The measurement of intracellular reactive oxygen species in the GMF-beta-overexpressing cells showed a sustained increase in H2O2 in response to tumor necrosis factor-alpha, angiotensin II, and H2O2 stimuli. The sustained increase in H2O2 was caused by an increase in the activity of the H2O2-producing enzyme copper/zinc-superoxide dismutase, a decrease in the activities of the H2O2-reducing enzymes catalase and glutathione peroxidase, and a depletion of the content of the cellular glutathione peroxidase substrate GSH. The p38 pathway was significantly involved in the sustained oxidative stress to the cells. Taken together, the alteration of the antioxidant enzyme activities, in particular the peroxide-scavenging deficit, underlies the susceptibility to cell death in GMF-beta-overexpressing cells. In conclusion, we suggest that the proteinuria induction of GMF-beta in renal PT cells may play a critical role in the progression of renal diseases by enhancing oxidative injuries.
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PMID:Induction of glia maturation factor-beta in proximal tubular cells leads to vulnerability to oxidative injury through the p38 pathway and changes in antioxidant enzyme activities. 1279 1

Acute cellular allograft rejection is characterized by leukocyte invasion and tissue destruction, associated with qualitative and quantitative alterations in the extracellular matrix (ECM) compartment. Metabolism of ECM proteins is mainly regulated by matrix metalloproteinases (MMP), that are zinc depended endoproteinases. MMP, especially basement membrane degrading MMP-2 and MMP-9, also facilitate tissue invasion of leukocytes. In addition, MMP-2 exerts a direct pro-inflammatory effect upon glomerular mesangial cells. Therefore, the investigation of the role of MMP in transplant rejection may lead to novel approaches in the therapy of rejection processes. To our knowledge, this is the first study of acute allograft rejection, formally addressing expression and activity of MMP, including the effect of a MMP inhibiting agent. For our studies, we used the orthotopic kidney allograft model in the stringent Dark Agouti-to-Lewis rat strain combination. Animals were divided into four groups: group A, healthy untreated Lewis rats (n=3); group B, sham operated Lewis rats (n=3); group C, transplanted Lewis rats treated with vehicle solution only (n=12); group D, transplanted Lewis rats treated with MMP inhibitor BB-94 (n=12). Respective animals were treated once daily intraperitonealy with BB-94 (30 mg/kg) or vehicle solution only. Treatment lasted from the third preoperative day until the end of the experiment, the time of severe rejection at day +7. Acute kidney allograft rejection led to alterations in the expression and activity of MMP. Overall MMP activity slightly increased despite severe destruction of kidney histology. The MMP inhibitor BB-94 successfully inhibited MMP activity to a high extent. MMP expression did not show uniform findings, since acute rejection led to differential expression of MMP-2 and MMP-9. During the rejection process, MMP-9 showed a small but significant increase, whereas MMP-2 production decreased substantially. Interestingly, BB-94 was able to keep proteinuria at a low level in transplanted animals. In conclusion, MMP-especially MMP-9-appear to represent new mediators involved in acute kidney transplant rejection.
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PMID:Differential expression of MMP-2/MMP-9 and potential benefit of an MMP inhibitor in experimental acute kidney allograft rejection. 1279 96


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