UMLS:C0035078 - FACTA Search

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Query: UMLS:C0035078 (renal failure)
31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The p38 mitogen-activated protein kinase (MAPK) pathway is a proinflammatory signal transduction pathway for the production of cytokines and cellular response to stress, such as bacterial LPS or ischemia. We examined the effects of FR167653, a specific inhibitor of p38 MAPK, to explore the relationship between intestinal barrier damage and remote renal dysfunction. Immunohistochemical data showed the accumulation of neutrophils in the intestine after burn, and a horseradish peroxidase (HRP) tracer experiment showed burn-induced intestinal barrier damage. Our quantitative bacterial culture data demonstrated that viable bacteria reached the remote organs after burn and prevented the invading viable bacteria from using FR167653. Western blotting identified increased phosphorylation of p38 MAPK in the kidney after burn, and it may also have shown the possibility that endotoxin associated with the bacterial translocation enhances the activation of the p38 MAPK pathway. We blocked the intestinal barrier damage using FR167653, which resulted in reduced neutrophils in the intestine. FR167653 also prevented the increased phosphorylation of p38 MAPK in the kidney, which resulted in reduced neutrophils in the glomerulus and the reduction of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta mRNA in the kidneys, and, finally, prevented burn-induced renal failure. This study provides evidence for the hypothesis that the p38 MAPK pathway controls inflammatory mediators and not only improves intestinal function but also reduces remote renal failure after burn. We identified the pathophysiologic role of the p38 MAPK pathway in the development of renal failure after burn.
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PMID:Role of p38 mitogen-activated protein kinase pathway on renal failure in the infant rat after burn injury. 1516 82

A 73-year-old man was admitted to the hospital because of progressive lethargy and fever. He had a history of hypertension since the age of 40, and was diagnosed as having a testicular tumor at the age of 50. On admission, he looked pale and stuporous. Laboratory examination revealed microscopic hematuria. The erythrocyte sedimentation rate was 110 mm/hr, and the serum CRP was 14.3 mg/dl. The titer of myeloperoxidase-antineutrophilic cytoplasmic antibodies (MPO-ANCA) was higher than 1:1000. On the sixth hospital day, he required ventilatory assistance because of aspiration pneumonia and was connected to a respirator. He was treated with intravenous corticosteroids, to which he responded in the short term with resolution of the fever and decrease in the serum CRP level, however, the consciousness disturbance persisted and the fever recurred soon thereafter. He developed gross hematuria and the renal function deteriorated. He eventually died of renal failure and pulmonary hemorrhage. Although his clinical course and laboratory findings were consistent with those of microscopic polyangitis, the pathological diagnosis was crescentic glomerulonephritis with no evidence of vasculitis.
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PMID:A 73-year-old man with confusion, fever, and positive MPO-ANCA. 1524 15

We present a case of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis that demonstrated a systemic granulomatous lesion at autopsy. The patient initially showed anorexia, general malaise and anemia. Colon fiber was examined to detect the bleeding site, which revealed ischemic mucosal damage associated with venous fibrin thrombus. Because a high titer of MPO-ANCA was found, ANCA-associated vasculitis was suspected and the patient was started on steroid pulse therapy. However, anemia, renal failure and respiratory failure worsened and the patient died of sudden cardiac failure 2 days after the start of the therapy. An autopsy revealed systemic arteritis in multiple organs including the kidneys, liver, spleen, gastrointestinal system and genital organs that indicated fibrinoid necrosis accompanied by granulomatous reaction with multinucleated giant cells; the granulomatous reaction further extended along the splenic capsule. Glomerulonephritis and diffuse pulmonary damage, which are common in MPO-ANCA-associated vasculitis, were almost absent but parapleural fibrosis was present. The direct cause of death was presumed to be hemorrhagic shock due to rupture of an aneurysm in the gastric subserosa. As far as we know, this is the first case of a systemic granulomatous reaction in MPO-ANCA-positive vasculitis, although the cause of the granulomatous lesion is unknown.
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PMID:Systemic granulomatous necrotizing vasculitis in a MPO-ANCA-positive patient. 1526 Aug 56

A 64-year-old woman with scleroderma without marked dermatological change developed anti-neutrophil cytoplasmic autoantibody (ANCA)-related renal failure. She had neither malignant hypertension nor elevation of plasma renin concentration. Renal biopsy showed crescentic glomerulonephritis (pauci-immune type) and the myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) titer was found to be elevated to 757 IU/ml. Methylprednisolone pulse therapy followed by oral prednisolone effectively suppressed renal failure and lowered the MPO-ANCA titer. We believe this is a rare case of ANCA-related renal failure in a patient with scleroderma without marked dermatological change.
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PMID:ANCA-related crescentic glomerulonephritis in a patient with scleroderma without marked dermatological change and malignant hypertension. 1528 87

An optical array biosensor encapsulated with hydrolase and oxidoreductase using sol-gel immobilization technique has been fabricated for simultaneous analysis and screening of multiple samples to determine the presence of multianalytes which are clinically important in relation to renal failure. Urease and creatinine deiminase were used to detect urea and creatinine, while glucose oxidase and uricase were coimmobilized with horseradish peroxidase to quantify glucose and uric acid. Moreover, the concentrations of analytes in fetal calf serum were measured and quantified using the developed sensing system. The array biosensor showed good specificity for the simultaneous analysis of multiple samples for multianalytes without obvious cross-interference. The analytical ranges of the four analytes were between 0.01 and 10mM with detection limits of 2.5-80 microM. High precision with relative standard deviations of 3.8-9.2% (n=45) was also demonstrated. The reproducibility of array-to-array in 3 consecutive months was 5.4% (n=3). Moreover, the concentrations of analytes in fetal calf serum were 5.9 mM for urea, 0.13 mM for creatinine, 3.3mM for glucose, and 0.15 mM for uric acid, which were in good agreement with results obtained using the traditional spectroscopic methods. These results demonstrate the first use of a sol-gel-derived optical array biosensor for simultaneous analysis of multiple samples for the presence of multiple clinically important renal analytes.
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PMID:Simultaneous determination of renal clinical analytes in serum using hydrolase- and oxidase-encapsulated optical array biosensors. 1546 67

We report a case of microscopic polyangitis presenting with acute pericarditis. A 75-year-old man, who had recurrent acute pericarditis, was referred by a cardiologist because of bilateral infiltrates in the chest radiograph, microhematuria and progressive renal failure. The test for MPO-ANCA was positive. Transbronchial and renal biopsies were compatible with microscopic polyangitis, showing alveolar hemorrhage and crescentic glomerulonephritis. After 3 days, intravenous methylpredonisolone was given, followed by oral prednisolone 40 mg/day, and the patient's radiographic infiltrates cleared and renal dysfunction improved. However, he died from opportunistic infection 109 days after the onset of treatment.
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PMID:[A case of microscopic polyangitis presented with acute pericarditis]. 1550 Jan 49

Autoantibodies to myeloperoxidase (MPO) are associated with the autoimmune disease, systemic vasculitis, in humans. This results in severe inflammation and microscopic necrosis of multiple organs, especially the kidneys, leading to renal failure and death. The discovery of MPO autoantibodies has permitted the development of new diagnostic tests allowing earlier diagnosis and more effective therapy. Furthermore these antibodies are directly implicated in tissue injury by binding to MPO on the neutrophil cell membrane and stimulating neutrophil activation and degranulation. The causes for the breakdown in tolerance to MPO are not known although rare cases are drug-induced and remit on drug withdrawal. An understanding of the biology of MPO and its involvement in the pathogenesis of vasculitis is of importance in understanding the pathogenesis of vasculitis and the development of newer therapies.
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PMID:The clinical features and pathology of vasculitis associated with anti-myeloperoxidase autoantibodies. 1550 56

In the field of forensic medicine, shock has been identified as a cause of death owing to various kinds of exogenous insults. The etiology and pathogenesis of shock cannot be explained well by the usual gross appearance in medicolegal autopsies, because it is now generally established that the shock is a functional reaction of the vascular system to bodily injury, and that several organs are secondarily impaired during shock. Thus it seemed to forensic pathologists that these morphological changes in several organs after shock did not reveal any significant differences among the causes of death. We approached to the induction mechanism of shock, and we investigated what etiology induced these morphological changes after shock in order to identify shock as the cause of death. It is now generally accepted that the kidney is a target organ of shock, so we mainly investigated the cause of kidney disorder in a case of burn shock and hemorrhagic shock. 1. Consequences of bacterial translocation (BT) in the shock. The concept of BT indicates that the beginning of shock is induced by the loss of gut barrier function and consequent translocation of bacteria. In general, impaired gut barrier function can be caused either during the shock period by decreased intestinal blood flow and reduced oxygen delivery, resulting during reperfusion in a stage of increased intestinal blood flow, or at a later stage again by reduced flow. A variety of physiological stresses, such as trauma, hemorrhage, thermal injury, surgical operation, various kinds of drags and mental stress, have been shown to cause failure of the gut mucosal barrier, with translocation of bacteria/endotoxin from the gastrointestinal into the mesenteric lymph nodes, and translocation into remote organs and systemic circulation. 2. Burn shock. We designed to evaluate the BT in a burn shock rat model (following 20% full-thickness scald injury). The p38 MAPK pathway is an important stress-responsive signal molecule pathway, and it is responsible for the production and signal transduction of cytokines. This pathway is activated by the bacterial LPS or ischemia, so we examined the effects of FR167653, a specific inhibitor of p38 MAPK, on the development of renal failure after the burn-induced intestinal barrier damage. Our study demonstrated that viable bacteria reached the remote organs after burn by quantitative bacterial culture data and FR167653 blocked the burn-induced intestinal barrier damage, and the immunohistochemical data showed that FR167653 prevented the accumulation of polymorphonuclear leukocytes (PMNs) in the glomerular capillaries after burn, and blockaded the burn-induced renal failure by serum UN assay. FR167653 especially decreased the phosphorylation levels of p38 MAPK in the infant kidney after burn, and TNF-alpha and IL-1beta mRNA decreased through the p38 MAPK pathway. The above-mentioned facts do provide additional support for the hypothesis that postburn renal failure is mediated by endotoxin associated with the bacterial translocation, and we identified the pathophysiologic role of p38 MAPK pathway in the development of renal failure after the burn-induced intestinal barrier damage. 3. Hemorrhagic shock. We evaluated the role of endogenous TNF-alpha in the renal failure and gut bacterial translocation induced by mild hemorrhagic shock (16.7% bleeding of total body blood via a common carotid catheter without fluid resuscitation). FR167653, a potent inhibitor of TNF-alpha up regulation through p38 MAPK pathway, significantly inhibited these increases of TNF-alpha. Adding to this, our study demonstrated that FR167653 prevented renal failure, such as the infiltration of inflammatory cells and tubular cell necrosis after hemorrhage, and the intestinal barrier damage was also dramatically improved by FR167653 treatment. These results show that derived endogenous TNF-alpha plays a key role in renal failure through p38 MAPK activation during the early phase of mild hemorrhagic shock, including the possible participation of BT. According to these results, we hypothesized that the invading leukocytes induced these organs failures after hemorrhagic shock, so we examined the appearances of leukocytes by the immunohistochemical myeloperoxidase (MPO) staining (marker staining for PMNs). The incidences of PMNs in these organs after mild hemorrhagic shock increased significantly, and FR157653 prevented the appearance of PMNs. These results showed the possible effective role of the PMNs on the occurrence of organ failure caused by mild hemorrhagic shock. 4. Forensic practice. Six hundred and seven forensic autopsy cases in our department of forensic medicine during the past 11 years between 1992 and 2002 were analyzed with regard to the cause of death. Shock cases accounted for 18% of all forensic autopsy cases, and among them 65% of cases identified hemorrhagic shock as the cause of death. So we investigated what good grounds to clearly identify the cause of death induced by hemorrhagic shock. Our experimental hemorrhagic shock data showed PMNs activation and priming during hemorrhagic shock, and it might be closely related to BT and remote organ failure. Consequently, we used the MPO staining method, and we immunohistochemically investigated several organs of our practical autopsy cases to detect the appearance of PMNs as a marker of shock induction. We compared the hemorrhagic shock with other causes of death, such as blood loss, asphyxia, drawing and head injury (intracranial hemorrhage). In every organ, a significant appearance of PMNs was observed in the hemorrhagic shock compared to the other causes of death. Especially, the appearance of PMNs in the heart was clear than that of the other organs in the hemorrhagic shock cases. Therefore, detecting the appearance of PMNs as a marker of shock induction is a very useful and significant method forjudging the cause of death in forensic practice.
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PMID:[Induction mechanism of shock: applying the etiology in judgment of the cause of death in forensic practice]. 1552 67

Increased endogenous generation of advanced glycation endproducts (AGEs) contributes importantly to the vascular complications of diabetes, in part owing to activation of the pro-inflammatory RAGE receptor. However, AGE-altered oligopeptides with RAGE-activating potential can also be absorbed from the diet, and indeed make a significant contribution to the plasma and tissue pool of AGEs; this contribution is especially prominent when compromised renal function impairs renal clearance of AGEs. Perhaps surprisingly, foods rich in both protein and fat, and cooked at high heat, tend to be the richest dietary sources of AGEs, whereas low-fat carbohydrate-rich foods tend to be relatively low in AGEs. Conceivably, this reflects the fact that the so-called "AGEs" in the diet are generated primarily, not by glycation reactions, but by interactions between oxidized lipids and protein; such reactions are known to give rise to certain prominent AGEs, such as epsilonN-carboxymethyl-lysine and methylglyoxal. Although roasted nuts and fried or broiled tofu are relatively high in AGEs, low-fat plant-derived foods, including boiled or baked beans, typically are low in AGEs. Thus, a low-AGE content may contribute to the many benefits conferred to diabetics by a genuinely low-fat vegan diet. Nonetheless, the plasma AGE content of healthy vegetarians has been reported to be higher than that of omnivores - suggesting that something about vegetarian diets may promote endogenous AGE production. Some researchers have proposed that the relatively high-fructose content of vegetarian diets may explain this phenomenon, but there so far is no clinical evidence that normal intakes of fructose have an important impact on AGE production. An alternative or additional possibility is that the relatively poor taurine status of vegetarians up-regulates the physiological role of myeloperoxidase-derived oxidants in the generation of AGEs - in which case, taurine supplementation might be expected to suppress elevated AGE production in vegetarians. Thus, a taurine supplemented low-fat vegan diet may be recommended as a strategy for minimizing AGE-mediated complications in diabetics and in patients with renal failure.
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PMID:The low-AGE content of low-fat vegan diets could benefit diabetics - though concurrent taurine supplementation may be needed to minimize endogenous AGE production. 1560 76

This study characterizes the causal relationship between peripheral polymorphonuclear leukocyte (PMNL) priming, systemic oxidative stress (OS), and inflammation in patients with varying degrees of renal insufficiency (chronic kidney disease [CKD] not on renal replacement therapy [RRT]: continuous ambulatory peritoneal dialysis or hemodialysis [HD]) and healthy control subjects. Rate of superoxide release was measured after stimulation of PMNL with phorbol 12-myristate 13-acetate or zymosan. Priming was estimated by the rate of superoxide release after phorbol 12-myristate 13-acetate stimulation. Systemic OS was related to PMNL priming and intracellular myeloperoxidase activity. Inflammation was linked to peripheral white blood cells and PMNL counts, PMNL apoptosis, and PMNL ex vivo survival in autologous and heterologous sera. PMNL priming and counts were related to the severity of renal failure in CKD not on RRT. Compared with control subjects, PMNL from all CKD patients showed increased priming, highest in HD, with a significant decrease in their response to zymosan. PMNL myeloperoxidase activity and apoptosis were increased in all renal failure patients. Decreased ex vivo cell survival and elevated leukocyte counts were found in all patients, highest in HD. Both PMNL priming and counts correlated negatively with the GFR. A positive significant correlation was shown between PMNL counts and their priming in all groups, suggesting that the increased PMNL count in peripheral blood is an adaptive response to PMNL priming. Hence, PMNL priming is a key mediator of low-grade inflammation and OS associated with renal failure, occurring before the onset of RRT and further augmented in chronic HD.
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PMID:Primed peripheral polymorphonuclear leukocyte: a culprit underlying chronic low-grade inflammation and systemic oxidative stress in chronic kidney disease. 1598 55

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