Non-traumatic acute rhabdomyolysis. (1/86)

A boy developed sudden severe generalized muscle stiffness, bulbar weakness and passed dark coloured urine. Laboratory tests revealed marked elevation of creatinine kinase(CK) levels and myoglobinuria. Histopathology of quadriceps muscle showed features of acute rhabdomyolysis. Patient made complete clinical recovery over a period of three weeks and CK returned to normal level. The possible aetiologies of non-traumatic rhabdomyolysis are discussed and the relevant literature reviewed.  (+info)

Renal cortical ceramide patterns during ischemic and toxic injury: assessments by HPLC-mass spectrometry. (2/86)

Ceramides are a class of signaling molecules that can acutely accumulate in tissues as part of a "stress response." They are classically measured by the diacylglycerol kinase assay, which, in general, measures total ceramide rather than individual moieties within the diverse ceramide family. The present study was undertaken to 1) adapt current HPLC-mass spectrometry technology for measuring individual renal ceramides, and 2) use this technique to more fully characterize the nature of the renal ceramide "stress" reaction. Renal cortical tissues were obtained from CD-1 mice under control conditions and 2 or 18 h after renal injury (ischemia-reperfusion and glycerol-mediated myohemoglobinuria). C24, C22, and C16 ceramides were identified in normal renal cortex, constituting 70, 10, and 20% of the total ceramide pool, respectively. Within each of these families, heterogeneity was apparent because of differing degrees of unsaturation (0-3 double bonds) in the constituent fatty acid of ceramide. Renal injury dramatically changed ceramide profiles: 1) total ceramide increased by approximately 300%; 2) although all ceramides participated in this reaction, they did so to differing degrees; 3) this caused pronounced changes in ceramide distribution patterns; 4) injury induced a striking shift toward unsaturated (vs. saturated) fatty acids within the C22 and C24 (but not the C16) ceramide pools; and 5) the extent of these qualitative changes differed according to the etiology of the initiating renal damage. Thus we conclude that ceramide stress response involves major qualitative (and not simply quantitative) changes in ceramide expression that are partially disease dependent. These findings underscore the fact that simply measuring total renal ceramide content (e.g., by diacylglycerol kinase assay) substantially oversimplifies the nature and, hence, the potential implications of the ceramide stress reaction.  (+info)

Acute alcoholic myopathy, rhabdomyolysis and acute renal failure: a case report. (3/86)

A case of middle aged male who developed swelling and weakness of muscles in the lower limbs following a heavy binge of alcohol is being reported. He had myoglobinuria and developed acute renal failure for which he was dialyzed. Acute alcoholic myopathy is not a well recognized condition and should be considered in any intoxicated patient who presents with muscle tenderness and weakness.  (+info)

Effects of LTB4 receptor antagonist on myonephropathic metabolic syndrome: an experimental study. (4/86)

The aims of this study were to determine the involvement of leukocytes in reperfusion injury following acute arterial occlusion and to evaluate the effect of the leukotriene B4 (LTB4), which is a chemical mediator of inflammation, receptor antagonist. We examined the usefulness of LTB4 receptor antagonist, ONO-4057, as a preventative drug for myonephropathic metabolic syndrome (MNMS). The experimental leg ischemic model was developed using Wistar strain rats. The rats were divided into 4 groups. In Group R3, the infra-renal abdominal aorta was clamped for 3 hrs and the right femoral muscle tissue was cut to block the development of a collateral artery. In Group R6, the infra-renal abdominal aorta was clamped for 6 hrs and the right femoral muscle tissue was cut. In Group C, the controls, there was no clamping of the abdominal aorta and the right femoral muscle tissue was cut. In Group M, the medicated group, rats were pretreated with an LTB4 receptor antagonist, ONO-4057, just before reperfusion. Blood serum interleukin-1 (IL-1), interleukin-8 (IL-8), creatine phosphokinase (CPK), and aldolase were measured and compared in each of those 4 groups. We also examined the intercellular adhesion molecule-1 (ICAM-1) expression in various organs (liver, heart and kidney) by immunohistochemistry. We found that IL-1 beta levels were low in all groups. CPK, aldolase and IL-8 levels after reperfusion in Group R6 significantly high compared with the levels in Group C (P < 0.03 about CPK, P < 0.05 about aldolase, and P < 0.05 about IL-8). The levels of CPK, aldolase, and IL-8 in Group M were significantly lower than those in Group R6 (P < 0.02 about CPK, P < 0.04 about aldolase, and P < 0.03 about IL-8). We determined immunohistochemically that the expression of ICAM-1 was positive on endothelial cells at the coronary artery and the small vein in Group R6 and that the expression of ICAM-1 was negative on endothelial cells in Group C. Those data suggested that ICAM-1 may play an important role in the progression of reperfusion injury, and the adhesion of neutrophilic leukocytes on endothelial cells may play a significant role in MNMS. LTB4 receptor antagonist may be useful for preventing reperfusion injury following acute aortic occlusion.  (+info)

Changes in free and esterified cholesterol: hallmarks of acute renal tubular injury and acquired cytoresistance. (5/86)

Acute tubular cell injury is accompanied by plasma membrane phospholipid breakdown. Although cholesterol is a dominant membrane lipid which interdigitates with, and impacts, phospholipid homeostasis, its fate during the induction and recovery phases of acute renal failure (ARF) has remained ill defined. The present study was performed to ascertain whether altered cholesterol expression is a hallmark of evolving tubular damage. Using gas chromatographic analysis, free cholesterol (FC) and esterified cholesterol (CE) were quantified in: 1) isolated mouse proximal tubule segments (PTS) after 30 minutes of hypoxic or oxidant (ferrous ammonium sulfate) injury; 2) cultured proximal tubule (HK-2) cells after 4 or 18 hours of either ATP depletion/Ca(2+) ionophore- or ferrous ammonium sulfate-mediated injury; and 3) in renal cortex 18 hours after induction of glycerol-induced myoglobinuric ARF, a time corresponding to the so-called "acquired cytoresistance" state (ie, resistance to further renal damage). Hypoxic and oxidant injury each induced approximately 33% decrements in CE (but not FC) levels in PTS, corresponding with lethal cell injury ( approximately 50 to 60% LDH release). When comparable CE declines were induced in normal PTS by exogenous cholesterol esterase treatment, proportionate lethal cell injury resulted. During models of slowly evolving HK-2 cell injury, progressive CE increments occurred: these were first noted at 4 hours, and reached approximately 600% by 18 hours. In vivo myoglobinuric ARF produced comparable renal cortical CE (and to a lesser extent FC) increments. Renal CE accumulation strikingly correlated with the severity of ARF (eg, blood urea nitrogen versus CE; r, 0.84). Mevastatin blocked cholesterol accumulation in injured HK-2 cells, indicating de novo synthesis was responsible. Acute tubule injury first lowers, then raises, tubule cholesterol content. Based on previous observations that cholesterol has cytoprotectant properties, the present findings have potential relevance for both the induction and maintenance phases of ARF.  (+info)

Acute cardiomyopathy with rhabdomyolysis in chronic alcoholism. (6/86)

Of five chronic alcoholics with acute skeletal muscle necrosis (rhabdomyolysis) three developed acute heart failure with disturbances of rhythm and conduction. Symptoms came on abruptly after a period of intensified drinking. Myocardial infarction, thiamine deficiency, and cobalt intoxication were excluded. Probably the whole spectrum of muscle disease in chronic alcoholism may be commoner than has been suspected.  (+info)

Altered cholesterol localization and caveolin expression during the evolution of acute renal failure. (7/86)

BACKGROUND: Renal cortical/proximal tubule cholesterol accumulation, with preferential localization within plasma membrane "detergent resistant microdomains" (DRMs: rafts/caveolae), is a hallmark of the maintenance phase of acute renal failure (ARF). This study addressed two related issues: (1) Are maintenance-phase cholesterol increases accompanied by an up-regulation of caveolin, a DRM/caveolar-associated cholesterol binding protein? (2) Is DRM cholesterol/caveolin homeostasis acutely altered during the induction phase of ARF? METHODS: Mouse kidneys were subjected to ischemia +/- reperfusion (I/R) followed by assessment of cholesterol DRM partitioning. Acute cell injury effects on potential caveolin release from isolated proximal tubules or into urine also were assessed. Finally, renal cortical/isolated proximal tubule caveolin levels were determined 18 hours after I/R or myoglobinuric ARF. RESULTS: Acute ischemia causes a rapid shift of cholesterol into cortical DRMs (>22%). Cholesterol migration into DRMs also was observed in ATP-depleted cultured proximal tubule (HK-2) cells. Acute hypoxic or toxic tubule injury induced plasma membrane caveolin release (Western blot). By the maintenance phase of ARF, marked renal cortical/proximal tubule caveolin increases resulted. CONCLUSIONS: Acute proximal tubular injury damages caveolar/DRM structures, as determined by cholesterol maldistribution and caveolin release. Post-injury, there is a dramatic up-regulation of renal cortical/proximal tubule caveolin, suggesting an increased caveolar mass. These findings indicate, to our knowledge for the first time, that dysregulation of caveolae/raft microdomain expression is a correlate of, and potential participant in, the induction and maintenance phases of ischemic and toxic forms of experimental ARF.  (+info)

A3 adenosine receptor knockout mice are protected against ischemia- and myoglobinuria-induced renal failure. (8/86)

A(3) adenosine receptor (AR) activation and inhibition worsen and improve, respectively, renal function after ischemia-reperfusion (I/R) injury in rats. We sought to further characterize the role of A(3) ARs in modulating renal function after either I/R or myoglobinuric renal injury. A(3) knockout mice had significantly lower plasma creatinines compared with C57 controls 24 h after I/R or myoglobinuric renal injury. C57 control mice pretreated with the A(3) AR antagonist [3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5 dicarboxylate] or agonist [0.125 mg/kg N(6)-(3-iodobenzyl)-N-methyl-5'-carbamoyladenosine (IB-MECA)] demonstrated improved or worsened renal function, respectively, after I/R or myoglobinuric renal injury. Higher doses of IB-MECA were lethal in C57 mice subjected to renal ischemia. H(1) but not H(2) histamine receptor antagonist prevented death in mice pretreated with IB-MECA before renal ischemia. Improvement in renal function was associated with significantly improved renal histology. In conclusion, preischemic A(3) AR activation (0.125 mg/kg IB-MECA) exacerbated renal I/R injury in mice. Mice lacking A(3) ARs or blocking A(3) ARs in wild-type mice resulted in significant renal protection from ischemic or myoglobinuric renal failure.  (+info)