Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A randomized, prospective comparison of OKT3 vs. ALG (University of Minnesota) was performed in patients who had acute renal failure after a cadaver renal transplantation. Criteria for admission to the study were oliguria or increasing serum creatinine in the first 12 hr after renal transplantation. ALG or OKT3 was administered after randomization beginning 12-36 hours posttransplantation. There were no significant differences in age, sex, original disease, ischemia time, or HLA matching between groups. Graft survivals at 1 and 6 months were 84% and 84%, respectively for the ALG group. One- and 6-month graft survival for the OKT3 group was 88% and 84%, respectively. These differences were not statistically significant. The number of rejection episodes and the number of patients with rejection episodes were greater, and the time to first rejection was shorter in the OKT3 group compared with the ALG group, although none of these differences reached statistical significance. There were significantly less side effects in the ALG group compared with the OKT3 group (P less than .05). The greatest reductions in side effects were in fever and hypotension. Patients were monitored with flow cytometry analysis measuring the number of CD2 (T11) and CD3 (T3) cells to adjust the dose of both OKT3 and ALG. Starting doses were 10 mg/kg/day of ALG and 5 mg/day of OKT3. There were no significant differences in the incidence of infections (viral or bacterial) between the two groups. There were no rejection episodes during the prophylactic therapy with either ALG or OKT3. In summary, both ALG and OKT3 provided effective prophylaxis for patients with acute renal failure after renal transplantation. OKT3 was associated with a statistically significant increase in incidence of symptomatic side effects.
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PMID:Comparison of OKT3 with ALG for prophylaxis for patients with acute renal failure after cadaveric renal transplantation. 167 2

The urinary activities of N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl transpeptidase (gamma-GTP) and alanine aminopeptidase (AAP) are known to elevate markedly in initial phase of clinical acute renal failure (ARF). This study was performed to clarify the pathophysiological mechanism of the activation of these enzymes using experimental postischemic reperfusion ARF in rats. The relation between the levels of the lysosomal enzymes and lipid peroxidation induced by oxidant stress in these animal models was the main focus of this study. Renal ischemia was made by clamping renal artery for 30 minutes to create a complete ischemia and reflow. Catheterized urine was collected to measure changes of the activities of NAG. gamma-GTP and AAP from 60 to 480 minutes after reperfusion of the kidney. The activities of renal tissue glutathione peroxidase (GSH-Px), NAG and gamma-GTP, and the values of renal contents of glutathione (GSH) and malondialdehyde (MDA) were measured in each sample. It is already known that GSH redox cycle plays an important role in removing various hydroperoxides induced by oxidant stress, generating oxidated GSH from GSH in scavenging process. In order to confirm if GSH plays an important role in intrinsic anti-oxidant system in this model, buthionine sulfoximine (BSO) which is gamma-glutamylcysteine synthetase inhibitor, was administered intraperitoneally to decrease renal GSH contents before the procedure renal ischemia. The following results were obtained; 1) urinary activities of NAG, gamma-GTP and AAP were elevated markedly in GSH depleted rats compared with controls, 2) renal tissue activities of NAG were higher in BSO administered rats than controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Experimental studies on the elevation of urinary enzyme activities and its pathogenesis in acute renal failure]. 167 93

Acute renal failure is an infrequent adverse reaction following the administration of dextran-40. We report a case of anuric acute renal failure in a 59-year-old female following the administration of 90 gm of dextran-40 and radiocontrast. An increased risk secondary to radiocontrast-induced ischemia is discussed in relationship to the pathogenesis of the dextran-induced acute renal failure. In addition, plasmapheresis is demonstrated to be of potential therapeutic benefit.
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PMID:Case report: dextran-induced acute anuric renal failure. 171 52

This study assessed gentamicin's effects on ischemia/reperfusion renal injury to better understand when and how it worsens postischemic acute renal failure. Rats were subjected to 25 minutes of renal pedicle occlusion with and without preischemic (15-minute) or postischemic (15-minute or 8-hour) gentamicin treatment (100 mg/kg, by itself a subtoxic dose). Gentamicin's impact on hypoxia/reoxygenation injury to isolated rat proximal tubular segments was also assessed. Preischemic and postischemic gentamicin worsened the severity of acute renal failure to the same degree, suggesting that pretreatment induces its effect in the reperfusion period. Gentamicin paradoxically lessened hypoxic damage to proximal tubular segments (assessed by lactate dehydrogenase release), again implying no adverse impact on oxygen deprivation-induced tubular injury. From 0-4 hours of reperfusion, gentamicin approximately halved ATP/ADP ratios (due to increased ADP), indicating a drug-induced defect in cellular energetics. This abnormality temporally correlated with evolving morphological damage. Although antioxidants (deferoxamine and sodium benzoate) have been reported to protect against pure aminoglycoside nephrotoxicity, they did not mitigate gentamicin's adverse impact on postischemic acute renal failure. Gentamicin did not influence ischemia/immediate reperfusion deacylation/reacylation (assessed by renal free fatty acid content) despite its known antiphospholipase activity. Although in the normal kidney gentamicin preferentially accumulated in cortex, in the postischemic kidney, both cortex and outer medullary stripe developed striking (approximately threefold to fivefold) and comparable gentamicin increments. In conclusion, gentamicin appears to exacerbate postischemic acute renal failure by adversely influencing the reperfusion, not the ischemic injury, process. This may occur because increased gentamicin accumulation negatively impacts on reperfusion cellular energetics.
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PMID:Gentamicin effects on renal ischemia/reperfusion injury. 172 86

There have been recent reports of rhabdomyolysis associated with cocaine abuse. The pathologic findings from these cases have not been described. Pathologic abnormalities in two fatalities with cocaine-associated rhabdomyolysis, including one with hyperpyrexia, acute renal failure, and disseminated intravascular coagulation, are discussed in detail. Skeletal muscle in both cases showed necrosis without evidence of vasculitis, polarizable foreign crystals, or other specific lesions. The individual with renal failure showed acute tubular necrosis with granular myoglobin casts in tubules. The mechanism of cocaine-associated rhabdomyolysis is unclear, but potentially includes ischemia due to vasoconstriction, direct toxicity, hyperpyrexia, and increased muscle activity from agitation or seizure. Adulterants may also play a role. In unexplained cases of rhabdomyolysis, toxicologic evidence of cocaine should be sought. In those cases of rhabdomyolysis associated with acute renal failure, the presence of cocaine in blood may be prolonged because of impaired renal clearance.
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PMID:Rhabdomyolysis associated with cocaine abuse. 174 98

We evaluated the acute changes in cortical and outer medullary oxygen tension and the alterations in renal function and morphology within the first 90 minutes after the administration of indomethacin and iothalamate to anesthetized Sprague-Dawley rats. Both agents were found to produce marked and protracted outer medullary hypoxia averaging 12 +/- 4 and 9 +/- 2 mm Hg, respectively (mean +/- SE). Given together to salt depleted uninephrectomized rats they produced an early hypoxic injury localized selectively in the outer medulla. This lesion progressed from 3 +/- 1% of medullary thick ascending limbs (mTALs) at 15 minutes to 22 +/- 7% at 24 hours. Condensed "dark" cells were observed at 15 minutes, probably representing a type of early injury. Residual red cell mass, quantified in the outer medullary vasculature of perfusion-fixed kidneys and presumably reflecting stasis, was substantially increased in iothalamate treated rats. Red cell mass in the interbundle zone correlated with mTAL necrosis. Taken together, these results show an early period of medullary hypoxia, accompanied by a selective injury to mTALs in the central interbundle zone with apparent stasis. These findings contrast sharply with the ischemia-reflow pattern of renal damage and emphasize the important role of medullary hypoxia in the genesis of acute renal failure in this model.
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PMID:Early renal medullary hypoxic injury from radiocontrast and indomethacin. 174 12

Renal ischemia injures the renal tubular cell by disrupting the vital cellular metabolic machinery. Further cell damage is caused by restoration of blood flow when oxygen free radicals are produced. Cellular sources of oxygen free radicals include the electron transport chain, the microsomal electron transport chain, oxidant enzymes (xanthine oxidase, cyclo-oxygenase), phagocytes, and cellular auto-oxidation of Fe2+ and epinephrine. Oxygen radicals cause lipid peroxidation of cell and organelle membranes, disrupting the structural integrity and capacity for cell transport and energy production. Studies in models of acute renal failure have yielded convincing evidence that oxygen free radical production occurs during ischemia/reperfusion. More than a dozen reports have demonstrated the ability of exogenous antioxidants to ameliorate renal injury in vivo. Direct demonstration of increased oxygen free radical production during reoxygenation following hypoxia has been shown in cultured renal epithelial cells. Oxygen free radicals also play a role in toxic acute renal failure. The therapeutic usefulness of free radical scavengers remains to be tested.
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PMID:Oxygen free radicals in acute renal failure. 175 21

In this review, structural and ultrastructural alterations in the kidney in acute renal failure are described and illustrated in some detail. Morphologic findings in clinical and experimental acute renal failure of the type produced by ischemia and some nephrotoxins, so-called 'acute tubular necrosis' are compared and discrepancies between findings in clinical specimens and experimental models noted and discussed. Since perturbations in intrarenal electrolyte species almost surely play a major pathogenic role in renal injury and dysfunction, correlations between altered intrarenal electrolyte transport and abnormal cellular ion concentrations, and morphologic alterations are emphasized in this review.
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PMID:Structural correlates of renal electrolyte alterations in acute renal failure. 175 23

We investigated the role of complement activation on the resolution of acute ischemic renal failure in the rat. Acute renal failure was induced by clamping of the renal arteries of Sprague-Dawley rats for 45 minutes (Day 0). On subsequent days, groups of rats with acute renal failure were exposed to daily zymosan infusion (an activator of the complement system), or to blood incubated with cuprophane (CUP) or polyacrylonitrile (PAN) dialysis membranes. We serially measured the change in BUN daily, glomerular filtration rate and 24-hour proteinuria on Day 3 and Day 5 following ischemia. On Day 6, the animals were sacrificed and their kidneys examined histologically. Zymosan and cuprophane exposed rats had a significant delay in the recovery of renal failure, reduced glomerular filtration rate, and histologically had more neutrophil infiltration than control or PAN exposed animals. To investigate the potential pathophysiology of these observations, we assessed the response of zymosan-exposed rats to infusion of deferoxamine (DFO), a potent inhibitor of hydroxyl radical formation (OH.). Infusion of DFO prior to zymosan significantly improved recovery of renal function. We also measured urinary thromboxane B2 levels in these groups of rats. While the groups of rats exposed to zymosan had the highest levels of thromboxane B2, these levels were not different between the groups exposed to zymosan alone, or to zymosan and DFO. These observations suggest a role for hydroxyl radicals in the prolongation of renal failure in this model. Taken together, these findings may have implications for the dialytic intervention in patients with acute renal failure.
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PMID:Complement activation retards resolution of acute ischemic renal failure in the rat. 176 8

To determine the mechanism of observed differences in vasoreactivity in norepinephrine-induced (NE) and renal artery clamp (RAC) models of ischemic acute renal failure (ARF), induction renal blood flow (RBF) was measured and vascular reactivity examined one week thereafter in NE- and RAC-ARF rat kidneys that had identical levels of renal dysfunction. Morphology also was compared at 48 hours and one week. In NE-ARF, RBF was 14% during 90 minutes of induction and by 60 minutes post-NE infusion was only 18% of baseline. In contrast, in RAC-ARF RBF was effectively 0 for 75 minutes but returned to 95% of baseline by 60 minutes after clamp release. At one week there was a paradoxical increase in renovascular resistance (RVR) to renal perfusion pressure (RPP) reduction in the autoregulatory range and an augmented vasoconstriction to renal nerve stimulation (RNS) in NE-ARF, but no change in RVR and minimal reduction in RBF to these same respective stimuli in RAC-ARF (both different at P less than 0.001). NE-ARF were more sensitive to intrarenal norepinephrine than RAC-ARF kidneys (P less than 0.001). Neither NE- nor RAC-ARF kidneys responded to endothelium-dependent acetylcholine (ACh). Vasodilation to endothelium-independent prostacyclin (PGI2) in NE- was similar to sham-ARF, but there was an attenuated response in RAC-ARF kidneys (P less than 0.001). Morphology at 48 hours showed smooth muscle necrosis in half of the resistance vessels in RAC- but in less than 10% of those in NE-ARF. Except for a slightly greater frequency of tubular casts at 48 hours in RAC-ARF, tubular injury was indistinguishable. It is concluded that NE-ARF has evidence of a predominant functional endothelial vascular injury while RAC-ARF has both morphologic and functional evidence of a predominant smooth muscle injury. Differences in vascular injury between the two models, at least in part, may be the consequence of differences in severity of initial ischemia and/or the rates of recovery of RBF; however, an additional or separate toxic effect of infused NE cannot be excluded.
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PMID:Differences in vascular reactivity in models of ischemic acute renal failure. 189 63


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