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)

Temporary renal ischemia is followed by increased DNA synthesis and cell division as the kidney restores the continuity of the renal epithelium. We sought to characterize some of the changes in proto-oncogene and growth factor expression during this proliferative response. Northern analysis of polyadenylated RNAs of kidney cortical and outer stripe of outer medullary tissue from male Sprague-Dawley rats was performed following release of renal hilar clamping of 50 minutes duration. Ischemia produced an increase in c-fos mRNA that reached a peak at one hour and declined rapidly to control levels by four hours after release of the clamp. A similar rapid increase and decrease in early growth response 1 (Egr 1) mRNA was noted. The response of these immediate early genes was typical of their response to mitogens, suggesting that they served a similar role in renal cell regeneration. Levels of c-Ki-ras and glyceraldehyde phosphate dehydrogenase mRNA were unchanged. Renal preproEGF mRNA decreased at two hours, was virtually absent by 24 hours and remained low for at least four days after ischemia. Urinary excretion of EGF fell immediately after release of ischemia and before the decline in preproEGF mRNA or SNGFR, suggesting post-transcriptional affects of ischemia on renal EGF production. EGF excretion returned to only 50% of control by day 21. Specific 125I-EGF binding increased in membrane fractions of cortex, outer medulla and inner medulla as early as 24 hours after release of the clamp. Cortical 125I-EGF binding increased in the proximal tubule but not in the glomerulus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in gene expression after temporary renal ischemia. 236 5

Recently we reported that maintaining rats on restricted dietary protein regimens prior to renal ischemia will significantly improve postischemic survival rates. This effect required a week or more of maintenance on a restricted protein diet prior to the renal insult and appeared to be independent of the postischemic dietary protein regimen. The present study was designed to evaluate the role of systemic toxicity in this protection. Adult male Sprague-Dawley rats were pair-fed by weight on restricted or high isocaloric protein diets for 8-10 days prior to 45 min of renal ischemia induced by renal pedicle clamping. When placed on a normal dietary protein regimen immediately following ischemia, the rats preconditioned to restricted dietary protein exhibited significantly less acidosis, less hyperkalemia, lower blood urea nitrogen values, and improved survival rates compared with rats preconditioned on a high dietary protein regimen. In order to separate the possible effects of prior dietary protein regimen on acute tubular necrosis suffered during renal ischemia from its effects on the uremic response, bilateral nephrectomies were performed on rats preconditioned for 14 days to low, normal, and high dietary protein regimens. Although all of the rats were placed on the same dietary protein regimen immediately following bilateral nephrectomy, those that had previously been on a lower dietary protein regimen exhibited a significantly reduced uremic response and lived longer. These findings indicate that dietary protein regimen prior to renal ischemia is a risk factor which can have a significant lingering effect on the severity of postischemic systemic toxicity.
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PMID:Dietary protein regimen prior to renal ischemia significantly affects the postischemic uremic response. 237 Sep 27

Most urinary tract infections occur without either obstruction or vesicoureteral reflux. Children become colonized by their mother's bacterial flora, that within the nursery or by siblings. Bacterial adherence may lead to colonization of the perineum in girls and of the prepuce in boys (if uncircumcised). Nephropathogenic bacteria ascend the urinary tract because of the P-fimbriae of Escherichia coli which adhere to a specific urothelial cell glycolipid. The endotoxin effect on ureteral peristalsis leads to intrarenal reflux, adherence in the kidney and acute pyelonephritis. Complement activation then causes granulocytic aggregation in capillaries with renal ischemia and activates granulocytes to produce the respiratory burst of phagocytosis, which releases superoxide into both phagosomes and the tubular lumen. Bacteria are thus killed as are renal tubules, leading to nephron loss. Untreated, the ischemia and respiratory burst lead to a loss of renal function and scar formation ending as chronic pyelonephritis (or reflux nephropathy).
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PMID:Norwich-Eaton lectureship. Pathogenesis of nonobstructive urinary tract infections in children. 237 23

To investigate the functional role of renal intrinsic antioxidant enzymes (AOEs), the levels of AOE activities in isolated glomeruli and the changes in renal function to oxidant insults were assessed in normal control rats (NC, N = 23) and rats subjected to 30-minutes of complete renal ischemia for three days (day-3, N = 20) or six days (day-6, N = 23) prior to study. When compared to NC, the activities of total and manganese (cyanide-insensitive) superoxide dismutase, glutathione peroxidase, and catalase were increased more than twofold in day-6 animals, on average, from 36 +/- 4 U/mg protein, 9 +/- 1 U/mg protein, 129 +/- 21 U/mg protein and 1.32 +/- 0.20 k/mg protein, respectively, to 80 +/- 5, 27 +/- 3, 283 +/- 41 and 3.20 +/- 0.20, respectively (P less than 0.05 for all). There were no changes in AOE activities in day-3 animals. In day-6 animals, however, the activities of non-AOEs, LDH and fumarase were found to be unaffected. Separate groups of NC (N = 12), day-3 (N = 5) and day-6 (N = 12) rats were subjected to either 30 minutes of ischemia plus 60 minutes of reperfusion (I/R) or unilateral i.a. infusion of hydrogen peroxide (H2O2, 35 mu moles in 1 hr). The degree of reduction in inulin and para-amino hippurate clearance rates following I/R were significantly less in day-6 (-21 +/- 3% and -12 +/- 2, respectively) compared to NC (-69 +/- 9% and -59 +/- 11, respectively) or day-3 rats (-73 +/- 7% and -62 +/- 10, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of intrinsic antioxidant enzymes in renal oxidant injury. 240 19

The effect of 45-min clamping of the renal artery was studied in the conscious uninephrectomized rat to reproduce the syndrome of hemodynamically mediated acute renal failure in humans after a single ischemic insult. Twenty-four hours after ischemia, creatinine clearance was reduced by 90%, whereas fractional excretion of sodium was markedly increased; over the subsequent 5 days, both values returned to normal. The animals were nonoliguric. Fractional clearances of graded sizes of neutral dextrans (radii 20-44 A), employed to detect transtubular backleak of inulin, were not significantly different 24 or 48 h postischemia from those in normal animals. The implication that the normal fractional dextran clearances excluded tubular backleak was tested directly by microinjecting [methoxy-3H]inulin into the proximal tubule. In most tubules injected, the recovery of radioactivity in the urine was markedly lower 24 and 48 h postischemia than that in normal rats; in a few injected tubules of postischemic kidneys, recovery was not different from that in normal animals. The low recovery of radioactive inulin was accounted for, at least in part, by transtubular backleak, as shown in experiments in which rats subjected to renal ischemia were cross-transfused with normal animals. These studies indicate that, despite the normal fractional dextran clearances, most tubules were severely injured as shown by tubule backleak of inulin.
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PMID:Course and pathogenesis of postischemic acute renal failure in the rat. 245 26

Total renal ischemia for various time intervals (0-50 min) resulted in the rapid and duration-dependent redistribution of polarized membrane lipids and proteins in renal proximal tubule cells. Following only 15 min of ischemia, apical membrane enrichment of NaK-ATPase, normally a basolateral membrane (BLM) enzyme, had increased (1.6 +/- 0.6 vs. 2.9 +/- 1.2, P less than 0.01). In vivo histochemical localization of NaK-ATPase showed reaction product throughout the apical microvillar region. PTH-stimulatable adenylate cyclase, another BLM protein, was also found in ischemic but not control apical membrane fractions. One dimensional SDS-PAGE showed four bands, present in control BLM and ischemic apical membranes, which could not be found in control apical membrane fractions. Immunohistochemical localization of leucine aminopeptidase (LAP) showed the enzyme was limited to the apical domain in control cells. Following ischemic injury (50 min), LAP staining could be seen within the cell and along the BLM. Following 24 hr of reperfusion, the BLM distribution of LAP was further enhanced. With cellular recovery from ischemic injury (5 days), LAP was again only visualized in the apical membrane. Duration-dependent alterations in apical and BLM lipids were also observed. Apical sphingomyelin and phosphatidylserine and the cholesterol-to-phospholipid ratio decreased rapidly while apical phosphatidylcholine and phosphatidylinositol increased. Taken together, these results indicate renal ischemia causes rapid duration-dependent reversible loss of surface membrane polarity in proximal tubule cells.
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PMID:Characterization of ischemia-induced loss of epithelial polarity. 246 76

Experiments were performed on rats to examine the cause of the vascular congestion that accompanies renal ischemia, and the potential role of cell swelling in its generation. Renal function and gross morphology were examined after reflow, whereas tissue morphometry was performed both before and after reflow in kidneys. Small doses of mannitol applied into the renal artery just before ischemia greatly reduced the incidence of vascular congestion and the depression of renal function. During ischemia the outwardly directed swelling of the proximal tubule depleted the interstitial and vascular space of the cortex and outer medullary outer stripe and the inwardly directed swelling of the thick ascending limb occluded the lumen. Mannitol reduced cell swelling, lessened the depletion of the interstitial and vascular space and eliminated the occlusion of the thick ascending limb. It is proposed that the loss of interstitial and vascular fluid during ischemia is the cause of the vascular congestion, which, in turn, is responsible for the poor perfusion and impaired renal function seen after ischemia.
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PMID:Vascular congestion in ischemic renal failure: the role of cell swelling. 249 26

The addition of the disaccharides maltose (10, 20, 30 mM) and sucrose (30, 60 mM) to Bretschneider's organ protective HTK solution was evaluated to improve renal protection by an enhanced glycolytic energy supply. Canine kidneys were perfused for 8 min with either HTK solution or HTK solution containing additional disaccharides. After nephrectomy the kidneys were incubated at 25 degrees C and metabolic parameters were determined at regular intervals. Maltose and sucrose are slowly cleaved during renal ischemia but maltose distinctly faster than sucrose. Maltose increases intraischemic ATP supply. However, 30 mM maltose was no better than 10 mM. 60 mM sucrose was about as effective for glycolysis as 10 mM maltose. However, possibly due to fructose release there was an accelerated decrease of adenine nucleotides with sucrose. Although fructose enters glycolysis it seems to have negative side-effects. Hence, probably neither sucrose nor fructose are appropriate for renal substrate supply during ischemia.
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PMID:Intraischemic metabolic effects of different disaccharides on protected canine kidneys. 251 81

The present experimental study investigates whether the atrial natriuretic factor (ANF) is able to prevent the nephrotoxic effects of cyclosporine infused after 30 min of warm renal ischemia in the rat. At 2 hr after the end of ischemia, the glomerular filtration rate was improved by an ANF infusion: 390 +/- 19 microliters/min/100 g versus 298.3 +/- 31 microliters/min/100 g in ANF and saline-infused rats, respectively (P less than 0.05). Intravenous CsA infusion at a dose of 2.5 mg/kg/day produced a more pronounced fall in GFR when compared with the control: 205.4 +/- 19.7 microliters/min/100 g versus 298.3 +/- 31 microliters/min/100 g in CsA and saline, respectively (P less than 0.05). In contrast, a synthetic rat atriopeptin III (0.5 microgram/kg/min) infusion after ischemia given together with CsA prevented its deleterious effects upon GFR: 316 +/- 22 microliters/min/100 g versus 205.4 +/- 19 microliters/min/100 g in ANF/CsA versus CsA alone (P less than 0.001). Moreover, the natriuretic ANF effects remained unaffected by high plasma CsA peak levels: indeed, other parameters of renal function--urinary flow, urinary sodium concentration and excretion rates, and urinary sodium reabsorption and fractional excretion rates, were significantly increased in ANF alone or CsA/ANF groups. These preliminary results suggest that ANF may be useful in renal transplantation or in the management of patients given large doses of CsA (liver or heart transplant) since, despite nephrotoxic CsA levels (greater than 1500 ng/ml), ANF provides an improved GFR and tubular function after ischemia.
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PMID:Prevention of acute cyclosporine nephrotoxicity by atrial natriuretic factor after ischemia in the rat. 252 54

We have evaluated the impact of inhibiting adenine nucleotide dephosphorylation on the metabolic and functional consequences of renal ischemia. Intramuscular injection of the ADP-analogue adenosine alpha, beta-methylene diphosphate (AMP-CP) achieved a 70% reduction in 5'-nucleotidase activity, as measured in crude extracts of rat kidney. AMPCP-treated animals had an increased residual nucleotide pool at the end of 45 min of ischemia compared with untreated rats. Assessment of renal ATP by 31P-nuclear magnetic resonance (31P-NMR) in vivo during reflow demonstrates the following: 1) higher rapid initial recovery of ATP (69.3 +/- 1.2 vs. 50.0 +/- 0.5% control value, P less than 0.005), 2) accelerated rate of ATP restoration (0.20 +/- 0.02 vs. 0.11 +/- 0.01% control/min, P less than 0.005), and 3) significantly enhanced renal ATP content after 120 min (93.6 +/- 2.0 vs. 63.1 +/- 0.7% control, P less than 0.005). Kidney function, as measured by the rate of inulin clearance 24 h after the insult, was also significantly improved in AMPCP-treated rats (725 +/- 50 vs. 313 +/- 28 microliters.min-1.100 g body wt-1). Thus inhibition of 5'-nucleotidase results in enhanced metabolic and functional recovery from a renal ischemic insult.
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PMID:Protection of the kidney against ischemic injury by inhibition of 5'-nucleotidase. 253 26


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