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)

Although cyclosporine (CSA) is established in the prevention of allograft rejection, its use has been associated with dose-limiting toxicities, most notably to the kidney and liver. To date, the pathogenesis of the acute form of nephrotoxicity is unclear but may be related to inhibition of vasodilatory prostaglandins resulting in vasoconstriction and ischemia. The present study investigated the coadministration of CSA with a unique hemorheologic agent, pentoxifylline (PTX), in the murine model. A total of 48 rats were orally dosed with CSA 25 mg/kg for 10 days with either PTX 45 mg/kg i.p. or saline every 12 hr. Posttreatment renal function, assessed by creatinine (CCR) and inulin (CIN) clearances and renal electrolyte handling, was compared with baseline data and between groups. In an attempt to assess prostaglandin-mediated changes in enteral absorption, oral CSA pharmacokinetics with and without PTX were compared to the pharmacokinetics of similar groups (N = 8) administered i.v. CSA. Mean CIN of rats coadministered CSA and PTX (942 +/- 214 microliters/min/g KW) was similar to control rats 884 +/- 185 microliters/min/g KW); both were significantly greater than CSA alone (537 +/- 211 microliters/min/g KW; p less than .01). Likewise, percent of baseline CCR was significantly reduced in rats treated CSA (61 +/- 24%) compared to controls 113 +/- 41%) and rats coadministered PTX (117 +/- 75%; p less than .05). No differences in percent change from baseline electrolyte handling were observed among groups. Further, no differences in CSA pharmacokinetics with or without PTX were found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of cyclosporine-induced nephrotoxicity with pentoxifylline. 251 44

The effects of calcium blockade with verapamil on postischemic renal failure were tested in dogs. Two experiments were performed. In experiment 1 (n = 7), one kidney in each dog received an infusion of verapamil and the other received saline for 30 minutes prior to induction of 1 hour of ischemia. Inulin clearance (CIN), urine flow, and renal blood flow (RBF) were measured. Infusion of verapamil increased urine flow from 0.99 to 4.29 ml/min (P less than 0.001). CIN and RBF did not change significantly nor did urine flow in the saline-treated kidney. Three hours after ischemia there was no significant difference in CIN, although it was lower in verapamil-treated kidneys. RBF declined in both treatments. In experiment 2 (n = 6) kidneys were treated with verapamil and saline for 50 minutes beginning immediately after 1 hour of ischemia. Urine flow and CIN were significantly higher in verapamil-treated kidneys during the infusion (3.09 +/- 0.44 versus 0.26 +/- 0.12 ml/min, P less than 0.001; 28.6 +/- 7 .4 versus 6.2 +/- 3.1 ml/min, P less than 0.025, respectively). CIN remained elevated in verapamil-treated kidneys at 3 hours, however RBF was depressed in both verapamil- and saline-treated kidneys. These results suggest that verapamil is a potent diuretic and that verapamil can be given after renal ischemia with significant attenuation of postischemic renal failure.
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PMID:Beneficial effects of verapamil on postischemic renal failure. 687 43

The effects of a protein-restricted diet on renal recovery following renal ischemia were studied. The renal function was assessed by measuring the inulin clearance (CIN), the p-aminohippurate clearance (CPAH), and the percent fractional sodium excretion (%FENa) 24 h after 45 min renal ischemia. In rats fed with a regular diet (containing 19.6% protein), CIN was 10.0 +/- 2.2 microL/min/100 g body weight (BW), CPAH 0.08 +/- 0.02 mL/min/100 g BW, and %FENa 14.8 +/- 2.0, 24 h after renal ischemia. In contrast, feeding rats with a no-protein diet (0% protein) for 1 week prior to the ischemic insult significantly improved renal recovery (CIN 48.0 +/- 9.3 microL/min/100 g BW, CPAH 0.16 +/- 0.04 mL/min/100 g BW, and %FENa 2.43 +/- 0.58). Feeding rats with a no-protein diet for 3 weeks prior to ischemic insult further improved the renal recovery (CIN 113 +/- 30 microL/min/100 g BW, CPAH 0.47 +/- 0.17 mL/min/100 g BW, and %FENa 1.55 +/- 0.29). When rats fed with a regular diet were exposed to 45 min of ischemia, the survival rate on day 7 was 16.7%. In rats fed with the no-protein diet for 1 week and for 3 weeks, the 7-day survival rate was 100% in each case. The survival rate of rats fed for 3 days instead of 7 days with the no-protein diet was 87.5%. When a no-protein feeding was shortened to 1 day, no beneficial effects were observed and survival rate was 14.3%. (ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein-restricted diet prior to renal insult improves the recovery of renal function following ischemia. 829 Jul 2

Studies over the past decade have demonstrated that lactate is produced aerobically during brain activation and it has been suggested to be an obligatory aerobic energy substrate postischemia. It has been also hypothesized, based on in vitro studies, that lactate, produced by glia in large amounts during activation and/or ischemia/hypoxia, is transported via specific glial and neuronal monocarboxylate transporters into neurons for aerobic utilization. To test the role of lactate as an aerobic energy substrate postischemia in vivo, we employed the cardiac-arrest-induced transient global cerebral ischemia (TGI) rat model and the monocarboxylate transporter inhibitor alpha-cyano-4-hydroxycinnamate (4-CIN). Once 4-CIN was establish to cross the blood--brain barrier, rats were treated with the inhibitor 60 min prior to a 5-min TGI. These rats exhibited a significantly greater degree of delayed neuronal damage in the hippocampus than control, untreated rats, as measured 7 days post-TGI. We concluded that intra-ischemically-accumulated lactate is utilized aerobically as the main energy substrate immediately postischemia. Blockade of lactate transport into neurons prevents its utilization and, consequently, exacerbates delayed ischemic neuronal damage.
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PMID:Blockade of lactate transport exacerbates delayed neuronal damage in a rat model of cerebral ischemia. 1125 89

Glial-derived monocarboxylate lactate is thought to be an important energy source for neurons during brain activation or in hypoxia-ischemia. Treatment with alpha-cyano-4-hydroxycinnamate (4-CIN), a monocarboxylate transporter inhibitor, has been recently reported to exacerbate delayed neuronal damage in a rat model of cerebral ischemia, an effect ascribed to inhibition of lactate/pyruvate transport. Since monocarboxylate transporters are abundant in the retina, we examined the effect of 4-CIN administration on the outcome of high intraocular pressure-induced retinal ischemia in rats. Retinal ischemic damage was assessed by changes in the electroretinogram (ERG), the retinal localization of choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS) immunoreactivities, and the loss of retinal mRNA for Thy-1. Intraperitoneal or intravitreal administration of 4-CIN had no effect on the ERG or the localization of ChAT and nNOS immunoreactivities in either the control retina or a retina subjected to ischemia/reperfusion. In addition, intravitreal injection of 4-CIN had no effect on ischemia-induced reduction of retinal mRNA levels for Thy-1. These results provide no evidence to support the view that blockade of lactate uptake and/or pyruvate entry into mitochondria for oxidative metabolism has an influence on the outcome of retinal ischemia/reperfusion.
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PMID:The monocarboxylate transport inhibitor, alpha-cyano-4-hydroxycinnamate, has no effect on retinal ischemia. 1451 20

This study was to examine the alterations in the phosphorylation of mitogen-activated protein kinase (MAPK) family in transient brain ischemia under a hyperglycemia and to highlight the molecular mechanisms by which hyperglycemia exacerbates brain damage resulting from stroke. Extracellular signal-regulated protein kinase (ERK) expression was studied in rats subjected to global brain ischemia with pre-ischemic normoglycemic (CIN) and hyperglycemic (CIH) conditions. In another group, the hyperglycemic ischemic rats were pretreated with ERK inhibitor U0126 (U0126). Increased phospho-ERK1/2 immunoreactive neurons in the cingulate cortex and hippocampal CA3 were detected in CIN after ischemia and reperfusion. The numbers of phospho-ERK1/2-positive neurons were further increased significantly in CIH compared to the CIN. Pretreatment with U0126 in CIH rats significantly decreased ERK1/2 immunoreactive cells. Western blot analyses confirmed that phospho-ERK1/2 increased significantly after 30 min ischemia and reperfusion compared to non-ischemic controls in both the CIN and CIH groups. The increase of phospho-ERK1/2 was more prominent in the CIH than in the CIN group after 3 and 6h of reperfusion. Treatment with U0126 significantly reduced phospho-ERK1/2 in the CIH group. The findings presented here suggest that ERK1/2 may play a role in mediating neuronal cells death under hyperglycemic condition.
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PMID:Hyperglycemia increased brain ischemia injury through extracellular signal-regulated protein Kinase. 1634 98