UMLS:C0022116 - FACTA Search

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Query: UMLS:C0022116 (ischemia)
91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats were anesthetized and their lift kidneys were made ischemic for 1 h by clamping of the aorta just above the left renal artery. Mannitol (2.5 g/kg), Dextran 70 (0.6 g/kg), methylprednisolone (50 and 100 mg/kg), and allopurinol (100 mg/kg body weight) were administered before, during, or after the ischemia period in order to test the effect of each of these drugs upon this model of renal injury. At 24 h after the release of the aortic clamp the left kidneys of the drug treated animals wwere perfusion fixed and processed for light and electron microscopy. Dextran administration to animals with ischemic kidneys gave rise to a pronounced vacuolization ("osmotic nephrosis"), in the entire proximal tubule and especially in the pars recta. This was in contrast to dextran administration to rats with nonischemic kidenys, which showed no or very mild "osmotic nephrosis." This demonstrates that ischemia makes rat kidneys more susceptible to the development of "osmotic nephrosis." In controls (no drug treatment) one hour of renal ischemia gave partial necrosis of pars recta of the proximal tubule, while the pars convoluta tubule survived. Mannitol treatment significantly reduced the amount of necrosis of the pars recta, whereas dextran, methylprednisolone, and allopurinol had no or a negative effect on the survival of the cells of the pars recta segment. It is suggested that mannitol protects against the development of necrosis by increasing medullary blood flow in combination with a counteractive influence on the cellular swelling, which is known to occur in ischemia.
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PMID:Effect of mannitol, dextran (macrodex), allopurinol, and methylprednisolone on the morphology of the proximal tubule of the rat kidney made ischemic in vivo. 40 53

The pars convoluta of the proximal tubule of the rat kidney was studied by light and electron microscopy during the recovery phase from transient ischemia. The left kidney was made ischemic by clamping the aorta just above the left renal artery leaving the blood supply to the right kidney and the intestine intact. The pars convoluta (P1 and P2 segments) of the proximal tubule was examined both immediately after various periods of ischemia (15, 30, 60 and 120 min) and after the same ischemic periods followed by 3, 6, 12 and 24 h of blood reflow (= recovery phase). It was found that ischemia for periods up to 60 min were compatible with cell survival whereas 120 min of ischemia gave rise to irreversible cellular changes. Before regaining a normal conformation during the recovery phase, cells made ischemic for 15 min were characterized by slightly decreased cell height, dispersed nuclear chromatin, mitochondria in orthodox conformation and increased numbers of digestive vacuoles and of lipid droplets (stage A2). Most cells made ischemic for 15 min appeared normal when examined after 24 h of reflow. Cells made ischemic for 30 min were also characterized by stage A2 changes after 3 h of reflow and remained in this stage during all recovery periods studied. Cells made ischemic for 60 min first passed into a stage designated A1 and then later during the recovery phase into stage A2. Stage A1 cells were characterized by decreased height, condensed mitochondria, apparently increased numbers and sizes of secondary lysosomes and slightly dilated rough surfaced endoplasmic reticulum; 120 min of ischemia followed by reflow was not compatible with cell survival. Cells made ischemic for 120 min showed the following alterations denoted as stages C and D: shrunken with pyknotic nuclei, swollen mitochondria with large flocculent densities, and filled with different sized vesicles in the apical portion (stage C). Stage D included cells which had undergone necrosis, i.e., phasma membranes and organelles were fragmented and occurred as debris in the tubule lumens.
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PMID:Studies on cellular recovery from injury. II. Ultrastructural studies on the recovery of the pars convoluta of the proximal tubule of the rate kidney from temporary ischemia. 40 90

Rats were subjected to 25 min of unilateral renal artery occlusion and were studied at 5, 15, and 30 min and at 1, 2, 4, 8, 16, 24, and 48 hr following ischemia. The patterns of epithelial injury and repair in proximal tubule (PT) segments S1, S2, and S3 were followed, and associated changes in renal function were determined. We found that S1 and S2 cells alike are only reversibly injured and recover completely to normalcy within 4 hr, whereas S3 cells selectively undergo progressive cell injury and death and are exfoliated into tubular lumina. The necrotic S3 cells are replaced by mitotic division of survivor cells 24 to 48 hr following the ischemic insult. In addition, there was selective damage within tubular cells. Wiithin 5 min of blood reflow following ischemia, the majority of brush border microvilli (MV) in all three PT segments underwent coalescence by membrane fusion and thus were interiorized into the cytoplasm of PT cells. A minority of MV fragmented and were shed into PT lumina, but nephron obstruction by shed membranes was only mild and transient, unlike in the 1-hr ischemia model. Loss of MV reached a maximum of 15 min. By 30 min, MV began to reappear; by 2 hr, large numbers of MV had been regenerated; and by 4 hr, S1 and S2 cells appeared normal. The regenerative process included the luminal repositioning of previously interiorized MV membrane. MV regeneration occurred in S3 segments also, but before the process was complete, the cells developed features of irreversible cellular injury. Glomerular filtration rate (GFR) was 22% of control at 30 min of reflow, rose progressively to 55% of normal by 7 to 8 hr, and was normal at 24 hr. Single nephron filtration rate (SNGFR) was not significantly different from normal throughout. Proximal tubular sodium reabsorption was depressed and urinary sodium excretion increased at 30 min and at 2 to 3 hr, i.e., at times when MV alterations were prominent, but both were normal by 7 to 8 hr when MV in S1 and S2 cells had been fully reconstituted. Our major conclusions are: 1) There is differential susceptibility by cell type to ischemic injury in rat PT. 2) A rapid brush border loss/regeneration cycle occurs after ischemic injury. 3) Intact brush border may be required for normal sodium reabsorption by PT. Reasons for the GFR/SNGFR discrepancy are unclear, but tubular malfunction may partly explain the phenomenon.
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PMID:Ischemic damage and repair in the rat proximal tubule: differences among the S1, S2, and S3 segments. 68 23

The pars recta of the proximal tubule of the rat kidney was examined by means of light and electron microscopy after 15, 30, 60 and 120 min of ischemia produced by clamping of the aorta. Also the effects of 24 hrs of blood reflow following the same ischemia periods were determined. The maximal changes occurring after ischemic periods of up to 60 min included: marked cell swelling, swelling of the inner compartments of the mitochondria, swelling of the endoplasmic reticulum and of microvilli, pronounced chromatin clumping in the nuclei and distortion of the Golgi apparatus. These cell changes were reported to be reversible in the previous paper of this series. After 24 hrs of blood reflow it was found that with increasing periods of primary ischemia, ranging from 15 to 120 min, an increasing number of pars recta tubules cells were undergoing necrosis. Theses findings indicate that some additional mechanism other than the initial ischemia per se must be responsible for the progressive cellular damage leading to the necrosis. This is in contrast to the pars convoluta of the proximal tubule, which does not undergo further degenerative changes after the primary ischemia has been ended. The "no reflow" phenomenon may satisfactorily explain the necrosis seen in the pars recta segments following various periods of ischemia after 24 hrs of arterial renal reflow.
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PMID:Studies on the pathogenesis of ischemic cell injury. III. Morphological changes of the proximal pars recta tubules (P3) of the rat kidney made ischemic in vivo. 81 78

In summary, we have described the time course of changes of mitochondria following ischemia of the kidney proximal tubule. The sequence of morphological changes of matrix as well as inner membrane corresponds well with certain functional or physical parameters such as swelling, respiration, substrate metabolism, acceptor control and P/O ratio. This indicates that morphological parameters can be utilized to predict the functional alterations of mitochondria following ischemia in cells. The significant mitochondrial changes are early loss of granules (15-30 min) and condensation (15 min), swelling (30 min), appearance of fluffy densities (30 min) and flocculent densities (after 60 min), degeneration of cristal structure (240 min) and disintegration of mitochondria as structural units (24 h).
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PMID:Studies on the pathogenesis of ischemic cell injury. V. Morphologic changes of the pars convoluta (P1 and P2) of the proximal tubule of rat kidney made ischemic in vitro. 82 1

Studies on structural cell changes as a function of ischemia time and studies on the recovery process of ischemically injured cells have implications for our general understanding of the features of cellular reaction to injury. For this reason a model was worked out to follow the morphological changes taking place in the proximal tubule of the rat kidney during ischemia and during recovery from an ischemic episode. The pars convoluta and the pars recta of the proximal tubule were examined separately and compared with one another.
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PMID:A model to study cell injury: morphological changes of the proximal tubule of the rat kidney during ischemia and during recovery from ischemic injury in vivo. 97 90

The polar distribution of Na(+)-K(+)-ATPase to the basolateral membrane of proximal tubule cells is essential for the efficient and vectorial reabsorption of Na+ and may be dependent on the formation of a metabolically stable, detergent-insoluble complex of Na(+)-K(+)-ATPase with the actin membrane cytoskeleton. The present studies utilized immunocytochemical techniques to demonstrate and quantify the apical redistribution of Na(+)-K(+)-ATPase during mild ischemia (15 min) that occurred in proximal (1.3 +/- 0.9 vs. 4.5 +/- 1.1 particles/100 microns surface membrane, P less than 0.01) but not distal tubule cells. Treatment of control apical membranes with 2-(2-methoxyethoxy)ethyl 8-(cis-2-n-octylcyclopropyl)octanoate (A2C), a fluidizing agent, markedly increased membrane fluidity without any effect on Na(+)-K(+)-ATPase activity. In brush-border membrane vesicles isolated after ischemia, however, A2C further increased an already elevated Na(+)-K(+)-ATPase activity. During ischemia, total cellular Na(+)-K(+)-ATPase activity remained unaltered, but the Triton X-100-soluble (noncytoskeleton associated) fraction of Na(+)-K(+)-ATPase increased significantly following 15 and 30 min. There was a corresponding decrease in the Triton X-100-insoluble fraction of Na(+)-K(+)-ATPase, with the ratio of detergent-soluble to -insoluble Na(+)-K(+)-ATPase increasing from 13 +/- 2 to 32 +/- 5% (P less than 0.01) during 30 min of ischemia. Western blot analysis of the Triton X-100-soluble fraction, following 30 min of ischemic injury, revealed the presence of Na(+)-K(+)-ATPase, actin, fodrin, and uvomorulin. However, in a fraction highly enriched for Na(+)-K(+)-ATPase, neither actin, fodrin, nor uvomorulin was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytoskeleton disruption and apical redistribution of proximal tubule Na(+)-K(+)-ATPase during ischemia. 132 35

To determine whether heat shock proteins (HSPs) might be active in cellular recovery following transient ischemia, we examined rat kidneys for 70-kDa HSP (HSP-70) mRNA expression, protein elaboration, and intracellular localization after 45 min of renal ischemia and reflow of 15 min, 2, 6, and 24 h. Inducible HSP-70 mRNA is present at 15 min of reperfusion, peaks between 2 and 6 h, and falls by 24 h. Inducible 72-kDa HSP (HSP-72) protein accumulates progressively through 24 h and is found in both soluble and microsomal fractions following ischemia. Within proximal tubules, immunofluorescent localization of HSP-72 is restricted to the apical domain at 15 min, is dispersed through the cytoplasm in a vesicular pattern at 2 and 6 h, and has migrated away from the apical domain at 24 h. A portion of the vesicular HSP-72 is associated with lysosomes; no intranuclear HSP-72 is detected. The course of mRNA induction, protein elaboration, and HSP-72 localization coincides with previously described changes in proximal tubule morphology and polarity following sublethal ischemic injury. HSP-72 may be instrumental in cellular remodeling and restitution of epithelial polarity during recovery from ischemic renal injury.
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PMID:Induction and intracellular localization of HSP-72 after renal ischemia. 144 67

Experimental ischemic acute renal failure results in disruption of proximal tubule apical membranes. Previous work utilizing immunofluorescence with an anti-actin antibody has demonstrated that the apical cytoskeleton of proximal tubule cells is disrupted during ischemic injury. In this study, using rhodamine-phalloidin which stains only filamentous actin, we demonstrate that graded durations of ischemia resulted in progressive disruption of proximal tubule apical microfilaments. Quantification using spectrofluorometry showed that 5, 15 and 50 minutes of ischemia resulted in 32.8 +/- 4%, 48.8 +/- 2.5%, and 58.4 +/- 2.6% decreases in apical F-actin relative to controls. Ischemia did not qualitatively affect either glomerular or distal tubule F-actin structure, though there were nonprogressive increases in glomerular fluorescence. In summary, rhodamine-phalloidin staining can be used to qualitatively and quantitatively assess proximal tubule microfilaments in vivo. We conclude that ischemia results in very early loss of proximal tubule apical microfilaments, with the majority of F-actin loss occurring within five minutes.
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PMID:Microfilament disruption occurs very early in ischemic proximal tubule cell injury. 145 83

The ability of prostaglandins to protect the kidney against ischemic and toxic renal injury was evaluated by in vivo and in vitro models of renal ischemia. The prostaglandin E1 analogue, misoprostol, was found to provide significant protection against ischemia-induced renal dysfunction in rats subjected to 40 minutes of renal artery occlusion. Misoprostol-treated rats had glomerular filtration rates almost threefold greater than control animals, although renal blood flow and renal vascular resistance were not significantly different. Improved tubular function was reflected in a lower fractional excretion of sodium and a higher urine-to-plasma creatinine ratio. Misoprostol also provided similar protection in a model of toxic renal injury produced by mercuric chloride. In an in vitro model employing primary cultures of proximal tubule epithelial cells subjected to hypoxia and reoxygenation, misoprostol limited cell death. Posthypoxic cells had apical membrane disruption and loss of microvilli when examined by transmission electron microscopy. These changes were not seen in misoprostol-treated cells. The "cytoprotective" effect was also produced by prostaglandin E2 and prostacyclin. The ability of prostaglandin E to protect against toxic and ischemic renal injury did not appear to be due to an antioxidant effect because misoprostol did not limit lipid peroxidation in vivo and did not protect against oxidant injury by tert-butyl hydroperoxide in vitro. Although the exact mechanism of prostaglandin protection was not revealed, these studies demonstrate that prostaglandins protect renal tubule epithelial cells from hypoxic injury at the cellular level independent of hemodynamic factors or inflammatory responses. Such a "cytoprotective" effect of prostaglandins may be a generalized phenomenon since it has also been demonstrated in gastrointestinal epithelium.
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PMID:Prostaglandins protect kidneys against ischemic and toxic injury by a cellular effect. 147 66

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