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)

The object of this experimental study is to elucidate the limits of recovery in hydronephrosis. Hydronephrosis in the rabbit kidney was made by left ureteric ligation for 1, 2, 3 and 4 weeks, followed by relief of obstruction with uretero-ureteric anastomosis. Two and 4 weeks after relief, histopathological examination was performed. In proportion to the obstructive period, both proximal tubule and thin portion of Henle's loop showed atrophy of epithelial cells, multi-laminar thickening of basement membranes, and splitting between epithelium and basement membranes. The interstitium showed edema and subsequent fibrosis. These damages were thought to be due to severe ischemia, which such tubules did not recover and even showed more advanced damages after relief. On the other hand, thick portion of Henle's loop, distal tubule and collecting duct showed advanced compression atrophy and dilated lumen, while no severe ischemic damage was demonstrated. Therefore, after relief, they showed recovery, and, even in the case of no recovery, they showed no advanced damages. In hydronephrosis, severe ischemic damages brought about a loss of the ability of recovery.
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PMID:[The limits of recovery in hydronephrosis. An experimental pathological study]. 149 99

This report clarified the direct damage to renal cell ultrastructure on shock wave exposure. The renal cortex of the rabbit was exposed to the shock waves (1200 bar) generated by the piezo-ceramics. The change was examined by electron microscopy immediately after 20 shots exposure and 500 shots exposure as well as one week after 500 shots exposure. In all groups, the most critical damage was observed in the proximal tubule. Immediately after 20 shots exposure, large vacuoles were found to be enclosed by infoldings in the proximal tubular cell. The damaged cell lost its brush border and jutted out into the lumen. The ruins of organelles (nuclei, mitochondria, etc.) were seen in the lumina of proximal and distal tubules. The damage progressed, in the 500 shots exposure group, to include the distal tubular cytoplasm. One week after the 500 shots exposure, a few of atrophic tubular cells were found in wide scars. The tubular cell which contained a deformed nucleus and destroyed organelles was desquamated from the basement membrane. The change in the tubular cell after shock wave exposure was apparently different from that after such intervention as one hour ischemia. It was concluded that the direct damage to renal cells by underwater shock wave exposure was really present.
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PMID:[Ultrastructural renal damage after shock wave exposure]. 156 23

The proximal tubule undergoes hypertrophy in response to loss of functioning renal mass and hyperplasia following injury by ischemia or nephrotoxins. Both hypertrophic growth and cell proliferation are characterized by increases in the rate of protein synthesis. To investigate regulation of protein synthesis in mammalian proximal tubule cells, potential peptide mediators of proximal tubule growth, epidermal growth factor (EGF) and angiotensin II, were studied in cultured rabbit proximal tubule cells. Although only EGF stimulated DNA synthesis, both agonists stimulated protein synthesis. One potential regulatory mechanism of eukaryotic protein synthesis involves phosphorylation of ribosomal protein S6 by activation of a specific serine/threonine kinase (S6 kinase). Both EGF and angiotensin II stimulated S6 kinase activity and S6 phosphorylation. Phorbol 12-myristate 13-acetate was also found to activate S6 kinase, and 24 h of pretreatment to deplete protein kinase C inhibited subsequent S6 kinase activation by a high concentration (10(-6) M) of angiotensin II. To determine whether S6 kinase was also activated in the kidney in vivo, S6 kinase activity was examined after ablation of renal mass. Within 1 h after contralateral nephrectomy, S6 kinase activity increased in rat renal cortex. In summary, both EGF and angiotensin II stimulated protein synthesis and S6 kinase activity in cultured proximal tubule cells, and S6 kinase activity also increased in renal cortex after contralateral nephrectomy.
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PMID:Regulation of S6 kinase activity in renal proximal tubule. 163 37

Although reactive oxygen species are believed to participate in postischemic renal injury, the actual chemical species involved and the role of endogenous scavenging systems in protecting against injury requires additional study. Hydrogen peroxide, which derives from superoxide radical, is toxic and also yields toxic hydroxyl radical. 3-amino-1,2,4-triazole reacts with catalase to form irreversibly inactivated catalase only in the presence of hydrogen peroxide. We made use of this chemical reaction both to determine whether inhibition of the hydrogen peroxide-scavenging enzyme catalase would influence ischemic renal injury and to measure hydrogen peroxide production rates after ischemia. Sprague-Dawley rats were given aminotriazole (100 mg/kg) one hour before 40 min of renal ischemia. Twenty-four h after ischemia GFR had decreased to 300 microL/min in control animals and to 50 microL/min in aminotriazole-treated animals. Histologic evidence of injury was also worse in catalase-inhibited animals. To measure hydrogen peroxide production rates aminotriazole was given 60 min before measurement of renal catalase activity. In control animals, aminotriazole caused a 53.4% decrease in catalase activity. In animals subjected to 40 min of ischemia plus either 10 or 60 min of reflow catalase activity decreased by 33.9 and 49.5% (not significantly different from control). Thus, when measured by this method total renal hydrogen peroxide production was considerable but was not increased by ischemia. However, in isolated proximal tubule segments 60 min of anoxia and 30 min of reoxygenation caused a 42% increase in H2O2 released into the incubation medium. In summary, inhibition of catalase before ischemia led to exacerbation of ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hydrogen peroxide and ischemic renal injury: effect of catalase inhibition. 164 49

In an attempt to ameliorate the morphological abnormalities and decreased renal function produced by hypoxia in the isolated perfused rat kidney, adenosine triphosphate (ATP) was added to the perfusate medium. No improvement was noted in the histological changes or renal function. Paradoxically, however, in oxygenated control kidneys, ATP (2.5-10 mM), caused a severe injury remarkably limited to the S2 segments of proximal tubule. This injury was more destructive than that observed with complete ischemia for the same period of time or with inhibitors of glycolysis, intermediary metabolism, or respiratory chain function. Tubular damage produced by ATP was paradoxically prevented by hypoxia and mitochondrial inhibition. The mechanism of this selective toxic injury to the proximal tubule remains unclear and may depend upon intact transport metabolism of the cell.
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PMID:Toxicity of adenine nucleotides in the isolated perfused kidney: selective destruction of the S2 segment of the proximal tubule. 168 78

Tandem Scanning Confocal Microscopy (TSCM) allows one to section optically into and record real-time images of living organs and tissues in a noninvasive fashion. In this paper, we will present some initial TSCM observations of subcapsular nephrons in the living, intact kidneys of Munich-Wistar rats and evaluate the nephron's responses to temporary ischemia and to intravenous infusion of mannitol. The rats were anesthetized with Inactin and a laparotomy performed to expose the kidneys. Using a TSCM equipped with a 20 x water-immersion objective, we optically sectioned through the intact kidney capsule and recorded real-time images of living subcapsular glomeruli and uriniferous tubules. The proximal tubule brush border was highly reflective and allowed us to distinguish between the first and second segments of the proximal tubules as well as the distal tubules. Cellular elements of the blood could be seen passing rapidly through peritubular capillaries and individual glomerular capillary loops. With fluorescent filters in place, intravenously injected carboxyfluorescein was seen to pass through the glomerular capillary loops and then progressively through the different segments of the uriniferous tubules. Ligation of the renal artery resulted in rapid swelling of proximal tubule cells into the tubular lumens, loss of reflectiveness of the microvillous brush borders, and closure of the peritubular capillary spaces. Upon release of the ligature, the proximal tubule lumens again became patent, often opening up abruptly and in a zipper-like fashion down the length of the tubules. Increasing the glomerular filtration rate by intravenous infusion of mannitol resulted in increases in tubular luminal and perimeter dimensions. Mannitol also acted as an effective impermeant osmotic agent and prevented most of the cellular swelling which was otherwise seen in response to renal ischemia.
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PMID:Tandem scanning confocal microscopy (TSCM) of normal and ischemic living kidneys. 190 77

In order to elucidate the pattern of redistribution of cellular energy and the restoration of basic cellular metabolism following an ischemic renal insult, suspensions enriched in proximal tubule segments were studied after 45 min of bilateral artery occlusion and 15 min and 2 h of reflow from rats given either normal saline (control), ATP-MgCl2 (which enhances postischemic recovery of ATP), or alpha, beta-methyl adenosine diphosphate (AMPCP), which inhibits nucleotide degradation during ischemia. In non-ischemic control animals, approximately half of the energy is distributed to functional pump activity and half directed for non-transport purposes. When cellular ATP is reduced to 56% of control values, functional pump activity is significantly reduced to 61% of control, while energy delegated for non-transport purposes is decreased by a significantly smaller increment to only 78% of control at 15 min of reflow. In animals given ATP-MgCl2, the cellular and metabolic profile at 15 min of reflow was no different from ischemic control animals with cellular ATP levels similar at 58%. However, by 2 h, cellular ATP levels had increased significantly to 74%, and this was associated with a redistribution of cellular energy to functional pump activity (119% of control) with little change in non-transport function (76%). In animals treated with AMPCP, the cellular ATP levels were 74% of controls, similar to ATP-MgCl2-treated rats after 2 h of reflow. Despite the differences in reflow interval, the distribution of cellular energy was similar (functional pump activity 120% and non-transport activity 79%). By 2 h, cellular ATP was at 95% and both functional pump activity and non-transport activity were 100%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Redistribution of cellular energy following renal ischemia. 191 Nov 45

Proximal tubule cells play an essential role in the reabsorption of ions, water, and solutes from the glomerular filtrate. This is accomplished, in large part, by having a surface membrane polarized into structurally, biochemically, and physiologically distinct apical and basolateral membrane domains separated by cellular junctional complexes. Establishment and maintenance of these unique membrane domains are essential for the normal functioning of the cell. Ischemia results in the duration-dependent loss of apical and basolateral surface membrane lipid and protein polarity. Loss of surface membrane polarity is preceded by disruption of the microfilament network and opening of cellular tight junctions. Surface membrane lipids and proteins are then free to diffuse laterally within the bilayer into the alternate membrane domain. Functionally, ischemia-induced loss of epithelial polarity has been shown to be responsible for reduced sodium and glucose reabsorption. Reduced Na+ reabsorption has been related to redistribution of Na+, K(+)-ATPase into the apical membrane. During recovery from ischemic injury, proximal tubule cells undergo remodeling of the surface membrane such that the unique apical and basolateral membrane domains are reestablished, allowing for the return of normal cellular function.
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PMID:New insights into the cell biology of ischemic acute renal failure. 191 88

S-(1,2-Dichlorovinyl)-L-cysteine (L-DCVC), a substrate for the renal cysteine conjugate beta-lyase, and other related chemicals were administered intravenously to pentobarbital-anesthetized dogs. Six pertinent findings emerged regarding their nephrotoxicity. (1) L-DCVC was acutely nephrotoxic in the dog. (2) The earliest indicator of L-DCVC-induced renal damage was an increase in the urinary excretion rate of protein. (3) Contrary to results from other species, L-DCVC induced renal ultrastructural lesions only in the S1 and S2 cells of the proximal tubule. (4) The toxicity of L-DCVC (23.15 mumol/kg, iv) to S1 and S2 cells resulted from a direct tubular insult and not from overlapping episodes of hypoxia or ischemia. (5) L-DCVC could be detected in plasma only during the first 30 min after its injection. In addition, no L-DCVC and only small amounts of N-acetyl-L-DCVC and S-(1,2-dichlorovinyl)mercaptoacetic acid (DCV-MAA) (1.5% and less than 1% of the administered dose, respectively) were detectable in urine during the 6 hr following L-DCVC administration. (6) DCV-MAA and chloroacetic acid as well as other compounds that are not substrates for the renal cysteine conjugate beta-lyase (i.e., S-allyl-L-cysteine, vinthionine, and S-(1,2-dichlorovinyl)-D,L-alpha-methylcysteine) were not acutely nephrotoxic. These findings provide indirect evidence for the involvement of beta-lyase in the toxification of L-DCVC in the dog.
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PMID:The acute effects of S-(1,2-dichlorovinyl)-L-cysteine and related chemicals on renal function and ultrastructure in the pentobarbital-anesthetized dog: structure-activity relationships, biotransformation, and unique site-specific nephrotoxicity. 191 74

Proximal tubule cells play a major role in the reabsorption of ions, water, and solutes from the glomerular filtrate. This is accomplished, in large part, by a surface membrane polarized into structurally, biochemically, and physiologically distinct apical and basolateral membrane domains separated by cellular junctional complexes. Establishment and maintenance of these unique membrane domains is essential for the normal functioning of proximal tubular cells and is dependent on cortical actin cytoskeletal-surface membrane interactions. Ischemia results in the duration-dependent loss of apical and basolateral surface membrane lipid and protein polarity. This loss of surface membrane polarity is associated with disruption of the cortical actin microfilament network and the opening of cellular tight junctions. Surface membrane lipids and proteins are then free to diffuse laterally within the membrane bilayer into the alternate membrane domain. Functionally, ischemia-induced loss of epithelial polarity is, in part, responsible for reduced sodium and glucose reabsorption. With recovery, proximal tubule cells undergo remodeling of the surface membrane such that the unique apical and basolateral membrane domains are reestablished allowing normal cellular function to return.
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PMID:Ischemia-induced loss of epithelial polarity: potential role of the actin cytoskeleton. 205


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