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)

Effect of diltiazem on subcellular distribution of lysosomal enzymes, high-energy phosphate metabolism and mechanical function in the ischemic heart was studied. Ischemia was induced by lowering the afterload pressure of the perfused working rat heart. The activities of cathepsin D, beta,N-acetylglucosaminidase and acid phosphatase were determined in the nonsedimentable and sedimentable fractions after centrifugation of the tissue extract to assess the subcellular distribution of lysosomal enzymes. After ischemia, decreases in the mechanical function and the tissue level of high-energy phosphates were observed. In addition, ischemia caused subcellular redistribution of lysosomal enzymes from the lysosomes to the cytoplasm. Reperfusion of the ischemic heart did not restore the mechanical function and the level of high-energy phosphates completely. Diltiazem (2.21 X 10(-6), 1.11 X 10(-5) and 2.21 X 10(-5) M) was provided for the heart 5 min before the onset of ischemia. Diltiazem preserved high-energy phosphates in the ischemic heart, and inhibited the subcellular redistribution of lysosomal enzymes being caused by ischemia, depending on its concentration. Reperfusion after ischemia with diltiazem recovered the mechanical function that had been decreased by ischemia. These results may indicate that diltiazem can protect the myocardium against ischemic damage.
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PMID:Inhibition of ischemia-induced subcellular redistribution of lysosomal enzymes in the perfused rat heart by the calcium entry blocker, diltiazem. 365 10

A comprehensive morphological study of the ischemic skeletal muscles of the limbs was performed in experiments on dogs. Ischemia of the muscle tissue was induced by artificial embolic occlusion of the terminal part of the aorta. A quantitative functional and morphological study revealed serious disturbances in metabolism of the skeletal muscle that was subjected to a 6-hour ischemia. Depression of aerobic metabolism, ineffectiveness of anaerobic glycolysis (a spare pathway of the synthesis of macroergic substances), a dramatic lowering of ATPase activity, and activation of acid phosphatase in experiments of such a duration are important signs of a probably compromised adaptation process and irreversibility of the lesions in the tissue. The data should be taken into consideration in determining the optimal periods of the blood flow recovery in the limbs. Morphological changes in muscle fibers under ischemia progress with an increase in the experiment duration (up to 9 and 12 h). An important morphological sign of ischemia is a disturbed typification of muscle fibers.
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PMID:[Morphological characteristics of the changes in the skeletal muscle tissue in acute experimental ischemia of the extremities]. 400 20

Intracellular enzyme activities can be greatly influenced by alterations of pH, and non-physiologic pH may inhibit cell metabolism. The study was undertaken to examine the influence of pH values in preservation solution on ischemic tolerance time of the liver. BDE rat livers were used. Livers were preserved for 20 min or 2 h in warm ischemia after an initial perfusion with Ringer's solution at pH 9.0, 7.4, and 6.0. The values of total adenine nucleotide (TAN) and energy reserve (ER) in the livers were determined at the end of the preservation. After 20 min of warm ischemia, TAN values at pH 9.0 and 7.4 fell to 2.727 +/- 0.255 and 2.410 +/- 0.164 mumol/g, respectively (normal values: 3.414 +/- 0.270 mumol/g) and ER values to 0.786 +/- 0.186 mumol/g at pH 9.0 and to 0.446 +/- 0.095 mumol/g at pH 7.4 (normal values: 2.962 +/- 0.214 mumol/g). A similar trend was also observed after 2 h of warm ischemia. The preservation with a solution at pH 6.0 did not present any difference as compared to that at pH 7.4. Four-hour preservation in cold ischemia with Ringer's solution at pH 9.0 rendered higher values of TAN (2.635 +/- 0.085 mumol/g) and ER (0.336 +/- 0.026 mumol/g) than those in preservation at pH 7.4. No significant difference between TAN and ER values was found when 4-h preservation at pH 7.4 and 6.0 was compared. In another group an intermittent liver perfusion at 1-h interval was performed with chilled Ringer's solution; afterwards GOT, GPT, beta-glucuronidase, and acid phosphatase values in the effluents were evaluated. All of these enzymes showed higher concentration in the effluent with solution at pH 7.4 than that at 9.0. These results suggested that better intracellular energy reserve and organ viability can be maintained by preservation with alkaline solution. Furthermore, ER values seemed to be an excellent indicator of the organ viability during preservation. These were also confirmed by orthotopic hepatic transplantation in pigs. Livers were successfully preserved with alkaline Ringer's solution for up to 12 h. However, without change of pH, livers could not be preserved for more than 4.5 h.
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PMID:[Prolongation of ischemic tolerance time of donor livers by alkaline preservation solutions]. 647 1

Alterations in myocardial acid hydrolases in acute ischemia were studied in relation to the evolution of cardiac cellular necrosis by the determination of cathepsin D, acid phosphatase (AcPase), and beta-glucuronidase activities of the myocardial fractions and by electron microscopic cytochemical studies on AcPase in the canine heart. In the normal myocardium, the same level of activity of acid hydrolases was found in sarcoplasmic reticulum (SR) as in the lysosome fraction. In electron microscopy, AcPase reaction products were observed markedly in SR and moderately in lysosomes, in residual bodies, and in Golgi apparatus. In the ischemic myocardium, at 20 to 30 min after coronary ligation, activation of these enzymes was observed in both SR and lysosomes, and at 60 to 90 min they were decreased in the particles and, in turn, increased in the cytoplasm accompanying the ischemic fine structural changes. At 2 to 3 hr those acid hydrolase activities in the cytosol were decreased, indicating the loss of enzymes from necrotic myocardial cells. Acid hydrolases are the most important factor for the evolution of ischemic myocardial necrosis by being activated not only in lysosomes but also in SR and by being released to the cytoplasm to disintegrate the cellular structures.
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PMID:Acid hydrolases in the initiation of ischemic myocardial necrosis. 685 64

Activities and subcellular distributions of acid hydrolases, cathepsin D, acid phosphatase and beta-glucuronidase in myocardial subfractions were determined serially with reference to the initiation of myocardial necrosis in dog hearts with acute ischemia. The following results were obtained: 1) In the normal myocardium, respectable activities of three enzymes were obtained either in the sarcoplasmic reticulum or in the lysosome-containing fraction. 2) Thirty min after coronary ligation, an increase in the activities was observed in both lysosome and sarcoplasmic reticulum fractions of the ischemic heart muscle. After 60 to 90 min these activities were decreased rapidly in both fractions to about 70% of those of the normal myocardium with an increase in the cytosolic activity. Two to 3 hours after ligation, the reduction in the cytosolic activity was noted, indicating an escape of the enzymes from the necrotic myocardium. The subcellular distribution of these enzymes was further altered in the ischemic heart muscle for 12 to 14 hours reflecting an infiltration of the interstitial cells. These findings suggest that activation and release of acid hydrolases not only in lysosomes but also in the sarcoplasmic reticulum are one of the primary and the earliest factors for the evolution of ischemic myocardial injury which leads to necrosis.
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PMID:Studies on intracardiac acid hydrolases in the ischemic myocardial necrosis. 714 2

The paper contains the results of light microscopical, electron microscopical and histochemical examinations of chronic otitis media, with and without cholesteatoma, with special focus on the problems regarding bone resorption. It is demonstrated that bone resorption takes place without the presence of cholesteatoma itself, even though the magnitude of resorption is higher in the cases with cholesteatoma. It is demonstrated that there is always a layer of subepithelial granulation tissue between the cholesteatoma membrane and the underlying bone. The picture in the resorbing zone is dominated by mononuclear histiocyte like cells, containing dense cytoplasmatic bodies, called lysosomes, and it is demonstrated that the marker enzyme for acid hydrolases, the acid phosphatase, is present in large quantities, both in the histiocytes, as well as spread along the bony surface. It is concluded that a possible mechanism for bone resorption is performed by the acid hydrolases, contained in the histiocytes, working at acid pH. It is noteworthy that the multinucleated osteoclast is not demonstrated in the resorbing margin of bone and that the picture is dominated by capillary proliferation, indicating that ischemia does not play a role in bone resorption. On the contrary, this is in the author's opinion caused by inflammation and hyperemia. The various factors influencing bone resorption in general and in chronic otitis media are discussed and a new model for studying cholesteatoma pathology in the middle ear is presented.
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PMID:Bone resorption in chronic otitis media. The role of cholesteatoma, a must or an adjunct? 726 54

We investigated whether intraportal injection of 150 mg/kg N-acetylcysteine (NAC) into rats reduced hepatic ischemia-reperfusion injury after 48 hours of cold storage and 2 hours of reperfusion. The organ was isolated and perfused to evaluate liver function. The control group received an intraportal injection of 5% dextrose. NAC increased L-cysteine concentrations 15 minutes after injection (1.29 +/- 0.11 mumol/g vs. 2.68 +/- 0.4 mumol/g, P < .05). However, neither treatment modified glutathione liver concentrations relative to preinjection values. After 48 hours of cold storage and 2 hours of reperfusion, livers from NAC-treated rats produced larger amounts of bile than those in the control group (5.04 +/- 1.92 vs. 0.72 +/- 0.37 microL/g liver; P < .05), and showed a significant reduction in liver injury, as indicated by reduced release of lactate dehydrogenase (679.4 +/- 174.4 vs. 1891.3 +/- 268.3 IU/L/g; P < .01), aspartate transaminase (AST) (13.94 +/- 3.5 vs. 38.75 IU/L/g; P < .01), alanine transaminase ALT) (14.92 +/- 4.09 vs. 45.91 +/- 10.58 IU/L/g; P < .05), and acid phosphatase, a marker of Kupffer cell injury (344.4 +/- 89.6 vs. 927.3 +/- 150.8 IU/L/g; P < .01) in the perfusate. Reduced glutathione concentrations in the perfusate were similar in the two groups (805 +/- 69 vs. 798 +/- 252 nmol/L/g), whereas oxidized glutathione (GSSG) concentrations were higher in the control group (967 +/- 137 vs. 525 +/- 126 nmol/L/g; P < .05). Reduced glutathione (GSH) concentrations in liver tissue collected at the end of perfusion were significantly higher in the NAC group (7.3 +/- 0.9 vs. 4.1 +/- 1.0 mumol/g; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effects of N-acetylcysteine on hypothermic ischemia-reperfusion injury of rat liver. 763 22

Lipid peroxidation of membranes by oxygen free radicals has been implicated in various disease states. Different antioxidants and iron chelators have been used to reduce lipid peroxidation. Lazaroids have been used for the acute treatment of central nervous system disorders such as trauma and ischemia wherein lipid peroxidative processes take place. In this study we evaluated the effect of lazaroids (U-78518F and U-74389F) on the release of acid phosphatase activity and formation of malondialdehyde (MDA) in rat liver lyosomes subjected to exogenously generated oxygen free radicals. There was a significant increase in the acid phosphatase release and MDA formation in the presence of oxygen free radicals. This was prevented by both the lazaroids. In a separate study the effect of lazaroid U-74389F was seen on the zymosan-stimulated polymorphonuclear (PMN) leukocyte-derived chemiluminescence. The PMN leukocyte chemiluminescent activity was attenuated by the lazaroid in a dose-dependent manner. These studies suggest that lazaroids may inhibit lipid peroxidation and stabilize the membrane.
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PMID:Protective effects of lazaroids against oxygen-free radicals induced lysosomal damage. 784 65

In the present study we have investigated whether enzyme histochemical parameters can be applied to detect early ischemic damage in rat heart after ischemia without restoration of the blood flow. Ischemia was induced by incubating heart fragments for 0, 10, 20, 30, 60, 120 and 240 min at 37 degrees C. The activity and localization of the following enzymes was studied in unfixed cryostat sections using quantitative histochemical methods: lactate dehydrogenase, creatine kinase, succinate dehydrogenase, phosphofructokinase, acid phosphatase, 5'-nucleotidase and glycogen phosphorylase. Moreover, the ultrastructure of the tissue was studied with special attention to the appearance of flocculent densities in mitochondria, which can be seen as a sign of irreversible cell damage. It was shown that glycogen phosphorylase activity in rat heart decreased after short periods (30 min) of in vitro ischemia, whereas all other enzymes studied were not decreased up to 240 min, with the exception of lactate dehydrogenase and phosphofructokinase activities which were diminished only at 240 and 120 min of ischemia, respectively. Some reaction product was found after incubating for 5'-nucleotidase activity in the absence of substrate, indicating the presence of endogenous substrate(s). This endogenous substrate disappeared from the myocytes after 20 min of ischemia. It is assumed that AMP and/or other phosphate-containing compounds play an essential role in the activation of glycogen phosphorylase. Significant reduction of glycogen phosphorylase activity is correlated with the irreversible stage of damage of myocytes as judged from the ultrastructure.
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PMID:Histochemical detection of glycogen phosphorylase activity as parameter for early ischemic damage in rat heart. 850 31

To understand better the pathophysiology of random skin flaps, randomized skin flaps of human (3 cases) and guinea pig (53 cases) were investigated. Proximal (normal), proximomedial (viable), mediodistal (between viable and necrotic parts), and distal (necrosis) locations of the skin flaps were biopsied. Lipid peroxidase, hydrolytic enzymes of cytosol (Ca(2+)-dependent cysteine protease: calpain), and lysosome (acid phosphatase) of skin were used as markers. Measurements were taken of the flap blood flow; the numbers of capillaries, postcapillary venules, pericapillary arterioles, leukocytes, and mast cells per unit square of dermis. Apoptotic cells were identified by specific staining. Flaps were sampled at postoperative weeks 1 and 3 (human) and hours 1 and 6, and days 1 to 7 (guinea pig). The values for normal skin were regarded as the control. Obstruction (by leukocytes) of venous microvessels, rather than arterial microvessels, was the major cause of temporary hypoxia in the proximomedial location, constant hypoxia (venous stasis) in the mediodistal location, and ischemia in the distal location. Increases in the number of mast cells (mastocytosis) and microvessels (angiogenesis) were significant only in the viable parts of the flaps. This phenomenon and the rate of blood flow increased with time in viable locations (guinea pig). Epidermal necrosis, dermal fibrosis, and apoptosis were evident mostly in the mediodistal location. Elevated levels of leukocytes, lipid peroxidase, acid phosphatase, and calpain, combined with necrotic changes, were seen mostly in the distal skin location. There is a strong possibility that the following factors are involved: lipid piroxidation and hydrolysis in necrosis of the distal flap location after ischemia; constant hypoxia in fibrosis and apoptosis in the mediodistal location; and initial or temporary hypoxia in mastocytosis-induced angiogenesis in the viable location. The results presented here indicate that guidelines for further investigations include combined suppression of leukotaxis, lipid peroxidase, and hydrolysis, or the application of mast cell growth factors in an effort to salvage the flap maximally.
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PMID:Possible contributions of mastocytosis, apoptosis, and hydrolysis in pathophysiology of randomized skin flaps in humans and guinea pigs. 870 Sep 87


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