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)

We examined the influence of diabetes on ischemia/reperfusion-induced gastric damage in rats, in relation to the antioxidative system. Animals were injected with streptozotocin (STZ: 70 mg/kg, i.p.) and used after 5 weeks of diabetes with blood glucose levels of >350 mg/dl. Gastric mucosal blood flow (GMBF) was measured before, during and after 20 min of ischemia (1.5 ml bleeding per 100 g body weight from the carotid artery) followed by a 15-min reperfusion in the presence of acid (100 mM HCI). At the end of each experiment, gastric damage was observed macroscopically. GMBF was reduced by ischemia in all groups of rats, followed by a gradual return after reperfusion. Ischemia/reperfusion produced hemorrhagic lesions in normal rat stomachs in the presence of 100 mM HCl. These lesions were significantly aggravated when the animals were pretreated with diethyldithiocarbamate, an inhibitor of superoxide dismutase (SOD). Ischemia/reperfusion-induced damage was also markedly exacerbated in STZ-diabetic rats, but this aggravation was significantly suppressed by pretreatment with exogenous SOD or glutathione (GSH). Diabetic rat stomachs showed significantly less SOD activity as well as GSH content than normal rat stomachs. In addition, the deleterious influence of diabetes on the gastric ulcerogenic response to ischemia/reperfusion was significantly mitigated by decreasing the blood glucose levels by daily insulin treatment. These results suggest that the gastric mucosa of diabetic rats is more vulnerable to ischemia/reperfusion-induced injury, and the mechanism may be partly accounted for by impairment of the antioxidative system associated with a reduced SOD activity and GSH content.
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PMID:Aggravation of ischemia/reperfusion-induced gastric lesions in streptozotocin-diabetic rats. 1102 55

The objective of this study was to investigate the effect of singlet oxygen ((1)O2) scavengers on functional recovery and ascorbyl free radical (AFR) formation in isolated ischemic rat hearts. Hearts were subjected to 40 min. of global ischemia followed by 30 min. of reperfusion. Hemodynamics were measured as heart rate (HR), coronary flow (CF), left ventricular developed pressure (LVDP) and contractility (dP/dt). Electron paramagnetic resonance (EPR) spectroscopy was used to measure AFR release in coronary perfusate during the first two min. of reperfusion as a function of ROS scavengers. Relative to ischemic controls the administration of the (1)O2 scavengers 2,2,6,6-tetramethyl-4-piperidone x HCl (4-oxo-TEMP), carnosine (beta-alanyl-L-histidine) or a combination of the two significantly improved functional recovery as measured by LVDP. While no AFR signal was detected in coronary perfusate collected during preischemic perfusion with and without (1)O2 scavengers, the AFR background signal due to ischemia was significantly increased with the (1)O2 and *O2- scavengers. No such increase was observed with the hydroxyl radical (*OH) scavenger mannitol. Besides the AFR increase with the (1)O2 and *O2- scavengers the functional recovery was only significantly improved with the (1)O2 scavengers. In contrast to previous AFR studies we found with endogenous AFR that an increased AFR formation is not necessarily only reflecting increased oxidative stress but can also report improved functional recovery. Combining the hemodynamic data with increased AFR formation in the presence of several different ROS scavengers gives supportive evidence for (1)O2 also being involved in reperfusion injury.
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PMID:Increased endogenous ascorbyl free radical formation with singlet oxygen scavengers in reperfusion injury: an EPR and functional recovery study in rat hearts. 1115 83

Water extract fractions of leaves from Artemisia vulgaris L. (commonly known as mugwort) were tested for their effects on tissue damage brought about by ischemia-reperfusion injury in the rat mesentery. Male Sprague-Dawley rats, 200-300 grams in weight were divided into two groups, control and treatment (AV) group. All rats were anesthetized with ketamine HCl administered intramuscularly, tracheotomized and cannulated in one carotid artery and one jugular vein. After a midline abdominal incision, the mesenteric area was exteriorized and observed using videomicroscopy. After baseline observations of systemic blood pressure, heart rate, venular diameters and leukocyte adhesion along venules, the mesenteric artery and vein were occluded for 10 minutes. Prior to occlusion, A. vulgaris-treated animals were given a bolus injection of a 1% w/v solution of extracts, while the control group received saline. Monastral Blue dye was also administered before the occlusion at a dose of 30 mg/kg via the jugular vein in order to assess transendothelial leakage. Hemodynamic and cellular parameters were measured immediately after the release of occlusion and at 10 minute intervals thereafter. Results show that the extracts had no significant effects on mean blood pressures and heart rates, but appeared to significantly reduce leukocyte adherence and transendothelial leakage while improving flow in the ischemia-reperfused organ. The extract fractions contain yomogin, which has been previously shown to inhibit iNOS activity, and may therefore explain the anti-inflammatory property of the plant.
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PMID:In vivo microvascular actions of Artemisia vulgaris L. in a model of ischemia-reperfusion injury in the rat intestinal mesentery. 1132 36

To identify whether muscle metaboreceptor stimulation alters baroreflex control of muscle sympathetic nerve activity (MSNA), MSNA, beat-by-beat arterial blood pressure (Finapres), and electrocardiogram were recorded in 11 healthy subjects in the supine position. Subjects performed 2 min of isometric handgrip exercise at 40% of maximal voluntary contraction followed by 2.5 min of posthandgrip muscle ischemia. During muscle ischemia, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.001) during posthandgrip muscle ischemia (-201.9 +/- 20.4 units. beat(-1). mmHg(-1)) when compared with control conditions (-142.7 +/- 17.3 units. beat(-1). mmHg(-1)). No significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. However, both curves shifted during postexercise ischemia to accommodate the elevation in blood pressure and MSNA that occurs with this condition. These data suggest that the sensitivity of baroreflex modulation of MSNA is elevated by muscle metaboreceptor stimulation, whereas the sensitivity of baroreflex of modulate heart rate is unchanged during posthandgrip muscle ischemia.
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PMID:Baroreflex modulation of muscle sympathetic nerve activity during posthandgrip muscle ischemia in humans. 1156 50

We examined the effect of ellagic acid (EA), one of the polyphenols that are abundantly contained in whisky as a nonalcoholic component, on gastric lesions induced by ammonia plus ischemia or ischemia/reperfusion in rats, in relation to the antioxidative system. Under urethane anesthesia, a rat stomach was mounted in an ex vivo chamber, and the following two experiments were performed; 1) a stomach was made ischemic (1.5 ml/100 g body weight) for 20 min, followed by reperfusion for 15 min in the presence of 100 mM HCl; 2) a stomach was made ischemic by bleeding from the carotid artery (1 ml/100 g body weight), followed by intragastric application of ammonia (NH4OH: 120 mM). EA (0.1-10 mg/ml) was applied in the chamber 30 min before the onset of ischemia. Gastric potential difference (PD) and mucosal blood flow (GMBF) were measured before, during and after 20 min of ischemia. Ischemia/reperfusion caused a profound drop in GMBF followed by a return, and resulted in hemorrhagic lesions in the stomach in the presence of 100 mM HCI. These lesions were dose-dependently prevented by EA with suppression of lipid peroxidation but no effect on GMBF, and the effect at 6 mg/ml was almost equivalent to that of superoxide dismutase (SOD: 15000 unit/kg/hr) infused i.v. during a test-period. On the other hand, application of NH4OH to the ischemic stomach produced a marked reduction in PD, resulting in severe hemorrhagic lesions. These changes were prevented with both EA and SOD. In addition, EA had a potent scavenging action against monochloramine in vitro. These results suggest that EA exhibits gastric protective action against gastric lesions induced by NH4OH or reperfusion in the ischemic stomach, probably due to its anti-oxidative activity. This property of EA partly explains the less damaging effect of whisky in the stomach and may be useful as the prophylactic for Helicobacter pylori-associated gastritis.
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PMID:Effect of ellagic acid on gastric damage induced in ischemic rat stomachs following ammonia or reperfusion. 1184 98

We have previously demonstrated that maternal cocaine injections result in a gradient of fetal brain cocaine levels that decrease as a function of the fetuses' proximity to the ovaries at embryonic (E) day 15. Our prior data suggest that cocaine-induced vasoconstriction may (1) limit cocaine's entry into the brain and (2) cause damage to DA neurons through injury associated with hypoxia or ischemia of the utero-placental junction. Therefore, using the microsphere technique (labeled with Ru(103)), the following study sought to determine whether the previously observed pattern of cocaine distribution among fetuses in the uterus were due to position-specific reductions in uterine or placental blood flow. On day 15, a single subcutaneous injection of 30 mg/kg cocaine HCl was administered to each rat. Thirty minutes after the cocaine injection, reference blood samples were drawn from the ventral tail artery. Uterine segments and placentae were removed and subjected to gamma counting. While results regarding placental blood flow were equivocal, cocaine significantly reduced average uterine blood flow by 54.6%. In addition, as one moves more proximal to the ovaries, cocaine progressively attenuates blood flow in uterine tissue segments. These data support the hypothesis that the pattern of drug distribution and subsequent brain alterations from prenatal cocaine exposure in our previous reports are likely due to differences in uterine blood flow.
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PMID:Prenatal cocaine exposure induces an attenuation of uterine blood flow in the rat. 1194 2

MgATP substantially inhibited 1-alkyl-sn-glycero-3-phosphate (AGP) acetyltransferase found in neuronal nuclei. Other nucleotides and the ATP analogue AMP-PNP did not show a comparable inhibition. MgATP inhibition decreased in the presence of bovine serum albumin or the fatty acyl CoA synthetase inhibitor, Triacsin C. MgATP inhibition increased when nuclei were preincubated in 50 mM Tris-HCl (pH 7.4)/1 mM MgCl(2) at 37 degrees C, and preincubations elevated levels of nuclear free fatty acid. Exogenous free fatty acid, added to the acetylation incubations, increased the inhibition seen in the presence of MgATP. Oleoyl CoA, in the absence of MgATP, also inhibited AGP acetylation. These results suggested that MgATP supported the conversion of nuclear free fatty acids to fatty acyl CoA. Fatty acyl CoA may directly inhibit nuclear AGP acetyltransferase, but inhibition brought about by MgATP was competitive for the AGP substrate, suggesting an inhibitor close in structure to AGP. 1-Hexadecyl-2-arachidonoyl-sn-glycero-3-phosphate was identified as a competitive inhibitor for AGP in the acetylation reaction. Neuronal nuclei can convert AGP to 1-alkyl-2-acyl-sn-glycero-3-phosphate (AAcylGP), a reaction dependent upon MgATP and the presence of acetyl CoA or free CoA. This nuclear acylation was increased by free fatty acid addition and was seen using oleoyl CoA in the absence of MgATP. Nuclear AAcylGP formation was inhibited by bovine serum albumin and by Triacsin C. Thus, nuclear AGP acetyltransferase may be regulated by AGP acyltransferase activity and the availability of MgATP, a nucleotide that is rapidly lost during brain ischemia.
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PMID:MgATP may depress de novo neuronal nuclear PAF generation by promoting the formation of alkylacylglycerophosphate, an inhibitor of alkylglycerophosphate acetyltransferase. 1245 14

Despite its safety and efficacy, the traumatic effects of high-energy shock waves (HESW) on renal morphology and function during long-term follow-up have yet to be elucidated. Although the main target of shock waves is the stone located in the kidney, the surrounding tissue and other organs are also subjected to trauma during this procedure. In contrast to renal blood flow evaluation after shock wave treatment, ischemic development, causing varying degrees of damage at the tissue level, has not been well evaluated. The renoprotective peptide adrenomedullin (AM) is a potent vasorelaxing, natriuretic and cell growth modulating peptide, which is thought to act as an autocrine/paracrine regulator in renal glomeruli and tubules. In this experimental study, renal parenchymal AM levels were assessed in an attempt to evaluate the effect of HESW on the tissue levels of this peptide, which may be responsible for the regulation of ischemia induced by extracorporeal shock wave lithotripsy(ESWL), in a rabbit model. Thirty white New Zealand rabbits, each weighing 3-5 kg were used. The animals were divided into three main groups, and varying numbers of shock waves (1000, 1500, 2000) were applied under fluoroscopic localization to the same kidney of all animals. Ketamine HCl anesthesia was administered (15-20 mg/kg) and all of the procedures were performed with a Multimed 2000 lithotriptor. Untreated contralateral kidneys were evaluated as controls. Following HESW application, the treated and untreated kidneys of each animal were removed through bilateral flank incisions under ketamine HCl anesthesia after 24 h and 7 days, respectively. Tissue AM levels were assessed with immunohistochemistry. During the early follow-up period (24 h), both treated and untreated kidneys showed a moderate to high degree of AM positivity. The number of tubules stained with AM increased as the number of shock waves increased and the expression of this protein became evident, possibly due to a higher degree of tissue damage. Additionally, a limited degree of AM positivity was noted in the contralateral kidneys although this was not as evident as the positivity seen in the treated kidneys. Assessment of tissue AM levels during late follow-up (7 days) in both kidneys demonstrated a moderate or limited degree of positivity in the treated kidneys. Limited or no positivity could be demonstrated in the contralateral kidneys at this time. Taking the certain traumatic effects of HESW, which causes transient ischemia during ESWL, into account, we conclude that the application of HESW results in a transient decrease in renal perfusion, causing ischemic injury in treated as well as in contralateral (untreated) kidneys. This ischemic event lasts for a short time and seemed to be dose- and time-dependent. Increased tissue levels of AM appear to be a potential defence against ESWL induced ischemia.
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PMID:Evaluation of adrenomedullin levels in renal parenchyma subjected to extracorporeal shockwave lithotripsy. 1283 Mar 37

Peripheral nerve injury secondary to injection of therapeutic agents is well-documented. Until recently, the precise mechanism of injury has been obscure; even today, the treatment of these nerve injection injuries remains controversial. The aim of this study was to determine the involvement of ischemia-reperfusion injury in the development of peripheral nerve injection injury. Wistar rats were randomized into three groups. Sciatic nerve was used as the standardized nerve injection injury model. Two commonly used agents, lidocaine HCl 1 percent and phenol 5 percent, were tested for their comparative effects on the sciatic nerve. Lidocaine and phenol were injected into the sciatic nerves of the rats in Groups 1 and 2, respectively. Physiologic saline was used in the controls (Group 3). All the agents were injected intrafascicularly. The effects of nerve injection injury were assessed by measuring thiobarbituric acid reactive substance (TBARS) levels and obtaining walking-track analyses (WTA). Nerve injection caused significant increases in TBARS levels, which were correlated with the severity of the injury. The TBARS levels were related to the severity of injury caused by the tested agents; TBARS levels in phenol-injected nerves were significantly higher than those of lidocaine-injected nerves. Patterns of alterations in TBARS levels also paralleled the changes in print-length factor. Injection of lidocaine and phenol resulted in near-normal walking tracks at 8 and 12 weeks, respectively, while saline injection caused only transient impairment in walking tracks. These findings indicate that reactive oxygen species are involved in the pathogenesis of experimental peripheral nerve injection injury. Indices of free oxygen radical damage correlate with the progression of functional alterations after nerve injection injury.
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PMID:Free radical-induced damage in experimental peripheral nerve injection injury. 1451 34

The acidic pH-sensitive controlled release of fibroblast growth factor-2 (FGF-2) from a biodegradable hydrogel without any denaturation of the FGF-2 was successfully performed by a combination of FGF-2 activity and acidic pH-sensitivity. We prepared semi-interpenetrating polymer network like hetero-gels (S72-netgels) composed of poly(gamma-glutamic acid) (gamma-PGA) and 72% sulfonated gamma-PGA (gamma-PGA-S72). S72-netgels including 36 mol % sulfonic acid (S72-netgel-36) showed wide acidic pH-sensitive deswelling properties at pH = 2.0-6.0, corresponding to the isoelectric point of carboxylic acid, because of the concentration of protons due to the neighboring sulfonic acids from the carboxylic acids. The S72-netgel-36 (the volume of hydrogel is 7.85 x 10(-2) cm3) can incorporate 280 ng of FGF-2 after 24 h immersion in Tris-HCl buffer (pH = 7.4), including 1.0 microg of FGF-2. The S72-netgel-36 still retained about 60% of the FGF-2 even after 15 days of incubation in fresh Tris-HCl buffer at 37 degrees C because of the stable interaction of FGF-2 with gamma-PGA-S72 in S72-netgel-36. The release of FGF-2 from the S72-netgel-36 was successfully controlled by alternating immersion in pH = 7.4 and acidic pH buffers. Furthermore, the FGF-2 released from the S72-netgel-36 retained its activity without denaturation because the gamma-PGA-S72 in S72-netgel-36 has a protective activity. The acidic pH-sensitive FGF-2 release property of the S72-netgel-36 without denaturation of the FGF-2 may be useful for tissue engineering fields such as neovascular treatment for ischemia and inflammation.
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PMID:Novel functional biodegradable polymer IV: pH-sensitive controlled release of fibroblast growth factor-2 from a poly(gamma-glutamic acid)-sulfonate matrix for tissue engineering. 1628 65


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