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 effect of cholecystokinin octapeptide sulfated type (CCK-8S) on dysfunction of CA1 pyramidal neurons induced by in vitro ischemic insult in hippocampal slices of stroke-prone spontaneously hypertensive rats (SHRSP). CCK-8S shortened the time required for partial recovery from block of a population spike produced by ischemia. Furthermore, CCK-8S reduced ischemic insult-induced accumulation of K+ in extracellular space. Suppression of the K+ conductance by the CCKB receptor activation is suggested to contribute to neuroprotection by CCK-8S.
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PMID:CCKB receptor activation protects CA1 neurons from ischemia-induced dysfunction in stroke-prone spontaneously hypertensive rats hippocampal slices. 765 2

Effects of prostaglandin (PG) E1 on ischemia-reperfusion (I-R) injury to the pancreas was evaluated using isolated in vivo perfused dog pancreas. Pancreatic endocrine and exocrine functions were stimulated with 10(-12) M cholecystokinin octapeptide (CCK-8). This amount of CCK-8 promoted production of insulin, glucagon, PGI2, and thromboxane (Tx) A2 in the pancreas. Sixty minutes of ischemia and subsequent reperfusion induced damage to pancreatic ductular, acinar, and beta cells. Intra-arterial administration of PGE1 at a dose of 0.5 microgram/kg/min throughout the experiment prevented the I-R injury, reducing plasma lipid peroxides, and elevating PGI2 without changing TxA2 in the pancreas. PGE1 thus appears to protect pancreatic function from I-R injury both by depressing the effect of free-radicals and by decreasing TxA2/PGI2 which predicts cell injury.
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PMID:Prostaglandin E1 protects dog pancreas from ischemia-reperfusion injury. 802 58

The effects of cholecystokinin (CCK) receptor agonists and antagonists on hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 presynaptic fiber spikes elicited by the stimulation of Schaffer collaterals were investigated using rat hippocampal slices. Treatment with the CCKB receptor agonist CCK tetrapeptide (CCK4, 0.01-10 microM) exacerbated the ischemia-induced decrease in the CA1 presynaptic potential in a concentration-dependent manner. Whereas, treatment with the CCKB receptor antagonist [(3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl)-N1-(3-methylphenyl)-urea] (L365260), and not with CCKA receptor antagonist [(3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl)-1H-indole-2-carboxamide] (L364718), produced a concentration-dependent attenuation of the ischemia-induced decrease. The magnitude of recovery of the CA1 field potentials in L365260-treated groups at 10 and 100 nM was 34% and 45%, respectively. The neuroprotective effect of L365260 (0.01 and 0.1 microM) was completely blocked by co-treatment with CCK4 (0.1 microM), a concentration that did not affect the decreased presynaptic potential induced by ischemia. These results demonstrated that the stimulation of the CCKB receptor played a detrimental role in the development of ischemic damage, whereas the blockade of CCKB receptors played a neuroprotective role in ischemic damage, suggesting a facilitatory role of CCK receptor-operated function in ischemia-induced neuronal deficits.
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PMID:Neuroprotective effect of cholecystokininB receptor antagonist on ischemia-induced decrease in CA1 presynaptic fiber spikes in rat hippocampal slices. 817 34

The insulin-like growth factor (IGF) system has a role in repair following hypoxic-ischemic injury in many tissues including the brain. To study the involvement of the IGF system following head trauma, we used a rat contusion model, which produces a focal lesion of the cerebral cortex. Molecules in the IGF system were analyzed using in situ hybridization at different times following impact. We observed a dramatic up-regulation of insulin-like growth factor binding protein-2 (IGFBP-2) mRNA in cortical areas adjacent to the injury 24 h after impact, with a peak 10-fold increase engaging most of the ipsilateral cortex 2 and 3 days post-contusion. Seven days after the contusion, IGFBP-2 expression was only moderately up-regulated and again concentrated around the injury. IGFBP-4 mRNA levels increased 4-fold ipsilateral to the site of injury, with retained pattern of cortical expression. IGFBP-3, IGFBP-5 and IGFBP-6 mRNA all displayed distinct expression patterns in the brain but no significant changes were observed following injury. In contrast, IGF-1 mRNA levels were very low prior to contusion, but increased markedly at the site of injury with a peak at day 3. We were unable to detect any changes in the type 1 IGF-receptor or IGF-2 mRNA following contusion. The neuropeptide cholecystokinin (CCK) mRNA was clearly up-regulated following contusion, with an even distribution over the ipsilateral cortex. The expression pattern of molecules in the IGF system post-contusion differs in part to changes observed following hypoxic-ischemia or ischemia alone, perhaps reflecting different regulatory mechanisms depending on the type of injury.
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PMID:Increase of insulin-like growth factor (IGF)-1, IGF binding protein-2 and -4 mRNAs following cerebral contusion. 879 17

Pancreatic hyperstimulation with simultaneous duct obstruction does not cause the typical features of acute pancreatitis, therefore the role of an additional challenge, such as either ethanol intoxication or short-term ischemia, was studied. Alcoholic pancreatitis was induced in 28 rats by acute ethanol intoxication (0.25 LD50) and an obstruction/hyperstimulation mechanism (clip of the biliopancreatic duct for 20 min and intravenous stimulation with 5 U of cholecystokinin and secretin each). Ischemic pancreatitis was performed by obstruction/hyperstimulation and subsequent pancreatic ischemia by clamping the supplying arteries for 40 min. The macro- and microscopic alterations were evaluated and graded by a scoring system. Additionally, the pancreas was removed in 50% of the animals and the pancreatic acini were prepared. From those acini the intracellular enzymes trypsinogen, kallikreinogen, amylase, lipase, glucuronidase, and acidic phosphatases were determined. While obstruction/hyperstimulation, 40 min of ischemia, or ethanol alone did not induce acute pancreatitis, a combination of obstruction/hyperstimulation with either ethanol or ischemia resulted in acute pancreatitis in 68 and 60% of treated rats, respectively. Similarly, both models were characterized by extrapancreatic fat necrosis and acinar necrosis at the periphery of the lobules. Almost all intracellular enzymes were elevated in both pancreatitis models compared to sham-operated controls. Both alcohol and ischemia were insults that sensitize the pancreas to develop acute pancreatitis after obstruction/hyperstimulation. Since the observed morphologic and enzymatic alterations in both models are very similar, alcohol and ischemia might have some common pathways by which they make the pancreas vulnerable to enzymatic attacks.
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PMID:Similar morphological and intracellular biochemical changes in alcoholic acute pancreatitis and ischemic acute pancreatitis in rats. 898 5

In healthy subjects, the 3 known pancreatic trypsinogens, which are endopeptidases belonging to the chymotrypsin superfamily, are activated by enterokinase and partial autoactivation in the duodenum. The premature activation of trypsinogen in the pancreatic interstitium, with the subsequent activation of other pancreatic zymogens, is believed to lead to the autodigestion of the gland, this being the first event in acute pancreatitis. The mechanisms that lead to trypsinogen, activation in acute pancreatitis are largely unknown. However, ischemia, hypercalcemia and the activation of cathepsin B (by cholecystokinin) are thought to be of importance. The easiest and most reliable way to assess trypsinogen activation is the measurement of the activation peptide, TAP, in urine, plasma, pancreatic tissue or ascitic fluid. In the animal model of acute pancreatitis, TAP in ascites and pancreatic tissue has been shown to correlate with the presence and extent of necroses. It has proven to be a good marker for the severity of pancreatitis and is a useful marker in examining the pathophysiology and possible treatment modalities in the animal model of acute pancreatitis. Studies on TAP in human acute pancreatitis were most commonly focused on urinary TAP. Within a 48-hour time frame after the onset of the disease, TAP was a good predictor of the severity of acute pancreatitis. The main advantage over other markers, such as CRP, is that TAP is the earliest marker of necrosis to be increased. Also, increased levels of TAP in ascitic fluid were shown to correlate well with pancreatic necroses. In our experience, plasma TAP was found to have a "diagnostic window" within the first 3 days predicting pancreatic necroses. Positive TAP gave a very good positive prediction and a high specificity towards the development of pancreatic necroses, but did not differ between necrotizing pancreatitis with systemic complications or uncomplicated necrotizing pancreatitis. We therefore think that plasma TAP is a very good marker for local complication in acute pancreatitis and its routine measurements may help to identify patients at a high risk within the first days of the disease.
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PMID:Mechanism and role of trypsinogen activation in acute pancreatitis. 1057 41

The effects of ecabapide, a novel substituted benzamide compound (3-[2-(3,4-dimethoxyphenyl)ethylcarbamoylmethyl]amino-N-methylb enzamide) that has gastrointestinal prokinetic action, were examined on the discharge of extrinsic afferent nerves supplying the stomach and jejunum in anaesthetized rats. Ecabapide (60 and 180 microg kg(-1), i.v.) had no effect on the baseline discharge of vagal gastric distension-sensitive afferents or the stimulus-response profile to gastric distension. Ecabapide also had no effect on either spontaneous jejunal mesenteric afferent nerve discharge or responses to intestinal distension. Ecabapide (180 microg kg(-1)) significantly inhibited the maximum discharge of jejunal afferents induced by cholecystokinin (CCK8; 50 pmol, i.v.), whereas it failed to inhibit the excitatory action of 2-methyl-5-hydroxytryptamine (2Me-5-HT; 10 microg, i.v.), a selective 5-HT3 receptor agonist. A model of acute focal intestinal ischaemia was used to evaluate the actions of ecabapide on the discharge of activated jejunal afferents. Ischaemia produced a substantial increase in afferent discharge which was reproducible when the duration of ischaemia was limited to less than 10 min and repeated every 15 min. Ecabapide at doses of 60 and 180 microg kg(-1) significantly reduced ischaemia-induced increases in afferent discharge. In addition to its therapeutic efficacy as a gastrointestinal prokinetic agent, these findings show also that ecabapide may also have an inhibitory action on the discharge of intestinal afferents activated by ischaemia.
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PMID:Modulation of gastrointestinal afferent sensitivity by a novel substituted benzamide (ecabapide). 1078 88

Since Robert discovery that pretreatment with prostaglandin (PG) applied in non-antisecretory dose can prevent the injury of gastric mucosa induced by necrotizing agents, much attention was paid to the role of these cyclooxygenase (COX) products in the mechanism of gastric mucosal integrity and ulcer healing. The ability of exogenous PG to attenuate or even completely prevent mucosal damage caused by corrosive substances such as absolute ethanol, hyperosmolar solutions or concentrated bile has been termed "cytoprotection". Increased generation of endogenous PG in the gastric mucosa exposed to the topical contact with "mild irritant" such as 20% ethanol, 1 mM NaCl or 5 mM taurocholate also prevented gastric injury caused by strong irritants via phenomenon of adaptive cytoprotection. Other mediators such as growth factors, nitric oxide (NO) or calcitonin gene related peptide (CGRP) as well as some gut hormones including gastrin and cholecystokinin (CCK), leptin, ghrelin and gastrin-releasing peptide (GRP) have been also found to protect gastric mucosa against the damage induced by corrosive substances. This protective action of gut hormones has been attributed to the release of PG or activation of sensory nerves because it could be abolished by the pretreatment with indomethacin or large neurotoxic dose of capsaicin and restored by the addition of exogenous PGE(2) or CGRP, respectively. Short (5 min) ischemia of the stomach applied before prolonged ischemia-reperfusion (I/R) attenuated markedly the gastric lesions produced by this I/R and also prevented the mucosal damage provoked by necrotizing substances. This protection could be abolished by the pretreatment with non-steroidal anti-inflammatory drugs (NSAID) and was accompanied by an enhancement of gastric mucosal COX-2 expression and activity. Exposure of gastric mucosa to single insult of acidified aspirin (ASA) causes severe mucosal damage with occurrence of multiple haemorrhagic lesions but with repeated application of ASA, the attenuation of mucosal lesions is observed, despite the profound inhibition of PGE(2) generation. This phenomenon called "gastric adaptation" does not appear to depend upon endogenous biosynthesis of PG but possibly involves enhanced production of growth factors increasing cell proliferation and mucosal regeneration. Unlike short lived gastroprotection by PG, NO, CGRP, mild irritants or short ischemia, gastric adaptation appears to be long-lasting phenomenon accompanied by increased resistance of the adapted mucosa to subsequent damage induced by corrosive agents.
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PMID:Role of prostaglandins in gastroprotection and gastric adaptation. 1624 88

Impairment in gallbladder emptying, increase in residual volume, and reduced smooth muscle contractility are hallmarks of acute acalculous cholecystitis and seem to be related to ischemia/reperfusion (I/R). This study was designed to determine the effects of tempol, a general antioxidant, on I/R-induced changes in gallbladder contractile capacity, the mechanisms involved in the contractile process, and the level of inflammatory mediators. Experimental gallbladder I/R was induced in male guinea pigs by common bile duct ligation for 2 days, then a deligation of the duct was performed and after 2 days the animals were sacrificed. A group of animals was treated with tempol, administered in the drinking water at 1 mmol/l for 10 days prior the bile duct ligation and until animal sacrifice. Isometric tension recordings showed that KCl and cholecystokinin-induced contractions were impaired by I/R, which correlated with decreased F-actin content and detrimental effects on Ca(2+) influx. In addition, I/R depolarized mitochondrial membrane potential, as indicated by the reduction of the heterogeneity of the rhodamine123 fluorescence signal, and increased the expression of NF-kappaB, COX-2, and iNOS. Tempol treatment improved contractility via normalization of Ca(2+) handling and improvement of F-actin content. Moreover, the antioxidant ameliorated mitochondrial polarity and normalized the expression levels of the inflammatory mediators. These results show that antioxidant treatment protects the gallbladder from I/R, indicating the potential therapeutic benefits of tempol in I/R injury.
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PMID:Tempol protects the gallbladder against ischemia/reperfusion. 2057 64

The inhibitory effect of different reperfusion periods 45 min following hepatic ischemia on the expression of cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in the jejunum and the effect of salvia miltiorrhiza pretreatment were investigated, and the possible mechanism and implications were explored. Eighty rats were randomly divided into four groups: normal control group (CO group), sham-operated group (SO group), ischemia/reperfusion (I/R) injury group (IR group) and salvia miltiorrhiza pretreatment group (SM group). The rat model of I/R was established by using a non-invasive artery clamp to clip (45 min) or relax the hepatic pedicle. In the SM group, saline (40 mL/kg) and salvia miltiorrhiza injection (6 g/kg) were injected via the tail vein 30 min before clipping the hepatic pedicle. In the SO group only the porta hepatis was dissected after laparotomy without clamping the hepatic pedicle. At 0, 3, 12, 24 and 72 h post-reperfusion, respectively, upper jejunum samples were taken for immunohistochemistry of CCK and VIP. It was found that 0 h after I/R, the expression of CCK and VIP in the upper jejunum was upregulated. With prolongation of the reperfusion period, the expression of CCK and VIP was also increased, reached the peak at the 24th h, and gradually returned to the normal level at the 72nd h after reperfusion. The levels of both CCK and VIP in the SM group were lower than those in the IR group. It is suggested that the digestive tract congestion injury caused by liver ischemia can upregulate the expression of CCK and VIP in the jejunum following reperfusion. Salviae pretreatment can partly reduce the increased expression of CCK and VIP in the jejunum in the same period, which might contribute to the early recovery of gastrointestinal motility.
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PMID:Effect of Salvia miltiorrhiza pretreatment on the CCK and VIP expression in hepatic ischemia-reperfusion-induced digestive tract congestion. 2119 38


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