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)

1. Dogs were exposed to hypoxemia followed by a coronary angiogram at three different times: under control conditions, after ischemia-reperfusion injury, then 30 min later. 2. In the study group, the dogs were treated with trandolapril (0.05 mg/kg) and verapamil (0.1 mg/ kg) just prior to the final hypoxic challenge. 3. Under control conditions, the left anterior descending coronary artery (LAD) dilated in response to hypoxia. Following ischemia-reperfusion injury, however, it constricted significantly in response. 4. In the control group, repeat hypoxia 30 min later resulted in vasoconstriction of the LAD which was comparable to the preceding response. 5. However, in the study group, treatment with trandolapril plus verapamil inhibited the vasoconstriction in response to repeat hypoxia.
Gen Pharmacol 1996 Sep
PMID:Trandolapril plus verapamil inhibits the coronary vasospasm induced by hypoxia following ischemia-reperfusion injury in dogs. 890 91

1. Adenosine is a normal constituent of all body fluids and its levels are raised, for example, by hypoxia and ischemia. In addition, both adenosine and ATP can be released by endothelial cells and neutrophils in response to physiologic stimulation. 2. Human neutrophil leukocytes possess multiple adenosine receptors and P2 purinoceptors. 3. ATP can increase intracellular Ca2+ levels in neutrophils, cause degranulation and enzyme release, potentiate the oxidative burst and enhance their adhesion to the endothelium. ATP is broken down to adenosine by ecto-enzymes. Via A1 receptors, adenosine can increase neutrophil chemotaxis and, via A2A receptors, it can decrease the oxidative burst, degranulation and adhesion to endothelium. 4. Adenosine and adenine nucleotides are important endogenous modulators of neutrophil functions, and drugs may exert important actions via purinoceptors on neutrophil leukocytes.
Gen Pharmacol 1997 Mar
PMID:Purines and neutrophil leukocytes. 906 71

1. The aim of this review is to consider the relative roles of inhibitory and excitatory amino acid receptor-mediated events in the processes leading to pain transmission in the spinal cord. 2. Emphasis will be on the roles of the inhibitory and excitatory amino acids, GABA and glutamate, and how the relative balance between activity in these systems appears to determine the level of pain transmission. 3. The N-methyl-D-aspartate (NMDA) receptor for glutamate has been implicated in the generation and maintenance of central (spinal) states of hypersensitivity. It has been shown that activation of this receptor underlies wind-up, whereby the level of transmission of noxious messages is potentiated. Antagonists at this receptor-channel complex prevent or block enhanced (hyperalgesic) pain states induced by tissue damage, inflammation, nerve damage and ischemia. 4. Information concerning amplification systems in the spinal cord, such as the NMDA receptor, is a step toward understanding why and how a painful response is not always matched to the stimulus. Such events have parallels with other plastic events such as long-term potentiation (LTP) in the hippocampus. 5. However, the roles of inhibitory transmitter systems can also change insofar as opioid, adenosine and GABA transmission in the spinal cord can vary in different pain states. 6. Changes in GABA systems have been well-documented and discussion will center on whether this has clinical implications. 7. In addition to behavioral and electrophysiological approaches to the pharmacology of pain the current status of the use of markers of early onset genes such as c-fos, as monitors of activity, will be discussed. 8. Hyperalgesia would appear to be balanced by inhibitions during inflammatory conditions but not in neuropathic states, pains due to nerve damage. In the latter case, events reminiscent of LTP may predominate, whereas they are held in check by inhibitions under conditions of inflammation.
Gen Pharmacol 1997 May
PMID:The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of pain in the spinal cord. 918 94

1. Effects of a novel zinc compound (polaprezinc), N-(3-aminopropionyl)-L-histidinato zinc, on the mucosal ulcerogenic response induced by ammonia (NH4OH) and monochloramine (NH2Cl) were examined in rat stomachs. 2. Oral administration (1 ml) of NH4OH (> 600 mM) and NH2Cl (> 60 mM) produced severe hemorrhagic lesions in unanesthetized rat stomachs, whereas hypochlorous acid (HClO) even at 120 mM did not cause any macroscopic damage. 3. Pretreatment of the animals with polaprezinc (2-12 mg/ml, 1 ml, PO) showed a dose-dependent inhibition against gastric lesions induced by NH4OH (1,800 nM) or NH2Cl (120mM), and this effect was significant at > 6 mg/ml in either case. These lesions were also significantly prevented by prior administration of dmPGE2 (2 micrograms/ml, 1 ml, PO). 4. Mucosal application of NH4OH (300 mM) and NH2Cl (10 mM) caused a marked reduction of transmucosal potential difference (PD) in ex vivo stomachs of anesthetized rats. The reduced PD responses caused by NH4OH and NH2Cl were prevented dose dependently by preexposure of the mucosa to polaprezinc, but not affected by dmPGE2. 5. Mucosal exposure to NH4OH (60 mM) caused a marked PD reduction in ex vivo stomachs made ischemic by bleeding from the carotid artery (1 ml per 100 g body wt), followed by severe gastric lesions. These ulcerogenic and PD responses caused by NH4OH plus ischemia were attenuated by prior application of polaprezinc as well as taurine (25 mg/ml, 1 ml), while dmPGE2 prevented the lesions without affecting the reduced PD response. 6. These results suggest that (a) NH2Cl damages the gastric mucosa at much lower concentrations than NH4OH, (b) polaprezinc protects the stomach against injury caused by either NH2Cl or NH4OH, and (c) the mechanisms underlying the protective action of polaprezinc remain unclear but may be different from those of dmPGE2.
Gen Pharmacol 1997 Nov
PMID:Irritant action of monochloramine in rat stomachs: effects of zinc L-carnosine (polaprezinc). 934 15

1. We have investigated the ability of several compounds to diminish both infarct area and volume induced by middle cerebral artery occlusion in the mouse. 2. Lifarizine, ipsapirone and N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl (DPPE) all reduced both infarct area and volume. Ifenprodil diminished the infarct area, but the effect on total infarct volume was much less pronounced. 3. In addition, we tested the protective effects of some other drugs on infarct area only. Nimodipine, verapamil, diltiazem, N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazo lamine (R56865) and sabeluzole had no effect on infarct area. (S)-Emopamil significantly diminished infarct area. 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) also diminished infarct area significantly. 4. In some brain ischemia models hypothermia protects against ischemic damage. Mild hypothermia had no effect on infarct area in the present mouse model of focal ischemia.
Gen Pharmacol 1998 Feb
PMID:Focal cerebral ischemia in the mouse: hypothermia and rapid screening of drugs. 950 74

1. At least two different groups of molecules can be considered neurotrophic factors because they exert a variety of effects upon neural cells. The first consists of the numerous families of polypeptide growth factors known to take part in almost all stages of neural cell growth and functioning, including development, differentiation, survival and pathology. The second group also is characterized by extensive complexity of multiple forms, and consists of the sialic acid-containing glycosphingolipids or gangliosides. These molecules also take part in the transfer of information from the extracellular milieu to the cell interior, and, similarly to growth factors, are participants in such aspects as development, differentiation and functioning. 2. In this short overview, we consider the existing data on the neuroprotective effects of growth factors [e.g., basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and brain-derived neurotrophic factor] and one species of ganglioside (GM1) against retinal ischemia in vivo and cerebral excitotoxicity in vitro. 3. We used three different experimental models to investigate their relevance to ischemic and excitotoxic conditions in the retina and have shown that: (a) both bFGF and EGF show highly effective neuroprotection for rat retinal neurons exposed to toxic levels of glutamate or its nonphysiological agonist kainate in vitro (b) retinal glial cells suffer morphological perturbations after glutamate or kainate treatment, and this effect depends on neuron-glial interactions; (c) these glial changes can also be corrected by posttreatment with either bFGF or EGF in vitro; (d) with the use of an in vivo animal model involving anterior chamber pressure-induced ischemia in adult rats, either pretreatment by intraperitoneal injection of GM1 or posttreatment by intraocular injection of the same ganglioside significantly reduces histological damage to inner nuclear regions. 4. Hence both groups of trophic molecules show interesting features for retinal ischemic treatment.
Gen Pharmacol 1998 Mar
PMID:Growth factors and gangliosides as neuroprotective agents in excitotoxicity and ischemia. 951 73

1. Reactive oxygen species (ROS) can be generated in biological tissues, including the retina, in particular under or after ischemia. They can provoke cell necrosis by reacting with cell components or they can trigger programmed cell death by activating specific targets. 2. Experiments based on electroretinography and electron spin resonance spin trapping analysis show that ROS are produced in the rabbit retina during ischemic episodes themselves as well as reperfusion. ROS are also generated as a consequence of ischemia by overstimulation of glutamate ionotropic receptors and calcium-dependent activation of enzymes such as phospholipase A2 and nitric oxide synthase. 3. The targets of ROS that can be responsible for functional damage of the retina are numerous: Na+-K+-ATPase inhibition leads to ionic imbalance and electroretinogram alteration; inhibition of glutamate transporter contributes to excitotoxicity. In addition, ROS can be deleterious by inducing protein synthesis (e.g., apoptotic proteins, vascular endothelial growth factor/vascular permeability factor). 4. In this short review, we consider the various mechanisms of ROS generation in retinal ischemia and the different effects of ROS so as to suggest possible effects of neuroprotective agents.
Gen Pharmacol 1998 Mar
PMID:Free radicals in retinal ischemia. 951 74

1. The b-wave of the electroretinogram (ERG) is a particularly sensitive index of retinal ischemia. The present paper summarizes the changes in the b-wave observed in five in vivo models of retinal ischemia. 2. Although the amount of reduction in b-wave amplitude during ischemia corresponds to the severity of the insult, the degree of recovery of the b-wave during reperfusion depends on the duration of ischemia. 3. A massive release of glutamate, intracellular overload with calcium and enhanced production of free radicals are suggested to be three major pathophysiological processes that contribute to retinal ischemic damage. The b-wave of the ERG represents a functional measure for potential therapeutic efficacy of drugs interacting with these pathophysiological processes. 4. Several glutamate antagonists, such as MK-801, memantine, flupirtine or GYKI 52466, along with the free radical scavengers vitamin E, lipoate, superoxide dismutase and catalase, all reduce the depression of the b-wave during ischemia or accelerate the recovery of the b-wave during reperfusion or both. The calcium channel antagonists nimodipine and levemopamil exert only a slight beneficial effect on the recovery of the amplitude of the b-wave during reperfusion, provided that the blood pressure is not potently reduced.
Gen Pharmacol 1998 Mar
PMID:The b-wave of the electroretinogram as an index of retinal ischemia. 951 75

1. Glutamate is the neurotransmitter released by bipolar cells at their synapses with amacrine cells. The amacrine cells express ionotropic (NMDA, AMPA and kainate) and metabotropic (mGluR1, mGluR2, mGluR4 and mGluR7) glutamate receptors and may take up glutamate from the synaptic cleft. 2. Activation of the ionotropic glutamate receptors increases the intracellular free calcium concentration ([Ca2+]i), owing to Ca2+ entry through the receptor-associated channels as well as through voltage-gated Ca2+ channels. The [Ca2+]i response to glutamate may be amplified by Ca2+-induced Ca2+ release from intracellular sources. 3. Activation of NMDA and non-NMDA glutamate receptors stimulates the release of GABA and acetylcholine from amacrine cells. GABA is released by a Ca2+-dependent mechanism and by reversal of the neurotransmitter transporter. 4. Excessive activation of glutamate receptors during ischemia leads to amacrine cell death. An increase in [Ca2+]i due to Ca2+ influx through NMDA and AMPA/kainate receptor channels is related to cell death in studies in vitro. In other studies, it was shown that nitric oxide may also take part in the process of cell damage during ischemia.
Gen Pharmacol 1998 Mar
PMID:Glutamate in life and death of retinal amacrine cells. 951 76

1. Neurotrophins are molecules that regulate the survival, development and maintenance of specific functions in different populations of nerve cells. 2. In the present work, we studied the localization, at the cellular level, of the different neurotrophins and their receptors within the rat retina in control and after ischemia-reperfusion of the retina. We found variations in the localization of some of these molecules depending on the reperfusion time of the retina after the ischemic lesion. 3. Thus it is suggested that the changes in the distribution and concentration of neurotrophins and their receptors caused by ischemia are protective reactions related to neuronal damage and synaptic reorganization.
Gen Pharmacol 1998 Mar
PMID:Immunohistochemical distribution of neurotrophins and their receptors in the rat retina and the effects of ischemia and reperfusion. 951 78


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