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)

A novel delta-receptor selective compound, ARD-353 [4-((2R,5S)-4-(R)-(4-diethylcarbamoylphenyl)(3-hydroxyphenyl)methyl)-2, 5-dimethylpiperazin-1-ylmethyl)benzoic acid], was evaluated for activity on infarct size in a rat model of acute myocardial infarction. ARD-353 was characterized as having delta receptor selectivity using radioligand binding and had no apparent selectivity between delta receptor subtypes as determined by [(3)H] cyclic [D-Pen(2),D-Pen(5)]enkephalin (delta(1)) and [(3)H]Deltorphin II (delta(2)) competition binding. ARD-353 also showed selective delta receptor agonist activity in mouse-isolated vas deferens. There was no evidence of any seizure-like convulsions when ARD-353 was administered to mice either i.v. or p.o., implying minimal penetration of the blood-brain barrier. ARD-353 decreased infarct size in a left anterior descending coronary artery (LAD) occlusion model of myocardial infarction. In animals pretreated with ARD-353 (i.v.) and then subjected to 30 min of LAD occlusion followed by 90 min of reperfusion, infarct size was reduced in a dose-dependent manner compared with vehicle-treated controls. The effects of ARD-353 on infarct size were blocked by the delta(1)-opioid selective antagonist 7-benzylidenenaltrexone, indicating a significant role for the delta(1)-opioid receptor in the cardioprotective mechanism of ARD-353. ARD-353 (0.3 mg/kg i.v.) produced significant protection when administered 5 min and 12 and 48 h before ischemic insult or when given immediately after the ischemic insult (at the start of reperfusion). Given the lack of central nervous system effects and beneficial efficacy in the rat model of myocardial ischemia, it is felt that ARD-353 is the first nonpeptide delta-receptor agonist with true potential for clinical use before surgically induced ischemia or in an emergency setting.
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PMID:ARD-353 [4-((2R,5S)-4-(R)-(4-diethylcarbamoylphenyl)(3-hydroxyphenyl)methyl)-2,5-dimethylpiperazin-1-ylmethyl)benzoic acid], a novel nonpeptide delta receptor agonist, reduces myocardial infarct size without central effects. 1618 52

BACKGROUND The aim of this study was to evaluate the application of diffusion kurtosis imaging (DKI) in spinal cord ischemia/reperfusion (SCI/R) injury and to explore its association with pathology. MATERIAL AND METHODS Japanese male long-eared rabbits were chosen and divided into 7 groups (8 rabbits in each group): control group (C group), sham-operation control group (S group), and 5 experimental groups (E-2 h group, E-24 h group, E-48 h group, E-7 d group, and E-14 d group). Tarlov scoring and immunohistochemical staining were used to assess hindlimb motor function and observe the expression of glial fiber acidic protein (GFAP), respectively. The correlation between DKI and pathology after SCI/R injury was compared by 3.0TMR scanning DKI. RESULTS Neuroethology in each time point of E groups was significantly different from that in C and S groups (P<0.05). The E-24 h group had the lowest value (P<0.05), and the hindlimb motor function began to recover after 24 h. The expression of GFAP was gradually increased after SCI/R injury, and the maximum value was in the E-7 d group (P<0.05). MK (mean kurtosis) had a linear negative correlation with average optical density (OD) (r=-0.115, P<0.05) and was positively correlated with integral OD (IOD) (r=0.204, P<0.05), in which MD (mean dispersion) was positively correlated with OD and IOD, but without a significant difference (r=0.618, r=251, P>0.05). CONCLUSIONS DKI can be used to monitor the changes in SCI/R injury, and fractional anisotropy (FA) can reflect change in white matter structure. The changes in expression of MK and GFAP were related to the myelin sheath injury repair process.
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PMID:Diffusion Kurtosis Imaging and Pathology in Spinal Cord Ischemia/Reperfusion Injury in Rabbits: A Case-Control Study. 2882 Aug 64