BackgroundSudden cardiac death resulting from acute myocardial infarction (AMI) constitutes a significant percentage of the caseload for forensic and clinical pathologists. When sudden death occurs at an early stage (<6 h), pathologists experience difficulty in the postmortem diagnosis of AMI. Because of the specific tissue distribution of S100A1 and its relationship with acute ischemic heart disease, this study aimed to evaluate the performance of S100A1 in the postmortem diagnosis of AMI.MethodsWe constructed a rat model of AMI through permanent ligation of the left anterior descending coronary artery (LAD) to investigate the depletion of S100A1 from ischemic cardiomyocytes by immunohistochemistry and measuring S100A1 plasma concentrations by enzyme-linked immunosorbent assay at varying post-infarction intervals. In addition, immunohistochemical staining of S100A1 for definite infarction, suspected early infarction, and in normal human hearts, was also performed to test its practical feasibility for postmortem diagnosis of AMI at an early stage.ResultsAs early as 15 min after ligation of the LAD, depletion of S100A1 was observed in ischemic cardiomyocytes, and S100A1 plasma concentration was also significantly higher than that of the sham-operated group (P < 0.001). With continuation of the occlusion time, the depleted areas of S100A1 further expanded and S100A1 plasma concentrations further increased. For autopsy material, all human cases of definite myocardial infarction and suspected early infarction showed well-defined areas without S100A1 staining. None of the normal human cases showed diffuse depletion of S100A1.ConclusionOur results suggest that immunohistochemical detection of S100A1 is useful for the postmortem diagnosis of AMI at an early stage.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/4366650979519818
A high rate of relapse is a major clinical problem among drug-addicted individuals. Persistent traces of drug-associated reward memories contribute to intense craving and often trigger relapse. A number of interventions on drug-associated memories have shown significant benefits in relapse prevention. Among them are pre-or post-extinction pharmacological manipulations that facilitate the extinction of drug-associated behavior. Berberine, a bioactive isoquinoline alkaloid, has been recently reported to provide therapeutic benefits for a number of central nervous system (CNS) disorders, including morphine addiction. The present study aimed to investigate whether berberine could serve as a post-extinction pharmacological intervention agent to reduce risks of reinstatement of drug seeking. We found that an intragastric administration of berberine at doses of 25 and 50 mg/kg during the critical time window significantly facilitated the extinction of morphine-reward related behavior in free access and confined conditioned place preference (CPP) extinction paradigms, and subsequently, it prevented reinstatement and spontaneous recovery of morphine-induced CPP in mice. Intriguingly, the berberine treatment with or without extinction training altered expression of plasticity-related proteins such as brain-derived neurotrophic factor (BDNF), AMPA receptors (GluA1 and GluA2) in the nucleus accumbens (NAc). Moreover, the post-extinction berberine treatment significantly reduced reinstatement of cocaine-induced CPP and operant intravenous self-administration (IVSA) memories in rats. Altogether, our findings suggest that extinction training combined with the postextinction berberine treatment can facilitate extinction of drug-associated behavior making it an attractive therapeutic candidate in relapse prevention.
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