RESUMO
Ketamine, a non-competitive N-methyl-d-aspartate receptor antagonist, is commonly used as an anesthetic and analgesic but has recently shown promising research in treating certain psychiatric conditions such as depression, post-traumatic stress disorder (PTSD), suicidal ideation, and substance use disorder. Due to its euphoric, dissociative, and hallucinogenic properties, ketamine has been abused as a recreational drug, which has led to rigid regulation of medication. The COVID-19 pandemic has been an unprecedented challenge for the American population which was reflected in increased reports of problems regarding their mental health. Mood disorders have dramatically increased in the past two years. Approximately one in ten people stated that they had started or increased substance use because of the COVID-19 pandemic. Furthermore, rates of suicidal ideation have significantly increased when compared to pre-pandemic levels, with more than twice the number of adults surveyed in 2018 indicating suicidal thoughts "within the last 30 days" at the time they were surveyed. Moreover, many responders indicated they had symptoms of PTSD. The PubMed database was searched using the keyword "ketamine," in conjunction with "depression," "suicidal ideation," "substance use disorder," and "post-traumatic stress disorder." The inclusion criteria encompassed articles from 2017 to 2022 published in the English language that addressed the relationship between ketamine and mental health disorders. With this sharp increase in the prevalence of psychiatric disorders and an increased public interest in mental health combined with the promise of the therapeutic value of ketamine for certain mental health conditions, including suicidal ideation, this narrative review sought to identify recently published studies that describe the therapeutic uses of ketamine for mental health. Results of this review indicate that ketamine's therapeutic effects offer a potential alternative treatment for depression, suicidal ideation, substance use disorders, and PTSD.
RESUMO
Cardiac troponin I (cTnI) plays a critical role in regulation of cardiac function. Studies have shown that the deficiency of cTnI or mutations in cTnI (particularly in the C-terminus of cTnI) results in diastolic dysfunction (impaired relaxation) due to an increased myofibril sensitivity to calcium. The first clinical study revealing the association between restrictive cardiomyopathy (RCM) with cardiac troponin mutations was reported in 2003. In order to illustrate the mechanisms underlying the cTnI mutation caused cardiomyopathy, we have generated a cTnI gene knockout mouse model and transgenic mouse lines with the reported point mutations in cTnI C-terminus. In this paper, we summarize our studies using these animal models from our laboratory and the other in vitro studies using reconstituted filament and cultured cells. The potential mechanisms underlying diastolic dysfunction and heart failure caused by these cTnI C-terminal mutations are discussed as well. Furthermore, calcium desensitizing in correction of impaired relaxation in myocardial cells due to cTnI mutations is discussed. Finally, we describe a model of translational study, i.e., from bedside to bench and from bench to bedside. These studies may enrich our understanding of the mechanism underlying inherited cardiomyopathies and provide the clues to search for target-oriented medication aiming at the treatment of diastolic dysfunction and heart failure.
