ABSTRACT
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Subject(s)
Humans , Male , Female , Adult , Middle Aged , Outcome and Process Assessment, Health Care , Home Care Services, Hospital-Based , Mental Disorders/therapy , Suicide, Attempted , Socioeconomic Factors , SpainABSTRACT
Schizophrenia (SCZ) has been associated with serotonergic and endocannabinoid systems dysregulation, but difficulty in obtaining in vivo neurological tissue has limited its exploration. We investigated CB1R-5-HT2AR heteromer expression and functionality via intracellular pERK and cAMP quantification in olfactory neuroepithelium (ON) cells of SCZ patients non-cannabis users (SCZ/nc), and evaluated whether cannabis modulated these parameters in patients using cannabis (SCZ/c). Results were compared vs healthy controls non-cannabis users (HC/nc) and healthy controls cannabis users (HC/c). Further, antipsychotic effects on heteromer signaling were tested in vitro in HC/nc and HC/c. Results indicated that heteromer expression was enhanced in both SCZ groups vs HC/nc. Additionally, pooling all 4 groups together, heteromer expression correlated with worse attentional performance and more neurological soft signs (NSS), indicating that these changes may be useful markers for neurocognitive impairment. Remarkably, the previously reported signaling properties of CB1R-5-HT2AR heteromers in ON cells were absent, specifically in SCZ/nc treated with clozapine. These findings were mimicked in cells from HC/nc exposed to clozapine, suggesting a major role of this antipsychotic in altering the quaternary structure of the CB1R-5-HT2AR heteromer in SCZ/nc patients. In contrast, cells from SCZ/c showed enhanced heteromer functionality similar to HC/c. Our data highlight a molecular marker of the interaction between antipsychotic medication and cannabis use in SCZ with relevance for future studies evaluating its association with specific neuropsychiatric alterations.
Subject(s)
Antipsychotic Agents/pharmacology , Cannabinoid Receptor Agonists/pharmacology , Dronabinol/pharmacology , Marijuana Use , Neuroepithelial Cells , Olfactory Receptor Neurons , Receptor, Cannabinoid, CB1 , Receptor, Serotonin, 5-HT2A , Schizophrenia/metabolism , Adult , Cannabinoid Receptor Agonists/blood , Cells, Cultured , Clozapine/pharmacology , Cross-Sectional Studies , Dronabinol/blood , Female , Humans , Male , Neuroepithelial Cells/drug effects , Neuroepithelial Cells/metabolism , Olfactory Receptor Neurons/drug effects , Olfactory Receptor Neurons/metabolism , Receptor, Cannabinoid, CB1/drug effects , Receptor, Cannabinoid, CB1/metabolism , Receptor, Serotonin, 5-HT2A/drug effects , Receptor, Serotonin, 5-HT2A/metabolism , Young AdultABSTRACT
INTRODUCTION: Soft-tissue sarcomas (STS) are a heterogeneous group of diseases that are characterized by a historic lack of active treatment options. However, several new drugs and indications have become available in recent years. AREAS COVERED: This article reviews the most relevant phase II studies that utilize chemotherapy agents (aldoxorubicin, amrubicin, trabectedin alone or in combination with doxorubicin, and gemcitabine plus docetaxel), targeted therapies (Imatinib, dasatinib, regorafenib, tivozanib, palbociclib and selinexor), a combination of chemotherapy plus targeted therapies (fucusing on doxorubicin plus olaratumab) and immunotherapies (pembrolizumab, combination of nivolumab plus ipilimumab and adaptive cell therapy) in STS (other than gastrointestinal stromal tumors) (GIST) published from 2015. Some of these strategies are under further clinical development or will likely be assessed in future phase III studies. EXPERT OPINION: A series of novel treatments have shown encouraging results in STS in recent years. The most important is the combination of the standard cytotoxic agent doxorubicin plus the platelet-derived growth factor receptor (PDGFR) inhibitor olaratumab, although definitive results from a phase III trial are expected. Immunotherapy has not been as successful in STS so far. However, further investigations are ongoing.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Drugs, Investigational/administration & dosage , Sarcoma/drug therapy , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Clinical Trials, Phase II as Topic , Drug Design , Drugs, Investigational/pharmacology , Humans , Immunotherapy/methods , Molecular Targeted Therapy , Sarcoma/pathologyABSTRACT
Database URL: http://www.psygenet.org. PsyGeNET corpus: http://www.psygenet.org/ds/PsyGeNET/results/psygenetCorpus.tar.
Subject(s)
Data Curation/methods , Data Mining/methods , Databases, Genetic , Mental Disorders/genetics , Software , HumansABSTRACT
Se realizó un estudio descriptivo transversal, en el policlínico Camilo Torres Restrepo de Santiago de Cuba, en el periodo de Enero a Julio de 2008; con el objetivo de describir el comportamiento de las Urgencias Médicas en la APS, identificando las urgencias más frecuentes, así como la nueva aplicación del tratamiento trombolítico en nuestro policlínico de nuevo tipo. El universo estuvo constituido por 182 personas atendidas en la Sala de Emergencia del policlínico, de la cual se estudiaron 65 pacientes ingresados en dicha sala siguiendo los criterios de inclusión y exclusión. Se utilizaron variables cualitativas como Urgencias médicas y Preparación, y variables cuantitativas como Aplicación de Trombolisis y Defunciones. Se demostró que la patología que más pacientes aportó a la sala de Emergencia de nuestro policlínico, fue el infarto agudo del miocardio (IMA), el accidente vascular encefálico además de la emergencia hipertensiva. También se aplicó el tratamiento trombolítico, reperfusor de doce pacientes con IMA a tres para un 25 por ciento. Además no hubo defunciones en el sistema y solo se registraron 7 defunciones después de remitidos al hospital de 65 pacientes para un 11.0 por ciento. En cuanto a la preparación, se demostró que la mayor parte del personal se encontraba preparada para brindar estos nuevos servicios a la población. Todos estos nuevos servicios conllevan a mejorar la calidad de vida de los pacientes, disminuyendo las defunciones en este subsistema y teniendo en cuenta siempre la preparación de todo el personal relacionado con la atención en la salud(AU)
