Effects of Pregnanolone Glutamate and Its Metabolites on GABAA and NMDA Receptors and Zebrafish Behavior.

Multiple molecular targets have been identified to mediate membrane-delimited and nongenomic effects of natural and synthetic steroids, but the influence of steroid metabolism on neuroactive steroid signaling is not well understood. To begin to address this question, we set out to identify major metabolites of a neuroprotective synthetic steroid 20-oxo-5ß-pregnan-3α-yl l-glutamyl 1-ester (pregnanolone glutamate, PAG) and characterize their effects on GABAA and NMDA receptors (GABARs, NMDARs) and their influence on zebrafish behavior. Gas chromatography-mass spectrometry was used to assess concentrations of PAG and its metabolites in the hippocampal tissue of juvenile rats following intraperitoneal PAG injection. PAG is metabolized in the peripheral organs and nervous tissue to 20-oxo-17α-hydroxy-5ß-pregnan-3α-yl l-glutamyl 1-ester (17-hydroxypregnanolone glutamate, 17-OH-PAG), 3α-hydroxy-5ß-pregnan-20-one (pregnanolone, PA), and 3α,17α-dihydroxy-5ß-pregnan-20-one (17-hydroxypregnanolone, 17-OH-PA). Patch-clamp electrophysiology experiments in cultured hippocampal neurons demonstrate that PA and 17-OH-PA are potent positive modulators of GABARs, while PAG and 17-OH-PA have a moderate inhibitory effect at NMDARs. PAG, 17-OH-PA, and PA diminished the locomotor activity of zebrafish larvae in a dose-dependent manner. Our results show that PAG and its metabolites are potent modulators of neurotransmitter receptors with behavioral consequences and indicate that neurosteroid-based ligands may have therapeutic potential.

Conceptions and practices of an integrative treatment for substance use disorders involving Amazonian medicine: traditional healers' perspectives

Objective: The harmful use of psychoactive substances represents one of today's largest public health problems. Yet, in spite of its global relevance, current treatment for substance use disorders (SUDs) is still not entirely successful. The purpose of this study was to investigate alternative treatments and conceptions from traditional Amazonian medicine adapted to SUDs. Methods: We conducted semi-structured interviews with 13 practicing experts at a well-established addiction treatment center in the Peruvian Amazon and performed qualitative content analysis on the collected data. Main categories were deductively defined and corresponding subcategories inductively developed. Results: Our findings revealed characteristic features and consequences, causes and antecedents, and treatment methods of SUDs as the main categories. Overall, concepts of disease etiology bore resemblance with contemporary biopsychosocial models of SUDs. The Amazonian therapeutic means however differed markedly from current Western ones. The main methods involved dietary retreats, healing ceremonies, and purging rituals. The integral application of Amazonian methods, as well as their traditional implementation according to prescribed ritual protocols, were emphasized by the experts as crucial for efficacy and safety of treatment delivery. Conclusion: We suggest further scientific attention to these therapies, including clinical studies, for which our results provide conceptual underpinnings. Findings from this research expand the cross-cultural understanding of SUDs and, in the long run, may enhance its treatment options.

Conceptions and practices of an integrative treatment for substance use disorders involving Amazonian medicine: traditional healers' perspectives.

OBJECTIVE: The harmful use of psychoactive substances represents one of today's largest public health problems. Yet, in spite of its global relevance, current treatment for substance use disorders (SUDs) is still not entirely successful. The purpose of this study was to investigate alternative treatments and conceptions from traditional Amazonian medicine adapted to SUDs. METHODS: We conducted semi-structured interviews with 13 practicing experts at a well-established addiction treatment center in the Peruvian Amazon and performed qualitative content analysis on the collected data. Main categories were deductively defined and corresponding subcategories inductively developed. RESULTS: Our findings revealed characteristic features and consequences, causes and antecedents, and treatment methods of SUDs as the main categories. Overall, concepts of disease etiology bore resemblance with contemporary biopsychosocial models of SUDs. The Amazonian therapeutic means however differed markedly from current Western ones. The main methods involved dietary retreats, healing ceremonies, and purging rituals. The integral application of Amazonian methods, as well as their traditional implementation according to prescribed ritual protocols, were emphasized by the experts as crucial for efficacy and safety of treatment delivery. CONCLUSION: We suggest further scientific attention to these therapies, including clinical studies, for which our results provide conceptual underpinnings. Findings from this research expand the cross-cultural understanding of SUDs and, in the long run, may enhance its treatment options.

["I want to die" ­ dealing with suicidal wishes in primary palliative care]. / "Ich möchte sterben" - Zum Umgang mit Suizidwünschen in der hausärztlichen Palliativbetreuung.

Different attitudes towards, and ideas about the end of life, represent an often experienced challenge in palliative care provided by family doctors. If values diverge too strongly, considerable strain can originate from it for the health care professionals, in particular if it is about assisted suicide. How do family doctors experience the incompatibility between patients' wishes and personal values? How do they succeed to bridge value divergences? Based on group discussions with family doctors in Switzerland the contribution focusses on these questions and identifies different strategies of family doctors. The results indicate that in particular 'convergence of perspectives' with patients can reduce the strain for family doctors and can at the same time guarantee high quality of care.

De las ciudadanías formales a las vindicaciones sociales por el derecho al agua en la ciudad: relaciones complejas entre agua, hábitat y ciudad / From formal citizenships to social claims for right to water in the city: complex relationships between water, habitat and city / Das cidadanias formales as reivindicações sociais pelo direito à água na cidade:relações complexas entre água, habitat e a cidade

El presente artículo de revisión es el resultado de la investigación titulada "Prácticas sociales del agua en Bogotá. Tras la adversa cultura del agua y los estilos de vida bogotanos (1850-1888)". En este texto se encontrará una revisión conceptual a la problemática sobre los usos sociales del agua en torno a las categorías hábitat y significaciones del agua en la ciudad. El despliegue de estos conceptos propone una metodología basada en el análisis documental dirigida a la rehistorización de las prácticas de los bogotanos en torno a los usos sociales del agua, de la higiene y de sus costumbres con relación a la ciudadanía y al discurso de la civilización.

This article presents the first steps of a research project entitled "Social practices of water in Bogotá. After the adverse water culture and Bogotan lifestyles (1850-1888)". Here is initially a conceptual reviewing to the approach of social uses of water around the habitat categories and meanings of water in the city, fundamental categories that will serve to track, along with a documentary analysis methodology accounts of foreign travelers in the nineteenth century, the practices of the Bogotan citizens of this time around the social uses of water, hygiene and customs in relation to citizenship and the discourse of civilization.

Este artigo recolhe os primeiros avanços de pesquisa intitulado "Práticas sociais da água em Bogotá. Após a cultura adversa da água e os estilos de vida de Bogotá (1850-1888)". Aqui é feita inicialmente uma revisão conceitual para a abordagem dos usos sociais da agua em torno das categorias de habitats e os significados da água na cidade, categorías fundamentais que serão usados para rastrear, juntamente com uma metodologia de análise documental dos relatos de viajantes estrangeiros no século XIX, as práticas dos bogotanos desta época sobre os usos sociais da agua, higiene e seus hábitos em relação a cidadania e ao o discurso da civilização.

Tissue and cell-specific transcriptional activity of the human cytomegalovirus immediate early gene promoter (UL123) in zebrafish.

The human cytomegalovirus (CMV) is a member of the herpesvirus superfamily and causes different diseases including encephalitis, gastrointestinal diseases, pneumonitis, hepatitis, and retinitis. The immediate early (IE) gene of the human cytomegalovirus is essential to the viral replication. The proximal promoter region of this gene behaves as a strong enhancer and was commonly used to overexpress genes in vitro and in vivo in numerous cell types and species. However, there was no detailed report on the spatial and temporal transcriptional activity of the human CMV-IE gene promoter in zebrafish. In the present study, we generated stable transgenic zebrafish lines carrying the eGFP reporter gene under the control of the human CMV-IE gene promoter (-602/-14). We demonstrated that the hCMV-IE:eGFP transgene was expressed in numerous tissues but transgene expression was either regionalized or restricted to specific cell types as embryo and larval development progressed. In adult, the global expression pattern was similar but not identical to that described for the simian CMV-IE gene promoter in stable zebrafish with high transgene expression in the spinal cord, olfactory organs, central nervous system, neuromasts, retina, and skeletal muscles. However, we describe additional major expression sites in the hepatocytes, the epithelial cells of the intestine, the epithelial cells of the renal tubules, and the oocytes. Interestingly, our study shows that the tissue and cell specific expression pattern of the human CMV-IE gene promoter is rather well conserved in stable transgenic zebrafish compared to that observed in mouse. The major expression sites described in zebrafish are in agreement with the targeted cells and symptoms resulting from CMV infections in human. Finally, the hCMV:eGFP transgenic lines described in the present study will be valuable tools to trace specific cell lineages in adult zebrafish.