ACUTE KIDNEY INJURY CAUSED BY Crotalus AND Bothrops SNAKE VENOM: A REVIEW OF EPIDEMIOLOGY, CLINICAL MANIFESTATIONS AND TREATMENT

SUMMARY Ophidic accidents are an important public health problem due to their incidence, morbidity and mortality. An increasing number of cases have been registered in Brazil in the last few years. Several studies point to the importance of knowing the clinical complications and adequate approach in these accidents. However, knowledge about the risk factors is not enough and there are an increasing number of deaths due to these accidents in Brazil. In this context, acute kidney injury (AKI) appears as one of the main causes of death and consequences for these victims, which are mainly young males working in rural areas. Snakes of the Bothrops and Crotalus genera are the main responsible for renal involvement in ophidic accidents in South America. The present study is a literature review of AKI caused by Bothrops and Crotalus snake venom regarding diverse characteristics, emphasizing the most appropriate therapeutic approach for these cases. Recent studies have been carried out searching for complementary therapies for the treatment of ophidic accidents, including the use of lipoic acid, simvastatin and allopurinol. Some plants, such as Apocynaceae, Lamiaceae and Rubiaceae seem to have a beneficial role in the treatment of this type of envenomation. Future studies will certainly find new therapeutic measures for ophidic accidents

A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol

EPIDEMIOLOGICAL PROFILE OF SNAKEBITE ACCIDENTS IN A METROPOLITAN AREA OF NORTHEAST BRAZIL

SUMMARY The aim of this study was to describe the epidemiological profile of snakebite accidents reported by the toxicological assistance center in Fortaleza, Ceará, Brazil. Database information on snakebite accidents was analyzed regarding the period from January 2003 to December 2011. A total of 1063 cases were found. The accidents occurred during the rainy months (March, April and May), in urban areas (52.3%), affecting individuals younger than 50 years and predominantly among males (70.7%). The lower limbs were the most frequently affected body area (33.7%). Most accidents involved non-venomous snakes (76.1%). The genus Bothrops was the main one involved in venomous accidents (83%). It is expected that this study can be used as the substrate to improve healthcare surveillance and implementing better measures for the treatment of this population

Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T). METHODS: In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn. RESULTS: From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocality (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death. CONCLUSION: s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy

Expansion of Cord Blood CD34+ Cells in Presence of zVADfmk and zLLYfmk Improved Their In Vitro Functionality and In Vivo Engraftment in NOD/SCID Mouse

BACKGROUND: Cord blood (CB) is a promising source for hematopoietic stem cell transplantations. The limitation of cell dose associated with this source has prompted the ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs). However, the expansion procedure is known to exhaust the stem cell pool causing cellular defects that promote apoptosis and disrupt homing to the bone marrow. The role of apoptotic machinery in the regulation of stem cell compartment has been speculated in mouse hematopoietic and embryonic systems. We have consistently observed an increase in apoptosis in the cord blood derived CD34(+) cells cultured with cytokines compared to their freshly isolated counterpart. The present study was undertaken to assess whether pharmacological inhibition of apoptosis could improve the outcome of expansion. METHODOLOGY/PRINCIPAL FINDINGS: CB CD34(+) cells were expanded with cytokines in the presence or absence of cell permeable inhibitors of caspases and calpains; zVADfmk and zLLYfmk respectively. A novel role of apoptotic protease inhibitors was observed in increasing the CD34(+) cell content of the graft during ex vivo expansion. This was further reflected in improved in vitro functional aspects of the HSPCs; a higher clonogenicity and long term culture initiating potential. These cells sustained superior long term engraftment and an efficient regeneration of major lympho-myeloid lineages in the bone marrow of NOD/SCID mouse compared to the cells expanded with growth factors alone. CONCLUSION/SIGNIFICANCE: Our data show that, use of either zVADfmk or zLLYfmk in the culture medium improves expansion of CD34(+) cells. The strategy protects stem cell pool and committed progenitors, and improves their in vitro functionality and in vivo engraftment. This observation may complement the existing protocols used in the manipulation of hematopoietic cells for therapeutic purposes. These findings may have an impact in the CB transplant procedures involving a combined infusion of unmanipulated and expanded grafts

Concepts of Health in Nursing Education in Undergraduate Schools of Brazil and Portugal

This article represents an extract of my PhD research regarding the concepts of health present in undergraduate schools of nursing of Brazil and Portugal. The objective of this research was to comprehend how the concepts of health are explicit in the documents of undergraduate courses and how they are expressed in the discourses of the nursing professors and students. For this, thematic content analysis was used to analyze the professional education of the nurses and the concepts of health present in the nursing courses. The presentation of the results was performed using the Collective Subject Discourse technique. The results showed that in the state of Santa Catarina in Brazil, the concepts of health follow the National Curriculum Guidelines and there is an emphasis directed towards reflection on the Brazilian National Health System (SUS); while in the city of Porto, in Portugal, these concepts follow the Study Plans of the Nursing courses and emphasize nursing care both for the healthy and the sick person. The data also reveal a concern in the construction of the concept of people-centered healthcare.Este artículo representa una parte de la investigación que realicé durante el doctorado sobre las concepciones de salud presentes en escuelas de graduación en enfermería de Brasil y Portugal. El objetivo de esta investigación fue comprender como las concepciones sobre la salud están explícitas en los documentos de los cursos de graduación y de qué forma se expresan en los discursos de los profesores y estudiantes de enfermería. Para esto, utilizamos el análisis de contenido temático sobre la educación profesional de los enfermeros y sobre las concepciones de la salud presentes en los cursos de enfermería. La presentación de los resultados fue realizada a través del Discurso del Sujeto Colectivo. Los resultados apuntaron que, en el estado de Santa Catarina, en Brasil, las concepciones de salud siguen las Directrices Curriculares Nacionales y existe un énfasis dirigido a reflexionar sobre el Sistema Único de Salud; en cuanto en la ciudad de Porto, en Portugal, esas concepciones siguen los Planos de Estudios de los cursos de Enfermería y se enfatiza el cuidado de Enfermería tanto a la persona saludable como a la enferma. Los datos revelan, también, una preocupación en la construcción del concepto de salud centrado en las personas.Este artigo representa um recorte de pesquisa de doutorado a respeito das concepções de saúde, presentes em escolas de graduação em enfermagem do Brasil e de Portugal. O objetivo foi compreender como as concepções de saúde estão explícitas nos documentos dos cursos de graduação e de que forma se expressam nos discursos dos professores e estudantes de enfermagem. Para tanto, utilizou-se análise de conteúdo temática sobre a educação profissional dos enfermeiros e sobre as concepções de saúde presentes nos cursos de enfermagem. A apresentação dos resultados foi realizada através do Discurso do Sujeito Coletivo. Os resultados apontaram que, no Estado de Santa Catarina, no Brasil, as concepções de saúde seguem as Diretrizes Curriculares Nacionais e há ênfase dirigida à reflexão sobre o Sistema Único de Saúde; enquanto na cidade do Porto, em Portugal, tais concepções seguem os Planos de Estudos dos Cursos de Enfermagem e se enfatiza o cuidado de Enfermagem tanto à pessoa saudável quanto à doente. Os dados revelam, ainda, preocupação na construção do conceito de saúde centrado na pessoa