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Currently, experimental animals are widely used in biological and medical research. However, the scientific community has raised several bioethical concerns, such as the number of animals required to achieve reproducible and statistically relevant results. These concerns involve aspects related to pain, discomfort, and unwanted animal loss. Retrospectively, we compare two different approaches for anesthesia dosage: a mobile app for dose calculation and a standard dose calculation. A total of 939 C57BL/6J and Swiss mice were analyzed. We collected data on intraoperative and anesthesia-related mortality as described in electronic or physical handwritten records. Our results showed that the mobile app approach significantly reduces anesthetic-related deaths upon using doses of ketamine and xylazine. The results suggest that anesthesia-related mortality can be minimized even more using information technology approaches, helping to solve an old but transversal challenge for researchers working with experimental mice. The mobile app is a free and open code which could be implemented worldwide as an essential requirement for all anesthetic procedures in mice using xylazine and ketamine combination. As an open code app, the Labinsane initiative could also represent the starting point to unify and validate other anesthetic procedures in different species and strains.
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Mounting evidence showing that local nitric oxide (NO) delivery may significantly improve the wound healing process has stimulated the development of wound dressings capable of releasing NO topically. Herein, we describe the preparation of a self-expandable NO-releasing hydrolyzed collagen sponge (CS), charged with the endogenously found NO donor, S-nitrosoglutathione (GSNO). We show that cold pressed and GSNO-charged CS (CS/GSNO) undergo self-expansion to its original 3D shape upon water absorption to a swelling degree of 2,300 wt%, triggering the release of free NO. Topical application of compressed CS/GSNO on wounds in an animal model showed that exudate absorption by CS/GSNO leads to the release of higher NO doses during the inflammatory phase and progressively lower NO doses at later stages of the healing process. Moreover, treated animals showed significant increase in the mRNA expression levels of monocyte chemoattractant protein-1 (MCP-1), murine macrophage marker (F4/80), transforming growth factor beta (TGF-ß), stromal cell-derived factor 1 (SDF-1), insulin-like growth factor-1 (IGF-1), nitric oxide synthase(iNOS), and matrix metalloproteinase(MMP-9). Cluster differentiation 31 (CD31), vascular endothelial growth factor (VEGF), and F4/80 were measured on Days 7 and 12 by immunohistochemistry in the cicatricial tissue. These results indicate that the topical delivery of NO enhances the migration and infiltration of leucocytes, macrophages, and keratinocytes to the wounded tissue, as well as the neovascularization and collagen deposition, which are correlated with an accelerated wound closure. Thus, self-expandable CS/GSNO may represent a novel biocompatible and active wound dress for the topical delivery of NO on wounds.
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Colágeno , Óxido Nítrico , S-Nitrosoglutatión , Cicatrización de Heridas/efectos de los fármacos , Heridas y Lesiones , Animales , Colágeno/química , Colágeno/farmacología , Modelos Animales de Enfermedad , Implantes de Medicamentos/química , Implantes de Medicamentos/farmacocinética , Implantes de Medicamentos/farmacología , Masculino , Ratones , Óxido Nítrico/química , Óxido Nítrico/farmacocinética , Óxido Nítrico/farmacología , S-Nitrosoglutatión/química , S-Nitrosoglutatión/farmacocinética , S-Nitrosoglutatión/farmacología , Heridas y Lesiones/tratamiento farmacológico , Heridas y Lesiones/metabolismo , Heridas y Lesiones/patologíaRESUMEN
Topical nitric oxide (NO) delivery has been shown to accelerate wound healing. However, delivering NO to wounds at appropriate rates and doses requires new biomaterial-based strategies. Here, we describe the development of supramolecular interpolymer complex hydrogels comprising PEO-PPO-PEO (F127) micelles embedded in a poly(acrylic acid) (PAA) matrix, with S-nitrosoglutathione (GSNO) molecules dissolved in the hydrophilic domain. We show that PAA:F127/GSNO hydrogels start releasing NO upon hydration at rates controlled by their rates of water absorption. SAXS measurements indicate that the supramolecular structure of the hydrogels retains long-range order domains of F127 micelles. The PAA/F1227 hydrogels displayed dense morphologies and reduced rates of hydration. The NO release rates remain constant over the first 200â¯min, are directly correlated with the hydration rates of the PAA:F127/GSNO hydrogels, and can be modulated in the range of 40â¯nmol/gâ¯h to 1.5⯵mol/gâ¯h by changing the PAA:F127 mass ratio. Long-term NO-release profiles over 5â¯days are governed by the first-order exponential decay of GSNO, with half-lives in the range of 0.5-3.4â¯days. A preliminary in vivo study on full-thickness excisional wounds in mice showed that topical NO release from the PAA:F127/GSNO hydrogels is triggered by exudate absorption and leads to increased angiogenesis and collagen fiber organization, as well as TGF-ß, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue. In summary, these results suggest that hydration-controlled NO release from topical PAA:F127/GSNO hydrogels is a potential strategy for enhancing wound healing. STATEMENT OF SIGNIFICANCE: The topical delivery of nitric oxide (NO) to wounds may provide significant beneficial results and represent a promising strategy to treat chronic wounds. However, wound dressings capable of releasing NO after application and allowing the modulation of NO release rates, demand new platforms. Here, we describe a novel strategy to overcome these challenges, based on the use of supramolecular poly(acrylic acid) (PAA):F127 hydrogels charged with the NO donor S-nitrosoglutathione (GSNO) from whereby the NO release can be triggered by exudate absorption and delivered to the wound at rates controlled by the PAA:F127 mass ratio. Preliminary in vivo results offer a proof of concept for this strategy by demonstrating increased angiogenesis; collagen fibers organization; and TGF-ß, IGF-1, SDF-1, and IL-10 gene expressions in the cicatricial tissue after topical treatment with a PAA:F127/GSNO hydrogel.
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Resinas Acrílicas , Hidrogeles , Óxido Nítrico , Polietilenos , Polipropilenos , Cicatrización de Heridas/efectos de los fármacos , Heridas y Lesiones , Resinas Acrílicas/farmacocinética , Resinas Acrílicas/farmacología , Animales , Citocinas/biosíntesis , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacocinética , Hidrogeles/farmacología , Ratones , Micelas , Óxido Nítrico/química , Óxido Nítrico/farmacocinética , Óxido Nítrico/farmacología , Polietilenos/química , Polietilenos/farmacocinética , Polietilenos/farmacología , Polipropilenos/química , Polipropilenos/farmacocinética , Polipropilenos/farmacología , S-Nitrosoglutatión/química , S-Nitrosoglutatión/farmacocinética , S-Nitrosoglutatión/farmacología , Heridas y Lesiones/tratamiento farmacológico , Heridas y Lesiones/metabolismo , Heridas y Lesiones/patologíaRESUMEN
RESUMO Objetivo Mensurar a carga de trabalho de enfermagem requerida por pacientes submetidos ao transplante de células-tronco hematopoiéticas (TCTH), autólogo e alogênico e analisar as atividades do Nursing Activities Score (NAS) executadas pela equipe de enfermagem durante a internação para o TCTH. Método Coorte prospectiva realizada de janeiro/2013 a abril/2014 com 62 pacientes internados na unidade de TCTH de um hospital universitário de Campinas/SP, Brasil. Mediu-se a carga de trabalho por meio do NAS e analisaram-se os dados utilizando os testes Qui-quadrado ou Exato de Fisher, Mann-Whitney e o coeficiente de correlação de Spearman; considerou-se nível de significância de 5%. Resultados A média da carga de trabalho de enfermagem foi de 67,3% (DP 8,2) em pacientes de TCTH autólogo e de 72,4% (DP 13,0) no TCTH alogênico (p=0,1380). O item Monitorização e controles apontou, em mais de 50% das observações, que os pacientes demandaram intensificação deste cuidado, exigindo duas horas ou mais em algum turno de trabalho por motivos de segurança, gravidade ou terapia. Conclusão A carga de trabalho de enfermagem e os itens do NAS mais pontuados refletem a magnitude, complexidade e especificidade dos cuidados demandados pelos pacientes submetidos ao TCTH.
RESUMEN Objetivo Medir la carga de trabajo de enfermería requerida por los pacientes sometidos al trasplante de células madre hematopoyéticas (TCTH), autólogo y alogénico, analizando actividades del Nursing Activities Score (NAS) emprendidas por equipo de enfermería en la internación para el TCTH. Método Cohorte prospectiva realizada entre enero/2013 y abril/2014 con 62 pacientes internados en la unidad de TCTH de hospital universitario en la ciudad de Campinas/SP (BR). En el análisis se utilizaron las pruebas Chi-cuadrado o test Exacto de Fisher, las no paramétricas Mann-Whitney o Kruskal-Wallis y el coeficiente de correlación de Spearman, conforme apropiado. Fijos los niveles de significación en 5%. Resultados La media de la carga de trabajo fue de 67,3% (DP 8,2) para los pacientes de TCTH autólogo y de 72,4% (DP 13,0) para los de TCTH alogénico (p=0,1380). El ítem Monitorización y controles apuntó que los pacientes, en más 50% de las observaciones, demandaban intensificación del cuidado por dos horas o más en algunos turnos de trabajo por cuestiones de seguridad, gravedad o terapia. Conclusión La carga de trabajo en enfermería y los ítems del NAS puntuados reflejan la magnitud, complejidad y especificidad de los cuidados demandados por los pacientes sometidos al TCTH.
ABSTRACT Objective Measure nursing workload required by patients submitted to autologous and allogeneic hematopoietic stem cell transplantation (HSCT) and analyze the Nursing Activities Score (NAS) of the nursing team during the hospitalization period for HSCT. Method A prospective cohort study conducted from January 2013 to April 2014 with 62 patients hospitalized in the HSCT unit of a university hospital in Campinas, São Paulo, Brazil. The workload was measured through NAS and data analysis was through chi-square test or Fisher’s exact test, Mann-Whitney test and Spearman’s correlation coefficient; with 5% significance level. Results Mean nursing workload was 67.3% (SD of 8.2) in autologous HSCT patients and 72.4% (SD of 13.0) in allogeneic HSCT patients (p=0.1380).Monitoring and titration showed, in more than 50% of the time, patients demanded intensified care, requiring two hours or more in a nursing shift for reasons of safety, severity or therapy. Conclusion The nursing workload and the NAS items with the highest scores reflect the magnitude, complexity and specificity of care required by patients submitted to HSCT.
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Humanos , Costos y Análisis de Costo , Industria Farmacéutica/economía , Factores Inmunológicos/economía , Inmunosupresores/economía , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/economía , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/economíaRESUMEN
Objective Measure nursing workload required by patients submitted to autologous and allogeneic hematopoietic stem cell transplantation (HSCT) and analyze the Nursing Activities Score (NAS) of the nursing team during the hospitalization period for HSCT. Method A prospective cohort study conducted from January 2013 to April 2014 with 62 patients hospitalized in the HSCT unit of a university hospital in Campinas, São Paulo, Brazil. The workload was measured through NAS and data analysis was through chi-square test or Fisher's exact test, Mann-Whitney test and Spearman's correlation coefficient; with 5% significance level. Results Mean nursing workload was 67.3% (SD of 8.2) in autologous HSCT patients and 72.4% (SD of 13.0) in allogeneic HSCT patients (p=0.1380).Monitoring and titration showed, in more than 50% of the time, patients demanded intensified care, requiring two hours or more in a nursing shift for reasons of safety, severity or therapy. Conclusion The nursing workload and the NAS items with the highest scores reflect the magnitude, complexity and specificity of care required by patients submitted to HSCT.
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Introdução: O transplante de células-tronco hematopoiéticas (TCTH) tornou-se um procedimento terapêutico mundialmente aceito sobretudo pelo impacto positivo na sobrevida e na qualidade de vida dos pacientes com doenças onco-hematológicas. No entanto, a mortalidade ainda é alta e influenciada por fatores de natureza individual e terapêutica. Objetivo: Analisar a mortalidade relacionada ao transplante (MRT) nos pacientes submetidos ao TCTH e seus fatores associados. Método: Coorte prospectiva realizada com 60 pacientes internados na unidade de TCTH do Hospital de Clínicas da Universidade Estadual de Campinas. Os dados foram obtidos pela análise diária dos prontuários. A variável dependente foi a MRT e as variáveis independentes foram demográficas e de evolução clínicas, incluindo escore de risco pré-TCTH (EBMT) e o SAPS II. Na análise dos dados foram utilizados os testes Qui-quadrado, Exato de Fisher, o teste t de Student e Mann-Whitney. Na análise da MRT utilizou-se o método de kaplan-Meier e o Modelo de Cox. Considerou-se nível de significância igual a 5%. Resultados: A MRT foi de 15% aos cem dias do TCTH, de 18,9% no grupo de pacientes de TCTH alogênico e de 8,7% para os de TCTH autólogo. A infecção foi a principal causa de óbito. Na amostra, o tempo médio de sobrevida dos pacientes foi de 83,2 dias (DP 32,7).No grupo de pacientes não sobreviventes a maioria pertencia ao sexo masculino, com média de idade de 48,7 anos e diagnóstico principal de leucemia. Quanto à gravidade destes pacientes, o escore de risco pré-TCTH (EBMT) foi de 4,1 pontos e do SAPS II geral foi de 52,6 pontos, o que correspondeu a um risco médio de morte de de 38,4%. Os fatores associados à MRT, em cem dias, foram faixa etária (p=0,0306), presença de infecção (p=0,0216), número de infecções (p=0,0386), ocorrência de enxertia (p<0,0001), uso de ventilação mecânica (p<0,0001) e de drogas vasoativas (p<0,0001). O índice de gravidade SAPS II foi fator preditor para MRT (p=0,0001). Conclusão: O índice de gravidade SAPS II, preditor para MRT em cem dias, mostrou que o paciente submetido ao TCTH é grave e necessita de cuidado especializado e intensivo.
Hematopoietic stem cells transplantation (HSCT) has become a therapeutic procedure accepted worldwide, particularly because of its positive impact on survival and quality of life of patients with onco-hematological diseases. However, the mortality is still high and it is influenced by factors of individual and therapeutic kinds. Objective: To analyze the transplant-related mortality (TRM) on patients submitted to HSCT and its associated factors. Methodology: Prospective cohort study with 60 patients hospitalized in the HSTC unit of the Clinical Hospital of the State University of Campinas (Unicamp). Data was obtained by daily analysis of the medical records. The dependent variable was the TRM and the independent variables were demographic and clinical development, including pre-HSCT risk score (EBMT) and SAPS II. For data analysis were used the Chi-square, Fishers exact tests, Students t-test, Mann-Whitney. On TRM analysis were used Kaplan-Meier and Cox Model method. It was considered a significance level of 5%. Results: The TRM was 15% to a hundred days of HSCT, 18,9% to allogeneic HSCT patients and 8,7% to autologous HSCT.Infection was the main cause of death. In the sample, the median survival time of the patients was 83,2 days (DP 32,7). In the group of non-surviving patients the most were male, with an average age of 48,7 years and the main diagnosis was leukemia. Regarding to the severity of these patients, the pre-HSCT risk score (EBMT) was 4,1 points and general SAPS II was 52,6 points, which corresponds to an average death risk of 38,4%. The TRM associated factors on a hundred days were age (p=0,0306), presence of infection (p=0,0216), number of infections (p=0,0386), occurrence of grafting (p<0,0001), mechanical ventilation use (p<0,0001) and vasoactive drugs (p<0,0001). The severity rate SAPS II was a predictive factor for TRM (p=0,0001). Conclusion: The severity rate SAPS II was predictive for TRM on a hundred days and showed that the patient submitted to HSCT is severe and demands specialized and intensive care.