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Oleaginous yeasts are promising platforms for microbial lipids production as a renewable and sustainable alternative to vegetable oils in biodiesel production. In this paper, a thorough in silico assessment of lipid production in batch cultivation by Rhodosporidium toruloides was developed. By means of dynamic flux balance analysis, the traditional two-stage bioprocess (TSB) performed by the native strain was contrasted with one-stage bioprocess (OSB) using four designed strains obtained by gene knockout strategies. Lipid titer, yield, content, and productivity were analyzed at different initial C/N ratios as relevant performance indicators used in bioprocesses. By weighting these indicators, a global lipid efficiency metric (GLEM) was defined to consider different scenarios. Under simulated conditions, designed strains for lipid overproduction in OSB outperformed the TSB in terms of lipid title (up to threefold), lipid yield (up to 2.4-fold), lipid content (up to 2.8-fold, with a maximum of 76%), and productivity (up to 1.3-fold), depending on C/N ratios. Using these efficiency parameters and the proposed GLEM, the process of selecting the most suitable candidates for lipid production could be carried out before experimental assays. This methodology holds the potential to be extended to other oleaginous microorganisms and diverse strain design techniques.
Assuntos
Basidiomycota , Rhodotorula , Basidiomycota/genética , Rhodotorula/genética , Biocombustíveis , LipídeosRESUMO
RESUMEN Introducción: Los factores sociodemográficos y socioculturales influyen en la donación de sangre en diversos países, nuestro objetivo de estudio fue determinar cuáles son los factores que influyen en la donación de sangre en el Perú. El estudio: Se realizó un estudio observacional, transversal en personas entre 18 a 60 años a nivel nacional, se analizaron los datos mediante SPSS v.20 Hallazgos: La muestra de estudio fue de 739 personas, el 50,4% hombres; se determinó que hay buen conocimiento acerca de la donación de sangre con un porcentaje mayor al 50% de preguntas contestadas correctamente, así mismo existe una actitud positiva frente a la donación de sangre Conclusiones: Los factores socioculturales que influyen en la donación de sangre es el desconocimiento, un 40% de los participantes desconoce los requisitos básicos para ser donante de sangre, otro factor es la falsa creencia que al estar tomando medicamentos no se puede donar sangre (47%).
ABSTRACT Background: Sociodemographic and sociocultural factors influence blood donation in various countries, our objective of study was to determine what are the factors that influence blood donation in Peru. The study: An observational, crosssectional study was conducted in people between 18 and 60 years at the national level, the data were analyzed using SPSS v.20 Findings: The study sample was 739 people, 50.4% men; It was determined that there is good knowledge about blood donation with a percentage greater than 50% of questions answered correctly, likewise there is a positive attitude towards blood donation Conclusions: The sociocultural factors that influence blood donation is ignorance, 40% of the participants do not know the basic requirements to be a blood donor, another factor is the false belief. because they are taking medication, they cannot donate blood (47%).
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The ability to modulate the host immune response has allowed some parasites to establish themselves in the tissues of an immunocompetent organism. While some parasite excretion/secretion products (ESPs) were recently reported to induce differentiation of regulatory T cells (Tregs), their identity is not known. This work is aimed to identify and characterize ESPs of Taenia crassiceps cysticerci linked with Treg induction in vivo. ESPs were obtained from cultures of T. crassiceps cysticerci and inoculated in mice, measuring Treg levels by flow cytometry. Proteins in ESPs were analyzed by electrophoresis; then, ESPs were classified as either differential or conserved. Differentially included proteins were MS-sequenced and functionally characterized. Only 4 of 10 ESPs induced Tregs. Proteins with catalytic activity and those involved in immunological processes predominated, supporting the idea that these molecules could play an important role in the induction of Tregs.
Assuntos
Parasitos , Taenia , Animais , Camundongos , Cysticercus , Linfócitos T Reguladores , Citometria de Fluxo , Camundongos Endogâmicos BALB CRESUMO
[This corrects the article DOI: 10.3389/fcell.2022.893099.].
RESUMO
Multiple comorbidities related to arsenic exposure through drinking water continue to be public problems worldwide, principally in chronically exposed populations, such as those in the Comarca Lagunera (CL), Mexico. In addition, this relationship could be exacerbated by an early life exposure through the placenta and later through breast milk. This study conducted a comparative analysis of arsenic levels in multiple biological samples from pregnant women and their neonates in the CL and the comparison region, Saltillo. Total arsenic levels in placenta, breast milk, blood, and urine were measured in pregnant women and their neonates from rural areas of seven municipalities of the CL using atomic absorption spectrophotometry with hydride generation methodology. The average concentrations of tAs in drinking water were 47.7 µg/L and 0.05 µg/L in the exposed and non-exposed areas, respectively. Mean levels of tAs were 7.80 µg/kg, 77.04 µg/g-Cr, and 4.30 µg/L in placenta, blood, urine, and breast milk, respectively, in mothers, and 107.92 µg/g-Cr in neonates in the exposed group, which were significantly higher than those in the non-exposed area. High levels of urinary arsenic in neonates were maintained 4 days after birth, demonstrating an early arsenic exposure route through the placenta and breast milk. In addition, our study suggested that breastfeeding may reduce arsenic exposure in infants in arsenic-contaminated areas. Further studies are necessary to follow up on comorbidities later in life in neonates and to provide interventions in this region.
Assuntos
Arsênio , Água Potável , Lactente , Recém-Nascido , Humanos , Feminino , Gravidez , Água Potável/análise , Arsênio/análise , Leite Humano/química , Aleitamento Materno , Espectrofotometria Atômica , MéxicoRESUMO
Abstract Salmonella enterica serovar Enteritidis (S. Enteritidis) is the most frequent serovar involved in human salmonellosis. It has been demonstrated that about 80% of infections are related to biofilm formation. There is scant information about the pathogenicity of S. Enteritidis and its relationship to biofilm production. In this regard, this study aimed to investigate the differential host response induced by S. Enteritidis biofilm and planktonic lifestyle. To this purpose, biofilm and planktonic bacteria were inoculated to BALB/c mice and epithelial cell culture. Survival studies revealed that biofilm is less virulent than planktonic cells. Reduced signs of intestinal inflammation and lower bacterial translocation were observed in animals inoculated with Salmonella biofilm compared to the planktonic group. Results showed that Salmonella biofilm was impaired for invasion of non-phagocytic cells and induces a lower inflammatory response in vivo and in vitro compared to that of planktonic bacteria. Taken together, the outcome of Salmonella-host interaction varies depending on the bacterial lifestyle.
Resumen Salmonella entérica serovar Enteritidis (S. Enteritidis) es la serovariedad más frecuentemente aislada en la salmonelosis humana. Se ha demostrado que alrededor del 80% de las infecciones están relacionadas con la formación de biopelículas. Sin embargo, la información disponible acerca de la patogenicidad de S. Enteritidis y su relación con la producción de biopelículas es escasa. Este trabajo tuvo como objetivo investigar la respuesta diferencial del huésped frente a S. Enteritidis en sus 2 estilos de vida: biopelícula y planctónico. Para ello, se inocularon bacterias en estado de biopelícula o planctónico en ratones BALB/c y cultivo de células epiteliales. Los estudios de supervivencia revelaron que Salmonella en biopelícula fue menos virulenta que su contraparte planctónica. Los animales inoculados con biopelículas presentaron una mayor conservación estructural del intestino y una menor translocación bacteriana que el grupo planctónico. Asimismo, Salmonella en biopelícula mostró una capacidad deficiente para invadir células no fagocíticas e indujo una menor respuesta inflamatoria in vivo e in vitro que las bacterias planctónicas. Se concluye que el resultado de la interacción Salmonella-huésped depende del estilo de vida bacteriano.
RESUMO
Knowledge about the relevance of the left inferior frontal gyrus (lIFG) and the left posterior superior temporal gyrus (lpSTG) in visual recognition of word categories is limited at present. tDCS is a non-invasive brain stimulation method that alters cortical activity and excitability, and thus might be a useful tool for delineating the specific impact of both areas on word recognition. The objective of this study was to explore whether the visual recognition process of verb categories is improved by a single tDCS session. lIFG and lpSTG areas were separately modulated by anodal tDCS to evaluate its effects on verbal recognition. Compared to sham stimulation, motor reaction times (RTs) were reduced after anodal tDCS over the lpSTG, and this effect was independent of the performing hand (right/left). These findings suggest that this region is involved in visual word recognition independently from the performing hand.
Assuntos
Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Idioma , Análise e Desempenho de Tarefas , Córtex Pré-Frontal/fisiologia , Tempo de Reação/fisiologiaRESUMO
Shewanella is a microbial group with high potential to be applied in textile effluents bioremediation due to its ability to use a wide variety of substrates as a final electron acceptor in respiration. The present research aimed to describe a new strain, Shewanella algae 2NE11, a decolorizing bacterium isolated from industrial effluent in Peru. S. algae 2NE11 showed an optimal growth under pH 6-9, temperature between 30-40 °C, and 0-4 % NaCl. It can tolerate high concentrations of NaCl until 10% and low temperatures as 4 °C. It decolorizes azo and anthraquinone dyes with a decolorization rate of 89-97%. We performed next-generation sequencing (Pacific Bioscience®) and achieved its complete genome sequence with a length of 5,030,813bp and a GC content of 52.98%. Genomic characterization revealed the presence of protein-coding genes related to decolorization like azoreductase, dyp-peroxidase, oxidoreductases, and the complete Mtr respiratory pathway. Likewise, we identified other properties such as the presence of metal resistant genes, and genes related to lactate and N-acetylglucosamine metabolism. These results highlight its potential to be applied in the bioremediation of textile effluents and guide future research on decolorization metabolic pathways.
RESUMO
Salmonellaenterica serovar Enteritidis (S. Enteritidis) is the most frequent serovar involved in human salmonellosis. It has been demonstrated that about 80% of infections are related to biofilm formation. There is scant information about the pathogenicity of S. Enteritidis and its relationship to biofilm production. In this regard, this study aimed to investigate the differential host response induced by S. Enteritidis biofilm and planktonic lifestyle. To this purpose, biofilm and planktonic bacteria were inoculated to BALB/c mice and epithelial cell culture. Survival studies revealed that biofilm is less virulent than planktonic cells. Reduced signs of intestinal inflammation and lower bacterial translocation were observed in animals inoculated with Salmonella biofilm compared to the planktonic group. Results showed that Salmonella biofilm was impaired for invasion of non-phagocytic cells and induces a lower inflammatory response in vivo and in vitro compared to that of planktonic bacteria. Taken together, the outcome of Salmonella-host interaction varies depending on the bacterial lifestyle.
Assuntos
Salmonelose Animal , Salmonella enteritidis , Animais , Biofilmes , Modelos Animais de Doenças , Humanos , Estilo de Vida , Camundongos , Camundongos Endogâmicos BALB C , Plâncton , Salmonelose Animal/microbiologia , Salmonella enteritidis/fisiologia , VirulênciaRESUMO
OBJECTIVE: Propose a pedestrian crosswalk safety rating (PCSR) for primary roads in Mexico City in order to rate crosswalk safety at intersections with a traffic light and then compare the PCSR with traffic accidents so as to empirically determine any association between the quality of the crosswalk and the traffic accident rate. METHODS: Identify criteria for the rating system through a state-of-the art review; weight the criteria to create a rating system through multicriterion analysis; design a stratified random sample of crosswalks (n = 490); and evaluate the data set. RESULTS: Through the PCSR, 91.3% of the crosswalks evaluated in Mexico City were found not to offer the conditions required to protect pedestrian safety; the "access" macro-criterion received the worst scores. The modelling shows that mixed land use and the length of the crosswalk are the most important variables in predicting traffic accidents. CONCLUSIONS: The analysis was relatively successful in showing the relationship between some variables (criteria) of the PCSR and traffic accidents. In many cases, this shows theoretical coherence; in others, research questions are raised.
OBJETIVO: Propor um índice de segurança de travessia de pedestres (ISTP) para as principais vias públicas na Cidade do México para classificar as travessias de pedestres semaforizadas e comparar o ISTP com os dados de trânsito para comprovar empiricamente se existe associação entre a qualidade dos locais de travessia e a taxa de acidentes. MÉTODOS: Foram identificados os critérios do índice com uma revisão do conhecimento atual e os critérios para gerar o ISTP foram ponderados com uso do método de análise de decisão multicritério e delineamento e avaliação de uma amostra aleatória estratificada de travessias de pedestres (n = 490). RESULTADOS: Com respeito à avaliação das travessias com o uso do ISTP, verificou-se que 91,3% das travessias avaliadas na Cidade do México não têm condições ideais para resguardar a segurança dos pedestres, com o macrocritério "acessibilidade" com a pior qualificação. Quanto à modelagem, observou-se que a mescla de usos do solo e a distância da travessia são as variáveis explicativas mais importantes para predizer a ocorrência de acidentes de trânsito. CONCLUSÕES: A análise demonstrou com relativo sucesso a relação entre algumas variáveis (critérios) que compõem o ISTP e acidentes de trânsito. Houve uma coerência teórica em muitos casos, porém em outros suscitou dúvidas a serem investigadas.
RESUMO
Phenotypic evolution is often exceptionally rapid on islands, resulting in numerous, ecologically diverse species. Although adaptive radiation proceeds along various phenotypic axes, the island effect of faster evolution has been mostly tested with regard to morphology. Here, we leveraged the physiological diversity and species richness of Anolis lizards to examine the evolutionary dynamics of three key traits: heat tolerance, body temperature, and cold tolerance. Contrary to expectation, we discovered slower heat tolerance evolution on islands. Additionally, island species evolve toward higher optimal body temperatures than mainland species. Higher optima and slower evolution in upper physiological limits are consistent with the Bogert effect, or evolutionary inertia due to thermoregulation. Correspondingly, body temperature is higher and more stable on islands than on the American mainland, despite similarity in thermal environments. Greater thermoregulation on islands may occur due to ecological release from competitors and predators compared to mainland environments. By reducing the costs of thermoregulation, ecological opportunity on islands may actually stymie, rather than hasten, physiological evolution. Our results emphasize that physiological diversity is an important axis of ecological differentiation in the adaptive radiation of anoles, and that behavior can impart distinct macroevolutionary footprints on physiological diversity on islands and continents.
Assuntos
Evolução Biológica , Regulação da Temperatura Corporal , Temperatura Corporal , Características de História de Vida , Lagartos/fisiologia , Animais , Ilhas , Filogenia , TermotolerânciaRESUMO
[RESUMEN]. Objetivo. Proponer un índice de seguridad de cruces peatonales (ISCP) sobre vialidades primarias en Ciudad de México para calificar los cruceros peatonales semaforizados, y contrastar el ISCP con hechos de tránsito para probar, en forma empírica, si hay alguna asociación entre la calidad de los cruceros y la siniestralidad. Métodos. Identificación de los criterios del índice mediante una revisión del estado del arte, ponderación de los criterios para generar el ISCP mediante el método de análisis multicriterio, diseño de una muestra aleatoria estratificada de cruces peatonales (n = 490) y su evaluación. Resultados. Relativo a la evaluación de los cruceros mediante el ISCP, destaca que 91,3% de los cruces evaluados en Ciudad de México no cuentan con las condiciones óptimas para resguardar la seguridad de los peatones, con el macrocriterio “Accesibilidad” como el peor calificado. En lo referente al modelaje, resalta que tanto la mezcla de usos del suelo como la distancia de cruce son las variables explicativas más importantes para predecir hechos de tránsito. Conclusiones. El análisis mostró con relativo éxito la relación entre algunas de las variables (criterios) que conforman el ISCP con los hechos de tránsito. En muchos casos, esto muestra coherencia teórica. En otros, abre preguntas de investigación.
[ABSTRACT]. Objective. Propose a pedestrian crosswalk safety rating (PCSR) for primary roads in Mexico City in order to rate crosswalk safety at intersections with a traffic light and then compare the PCSR with traffic accidents so as to empirically determine any association between the quality of the crosswalk and the traffic accident rate. Methods. Identify criteria for the rating system through a state-of-the art review; weight the criteria to create a rating system through multicriterion analysis; design a stratified random sample of crosswalks (n = 490); and evaluate the data set. Results. Through the PCSR, 91.3% of the crosswalks evaluated in Mexico City were found not to offer the conditions required to protect pedestrian safety; the “access” macro-criterion received the worst scores. The modelling shows that mixed land use and the length of the crosswalk are the most important variables in predicting traffic accidents. Conclusions. The analysis was relatively successful in showing the relationship between some variables (criteria) of the PCSR and traffic accidents. In many cases, this shows theoretical coherence; in others, research questions are raised.
[RESUMO]. Objetivo. Propor um índice de segurança de travessia de pedestres (ISTP) para as principais vias públicas na Cidade do México para classificar as travessias de pedestres semaforizadas e comparar o ISTP com os dados de trânsito para comprovar empiricamente se existe associação entre a qualidade dos locais de travessia e a taxa de acidentes. Métodos. Foram identificados os critérios do índice com uma revisão do conhecimento atual e os critérios para gerar o ISTP foram ponderados com uso do método de análise de decisão multicritério e delineamento e avaliação de uma amostra aleatória estratificada de travessias de pedestres (n = 490). Resultados. Com respeito à avaliação das travessias com o uso do ISTP, verificou-se que 91,3% das travessias avaliadas na Cidade do México não têm condições ideais para resguardar a segurança dos pedestres, com o macrocritério “acessibilidade” com a pior qualificação. Quanto à modelagem, observou-se que a mescla de usos do solo e a distância da travessia são as variáveis explicativas mais importantes para predizer a ocorrência de acidentes de trânsito. Conclusões. A análise demonstrou com relativo sucesso a relação entre algumas variáveis (critérios) que compõem o ISTP e acidentes de trânsito. Houve uma coerência teórica em muitos casos, porém em outros suscitou dúvidas a serem investigadas.
Assuntos
Acidentes de Trânsito , Pedestres , México , Acidentes de Trânsito , Prevenção de Acidentes , Pedestres , México , Pedestres , Prevenção de Acidentes , Acidentes de Trânsito , Prevenção de AcidentesRESUMO
In cancer, the adenosinergic pathway participates in the generation of an immunosuppressive microenvironment and in the promotion of tumor growth through the generation of adenosine (Ado). The present study analyzed the participation of Ado, generated through the functional activity of the cervical cancer (CeCa) pathway in CeCa cells, to induce the expression and secretion of TGF-ß1, as well as the participation of this factor to maintain CD73 expression. Ado concentrations greater than 10⯵M were necessary to induce an increase of over 50% in the production and expression of TGF-ß1 in CeCa tumor cells. Blockade of A2AR and A2BR with the specific antagonists, ZM241385 and MRS1754, respectively, strongly reversed the production of TGF-ß1. TGF-ß1 produced by CeCa cells was necessary to maintain CD73 expression because the addition of anti-TGF-ß neutralizing antibodies or the inhibition of TGF-ßRI strongly reversed the expression of CD73 in the CeCa cells. These results suggested a feedback loop in CeCa cells that favors immunosuppressive activity through the production of TGF-ß1 and Ado as well as the autocrine activity of TGF-ß1 and expression of CD73.
Assuntos
5'-Nucleotidase/metabolismo , Adenosina/metabolismo , Comunicação Autócrina/fisiologia , Fator de Crescimento Transformador beta1/metabolismo , Neoplasias do Colo do Útero/metabolismo , Acetamidas/farmacologia , Antagonistas do Receptor A2 de Adenosina/farmacologia , Linhagem Celular Tumoral , Feminino , Proteínas Ligadas por GPI/metabolismo , Células HeLa , Humanos , Terapia de Imunossupressão/métodos , Purinas/farmacologia , Receptor A2A de Adenosina/metabolismo , Receptor A2B de Adenosina/metabolismo , Triazinas/farmacologia , Triazóis/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológicoRESUMO
RESUMEN Objetivo Proponer un índice de seguridad de cruces peatonales (ISCP) sobre vialidades primarias en Ciudad de México para calificar los cruceros peatonales semaforizados, y contrastar el ISCP con hechos de tránsito para probar, en forma empírica, si hay alguna asociación entre la calidad de los cruceros y la siniestralidad. Métodos Identificación de los criterios del índice mediante una revisión del estado del arte, ponderación de los criterios para generar el ISCP mediante el método de análisis multicriterio, diseño de una muestra aleatoria estratificada de cruces peatonales (n = 490) y su evaluación. Resultados Relativo a la evaluación de los cruceros mediante el ISCP, destaca que 91,3% de los cruces evaluados en Ciudad de México no cuentan con las condiciones óptimas para resguardar la seguridad de los peatones, con el macrocriterio "Accesibilidad" como el peor calificado. En lo referente al modelaje, resalta que tanto la mezcla de usos del suelo como la distancia de cruce son las variables explicativas más importantes para predecir hechos de tránsito. Conclusiones El análisis mostró con relativo éxito la relación entre algunas de las variables (criterios) que conforman el ISCP con los hechos de tránsito. En muchos casos, esto muestra coherencia teórica. En otros, abre preguntas de investigación.
ABSTRACT Objective Propose a pedestrian crosswalk safety rating (PCSR) for primary roads in Mexico City in order to rate crosswalk safety at intersections with a traffic light and then compare the PCSR with traffic accidents so as to empirically determine any association between the quality of the crosswalk and the traffic accident rate. Methods Identify criteria for the rating system through a state-of-the art review; weight the criteria to create a rating system through multicriterion analysis; design a stratified random sample of crosswalks (n = 490); and evaluate the data set. Results Through the PCSR, 91.3% of the crosswalks evaluated in Mexico City were found not to offer the conditions required to protect pedestrian safety; the "access" macro-criterion received the worst scores. The modelling shows that mixed land use and the length of the crosswalk are the most important variables in predicting traffic accidents. Conclusions The analysis was relatively successful in showing the relationship between some variables (criteria) of the PCSR and traffic accidents. In many cases, this shows theoretical coherence; in others, research questions are raised.
RESUMO Objetivo Propor um índice de segurança de travessia de pedestres (ISTP) para as principais vias públicas na Cidade do México para classificar as travessias de pedestres semaforizadas e comparar o ISTP com os dados de trânsito para comprovar empiricamente se existe associação entre a qualidade dos locais de travessia e a taxa de acidentes. Métodos Foram identificados os critérios do índice com uma revisão do conhecimento atual e os critérios para gerar o ISTP foram ponderados com uso do método de análise de decisão multicritério e delineamento e avaliação de uma amostra aleatória estratificada de travessias de pedestres (n = 490). Resultados Com respeito à avaliação das travessias com o uso do ISTP, verificou-se que 91,3% das travessias avaliadas na Cidade do México não têm condições ideais para resguardar a segurança dos pedestres, com o macrocritério "acessibilidade" com a pior qualificação. Quanto à modelagem, observou-se que a mescla de usos do solo e a distância da travessia são as variáveis explicativas mais importantes para predizer a ocorrência de acidentes de trânsito. Conclusões A análise demonstrou com relativo sucesso a relação entre algumas variáveis (critérios) que compõem o ISTP e acidentes de trânsito. Houve uma coerência teórica em muitos casos, porém em outros suscitou dúvidas a serem investigadas.
Assuntos
Acidentes/estatística & dados numéricos , Acidentes de Trânsito/prevenção & controle , Pedestres , MéxicoRESUMO
Background: Hydroxyethyl starch (Hextend) has been used for hemorrhagic shock resuscitation, however, hydroxyethyl starch may be associated with adverse outcomes. Objective: To compare systolic blood pressure (sBP) in animals that had 30% of their blood volume removed and treated with intravenous hydroxocobalamin, hydroxyethyl starch, or no fluid. Methods: Twenty-eight swine (45-55 kg) were anesthetized and instrumented with continuous femoral and pulmonary artery pressure monitoring. Animals were hemorrhaged 20 mL/kg over 20 minutes and then administered 150 mg/kg IV hydroxocobalamin in 180 mL saline, 500 mL hydroxyethyl starch, or no fluid and monitored for 60 minutes. Data were modeled using repeated measures multivariate analysis of variance. Results: There were no significant differences before treatment. At 20 minutes after hemorrhage, there was no significant difference in mean sBP between treated groups, however, control animals displayed significantly lower mean sBP (p < 0.001). Mean arterial pressure and heart rate improved in the treated groups but not in the control group (p < 0.02). Prothrombin time was longer and platelet counts were lower in the Hextend group (p < 0.05). Moreover, thromboelastography analysis showed longer clotting (K) times (p < 0.05) for the hydroxyethyl starch-treated group. Conclusion: Hydroxocobalamin restored blood pressure more effectively than no treatment and as effectively as hydroxyethyl starch but did not adversely affect coagulation.
Assuntos
Pressão Sanguínea , Hemorragia , Hidroxocobalamina , Derivados de Hidroxietil Amido , Ressuscitação , Animais , Administração Intravenosa , Coagulação Sanguínea/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Serviços Médicos de Emergência/métodos , Serviços Médicos de Emergência/normas , Serviços Médicos de Emergência/estatística & dados numéricos , Hemorragia/tratamento farmacológico , Hidroxocobalamina/farmacologia , Hidroxocobalamina/normas , Hidroxocobalamina/uso terapêutico , Derivados de Hidroxietil Amido/farmacologia , Derivados de Hidroxietil Amido/normas , Derivados de Hidroxietil Amido/uso terapêutico , Ressuscitação/métodos , Ressuscitação/normas , SuínosRESUMO
The yeast Rhodosporidium toruloides has been extensively studied for its application in biolipid production. The knowledge of its metabolism capabilities and the application of constraint-based flux analysis methodology provide useful information for process prediction and optimization. The accuracy of the resulting predictions is highly dependent on metabolic models. A metabolic reconstruction for R. toruloides metabolism has been recently published. On the basis of this model, we developed a curated version that unblocks the central nitrogen metabolism and, in addition, completes charge and mass balances in some reactions neglected in the former model. Then, a comprehensive analysis of network capability was performed with the curated model and compared with the published metabolic reconstruction. The flux distribution obtained by lipid optimization with flux balance analysis was able to replicate the internal biochemical changes that lead to lipogenesis in oleaginous microorganisms. These results motivate the development of a genome-scale model for complete elucidation of R. toruloides metabolism.
Assuntos
Basidiomycota/metabolismo , Lipídeos/biossíntese , Modelos Biológicos , Trifosfato de Adenosina/metabolismo , Basidiomycota/efeitos dos fármacos , Basidiomycota/crescimento & desenvolvimento , Carbono/farmacologia , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Análise do Fluxo MetabólicoRESUMO
Reactive arthritis (ReA) is an inflammatory condition of the joints that arises following an infection. Salmonella enterocolitis is one of the most common infections leading to ReA. Although the pathogenesis remains unclear, it is known that IL-17 plays a pivotal role in the development of ReA. IL-17-producers cells are mainly Th17, iNKT, and γδT lymphocytes. It is known that iNKT cells regulate the development of Th17 lineage. Whether iNKT cells also regulate γδT lymphocytes differentiation is unknown. We found that iNKT cells play a protective role in ReA. BALB/c Jα18-/- mice suffered a severe Salmonella enterocolitis, a 3.5-fold increase in IL-17 expression and aggravated inflammation of the synovial membrane. On the other hand, activation of iNKT cells with α-GalCer abrogated IL-17 response to Salmonella enterocolitis and prevented intestinal and joint tissue damage. Moreover, the anti-inflammatory effect of α-GalCer was related to a drop in the proportion of IL-17-producing γδT lymphocytes (IL17-γδTcells) rather than to a decrease in Th17 cells. In summary, we here show that iNKT cells play a protective role against Salmonella-enterocolitis and Salmonella-induced ReA by downregulating IL17-γδTcells.
Assuntos
Artrite Reativa/prevenção & controle , Enterocolite/prevenção & controle , Interleucina-17/metabolismo , Linfócitos Intraepiteliais/metabolismo , Células T Matadoras Naturais/metabolismo , Salmonelose Animal/imunologia , Salmonella/patogenicidade , Animais , Anti-Inflamatórios/farmacologia , Enterocolite/imunologia , Enterocolite/microbiologia , Enterocolite/patologia , Galactosilceramidas/farmacologia , Regulação Bacteriana da Expressão Gênica/fisiologia , Íleo/efeitos dos fármacos , Íleo/patologia , Inflamação , Interleucina-17/genética , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Salmonelose Animal/patologia , Células Th17RESUMO
BACKGROUND: Hydrogen sulfide (H2 S) is a potentially deadly gas that naturally occurs in petroleum and natural gas. The Occupational Health and Safety Administration cites H2 S as a leading cause of workplace gas inhalation deaths. Mass casualties of H2 S toxicity may be caused by exposure from industrial accidents or release from oil field sites. H2 S is also an attractive terrorism tool because of its high toxicity and ease with which it can be produced. Several potential antidotes have been proposed for hydrogen sulfide poisoning but none have been completely successful. OBJECTIVE: The objective was to compare treatment response assessed by the time to spontaneous ventilation among groups of swine with acute H2 S-induced apnea treated with intravenous (IV) cobinamide (4 mg/kg in 0.8 mL of 225 mmol/L solution), IV hydroxocobalamin (4 mg/kg in 5 mL of saline), or saline alone. METHODS: Twenty-four swine (45-55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. After stabilization, anesthesia was adjusted such that animals would spontaneously ventilate with an FiO2 of 0.21. Sodium hydrosulfide (NaHS; concentration of 8 mg/mL) was begun at 1 mg/kg/min until apnea was confirmed for 20 seconds by capnography. This infusion rate was sustained for 1.5 minutes postapnea and then decreased to a maintenance rate for the remainder of the study to replicate sustained clinical exposure. Animals were randomly assigned to receive cobinamide (4 mg/kg), hydroxocobalamin (4 mg/kg), or saline and monitored for 60 minutes beginning 1 minute postapnea. G* power analysis using the Z-test determined that equal group sizes of eight animals were needed to achieve a power of 80% in detecting a 50% difference in return to spontaneous ventilations at α = 0.05. RESULTS: There were no significant differences in baseline variables. Moreover, there were no significant differences in the mg/kg dose of NaHS (5.6 mg/kg; p = 0.45) required to produce apnea. Whereas all of the cobinamide-treated animals survived (8/8), none of the control (0/8) or hydroxocobalamin (0/8)-treated animals survived. Mean (±SD) time to spontaneous ventilation in the cobinamide-treated animals was 3.2 (±1.1) minutes. CONCLUSIONS: Cobinamide successfully rescued the severely NaHS-poisoned swine from apnea in the absence of assisted ventilation.