3-Acetylpyridine-induced ataxic-like motor impairments are associated with plastic changes in the Purkinje cells of the rat cerebellum.

Ataxias are characterized by aberrant movement patterns closely related to cerebellar dysfunction. Purkinje cell axons are the sole outputs from the cerebellar cortex, and dysfunctional activity of Purkinje cells has been associated with ataxic movements. However, the synaptic characteristics of Purkinje cells in cases of ataxia are not yet well understood. The nicotinamide antagonist 3-acethylpyridine (3-AP) selectively destroys inferior olivary nucleus neurons so it is widely used to induce cerebellar ataxia. Five days after 3-AP treatment (65mg/kg) in adult male Sprague-Dawley rats, motor incoordination was revealed through BBB and Rotarod testing. In addition, in Purkinje cells from lobules V-VII of the cerebellar vermis studied by the Golgi method, the density of dendritic spines decreased, especially the thin and mushroom types. Western blot analysis showed a decrease in AMPA and PSD-95 content with an increase of the α-catenin protein, while GAD-67 and synaptophysin were unchanged. Findings suggest a limited capacity of Purkinje cells to acquire and consolidate afferent excitatory inputs and an aberrant, rigid profile in the movement-related output patterns of Purkinje neurons that likely contributes to the motor-related impairments characteristic of cerebellar ataxias.

NANOCELLULOSE MEMBRANE WITH VASCULAR ENDOTHELIUM GROWTH FACTOR (VEGF): FUTURE IN HEALING DEEP BURNS? / MEMBRANA DE NANOCELULOSE COM FATOR DE CRESCIMENTO DO ENDOTÉLIO VASCULAR (VEGF): FUTURO NA CICATRIZAÇÃO DE QUEIMADURAS PROFUNDAS?

Introduction: Burns are injuries caused by various agents that promote the destruction of the skin and can lead to the exposure of deeper tissues. To make better use of this variety of treatment options, it is important to know its causes, extent and treatment methods. Objective: Update the use of nanocellulose membranes with glycerol, vascular endothelial growth factor and other complements in burn healing. Method: Review carried out with material and analysis selected from research on virtual platforms (SciELO, Google Scholar, Virtual Health Library, Pubmed and Scopus) using the descriptors: "bacterial membrane proteins; vascular endothelial growth factor; VEGFR; biological dressings; dressings" with AND or OR search, considering the title and/or abstract. Afterwards, the articles were read in full. Result: 45 articles were included. Conclusion: Although more research is needed, published studies show that the enrichment of nanocellulose membranes with some additives such as Vascular Endothelial Growth Factor VEGF) and incorporation of sensors that can monitor wound conditions will result in highly effective dressings. Considering the technological advances to produce low-cost membranes, associated with artificial intelligence and the efforts of researchers, the benefit to public health will soon be evident.

Introdução: Queimaduras são lesões causadas por diversos agentes que promovem a destruição da pele podendo chegar à exposição de tecidos mais profundos. Para melhor uso desta variedade de opções de seu tratamento é importante conhecer-se suas causas, extensão e métodos de tratamento. Objetivo: Atualizar o uso de membranas de nanocelulose, fator de crescimento do endotélio vascular e outros complementos na cicatrização de queimaduras. Método: Revisão feita com material e análise  selecionados a partir de pesquisa em plataformas virtuais (SciELO, Google Scholar, Biblioteca Virtual em Saúde, Pubmed e Scopus) por meio dos descritores: "proteínas da membrana bacteriana; fator de crescimento do endotélio vascular; VEGFR; curativos biológicos; curativos" e seus equivalentes em inglês "bacterial outer membrane proteins; vascular endothelial growth fator; dressing; VEGFR; biological dressings" com busca AND ou OR, considerando o título e/ou resumo. Após, foi feita leitura na íntegra dos artigos. Resultado: Foram incluídos 45 artigos. Conclusão: Embora sejam necessárias mais pesquisas, estudos já publicados evidenciam que o enriquecimento das membranas de nanocelulose com alguns aditivos como o Fator de Crescimento do Endotélio Vascular VEGF) e incorporação de sensores que possam monitorar as condições das feridas resultará em curativos altamente eficazes. Considerando o avanço tecnológico para produzir membranas de baixo custo, associado à inteligência artificial e os esforços dos pesquisadores, em breve o benefício à saúde pública será evidente.

Rspo2-LGR4 exacerbates hepatocellular carcinoma progression via activation of Wnt/b-catenin signaling pathway / Rspo2-LGR4 agrava la progresión del carcinoma hepatocelular al activar la vía de señalización Wnt/beta-catenina

Background: The leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) plays an important role in stem cell differentiation, organ development and cancer. Whether LGR4 affects the progression of hepatocellular carcinoma (HCC) remains unknown. This study aimed to reveal the role of LGR4 in HCC. Methods: Clinical samples of HCC were collected to assess the expression of LGR4 and its correlation with patients’ clinical characteristics. The expression level of LGR4 in HCC cells was altered by pharmacological and genetic methods, and the role of LGR4 in HCC progression was analyzed by in vivo and in vitro assays. HCC was induced by diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) in wild-type and LGR4 deficient mice, the effect of LGR4 on HCC was examined by histopathological evaluation and biochemical assays. Results: LGR4 expression was up-regulated in HCC samples, and its expression level was positively correlated with tumor size, microvascular invasion (MVI), TNM stage and pathological differentiation grade of HCC patients. In the mouse HCC model induced by DEN+CCl4, knockdown of LGR4 effectively inhibited the progression of HCC. Silencing of LGR4 inhibited the proliferation, migration, invasion, stem cell-like properties and Warburg effect of HCC cells. These phenotypes were promoted by R-spondin2 (Rspo2), an endogenous ligand for LGR4. Rspo2 markedly increased the nuclear translocation of β-catenin, whereas IWR-1, an inhibitor of Wnt/β-catenin signaling, reversed its effect. Deficiency of LGR4 significantly reduced the nuclear translocation of β-catenin and the expression of its downstream target genes cyclinD1 and c-Myc. Conclusions: LGR4 promotes HCC progression via Wnt/β-catenin signaling pathway. (AU)

Antecedentes: El receptor de acoplamiento de proteínas G de secuencia repetida 4 (LGR4), rico en leucina, juega un papel importante en la diferenciación de células madre, el desarrollo de órganos y el cáncer. Se desconoce si LGR4 afecta la progresión del carcinoma hepatocelular (HCC). El objetivo de este estudio es revelar el papel de LGR4 en el HCC. Métodos: Se recolectaron muestras clínicas de HCC para evaluar la expresión de LGR4 y su correlación con los resultados clínicos de HCC. Alterar los niveles de expresión de LGR4 en las células de HCC mediante métodos farmacológicos y genéticos y analizar el papel de LGR4 en la progresión del cáncer de hígado mediante mediciones in vivo e in vitro. El HCC fue inducido en ratones de tipo salvaje y con defectos de LGR4 con Nitrosamina de dietilo (DEN) y cloruro de carbono (CCl4), y los efectos de LGR4 sobre el HCC fueron detectados por evaluación histopatológica y determinación bioquímica. Resultados: La expresión de LGR4 está regulada en HCC, y su nivel de expresión está positivamente relacionado con el tamaño tumoral, la infiltración microvascular (MVI), la etapa de TNM y el grado de diferenciación patológica en pacientes con HCC. En el modelo de HCC de ratón inducido por DEN+CCl4, golpear bajo LGR4 inhibió efectivamente la progresión del HCC. El silencio de LGR4 inhibe la proliferación, migración, invasión, propiedades similares a las células madre y el efecto Warburg de las células HCC. Estos fenotipos son promovidos por el ligando endógeno roof slab-specific sponge 2 (Rspo2)de LGR4. El Rspo2 aumentó significativamente la translocación nuclear de la proteína beta-catenina, mientras que el inhibidor de la señalización Wnt/beta-cateninaIWR-1 revirtió su acción... (AU)

Interferencia positiva de las paraproteínas en la determinación de bilirrubina total y su rol en el diagnóstico de gammapatías monoclonales / Positive interference of paraproteins in the determination of total bilirubin and its role in the diagnosis of monoclonal gammopathies / Interferência positiva de paraproteínas na determinação da bilirrubina total e seu papel no diagnóstico de gamopatias monoclonais

Resumen La interferencia por paraproteínas en los análisis clínicos ha sido extensamente informada a nivel mundial. Si bien se han propuesto estrategias metodológicas para evitar el informe de datos erróneos asociados a interferencias (p. ej. confirmación manual, sistema de alerta), en pocos casos se ha propuesto su detección como herramienta diagnóstica de patologías no sospechadas desde la clínica. A partir del trabajo conjunto de dos hospitales de la provincia de Buenos Aires se describió: i) la presencia de interferencia positiva de paraproteínas en la determinación de bilirrubina total con reactivos y autoanalizadores Wiener, y ii) su contribución, en un período inferior a los seis meses, a la detección de cuatro gammapatías no sospechadas (tres monoclonales). Se recomienda dar difusión de esta inferencia a nivel nacional y se propone un esquema de trabajo en laboratorio para identificar la interferencia así como un perfil mínimo de determinaciones para evaluar la existencia de gammapatías desconocidas.

Abstract Paraprotein interference in clinical biochemistry has been widely reported around the world. Methodological strategies have been proposed to avoid reporting erroneous data due to interferences (i.e. manual check, alert system); however, few cases have suggested its use as a diagnostic tool for unsuspected pathologies. Based on the joint work of two hospitals from Buenos Aires Province, the following has been described: i) the presence of positive interference of paraproteins in the assessment of total bilirubin with Wiener chemistry and autoanalizers, and ii) its contribution, in less than six months, to the diagnosis of four gammophaties previously unsuspected (three monoclonal ones). Sharing the occurrence of this interference in our country is recommended. An interference identification workflow is also propose, as well as a set of biochemical assays to evaluate the occurrence of unsuspected gammophaties.

Resumo A interferência da paraproteína na bioquímica clínica tem sido amplamente relatada em todo o mundo. Embora estratégias metodológicas para evitar a comunicação de dados errôneos associados a interferências tenham sido propostas (p. ex., verificação manual, sistema de alerta), em poucos casos sugerem seu uso como ferramenta diagnóstica para patologias não suspeitas a partir da clínica. Com base no trabalho conjunto de dois hospitais da Província de Buenos Aires, foi descrita: i) a presença de interferência positiva de paraproteínas na determinação da bilirrubina total com reagentes e autoanalisadores Wiener e ii) sua contribuição, em um período inferior aos seis meses, para o diagnóstico de quatro gamopatias não suspeitas (três monoclonais). Recomenda-se difundir essa interferência em nível nacional e se propõe um esquema de trabalho em laboratório para identificar a interferência bem como um perfil mínimo de determinações para avaliar a ocorrência de gamopatias desconhecidas.

Dietary intake in individuals with phenylketonuria: an integrative review / Ingesta dietética en individuos con fenilcetonuria: una revisión integradora

Introduction: the dietary intake of individuals with phenylketonuria (PKU) may vary widely according to different cultural eating habits, lifestyle,access to multidisciplinary team, and metabolic formulas available. Thus, knowing the dietary intake of this population makes it possible to tailornutritional treatment strategies to impact their health.Objective: to analyze the evidence on the dietary intake of individuals with PKU.Methods: an integrative literature review was conducted on the dietary intake of individuals with PKU in the databases PUBMED, BIREME andScience Direct. Original articles that addressed the energy and macronutrient food intake of children, adolescents and/or adults with PKU wereincluded in the study, without time restriction, in any language. A total of 384 articles were found and 27 articles were selected and analyzed.Results: evidence about the nutritional composition of their diet showed that individuals with PKU consume between 1160-2721 kcal of energy—7.2-17.4 % (32.4-76.9 g) of energy as protein, 45.9-69.2 % of energy as carbohydrates, 16.6-39 % of energy as lipids— and between7.6 and 20 g of fiber.Conclusion: most individuals with PKU have low energy, protein and fiber intake, adequate lipid intake, and high carbohydrate intake. Metaboliccontrol of the disease is still a challenge in all countries. Nutritional strategies to improve dietary nutritional composition and phenylalanine bloodlevels in individuals with PKU remain an urgent issue.(AU)

Introducción: la ingesta dietética de los individuos con fenilcetonuria (PKU) puede variar ampliamente debido a los diferentes hábitos culturalesde alimentación, el estilo de vida, el acceso al equipo multidisciplinar y las fórmulas metabólicas disponibles. Por ello, conocer la ingesta dietéticade esta población permite adaptar las estrategias de tratamiento nutricional para incidir en su salud.Objetivo: analizar la evidencia sobre la ingesta dietética de individuos con PKU.Métodos: se realizó una revisión bibliográfica integradora sobre la ingesta dietética de las personas con PKU en las bases de datos PUBMED,BIREME y Science Direct. El estudio incluyó artículos originales que abordaran la ingesta alimentaria de energía y macronutrientes de niños,adolescentes y/o adultos con PKU, sin restricción de tiempo, en cualquier idioma. Se encontraron 384 artículos y se seleccionaron y analizaron 27.Resultados: la evidencia de la composición nutricional de la dieta mostró que los individuos con PKU consumen entre 1160 y 2721 kcal deenergía —7,2-17,4 % (32,4-76,9 g) de la energía en forma de proteínas, 45,9-69,2 % de la energía en carbohidratos, 16,6-39 % de la energíaen lípidos— y entre 7,6 y 20 g de fibra.Conclusiones: la mayoría de los individuos con PKU tienen una ingesta baja de energía, proteínas y fibra, una ingesta adecuada de lípidos y unaingesta alta de hidratos de carbono. El control metabólico de la enfermedad sigue siendo un reto en todos los países. Siguen siendo urgenteslas estrategias nutricionales para mejorar la composición nutricional de la dieta y los niveles de fenilalanina en sangre de los individuos con PKU.(AU)

Rspo2-LGR4 exacerbates hepatocellular carcinoma progression via activation of Wnt/ß-catenin signaling pathway.

BACKGROUND: The leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4) plays an important role in stem cell differentiation, organ development and cancer. Whether LGR4 affects the progression of hepatocellular carcinoma (HCC) remains unknown. This study aimed to reveal the role of LGR4 in HCC. METHODS: Clinical samples of HCC were collected to assess the expression of LGR4 and its correlation with patients' clinical characteristics. The expression level of LGR4 in HCC cells was altered by pharmacological and genetic methods, and the role of LGR4 in HCC progression was analyzed by in vivo and in vitro assays. HCC was induced by diethylnitrosamine (DEN) and carbon tetrachloride (CCl4) in wild-type and LGR4 deficient mice, the effect of LGR4 on HCC was examined by histopathological evaluation and biochemical assays. RESULTS: LGR4 expression was up-regulated in HCC samples, and its expression level was positively correlated with tumor size, microvascular invasion (MVI), TNM stage and pathological differentiation grade of HCC patients. In the mouse HCC model induced by DEN+CCl4, knockdown of LGR4 effectively inhibited the progression of HCC. Silencing of LGR4 inhibited the proliferation, migration, invasion, stem cell-like properties and Warburg effect of HCC cells. These phenotypes were promoted by R-spondin2 (Rspo2), an endogenous ligand for LGR4. Rspo2 markedly increased the nuclear translocation of ß-catenin, whereas IWR-1, an inhibitor of Wnt/ß-catenin signaling, reversed its effect. Deficiency of LGR4 significantly reduced the nuclear translocation of ß-catenin and the expression of its downstream target genes cyclinD1 and c-Myc. CONCLUSIONS: LGR4 promotes HCC progression via Wnt/ß-catenin signaling pathway.

Dietary intake in individuals with phenylketonuria: an integrative review.

Introduction: Introduction: the dietary intake of individuals with phenylketonuria (PKU) may vary widely according to different cultural eating habits, lifestyle, access to multidisciplinary team, and metabolic formulas available. Thus, knowing the dietary intake of this population makes it possible to tailor nutritional treatment strategies to impact their health. Objective: to analyze the evidence on the dietary intake of individuals with PKU. Methods: an integrative literature review was conducted on the dietary intake of individuals with PKU in the databases PUBMED, BIREME and Science Direct. Original articles that addressed the energy and macronutrient food intake of children, adolescents and/or adults with PKU were included in the study, without time restriction, in any language. A total of 384 articles were found and 27 articles were selected and analyzed. Results: evidence about the nutritional composition of their diet showed that individuals with PKU consume between 1160-2721 kcal of energy -7.2-17.4 % (32.4-76.9 g) of energy as protein, 45.9-69.2 % of energy as carbohydrates, 16.6-39 % of energy as lipids- and between 7.6 and 20 g of fiber. Conclusion: most individuals with PKU have low energy, protein and fiber intake, adequate lipid intake, and high carbohydrate intake. Metabolic control of the disease is still a challenge in all countries. Nutritional strategies to improve dietary nutritional composition and phenylalanine blood levels in individuals with PKU remain an urgent issue.

Introducción: Introducción: la ingesta dietética de los individuos con fenilcetonuria (PKU) puede variar ampliamente debido a los diferentes hábitos culturales de alimentación, el estilo de vida, el acceso al equipo multidisciplinar y las fórmulas metabólicas disponibles. Por ello, conocer la ingesta dietética de esta población permite adaptar las estrategias de tratamiento nutricional para incidir en su salud. Objetivo: analizar la evidencia sobre la ingesta dietética de individuos con PKU. Métodos: se realizó una revisión bibliográfica integradora sobre la ingesta dietética de las personas con PKU en las bases de datos PUBMED, BIREME y Science Direct. El estudio incluyó artículos originales que abordaran la ingesta alimentaria de energía y macronutrientes de niños, adolescentes y/o adultos con PKU, sin restricción de tiempo, en cualquier idioma. Se encontraron 384 artículos y se seleccionaron y analizaron 27. Resultados: la evidencia de la composición nutricional de la dieta mostró que los individuos con PKU consumen entre 1160 y 2721 kcal de energía ­7,2-17,4 % (32,4-76,9 g) de la energía en forma de proteínas, 45,9-69,2 % de la energía en carbohidratos, 16,6-39 % de la energía en lípidos­ y entre 7,6 y 20 g de fibra. Conclusiones: la mayoría de los individuos con PKU tienen una ingesta baja de energía, proteínas y fibra, una ingesta adecuada de lípidos y una ingesta alta de hidratos de carbono. El control metabólico de la enfermedad sigue siendo un reto en todos los países. Siguen siendo urgentes las estrategias nutricionales para mejorar la composición nutricional de la dieta y los niveles de fenilalanina en sangre de los individuos con PKU.

Effects of Pasturella Multocida B:2 and its immunogens (LPS and OMP) on reproductive hormones in Nili-Ravi Buffaloes

Abstract Livestock is a fundamental part of the agriculture industry in Pakistan and contributes more than 11.53% to GDP. Among livestock species, the buffaloes are regarded as the black gold of Pakistan. Being the highest milk producers globally, Nili-Ravi buffaloes are the most famous ones. Buffaloes are affected by many endemic diseases, and "Hemorrhagic septicemia" (HS) is one of them. This study was designed to ascertain the effects of experimental exposure ofP. multocida B:2 (oral) and its immunogens, i.e., LPS (oral and intravenous) and OMP (oral and subcutaneous) on reproductive hormonal profiles in Nili-Ravi buffaloes. Repeated serum samples were collected from the jugular vein of experimental animals for 21 days (0, 02, 04, 08, 12, 16, 20, 24, 36, 48, 72, 120, 168, 216, 264, 360, 456 and 504 hours). Hormonal assays to determine the serum concentrations of Gonadotropin-releasing hormone (GnRH), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Estrogen (E2) and progesterone (P4) were performed using (MyBioSource) commercial Elisa kits. The hormonal profile of all treatment groups of the buffalo heifers exhibited significant (P 0.05) variations as compared to the control group (G-1). These results indicate suppression in Nili-Ravi buffaloes' reproductive hormonal profile on exposure to P. multocida B:2 and its immunogens. This influence warrants that exposure to H.S may be a possible reason for delayed puberty and poor reproduction performance in Nili-Ravi buffaloes.

Resumo A pecuária é uma parte fundamental da indústria agrícola no Paquistão e contribui com 11,53% do PIB nacional. Entre as espécies de gado, os búfalos são considerados o ouro negro do Paquistão. Sendo os maiores produtores de leite em todo o mundo, os búfalos Nili-Ravi são os mais famosos. Os búfalos são afetados por muitas doenças endêmicas, entre as quais a septicemia hemorrágica (SH). Este estudo busca verificar os efeitos da exposição experimental de P. multocida B:2 (oral) e seus imunógenos, ou seja, LPS (oral e intravenoso) e OMP (oral e subcutâneo), nos perfis hormonais reprodutivos em búfalos Nili-Ravi. Amostras de soro repetidas foram coletadas da veia jugular de animais experimentais por 21 dias (0, 2, 4, 8, 12, 16, 20, 24, 36, 48, 72, 120, 168, 216, 264, 360, 456 e 504 horas). Os ensaios hormonais para determinar as concentrações séricas do hormônio liberador de gonadotrofina (GnRH), hormônio foliculoestimulante (FSH), hormônio luteinizante (LH), estrogênio (E2) e progesterona (P4) foram realizados usando kits comerciais Elisa (MyBioSource). O perfil hormonal de todos os grupos de tratamento das novilhas bubalinas apresentou variações significativas (P 0,05) em relação ao grupo controle (G-1). Esses resultados indicam supressão no perfil hormonal reprodutivo de búfalos Nili-Ravi na exposição a P. multocida B:2 e seus imunógenos. Essa influência garante que a exposição à SH possa ser uma possível razão para o atraso da puberdade e o baixo desempenho reprodutivo em búfalos Nili-Ravi.

Effects of Pasturella Multocida B: 2 and its immunogens (LPS and OMP) on reproductive hormones in Nili-Ravi Buffaloes / Efeitos de Pasteurella multocida B: 2 e seus imunógenos (LPS e OMP) em hormônios reprodutivos em búfalos Nili-Ravi

Abstract Livestock is a fundamental part of the agriculture industry in Pakistan and contributes more than 11.53% to GDP. Among livestock species, the buffaloes are regarded as the black gold of Pakistan. Being the highest milk producers globally, Nili-Ravi buffaloes are the most famous ones. Buffaloes are affected by many endemic diseases, and "Hemorrhagic septicemia" (HS) is one of them. This study was designed to ascertain the effects of experimental exposure ofP. multocida B:2 (oral) and its immunogens, i.e., LPS (oral and intravenous) and OMP (oral and subcutaneous) on reproductive hormonal profiles in Nili-Ravi buffaloes. Repeated serum samples were collected from the jugular vein of experimental animals for 21 days (0, 02, 04, 08, 12, 16, 20, 24, 36, 48, 72, 120, 168, 216, 264, 360, 456 and 504 hours). Hormonal assays to determine the serum concentrations of Gonadotropin-releasing hormone (GnRH), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Estrogen (E2) and progesterone (P4) were performed using (MyBioSource) commercial Elisa kits. The hormonal profile of all treatment groups of the buffalo heifers exhibited significant (P<0.05) variations as compared to the control group (G-1). These results indicate suppression in Nili-Ravi buffaloes' reproductive hormonal profile on exposure to P. multocida B:2 and its immunogens. This influence warrants that exposure to H.S may be a possible reason for delayed puberty and poor reproduction performance in Nili-Ravi buffaloes.

Resumo A pecuária é uma parte fundamental da indústria agrícola no Paquistão e contribui com 11,53% do PIB nacional. Entre as espécies de gado, os búfalos são considerados o ouro negro do Paquistão. Sendo os maiores produtores de leite em todo o mundo, os búfalos Nili-Ravi são os mais famosos. Os búfalos são afetados por muitas doenças endêmicas, entre as quais a "septicemia hemorrágica" (SH). Este estudo busca verificar os efeitos da exposição experimental de P. multocida B:2 (oral) e seus imunógenos, ou seja, LPS (oral e intravenoso) e OMP (oral e subcutâneo), nos perfis hormonais reprodutivos em búfalos Nili-Ravi. Amostras de soro repetidas foram coletadas da veia jugular de animais experimentais por 21 dias (0, 2, 4, 8, 12, 16, 20, 24, 36, 48, 72, 120, 168, 216, 264, 360, 456 e 504 horas). Os ensaios hormonais para determinar as concentrações séricas do hormônio liberador de gonadotrofina (GnRH), hormônio foliculoestimulante (FSH), hormônio luteinizante (LH), estrogênio (E2) e progesterona (P4) foram realizados usando kits comerciais Elisa (MyBioSource). O perfil hormonal de todos os grupos de tratamento das novilhas bubalinas apresentou variações significativas (P < 0,05) em relação ao grupo controle (G-1). Esses resultados indicam supressão no perfil hormonal reprodutivo de búfalos Nili-Ravi na exposição a P. multocida B:2 e seus imunógenos. Essa influência garante que a exposição à SH possa ser uma possível razão para o atraso da puberdade e o baixo desempenho reprodutivo em búfalos Nili-Ravi.

Expressão da proteína recombinante Sm29 em Escherichia coli e purificação a partir dos corpúsculos de inclusão

Schistosomiasis is a neglected chronic parasitic tropical disease caused by the trematode worm Schistosoma spp., common in developing countries. Pharmacological treatments are available, but they are not effective due to the global epidemiological situation. A preventive vaccine could effectively contribute to reduce the infection. Among a number of antigens, the tegumental protein Sm29 from adult worm Shistosoma mansoni has been identified as a promising vaccine candidate. The gene Sm29 was cloned with 393 nucleotides, excluding a signal peptide and the transmembrane domain, to express the protein with 130 amino acids, approximately 18 kDa, with theoretical pI 6.5. Our objectives is to obtain the recombinant Sm29 protein expressed in Escherichia coli without histidine tag. Therefore, we must optimize the Sm29 obtaining processe, upstream and downstream, in order to design the industrial process, improving the yield and quality of the product to be used in clinical trials. Cells of E. coli BL21(DE3)_pET28_Sm29 were cultivated in bioreactor for Sm29 expression and they were separated by centrifugation. The cells were resuspended in buffer and lysed in French Press. The inclusion bodies (IB) were recovered by centrifugation and we studied the clarification of IB by washing with different solutions and using different centrifugation forces. The solubilization of IB was tested with 8 M Urea under different pH conditions. After the treatments, the protein profiles were analyzed by SDS-PAGE, to verify the presence of the expected band of ~18 kDa and the removal of contaminants. The washing solutions and the lower centrigugation speed helped to clarify the material, without causing losses. The pH of the solubilization solutions interfere with protein recovery, determining to work above pH 7.5, to seek the best balance between protein recovery and contaminant elimination. To meet regulatory requirements in the industrial process for vaccine production, we aim to replace purification by metal affinity chromatography (IMAC), allowed by the presence of the his-tag, added to the antigen as a purification strategy. Thus, the purification of rSm29 by IMAC was compared with studies of ion exchange chromatography, evaluating the binding of denatured or renatured proteins to the resins. It was found that the initial IB clarification parameters and solubilization conditions interfere in the chromatography and dialysis stages. It was determined that. to date. the best condition of binding is the renatured protein to the anion exchange resin, Q-Sepharose. As we identified an alternative purification method, we cloned the Sm29 gene without the his tag code to express the protein in BL21(DE3). Furthermore, the Sm29 gene was optimized for E. coli codon usage. The optimized gene was also cloned for expression in BL21(DE3), to evaluate whether it would modify the protein synthesis in terms of amount of expression and solubility. The first tests suggest that the amount of protein expression is similar to that obtained with the original gene. Tests of solubilization by pressurization are planned to analyze whether possible structural modifications in rSm29 may improves protein recovery.

A esquistossomose é uma doença tropical parasitária crônica negligenciada, causada pelo verme trematódeo Schistosoma spp., comum em países em desenvolvimento. Os tratamentos farmacológicos disponíveis não são eficazes devido à situação epidemiológica global. Uma vacina preventiva poderia contribuir eficazmente para a reduzir a infecção. Entre uma série de antígenos, a proteína tegumentar Sm29 do verme adulto Shistosoma mansoni foi identificada como uma promissora candidata a vacina. O gene Sm29 foi clonado com 393 nucleotídeos, excluindo um peptídeo sinal e o domínio transmembrana, para expressar a proteína com 130 aminoácidos, aproximadamente 18 KDa, com pI teórico 6,5. Nosso objetivo é obter a proteína Sm29 recombinante expressa em Escherichia coli sem cauda de histidina. Para tanto, devemos otimizar os processos de fermentação dos clones e os processos de purificação, para então, desenhar o processo industrial para melhorar o rendimento e a qualidade do produto a ser utilizado em ensaios clínicos. Células do clone E. coli BL21(DE3)_pET28_Sm29 foram cultivadas em biorreator para expressão de rSm29, separadas por centrifugação, ressuspensas em tampão e lisadas em “French Press”. Os corpos de inclusão (CI) foram recuperados por centrifugação e estudamos a etapa de clarificação dos CI por lavagens com diferentes soluções e forças de centrifugação. Testamos a solubilização dos CI com Ureia 8 M sob diferentes condições de pH. Após os tratamentos, analisamos os perfis proteicos por SDS-PAGE, verificando a banda esperada de ~18 kDa e a remoção de contaminantes. As soluções utilizadas na lavagem e a menor velocidade de centrifugação clarificam o material, sem causar perdas da proteína de interesse. O pH da solução de solubilização interfere na recuperação da proteína, determinando trabalhar com pH acima de 7,5 para buscar o melhor equilíbrio entre recuperação proteica e eliminação de contaminantes. Para atender aos requisitos regulatórios de processo industrial na produção de vacinas, temos o objetivo de substituir a purificação por cromatografia de afinidade a metal (IMAC) para poder remover a cauda de histidina, adicionada ao antígeno como estratégia de purificação. Assim, comparamos a purificação da rSm29 por IMAC com estudos de purificação por trocas iônicas, avaliando a ligação da proteína desnaturada ou renaturada com as resinas. Verificamos que os parâmetros iniciais de clarificação da CI e as condições de solubilização interferem nas etapas de cromatografia e diálise. Determinamos que a melhor condição, até o momento, é a ligação da proteína renaturada à resina de troca aniônica, Q-Sepharose. Identificado um método alternativo de purificação, clonamos o gene Sm29 sem a cauda de histidina e expressamos a proteína em BL21(DE3). Além disso, o gene Sm29 foi otimizado para uso de códons de E. coli. Um gene otimizado foi clonado para expressão em BL21(DE3), para avaliarmos se modificaria a estrutura da proteína durante a síntese da cadeia primária, em termos de quantidade de expressão e solubilidade. Os primeiros testes sugerem que a expressão é semelhante à obtida com o gene original. Testes de solubilização por pressurização estão planejados para analisar se a possível modificação estrutural na rSm29 melhoraria a recuperação do antígeno.

Baixa ingestão de proteínas está associada à mortalidade em idosos brasileiros / Low protein intake is associated with mortality in Brazilian older adults

Resumo Objetivo Estimar a associação entre baixa ingestão de proteínas e mortalidade em pessoas idosas. Métodos Estudo prospectivo realizado com 621 pessoas idosas da cidade de Viçosa (Minas Gerais), município de médio porte no Brasil. A ingestão de proteínas foi avaliada na linha de base (2009) pelo recordatório de ingestão habitual e foi utilizada a classificação de ingestão de proteínas proposta pela Sociedade Brasileira de Nutrição Parenteral e Enteral. Os dados de mortalidade foram coletados no período de acompanhamento (2009 a 2018) através do Sistema de Informações sobre Mortalidade. Modelos de regressão de Cox foram aplicados para estimar a associação independente entre ingestão total de proteínas e mortalidade, e estimativas de hazard ratio e seus respectivos intervalos de confiança de 95% foram calculados. Resultados Entre os 621 participantes do estudo, 52,7% eram do sexo feminino e a prevalência de baixa ingestão proteica foi de 60,9%. Ao longo dos 9 anos de acompanhamento ocorreram 154 óbitos (23,3%). No modelo ajustado, pessoas idosas com baixa ingestão de proteínas apresentaram maior risco de morte [HR: 1,72; IC 95%: 1,05 - 2.82]. Conclusão A baixa ingestão de proteínas pode aumentar o risco de morte em pessoas idosas.

Abstract Objective To estimate the association between low protein intake and mortality in older adults. Methods Prospective study carried out with 621 older adults in a medium-sized city (Viçosa, Minas Gerais) in Brazil. Protein intake was assessed at baseline (2009) by the usual intake recall and the protein intake classification was used as proposed by the Brazilian Society of Parenteral and Enteral Nutrition. Mortality data were collected in the follow-up period (2009 to 2018) from the Mortality Information System. Cox regression models were applied to estimate the independent association between total protein intake and mortality, and Hazard Ratio estimates and their respective 95% confidence intervals were calculated. Results Among the 621 participants in the study, 52.7% were female, and the prevalence of low protein intake was 60.9%. Over the 9 years of follow-up, there were 154 deaths (23,3%). In the adjust models, older adults with low protein intake showed increased risk of death [HR: 1.72; 95% CI: 1.05 - 2.82]. Conclusion Low protein intake may increase the risk of death in the older adults.

Gene de virulência oipA de Helicobacter pylori como marcador molecular de gastropatias severas / Helicobacter pylori oipa virulence gene as a molecular marker of severe gastropathies

ABSTRACT Background: Helicobacter pylori is an etiologic agent of gastroduodenal diseases. The microorganism, considered a type I carcinogen, affects about 50% of the global population. H. pylori virulence factors are determinant for the clinical outcome of the infection. The outer inflammatory protein A (oipA) gene encodes an outer membrane adhesin and is related to severe gastropathies, such as gastric cancer. Objective: The aim of this study was to evaluate the association of the oipA gene with the severity of gastroduodenal diseases in dyspeptic patients in region Central Brazil. Methods: The polymerase chain reaction (PCR) was used to determine the presence of H. pylori. Samples positives were used for molecular screening of the oipA gene. Gastropathies were categorized as non-severe and severe diseases. Results: Approximately 68% of patients had H. pylori and 36% were infected with H. pylori oipA+ strains. Infection was significantly associated in patients aged over 44 years (P=0.004). However, there was no association between oipA and patients' age (P=0.89). Approximately 46% of patients infected with oipA+ strains had some severe illness. Gastric adenocarcinoma was the most frequent severe gastropathy. The H. pylori oipA genotype was inversely associated with the severity of gastroduodenal diseases (OR=0.247, 95%CI: 0.0804-0.7149 and P=0.007). Conclusion: The characterization of possible molecular markers will contribute to personalized medicine, impacting the prognosis of patients.

RESUMO Contexto: Helicobacter pylori é um agente etiológico de doenças gastroduodenais. O microrganismo, considerado cancerígeno tipo I, afeta cerca de 50% da população mundial. Os fatores de virulência do H. pylori são determinantes para o desfecho clínico da infecção. O gene da proteína inflamatória externa A (oipA) codifica uma adesina da membrana externa e está relacionado a gastropatias severas, como o câncer gástrico. Objetivo: O objetivo deste estudo foi avaliar a associação do gene oipA com a gravidade das doenças gastroduodenais em pacientes dispépticos na região Brasil Central. Métodos: A reação em cadeia da polimerase (PCR) foi utilizada para determinar a presença de H. pylori. Amostras positivas foram utilizadas para triagem molecular do gene oipA. As gastropatias foram categorizadas como doenças não severas e severas. Resultados: Aproximadamente 68% dos pacientes apresentaram H. pylori e 36% estavam infectados com cepas H. pylori oipA+. A infecção foi significativamente associada em pacientes com idade superior a 44 anos (P=0,004). No entanto, não houve associação entre oipA e a idade dos pacientes (P=0,89). Aproximadamente 46% dos pacientes infectados com cepas oipA+ tiveram alguma doença severa. O adenocarcinoma gástrico foi a gastropatia severa mais frequente. O genótipo oipA de H. pylori foi inversamente associado à gravidade das doenças gastroduodenais (OR=0,247, IC95%: 0,0804-0,7149 P=0,007). Conclusão: A caracterização de possíveis marcadores moleculares contribuirá para a medicina personalizada, impactando no prognóstico dos pacientes.

Changes related to muscle autophagy after exhaustive exercise and blunt trauma / Cambios relacionados con la autofagia muscular tras ejercicio exhaustivo y traumatismo contuso / Alterações relacionadas à autofagia muscular após exercício exaustivo e trauma contuso

ABSTRACT Objective: To study the temporal changes of autophagy related factors in skeletal muscle of rats after exhaustive exercise and blunt trauma. Methods: Forty-two male SD rats were divided into 7 groups with 6 rats in each group: Quiet control group (C), immediately after exhaustive exercise (E0), 24 hours after exhaustive exercise (E24), 48 hours after exhaustive exercise (E48), immediately after blunt trauma (D0), 24 hours after blunt trauma (D24), 48 hours after blunt trauma (D48). All groups of rats were killed and samped respectively at different time points specified above, and the right gastrocnemius muscle was taken, which was divided into two parts, one for mRNAs of, Lamp-2, BNIP3 and NIX by real-time fluorescent quantitative PCR, and the other for p62 protein by Western blotting. Results: (1) Compared with group C, mRNA levels of p62, Lamp-2 and NIX in group E48 were significantly increased after exhaustive exercise(P<0.05), suggesting that autophagy increased in 48h after exhaustive exercise. (2) Compared with group C, p62mRNA and Lamp-2 mRNA levels were significantly increased immediately after blunt trauma(P<0.05) and decreased significantly in 48h after blunt trauma(P<0.05), suggesting that autophagy activity was enhanced immediately after blunt trauma and decreased in 48h after injury. Conclusions: Generally, there were differences at each recovery phase between blunt trauma and exhausted exercise models, and the basal autophagy factors and mitochondrial autophagy factors were also inconsistent. Basal autophagy factors p62 and Lamp-2 increased significantly 48 hours after eccentric exhaustive exercise and immediately after blunt trauma. Mitochondrial autophagy factor BNIP3 did not increase after exhaustive exercise and blunt trauma, but NIX only increased after exhaustive exercise. Its molecular mechanism needs to be further studied. Level of Evidence III; Therapeutic Studies Investigating the Results of Treatment.

RESUMEN Objetivo: Estudiar los cambios temporales de los factores relacionados con la autofagia en el músculo esquelético de ratas tras el ejercicio exhaustivo y el traumatismo contuso. Métodos: Se dividieron 42 ratas SD macho en 7 grupos con 6 ratas en cada grupo: grupo de control silencioso (C), inmediatamente después del ejercicio exhaustivo (E0), 24 horas después del ejercicio exhaustivo (E24), 48 horas después del ejercicio exhaustivo (E48), inmediatamente después de un traumatismo contuso (D0), 24 horas después de un traumatismo contuso (D24), 48 horas después de un traumatismo contuso (D48). Todos los grupos de ratas fueron sacrificados y rotulados, respectivamente, en diferentes momentos especificados anteriormente, y se extrajo el músculo gastrocnemio derecho, dividido en dos partes, una para los ARNm Lamp-2, BNIP3 y NIX mediante PCR cuantitativa fluorescente en tiempo real, y la otra para la proteína p62 mediante Western blotting. Resultados: (1) En comparación con el grupo C, los niveles de ARNm de p62, Lamp-2 y NIX en el grupo E48 aumentaron significativamente tras el ejercicio exhaustivo (P<0,05), lo que sugiere que la autofagia aumentó en las 48 horas posteriores al ejercicio exhaustivo. (2) En comparación con el grupo C, los niveles de ARNm de p62 ARNm y Lamp-2 aumentaron significativamente inmediatamente después del traumatismo contuso (P<0,05) y disminuyeron significativamente a las 48 horas después del traumatismo contuso (P<0,05), lo que sugiere que la actividad de autofagia aumentó inmediatamente después del traumatismo contuso y disminuyó a las 48 horas después de la lesión. Conclusión: En general, hubo diferencias en cada fase de recuperación entre los modelos de traumatismo contuso y ejercicio exhaustivo, y los factores de autofagia basal y los factores de autofagia mitocondrial también fueron inconsistentes. Los factores de autofagia basal p62 y Lamp-2 aumentaron significativamente 48 horas después del ejercicio excéntrico exhaustivo e inmediatamente después del traumatismo contuso. El factor de autofagia mitocondrial BNIP3 no aumentó tras el ejercicio exhaustivo y el traumatismo contuso, pero NIX sólo aumentó tras el ejercicio exhaustivo. Su mecanismo molecular debe investigarse con más detalle. Nivel de Evidencia III; Estudios Terapéuticos que Investigan los Resultados del Tratamiento.

RESUMO Objetivo: Estudar as alterações temporais dos fatores relacionados à autofagia no músculo esquelético de ratos após exercício exaustivo e trauma contuso. Métodos: Quarenta e dois ratos machos SD foram divididos em 7 grupos com 6 ratos em cada grupo: Grupo de controle silencioso (C), imediatamente após o exercício exaustivo (E0), 24 horas após o exercício exaustivo (E24), 48 horas após o exercício exaustivo (E48), imediatamente após o trauma contuso (D0), 24 horas após o trauma contuso (D24), 48 horas após o trauma contuso (D48). Todos os grupos de ratos foram mortos e rotulados, respectivamente, em diferentes momentos especificados acima, e o músculo gastrocnêmio direito foi retirado, dividido em duas partes, uma para mRNAs de Lamp-2, BNIP3 e NIX por PCR quantitativo fluorescente em tempo real, e a outra para a proteína p62 por imunotransferência. Resultados: (1) Em comparação com o grupo C, os níveis de mRNA de p62, Lamp-2 e NIX no grupo E48 aumentaram significativamente após o exercício exaustivo (P<0,05), sugerindo que a autofagia aumentou em 48 horas após o exercício exaustivo. (2) Em comparação com o grupo C, os níveis de mRNA de p62mRNA e Lamp-2 foram significativamente aumentados imediatamente após o trauma contuso (P<0,05) e diminuíram significativamente em 48 horas após o trauma contuso (P<0,05), sugerindo que a atividade de autofagia foi aumentada imediatamente após o trauma contuso e diminuiu em 48 horas após a lesão. Conclusão: Houve, via de regra, diferenças em cada fase de recuperação entre os modelos de trauma contuso e de exercício exaustivo, sendo que os fatores de autofagia basal e os fatores de autofagia mitocondrial também foram inconsistentes. Os fatores de autofagia basal p62 e Lamp-2 aumentaram significativamente 48 horas após o exercício excêntrico exaustivo e imediatamente após o trauma contuso. O fator de autofagia mitocondrial BNIP3 não aumentou após o exercício exaustivo e o trauma contuso, mas o NIX aumentou somente após o exercício exaustivo. Seu mecanismo molecular precisa ser investigado com mais detalhes. Nível de Evidência III; Estudos Terapêuticos que Investigam os Resultados do Tratamento.

Caracterización clínica y epidemiológica de la enfermedad pulmonar obstructiva crónica / Clinical and epidemiological characterization of chronic obstructive pulmonary disease

Objetivo: caracterizar clínica y epidemiológicamente a los pacientes con enfermedad pulmonar obstructiva crónica. Métodos: estudio descriptivo retrospectivo trasversal, que incluyó pacientes adultos con diagnóstico de enfermedad pulmonar obstructiva crónica en un hospital universitario de Medellín. Material y métodos: la fuente de información fue secundaria a través de historias clínicas, el análisis se realizó en el programa Jamovi, empleando un análisis univariado. Resultados y discusión: se incluyeron 552 pacientes, la edad mediana fue 76 años con predominio del sexo femenino (56.7%). Respecto a la exposición a sustancias tóxicas respiratorias importantes en el desarrollo de la enfermedad, 24.1% consumían cigarrillo y 23% exposición a biomasa. Al momento del ingreso hospitalario 17.9% fueron clasificados con disnea grado IV; 74.1% recibió beta-agonistas de corta acción y antimuscarínicos de corta acción 60%; 11.6% requirió ingreso a las unidades de cuidados intensivos o especiales y 7.8% fallecieron durante la hospitalización. Conclusiones: se evidencia subdiagnóstico espirométrico de la enfermedad que puede estar relacionado con las limitaciones económicas, tecnológicas y de recurso humano capacitado, lo cual afecta el adecuado diagnóstico y manejo de la enfermedad, así como impacta la calidad de vida de los pacientes.

Objective: clinical and epidemiological characterization of patients with chronic obstructive pulmonary disease (COPD). Methods: a retrospective, cross-sectional, descriptive study, which included adult patients with a diagnosis of COPD in a university hospital in Medellín. Data sources were secondary, based on medical records. The Jamovi program was used to perform a univariate analysis. Results and discussion: 552 patients were included. Median age was 76 years with a female predominance (56.7%). Regarding exposure to major respiratory toxic substances implicated in the development of the disease, 24.1% were tobacco smokers and 23% were exposed to biomass smoke. At the time of hospital admission,17.9% were classified as having grade 4 dyspnea; 74.1% received short acting beta-agonists and 60% short-acting antimuscarinics,11.6% required intensive care unit or special care unit admission, and 7.8% died in hospital. Conclusions: under-diagnosis of COPD by spirometry may be related to economic, technological, and trained human resource limitations, which affect adequate diagnosis and management of the disease, as well as patient ́s quality of life.

Impacto de la evaluación pulmonar ecográfica durante un lavado pulmonar total: caso pediátrico de proteinosis alveolar pulmonar / The impact of lung ultrasound assessment during a whole lung lavage: a paediatric case of pulmonary alveolar proteinosis

El lavado pulmonar total (LPT) es la principal terapia para la proteinosis alveolar pulmonar (PAP). Formulamos la hipótesis de la aplicabilidad de la ecografía pulmonar (EP) para guiar el alcance de la inundación alveolar en un varón de 15 años. El LPT de cada pulmón consistió en la instilación de solución salina, seguida de quinesioterapia y drenaje de líquidos. En el primer LPT, el proceso se repitió hasta observar el aclaramiento macroscópico progresivo del líquido de lavado, con visualización simultánea de las fases de aireación pulmonar mediante EP. En la segunda etapa, se utilizó un patrón de EP para guiar la extensión del lavado. La aparición del patrón de tipo tisular mediante broncograma del fluido definió la terminación temprana de la infusión salina. En conclusión, la EP contribuyó a monitorizar las fases de la desaireación pulmonar a lo largo del LPT, y redujo la cantidad total de solución salina instilada, con el fin de minimizar sus complicaciones inherentes.(AU)

Whole lung lavage (WLL) is the first-line treatment for pulmonary alveolar proteinosis. We hypothesized that lung ultrasound (LUS) would guide flooding during treatment in a 15-year-old boy. WLL of each lung consisted of instillation of saline followed by kinesiotherapy and fluid drainage. In the first WLL, the lung was repeatedly flooded until the lavage fluid was clear on macroscopic examination. During this process, LUS was used to visualise lung aeration. In the second WLL, we used LUS signs to guide the lavage volume. The appearance of the fluid bronchogram sign showed that saline infusion could be stopped earlier than in the first lavage. In conclusion, LUS helped monitor the different stages of controlled lung de-aeration during WLL and reduce the total amount of saline used. This technique will also reduce the risk of WLL-related complications.(AU)

La nueva era de las enfermedades neurodegenerativas. La base de los nuevos abordajes / The new age of neurodegenerative diseases. The basis of the new approaches

La detección por biomarcadores de los procesos fisiopatológicos y moleculares implicados en las enfermedades cerebrales por plegamiento anormal de proteínas está permitiendo delinear la historia natural de estos procesos. La gran mayoría de ellos tiene una fase preclínica prolongada, en la que los cambios biológicos son patentes. Las manifestaciones clínicas (fenotipos) no tienen una correspondencia unívoca con la patología subyacente, a pesar de que se han utilizado los epónimos anatomopatológicos para la descripción de los síndromes clínicos, lo que ha favorecido la imprecisión diagnóstica. Para realizar un adecuado manejo clínico debemos conocer los tres planos que definen actualmente los procesos neurodegenerativos más frecuentes. La precisión diagnóstica será un prerrequisito para las nuevas terapias dirigidas a modificar el curso de las enfermedades por plegamiento proteico cerebrales. (AU)

The detection by biomarkers of the pathophysiological and molecular processes involved in misfolding protein diseases making it possible to delineate the natural history of these processes. The great majority of protein misfolding diseases have a prolonged preclinical phase, in which the biological changes are patent. The clinical manifestations (i.e., phenotypes) do not have a univocal correspondence with the underlying pathology, despite the fact that pathological eponyms have been used for the description of the clinical syndromes, which has favored diagnostic inaccuracy. In order to perform an adequate clinical management, we must know the 3 planes that currently define the most common neurodegenerative processes. Diagnostic accuracy will be a prerequisite for new therapies aimed at modifying the course of brain protein misfolding diseases. (AU)

Fuerza prensil y composición corporal en escolares colombianos. Estudio piloto

Introducción: Algunos estudios han encontrado relación entre exceso de peso y baja fuerza de prensión relativa. En países de ingresos socioeconómicos medianos y bajos hay pocas evidencias que evalúen la fuerza prensil y su relación con la composición corporal en población pediátrica. Objetivo: Evaluar la correlación entre la fuerza prensil y la composición corporal de escolares de Bucaramanga, Colombia. Materiales y métodos: Se realizó un estudio piloto de corte transversal, analítico, correlacional. Participaron niños en edad escolar de Bucaramanga, Colombia. Las principales variables dependientes fueron masa muscular, agua corporal total, proteínas (kg) y el porcentaje de grasa corporal. La variable independiente correspondió a la fuerza prensil. Se usó el coeficiente de correlación de Spearman para explorar la relación entre variables. Resultados: El promedio de la fuerza prensil en el total de la muestra fue de 13,8 ± 3,2 Newton. Se encontraron correlaciones positivas y estadísticamente significativas entre la fuerza prensil y la masa musculoesquelética (r = 0,73), agua corporal total (r = 0,73) y proteínas (r = 0,74). Discusión: Nuestros resultados son consistentes con evidencias previas que identifican a la fuerza prensil como un indicador de la composición corporal, específicamente en las variables de masa musculoesquelética y proteínas. Conclusión: Los niños en el tercil más alto de fuerza prensil presentan los terciles más altos de masa musculoesquelética, agua corporal total y proteínas.

Introduction: Some studies have found a relationship between excess weight and low relative grip strength. In countries with medium and low socioeconomic income, there is little evidence evaluating grip strength and its relationship with body composition in the pediatric population. Objective: To evaluate the correlation between grip strength and body composition of schoolchildren from Bucaramanga, Colombia. Materials and Methods: A cross-sectional, analytical, correlational pilot study was conducted. Schoolchildren from Bucaramanga, Colombia participated. The main dependent variables were muscle mass, total body water, protein (kg), and percentage of body fat. The independent variable corresponded to the prehensile force. Spearman's Correlation Coefficient was used to explore the relationship between variables. Results: The average prehensile force in the total sample was 13.8±3.2 Newton. Positive and statistically significant correlations were found between grip strength and musculoskeletal mass (r=0.73), total body water (r=0.73), and protein (r=0.74). Discussion: Our results are consistent with previous evidence that identifies grip strength as an indicator of body composition, specifically in the variables of musculoskeletal mass and protein. Conclusion: Children in the highest tertile of prehensile strength present the highest tertiles of skeletal muscle mass, total body water, and protein.

A spurious elevation of serum creatinine level in a patient with Crohn's disease without histologic kidney damage: a case report and review of the literature / Elevação espúria do nível de creatinina sérica em ­paciente com doença de Crohn sem lesão renal histológica: relato de caso e revisão da literatura

ABSTRACT Patients with inflammatory bowel disease (IBD) are prone to develop kidney injury. Renal involvement in IBD patients is usually diagnosed by the measurement of serum creatinine and the estimation of the glomerular filtration rate. We describe a patient with IBD who presented with large fluctuations in his serum creatinine level (~3.0-fold) without significant histologic abnormalities and with a normal cystatin C level. This appears to be related to a high-protein diet and intermittent fasting. Even though the impact of a high-protein diet on mild elevations of the serum creatinine level has been described, large fluctuations in serum creatinine from diet alone, as seen in this case, have never been reported, raising the question about the potential contribution of inflamed bowel on gut absorption or metabolism of creatinine. This case highlights the importance of a detailed history, including the dietary habits, when encountering a patient with increased serum creatinine level, and careful interpretation of serum creatinine in a patient with a creatinine high-protein diet or underlying IBD.

RESUMO Pacientes com doença inflamatória intestinal (DII) são propensos a desenvolver lesão renal. O envolvimento renal em pacientes com DII é geralmente diagnosticado pela medição da creatinina sérica e pela estimativa da taxa de filtração glomerular. Descrevemos um paciente com DII que apresentou grandes flutuações em seu nível de creatinina sérica (~3,0 vezes) sem anormalidades histológicas significativas e com nível normal de cistatina C. Isso parece estar relacionado a uma dieta rica em proteínas e jejum intermitente. Ainda que o impacto de uma dieta rica em proteínas em elevações leves do nível de creatinina sérica tenha sido descrito, nunca foram relatadas grandes flutuações na creatinina sérica apenas devido à dieta, como observado neste caso, o que levanta a questão sobre a possível contribuição do intestino inflamado na absorção intestinal ou no metabolismo da creatinina. Esse caso destaca a importância de um histórico detalhado, incluindo os hábitos alimentares, ao se deparar com um paciente com nível de creatinina sérica aumentado, e a interpretação cuidadosa da creatinina sérica em um paciente com dieta rica em proteínas ou DII subjacente.

Effects of Chemical inhibition of histone deacetylase proteins in the growth and virulence of Macrophomina phaseolina (Tassi) Goid / Efectos de la inhibición química de las proteínas desacetilasas de histonas en el crecimiento y la virulencia de Macrophomina phaseolina (Tassi) Goid

Abstract Chromatin remodeling enzymes are important "writers'', "readers'' and "erasers'' of the epigenetic code. These proteins are responsible for the placement, recognition, and removal of molecular marks in histone tails that trigger structural and functional changes in chromatin. This is also the case for histone deacetylases (HDACs), i.e., enzymes that remove acetyl groups from histone tails, signaling heterochromatin formation. Chromatin remodeling is necessary for cell differentiation processes in eukaryotes, and fungal pathogenesis in plants includes many adaptations to cause disease. Macrophomina phaseolina (Tassi) Goid. is a nonspe-cific, necrotrophic ascomycete phytopathogen that causes charcoal root disease. M. phaseolina is a frequent and highly destructive pathogen in crops such as common beans (Phaseolus vulgaris L.), particularly under both water and high temperature stresses. Here, we evaluated the effects of the classical HDAC inhibitor trichostatin A (TSA) on M. phaseolina in vitro growth and virulence. During inhibition assays, the growth of M. phaseolina in solid media, as well as the size of the microsclerotia, were reduced (p <0.05), and the colony morphology was remark-ably affected. Under greenhouse experiments, treatment with TSA reduced (p <0.05) fungal virulence in common bean cv. BAT 477. Tests of LIPK, MAC1 and PMK1 gene expression during the interaction of fungi with BAT 477 revealed noticeable deregulation. Our results provide additional evidence about the role of HATs and HDACs in important biological processes of M. phaseolina.

Resumen Las enzimas remodeladoras de la cromatina son «escritores¼, «lectores¼ y «borradores¼ importantes del código epigenético. Estas proteínas son responsables de la localización, el reconocimiento y la remoción de las marcas moleculares sobre las terminaciones de las histonas que desencadenan cambios funcionales y estructurales en la cromatina. Es el caso de las desacetilasas de histonas (HDAC), enzimas que remueven grupos acetilo de las «colas¼ de las histonas, señalizando la formación de heterocromatina. La anterior es una actividad necesaria en los procesos de diferenciación celular de los eucariotas, y se conoce que la patogénesis fúngica en las plantas requiere de adaptaciones diversas para ocasionar enfermedad. Macrophomina phaseolina (Tassi) Goid. es un ascomiceto fitopatógeno, necrótrofo e inespecífico, causante de la pudrición carbonosa. Este es un hongo frecuente y altamente destructivo en cultivos como fríjol común (Phaseolus vulgaris L.), particularmente bajo estrés hídrico y térmico. En este trabajo evaluamos los efectos del inhibidor de HDAC clásicas tricostatina A (TSA) sobre el crecimiento in vitro y la virulencia de M. phaseolina. El TSA redujo el crecimiento de M. phaseolina en medio sólido y el tamano de los microesclerocios (p < 0,05), lo que afectó la morfología colonial. En invernadero, el tratamiento con TSA disminuyó (p<0,05) la gravedad de la infección en la variedad de frijol BAT 477. La expresión de los genes de patogenicidad LIPK, MAC1 y PMK1 durante la interacción del hongo con la planta reveló una desregulación importante. Estos resultados proporcionan evidencia adicional del papel que cumplen las HDAC en la regulación de procesos biológicos fundamentales de M. phaseolina. © 2023 Asociación Argentina de Microbiología. Publicado por Elsevier Espana, S.L.U.

Hemodiafiltración con reinfusión endógena del ultrafiltrado (HFR): hacia una diálisis convectiva, difusiva y adsortiva / Hemodiafiltration with endogenous reinfusion of the regenerated ultrafiltrate (HFR): Towards a convective, diffusive, and adsorptive dialysis

La hemodiafiltración con reinfusión endógena del ultrafiltrado (HFR) es una técnica de diálisis caracterizada por un cartucho de resina con poder adsorbente que combina los mecanismos difusión, convección y adsorción en un solo esquema terapéutico. Después de cerca de 20 años de experiencia clínica con HFR, el presente artículo revisa la evidencia acumulada con esta técnica, planteando si la adición de la adsorción, como tercer mecanismo depurativo, debería ser el siguiente paso en el tratamiento de los pacientes en hemodiálisis. La HFR, a pesar de producir una extensa eliminación de toxinas urémicas, ha demostrado reducir la pérdida de nutrientes y componentes fisiológicos durante la sesión de diálisis frente a la hemodiafiltración on-line, mitigando el estado inflamatorio y el estrés oxidativo en esta población. Además de su facilidad de uso, la técnica también es altamente biocompatible y puede utilizarse en situaciones de un acceso vascular comprometido. En base a estas observaciones, la HFR parece ser una técnica especialmente útil para pacientes con elevada comorbilidad, incluyendo aquellos con fragilidad, desnutrición o enfermedad cardiovascular. En esta revisión, como panel de consenso de nefrólogos con experiencia clínica en HFR, examinamos la literatura existente y resumimos nuestros puntos de vista sobre cómo usar esta técnica, qué perfil de paciente puede ser más adecuado para la HFR, y cómo prescribir y monitorizar de manera práctica esta modalidad de diálisis (AU)

Hemodiafiltration with endogenous reinfusion of the ultrafiltrate (HFR) is a dialysis technique characterized by a resin cartridge with adsorptive properties that combines the mechanisms of diffusion, convection, and adsorption in a single therapeutic regimen. After nearly 20 years of clinical experience with HFR, this article reviews the accumulated evidence with this technique, considering whether adsorption reduction, as a third purification mechanism, should be the next step in the treatment of hemodialysis patients. HFR, beyond producing an extensive removal of uremic toxins, has demonstrated to reduce the loss of nutrients and other physiological components during the dialysis session as compared to online hemodiafiltration, ameliorating the inflammatory state and oxidative stress in this population. In addition to its ease of use, the technique is also highly biocompatible and can be used in patients with a compromised vascular access. Based on these observations, HFR appears to be an especially useful therapy for high-comorbidity patients, including those with frailty, malnutrition, or cardiovascular disease. In this review, we, as a consensus panel of nephrologists experienced with HFR, survey existing literature and summarize our views on when to use this technique, which patients may be best suited for HFR, and how to effectively prescribe and monitor this modality of dialysis in daily clinical practice (AU)