Lipid-induced hepatocyte-derived extracellular vesicles regulate hepatic stellate cell via microRNAs targeting PPAR-γ.

Background&aimsHepatic stellate cells (HSCs) play a key role in liver fibrosis in various chronic liver disorders including nonalcoholic fatty liver disease (NAFLD). The development of liver fibrosis requires a phenotypic switch from quiescent to activated HSCs. The triggers for HSCs activation in NAFLD remain poorly understood. We investigated the role and molecular mechanism of extracellular vesicles (EVs) released by hepatocytes during lipotoxicity in modulation of HSC phenotype.MethodsEVs were isolated from fat-laden hepatocytes by differential centrifugation and incubated with HSCs. EV internalization and HSCs activation, migration and proliferation were assessed. Loss- and gain-of-functions studies were performed to explore the potential role of PPAR-γ-targeting miRNAs carried by EVs into HSC.ResultsHepatocyte-derived EVs released during lipotoxicity are efficiently internalized by HSCs resulting in their activation, as shown by marked up-regulation of pro-fibrogenic genes (Collagen-I, α-SMA and TIMP-2), proliferation, chemotaxis and wound healing responses. These changes were associated with miRNAs shuttled by EVs and suppression of PPAR-γ expression in HSC. Hepatocyte-derived EVs miRNA content included various miRNAs that are known inhibitors of PPAR-γ expression with miR-128-3p being the most effectively transferred. Furthermore loss- and gain-of-function studies identified miR-128-3p as a central modulator of the effects of EVs on PPAR-γ inhibition and HSC activation.ConclusionOur findings demonstrate a link between fat-laden hepatocyte-derived EVs and liver fibrosis and have potential implications for the development of novel anti-fibrotic targets for NAFLD and other fibrotic diseases

Reconhecimento e Execução de Sentenças Estrangeiras: análise do projeto em andamento na Conferência da Haia de Direito Internacional Privado

O presente artigo busca analisar a recente evolução dos trabalhos sobre jurisdição internacional e reconhecimento e execução de sentenças estrangeiras (Judgments Project) desenvolvidos pela Conferência da Haia de Direito Internacional Privado, organização internacional que se dedica a elaborar normas para a unificação progressiva dessa área do direito entre seus Membros. Nos últimos quatro anos, um grupo de especialistas e acadêmicos de várias universidades e centros de pesquisa brasileiros - Grupo de Sentenças Estrangeiras (GSE) - tem se reunido periodicamente no Rio de Janeiro para discutir os itens da agenda da Reunião do Conselho de Assuntos Gerais da Conferência, objetivando contribuir para o avanço dos trabalhos da organização em torno da possível elaboração e adoção de uma convenção multilateral em matéria de reconhecimento e execução de sentenças estrangeiras. Como metodologia de análise, além de identificar as principais questões pendentes, o GSE vem formulando conclusões e recomendações de modo a reiterar a posição acadêmica dos especialistas brasileiros a respeito do Projeto de Sentenças Estrangeiras na Conferência. Iniciativas da academia e sociedade civil, cujos resultados se verificam nas reuniões descritas, são fator de mobilização em torno do debate de questões do direito internacional privado em importante foro multilateral, que é a Conferência da Haia de Direito Internacional Privado

CONTAMINAÇÃO POR STAPHYLOCOCCUS AUREUS NOS CHASSIS RADIOGRÁFICOS EM HOSPITAL DE ENSINO

Uma das ações rotineiras em um hospital é a realização de exames de raios X, onde são utilizados chassis radiográficos não descartáveis em pacientes distintos. Este estudo objetiva investigar esses chassis de uso comum, como veículos de infecção hospitalar, ajudando na disseminação de Staphylococcus spp. quanto à prevenção e controle de infecção hospitalar. O estudo foi realizado em um Hospital de Ensino no interior de São Paulo, foram estudados dois chassis radiográficos (18x24cm) e obtidas amostras para as culturas de dois destes chassis, em três momentos diferentes. Foram observados presença de unidades formadoras de colônia (UFC) de Staphylococcus spp., sendo que no chassi 1, 14,43%, e no chassi 2, 1,37% das colônias apresentaram a prova da coagulase positiva indicando ser Staphylococcus aureus. Propõe-se a padronização de um procedimento operacional padrão de higienização para esses chassis radiográficos na tentativa de minimizar o risco de contaminação bacteriana por Staphylococcus spp

In vitro evaluation of cutaneous penetration of acyclovir from semisolid commercial formulations and relation with its effective antiviral concentration

The evaluation of drug permeation/penetration of semisolid formulations into animal skin can be useful to supplement the pharmaceutical equivalence. This paper describes the in vitro assessment of acyclovir (ACV) into porcine skin from commercial formulations with etermination of drug concentration in different layers of cutaneous tissue to correlate with effective antiviral concentration in order to improve the equivalence decision. Studies were conducted using Franz cells and porcine skin. Selected pharmaceutical creams containing ACV had identical (reference and generic) and different (similar) excipients. A software program was employed for the simulation of antiviral effectiveness in the skin. Regarding ACV skin penetration, the first batch of the generic product showed a significant difference from reference and similar products, while in the second batch all products demonstrated equivalent drug penetration in the skin. Simulation studies suggest that formulations analysed exhibit a pharmacological effect even when in contact with Herpes simplex strains of high IC50 (inhibitory concentration required to reduce viral replication by 50%). According to results, it can be assumed that the in vitro cutaneous permeation/penetration study does not supply sensitivity information regarding small alterations of ACV semisolid formulations due to the variability inherent to the method, although it can be relevant to pharmaceutical equivalence studies in the development of semisolid products

Confirming the presence of HTLV-1 infection and the absence of HTLV-2 in blood donors from Arequipa, Peru

Epidemiological studies conducted in Peru disclosed HTLV-1 to be prevalent in different ethnic groups, and found HTLV-2 in some Amazonian Indians and in men who have sex with men. No data concerning HTLV-1/2 infection in blood donors from Arequipa, a highlands region in southern Peru, is available. We searched for the presence of HTLV-1 and HTLV-2 antibodies in 2,732 serum samples obtained from blood donors from this geographic area. HTLV-1/2-specific antibodies were detected using an enzyme-linked immunosorbent assay (ELISA) and were confirmed by Western blot (WB). Reactive sera had their blood bags discarded from donation, and the demographic characteristics of the donors were analyzed. Thirty-five sera (1.2%) were HTLV seroreactive by ELISA, and 25 were confirmed HTLV-1-positive by WB. One serum disclosed HTLV-positivity, and the remaining nine serum samples showed indeterminate results by WB; three of which had an HTLV-1 indeterminate Gag profile. The median age of HTLV-positive individuals was 34.6 years; 27 were male and eight were female. All individuals were from southern Peru: 27 from Arequipa, five from Puno, and three from Cuzco. HTLV co-positivity with hepatitis B (five sera) and syphilis (one serum) were detected. Previous transfusion and tattooing were observed in two and one individuals, respectively. No serum was positive for HTLV/HIV co-infection. This study confirmed, for the first time, HTLV-1 infection and the absence of HTLV-2 infection in blood donors from Arequipa, Peru and suggests vertical transmission as the major route of HTLV-1 transmission and acquisition in this geographic region.Estudos epidemiológicos conduzidos no Peru apontam a infecção por HTLV-1 como prevalente em diferentes grupos étnicos e por HTLV-2 restrita a alguns índios da região Amazônica e a homens que fazem sexo com homens. Não existem dados sobre a infecção por HTLV-1/2 em doadores de sangue de Arequipa, região montanhosa do sul do Peru. Portanto, o presente estudo pesquisou anticorpos anti-HTLV-1 e HTLV-2 em 2.732 doadores de sangue desta região geográfica. Foram utilizados na triagem sorológica os testes imunoenzimáticos (ELISA) e para confirmação dos resultados o Western Blot (WB). Soros reagentes no ELISA tiveram suas bolsas de sangue descartadas. Os resultados obtidos foram analisados de acordo com características demográficas dos indivíduos. Trinta e cinco soros (1,2%) resultaram HTLV-1/2 reagentes no ELISA, 25 confirmaram infecção por HTLV-1 no WB. Um soro resultou HTLV positivo e os nove soros restantes resultaram em padrão indeterminado no WB: três com perfil HTLV-1 Gag indeterminado. A média de idade dos indivíduos HTLV positivos foi de 34,6 anos; 27 do gênero masculino e oito do gênero feminino. Todos eram da região sul do país: 27 de Arequipa, cinco de Puno e três de Cuzco. Foi detectada co-positividade HTLV com hepatite B (cinco soros) e sífilis (um soro). Nenhum soro resultou positivo para a co-infecção HIV/HTLV. Havia dois indivíduos com transfusão prévia e um com tatuagem. Este trabalho confirma pela primeira vez infecção por HTLV-1 e ausência de infecção por HTLV-2 em doadores de sangue de Arequipa, sul do Peru e sugere que a transmissão vertical seja a principal via de transmissão/aquisição de HTLV-1 nesta região geográfica

Private internacional law chronicles

PRIVATE INTERNATIONAL LAW CHRONICLE

Experience of the cleft lip and palate clinic at the hospital general de México 2017-2023

Background: The care of cleft lip and palate patients at the general hospital of Mexico has nearly 70 years of experience. Methods: An observational study of a 7-year cohort of resolved cases of cleft lip and palate by the plastic and reconstructive surgery service of the general hospital of Mexico (2017-2023) was conducted. Results: The 121 patients were recorded, with 47 palatoplasties, 44 primary cheiloplasties, 24 secondary cheiloplasties, and 11 veloplasties performed. All patients are evaluated by a multidisciplinary team composed of plastic surgery, dentistry, clinical nutrition, speech therapy, audiology, genetics, and psychology to determine a comprehensive treatment plan. Conclusions: The data reported by the cohort in this work aligns with international reports. The frequency of cases decreased due to the COVID-19 pandemic, but has increased in recent years

Alterations and Chromosomal Variants in the Ecuadorian Population

Medical genetics is a field marked by fast progress. Even though it was at one point confined to a group of relatively rare diseases, today it has become a central component in the understanding of disorders and it is the subject of interest for all medical specialties. This paper, shares data on the chromosomal alterations and variations that have been diagnosed in Ecuadorian patients since 1998. A total of 2,636 individual cases have been analyzed by G-banding technique until February 2012. The present work shows this collection of data and the important findings that have appeared throughout these years in hopes that it can contribute to have a deeper understanding of the incidence of chromosomal aberrations and alterations in the Ecuadorian population