Research progress on the effect of mitochondrial network remodeling on macrophages / 细胞与分子免疫学杂志

Remodeling of the mitochondrial network is an important process in the maintenance of cellular homeostasis and is closely related to mitochondrial function. Interactions between the biogenesis of new mitochondria and the clearance of damaged mitochondria (mitophagy) is an important manifestation of mitochondrial network remodeling. Mitochondrial fission and fusion act as a bridge between biogenesis and mitophagy. In recent years, the importance of these processes has been described in a variety of tissues and cell types and under a variety of conditions. For example, robust remodeling of the mitochondrial network has been reported during the polarization and effector function of macrophages. Previous studies have also revealed the important role of mitochondrial morphological structure and metabolic changes in regulating the function of macrophages. Therefore, the processes that regulate remodeling of the mitochondrial network also play a crucial role in the immune response of macrophages. In this paper, we focus on the molecular mechanisms of mitochondrial regeneration, fission, fusion, and mitophagy in the process of mitochondrial network remodeling, and integrate these mechanisms to investigate their biological roles in macrophage polarization, inflammasome activation, and efferocytosis.

Oxytocin & well-being as promoters of affect regulation and homeostasis: a neuroscientific review / Ocitocina & bem-estar como promotores da regulação afetiva e da homeostase: uma revisão neurocientífica / Oxitocina y bienestar como promotores de la regulación del afecto y de la homeostasis: una revisión neurocientífica

Context: The term "Well-being" [WB] has many different meanings in scientific literature. Objectives: To search specific situations and related semantics for feelings of well-being [WB] associated to oxytocin [OT] release. Data sources: A systematic review using PRISMA guidelines in PubMed, BVS Virtual (Medline, Lilacs) and SIBI-USP Portal de Busca Integrada (1970-1999 & 2014-2018). Study selection: Reviews and clinical trials (PICOS) on OT, & WB and similar concepts in humans. Data extraction: Independent selection of articles by two reviewers; selection of articles by one reviewer, using predefined criteria. Data synthesis: 46 articles were selected out of 339, with 26 additional articles. Main data referred to social situations, sensorial stimuli, trust and psychiatric and health studies. Conclusions: The identified variables involved brain-body-mind interactions, and health/disease; translational neuroscience seems to be the best theoretical reference to investigate it.

Contexto: O termo "Bem-estar" [WB] apresenta muitos significados diferentes na literatura. Objetivos: Buscar situações específicas e semânticas relacionadas a sentimentos de bem-estar [WB] ligados à ocitocina [OT]. Fontes de dados: Revisão sistemática a partir das Referências PRISMA nas bases de dados PubMed, BVS Virtual (Medline, Lilacs) and SIBI-USP Portal de Busca Integrada (1970-1999 & 2014-2018). Seleção do estudo: revisões e ensaios clínicos (PICOS) sobre OT, & WB e sinônimos, em humanos. Extração de dados: seleção independente de artigos por dois revisores. Um revisor selecionou os textos utilizando critérios pré-definidos. Síntese dos dados: Dentre 339 artigos, 46 foram selecionados, e mais 26 posteriormente adicionados. Os principais dados obtidos referiam-se a situações sociais, estímulos sensoriais, confiança e estudos psiquiátricos e de saúde. Conclusões: As variáveis identificadas envolveram interações cérebro-corpo-mente e saúde; A neurociência translacional parece ser o melhor referencial teórico para investigá-la.

Contexto: El termo "Bienestar" [WB] abarca muchos significados diferentes en la literatura científica. Objetivos: buscar situaciones y semánticas sobre sentimientos de bienestar [WB] asociados con la produccion de oxitocina [OT]. Fuentes de datos: Revisión sistemática en PubMed, BVS Virtual (Medline, Lilacs) y SIBI-USP Portal de Busca Integrada (1970-1999; 2014-2018). Selección de estudios: revisiones y ensayos clínicos (PICOS) en OT, & WB y sinónimos, en humanos. Extracción de datos: Extracion independiente de artículos por dos revisores; selección de artículos por un revisor, utilizando criterios predefinidos. Síntesis de datos: se seleccionaron 46 artículos dentre 339, y mas 26 adicionales. Los datos principales se referían a situaciones sociales, estímulos sensoriales, confianza y estudios psiquiátricos y de salud. Conclusiones: Las variables identificadas involucraron interacciones cerebro-cuerpo-mente y salud; La neurociencia traslacional parece ser el mejor marco teórico para investigarlo.

Fluid and hemodynamic management in hemodialysis patients: challenges and opportunities / Manejo hídrico e hemodinâmico em pacientes em hemodiálise: desafios e oportunidades

Abstract Fluid volume and hemodynamic management in hemodialysis patients is an essential component of dialysis adequacy. Restoring salt and water homeostasis in hemodialysis patients has been a permanent quest by nephrologists summarized by the 'dry weight' probing approach. Although this clinical approach has been associated with benefits on cardiovascular outcome, it is now challenged by recent studies showing that intensity or aggressiveness to remove fluid during intermittent dialysis is associated with cardiovascular stress and potential organ damage. A more precise approach is required to improve cardiovascular outcome in this high-risk population. Fluid status assessment and monitoring rely on four components: clinical assessment, non-invasive instrumental tools (e.g., US, bioimpedance, blood volume monitoring), cardiac biomarkers (e.g. natriuretic peptides), and algorithm and sodium modeling to estimate mass transfer. Optimal management of fluid and sodium imbalance in dialysis patients consist in adjusting salt and fluid removal by dialysis (ultrafiltration, dialysate sodium) and by restricting salt intake and fluid gain between dialysis sessions. Modern technology using biosensors and feedback control tools embarked on dialysis machine, with sophisticated analytics will provide direct handling of sodium and water in a more precise and personalized way. It is envisaged in the near future that these tools will support physician decision making with high potential of improving cardiovascular outcome.

Resumo O volume de fluidos e o controle hemodinâmico em pacientes em hemodiálise é um componente essencial da adequação da diálise. A restauração da homeostase do sal e da água em pacientes em hemodiálise tem sido uma busca constante por parte dos nefrologistas, no que condiz à abordagem do "peso seco. Embora essa abordagem clínica tenha sido associada a benefícios no desfecho cardiovascular, recentemente tem sido questionada por estudos que mostram que a intensidade ou agressividade para remover fluidos durante a diálise intermitente está associada a estresse cardiovascular e dano potencial a órgãos.para remover fluidos durante a diálise intermitente está associada a estresse cardiovascular e dano potencial a órgãos. Uma abordagem mais precisa é necessária para melhorar o desfecho cardiovascular nessa população de alto risco. A avaliação e monitorização do estado hídrico baseiam-se em quatro componentes: avaliação clínica, ferramentas instrumentais não invasivas (por exemplo, US, bioimpedância, monitorização do volume sanguíneo), biomarcadores cardíacos (e.g. peptídeos natriuréticos), algoritmos e modelagem de sódio para estimar a transferência de massa. O manejo otimizado do desequilíbrio hídrico e de sódio em pacientes dialíticos consiste em ajustar a remoção de sal e líquido por diálise (ultrafiltração, dialisato de sódio), e restringir a ingestão de sal e o ganho de líquido entre as sessões de diálise. Tecnologia moderna que utiliza biosensores e ferramentas de controle de feedback, hoje parte da máquina de diálise, com análises sofisticadas, proporcionam o manejo direto sobre o sódio e a água de uma maneira mais precisa e personalizada. Prevê-se no futuro próximo que essas ferramentas poderão auxiliar na tomada de decisão do médico, com alto potencial para melhorar o resultado cardiovascular.

Functional Features of Hemocoagulation in rats with Experimentally formed Arterial Hypertension in Conditions of Increased Motor Activity

In rats with experimentally formed arterial hypertension, lipid perxidation in the plasma, amplification of blood chotting mechanisms with a decrease in anticoagulation and fibrinolysis was noted. Regular forced jogging provided the experimental rats with a positive dynamic of all the indicators considered. Thus, with increased muscular activity, the level of acyl hydro-peroxides of plasma decreased in rats with arterial hypertension formed due to the enhancement of its antioxidant activity. In addition, with the increase in muscle activity in experimental rats, normalization of clotting factor activity, indices of general coagulation tests, antithrobin III activity and protein C was achieved. This was accompanied by a normalization of the level of plasminogen, a2-antiplasmin and spontaneous euglobulin lysis time. In rats with formed arterial hipertension with stgandard physical activity, the initial violations of the measured parameters were completely preserved (AU)

The effect of continuous ventilation on thiol-disulphide homeostasis and albumin-adjusted ischemia-modified albumin during cardiopulmonary bypass

Abstract Objective: To investigate the effect of continuous lung ventilation with low tidal volume on oxidation parameters, such as thiol/disulphide homeostasis and albumin-adjusted ischemia-modified albumin (AAIMA), during cardiopulmonary bypass (CBP) in coronary artery bypass grafting (CABG). Methods: Seventy-four patients who underwent elective CABG with CPB were included in the study. Blood samples were taken in the preoperative period, 10 minutes after CPB, and six and 24 hours postoperatively. Patients were assigned to the continuous ventilation group (Group 1, n=37) and the non-ventilated group (Group 2, n=37). The clinical characteristics, thiol/disulphide homeostasis, ischemia-modified albumin (IMA), and AAIMA levels of the patients were compared. Results: A significant difference was found between the groups regarding native thiol, total thiol, and IMA levels at the postoperative 24th hour (P=0.030, P=0.031, and P=0.004, respectively). There was no difference between the groups in terms of AAIMA. AAIMA levels returned to preoperative levels in Groups 1 and 2, at the 6th and 24th postoperative hours, respectively. Length of hospital stay was significantly shorter in Group 1 (P<0.001) than in Group 2. Conclusion: Continuous ventilation during CPB caused an increase in native and total thiol levels, an earlier return of AAIMA levels, and shorter hospital stay. Continuous ventilation may reduce the negative effects of CPB on myocardium (Table 2, Figure 1, and Reference 31).

The differences in homeostasis model assessment values in type 2 diabetic patients with different lengths of history of diabetes

ABSTRACT Objective Type 2 diabetes (T2DM) is characterized by the progressive deterioration of pancreatic islet β-cell function over time and insulin resistance. Knowing more about the differences in pancreatic islet function in T2DM patients who have had diabetes for different lengths of time can help improve therapy for T2DM. Subjects and methods We conducted a cross-sectional study to compare islet β-cell function and insulin resistance in T2DM patients (n = 3,254) who had had diabetes for different lengths of time and those in normal controls (n = 794) using ANOVA and LSD analysis. Results We found that compared with that in normal controls, HOMA-β in T2DM patients with a history of diabetes of less than 1 year was lower (approximately 52% of that of normal controls, p = 0.003), while HOMA-IR in these patients was higher (approximately 50% of that of normal controls, p = 0.007). Compared with that in other diabetic patients, HOMA-β in patients with a history of diabetes of more than 30 years was the lowest. HOMA-IR in patients with a history of diabetes of between 20 and 30 years was lower than that in other diabetic patients (p < 0.05). Conclusions There were obvious decreases in HOMA-β and increases in HOMA-IR in T2DM patients with a history of diabetes of less than 1 year compared with those in normal controls. Therefore, early screening and intervention for T2DM might help improve islet function and delay the progression of diabetes.

Tendências temporais da prevalência de Helicobacter pylori em Itajaí - SC: um estudo retrospectivo de 25 anos baseado em banco de dados endoscópicos / Time trends of helicobacter pylori prevalence in itajaí - sc: a retrospective study of 25 years based on endoscopic database

ABSTRACT BACKGROUND: The bacterium Helicobacter pylori is strongly associated with the development of gastric adenocarcinoma. Currently, the prevalence in developed countries is 40%, but this value increases considerably in developing countries, which can reach rates bigger than 90%. OBJECTIVE: The objective of this study was to determine the mean and annual prevalence of Helicobacter pylori infection in patients from Itajaí during the period from July 1992 to April 2016, as well as the gender and age groups most affected. METHODS: After consent of the clinical director of the Gastroclinica Itajaí and confidentiality commitment about the research, the database of the Endoscopy Service of the clinic was evaluated. All the patients who underwent their first upper digestive endoscopy with urease test and/or histological analysis were included. The data were submitted to statistical analysis of prevalence by gender, age group and years of study, with subsequent correction through the confidence interval. RESULTS: The mean prevalence of Helicobacter pylori infection thru all years of study was 50.07%. With the calculation of the annual prevalences, it was evident the gradual reduction of infection in the population of Itajaí, that was 81.3% in 1992, declining to 33% in the year of 2016. When classifying the prevalence of infection by gender, it was higher in males (53.59%), and gender distribution by age group showed no statistically significant difference among genders between the ages of 40 and 80 years. In relation to the age group, the highest prevalence was in the group between 40 and 49 years. CONCLUSION: Although this study is retrospective and based on endoscopic database analysis, without access to clinical data of patients such as prior use of proton pump inhibitor and antibiotics to endoscopy, its results are important because they may reflect the current panorama of Helicobacter pylori infection in the city under study, where it has been presenting a gradual reduction of prevalence over the years, with current rates similar to that of developed countries (33%). Future studies are needed to confirm our data.

RESUMO CONTEXTO: A bactéria Helicobacter pylori associa-se fortemente ao desenvolvimento do adenocarcinoma gástrico. Atualmente, a prevalência em países desenvolvidos é de 40%, porém esse valor cresce consideravelmente em países em desenvolvimento, que chegam a alcançar taxas de até 90%. OBJETIVO: O objetivo desta pesquisa foi determinar a prevalência média e anual da infecção por Helicobacter pylori nos pacientes de Itajaí durante o período de julho de 1992 a abril de 2016, assim como o sexo e as faixas etárias mais acometidas. MÉTODOS: Após consentimento do diretor técnico da Gastroclínica Itajaí e comprometimento de sigilo em relação à pesquisa, foi avaliada a base de dados do Serviço de Endoscopia da clínica. Foram selecionados todos os pacientes que realizaram pela primeira vez o exame de endoscopia digestiva alta com teste da urease e/ou análise histológica. Os dados obtidos foram submetidos à análise estatística de prevalência por sexo, faixa etária e anos do estudo, com posterior correção dos dados através do intervalo de confiança. RESULTADOS: A prevalência média da infecção por Helicobacter pylori em todos os anos de estudo foi de 50,07%. Com o cálculo das prevalências anuais, ficou evidente a redução gradual da infecção na população de Itajaí, que era de 81,3% em 1992, passando a 33% no ano de 2016. Ao classificar a prevalência da infecção por gênero, foi maior no sexo masculino (53,59%) e a distribuição dos gêneros por faixa etária não mostrou diferença estatisticamente significativa entre os sexos entre as idades de 40 a 80 anos. Em relação à faixa etária, a maior prevalência foi no grupo entre 40 e 49 anos. CONCLUSÃO: Embora este estudo seja retrospectivo e baseado em análise de banco de dados de endoscopias digestivas, sem acesso a dados clínicos de pacientes como uso prévio de nibidor de bomba de próton e antibióticos à endoscopia, seus resultados são importantes, pois podem refletir o panorama atual da infecção por Helicobacter pylori no município em estudo, que vem apresentando uma redução gradual da prevalência ao longo dos anos, com taxas atuais semelhantes às dos países desenvolvidos (33%). Estudos futuros são necessários para confirmar nossos dados.

Correlação entre a circunferência do pescoço e resistência a insulina em pacientes com DHGNA / The correlation of neck circumference and insulin resistance in nafld patients

ABSTRACT BACKGROUND: Insulin resistance, especially that induced by obesity, plays a central role in the development of non-alcoholic fatty liver disease. Although the evaluation of overweight patients is important, the nutritional assessment tools used in clinical practice have limitations. Neck circumference (NC), from this, becomes a viable and low-cost alternative, which seems to be related to the accumulation of fat in the hepatic tissue. OBJECTIVE: To evaluate the association between NC and metabolic alterations in patients with non- alcoholic fatty liver disease. METHODS: A cross-sectional study performed in 82 patients, of whom 76 underwent liver biopsy. We performed weight, height, abdominal circumference and NC measures. Values of NC ≥42 cm and ≥36 cm were considered as altered for men and women, respectively. Laboratory tests and liver biopsy result were collected in the participants' charts. We evaluated fasting blood glucose levels, insulin, glycosylated hemoglobin, triglycerides, total cholesterol, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), ferritin, alkaline phosphatase, gamma glutamyltransferase, albumin, total bilirubin, direct bilirubin, glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase and the HOMA-IR index. RESULTS: We evaluated eighty-two patients. Patients with altered NC had increased body mass index (P=0.043), abdominal circumference (P=0.007), insulin (P=0.003) and HOMA-IR (P=0.029) when compared to those with adequate NC. NC was significantly correlated with reduced levels of high-density cholesterol (HDL-C) in men (r= -042, P<0.05), increased insulin levels in men and female (rs=0.47; P<0.05 and rs=0.51; P<0.01, respectively), as well as higher HOMA-IR index both males (rs=0.49; P<0.01) and female (rs=0.30; P<0.05). There was no significant association between NC and liver outcomes (r=0.145; P=0.36). CONCLUSION: NC is associated with the HOMA-IR index in patients with non-alcoholic fatty liver disease. NC can be used in the screening of insulin resistance in these patients, considering that insulin resistance plays a key role in the progression of the disease.

RESUMO CONTEXTO: A resistência à insulina, em especial a induzida pela obesidade, desempenha papel central no desenvolvimento da doença hepática gordurosa não alcoólica (DHGNA). Embora seja importante a avaliação de pacientes com excesso de peso, as ferramentas de avaliação nutricional utilizadas na prática clínica apresentam limitações. A circunferência do pescoço, a partir disso, torna-se uma alternativa viável e de baixo custo, a qual parece estar relacionada ao acúmulo de gordura no tecido hepático. OBJETIVO: Avaliar a associação entre a circunferência do pescoço (CP) e as alterações metabólicas em pacientes com DHGNA. MÉTODOS: Estudo transversal realizado em 82 pacientes, dos quais 76 foram submetidos à biópsia hepática. Foram realizadas as medidas de peso, altura, circunferência abdominal e CP. Valores de CP ≥42 cm e ≥36 cm foram considerados alterados para homens e mulheres, respectivamente. Os exames laboratoriais e o resultado da biópsia hepática foram coletados dos prontuários dos participantes. Foram avaliados os níveis glicêmicos em jejum, insulina, hemoglobina glicosilada, triglicerídeos, colesterol total, lipoproteína de alta densidade (HDL-C), lipoproteína de baixa densidade (LDL-C), ferritina, fosfatase alcalina, gama glutamiltransferase, albumina, bilirrubina total, bilirrubina direta, transaminase glutâmico-oxalacética, transaminase glutâmico-pirúvica e o índice HOMA-IR. RESULTADOS: Foram avaliados 82 pacientes. Os pacientes com CP alterada apresentaram aumento do índice de massa corporal (P=0,043), circunferência abdominal (P=0,007), insulina (P=0,003) e HOMA-IR (P=0,029) quando comparados àqueles com CP adequada. A CP foi significativamente correlacionada com níveis reduzidos de colesterol de alta densidade (HDL-C) em homens (r= -042, P<0,05), aumento dos níveis de insulina em homens e mulheres (rs=0,47, P<0,05 e rs = 0,51; P<0,01, respectivamente), bem como maior índice HOMA-IR, tanto do sexo masculino (rs=0,49; P<0,01) quanto do feminino (rs=0,30; P<0,05). Não houve associação significativa entre CP e os desfechos hepáticos (r=0,145, P=0,36). CONCLUSÃO: A CP está associada com o índice HOMA-IR em pacientes com DHGNA. A CP pode ser utilizada no rastreamento da resistência à insulina nesses pacientes, considerando que a resistência à insulina desempenha um papel fundamental na progressão da doença.

ABSI is a poor predictor of insulin resistance in Chinese adults and elderly without diabetes

ABSTRACT Objective: Recently, a new obesity index (A Body Shape Index, ABSI) based on waist circumference (WC) was developed, and high ABSI corresponds to a more central concentration of body volume. It is well known that central obesity is closely linked with insulin resistance (IR). Therefore, our study aimed to examine the discriminatory power of ABSI for IR in Chinese adults and elderly without diabetes. Subjects and methods: In 2007, a cross-sectional study was made. In this study, 570 individuals without diabetes were available for analysis (male: 56.1%, mean age: 62.3 ± 6.5 years). Insulin resistance was assessed by homeostasis model assessment (HOMA-IR). Areas under the receiver operating characteristic (ROC) curves were determined to identify variables/models that could predict insulin resistance. Results: ABSI was associated with IR, the cut-off points was 0.0785 m11/6kg-2/3 to identifying IR and the area under the ROC (AUC) curve was 0.618 (95%CI: 0.561-0.675), which was not better than body mass index BMI (AUC = 0.753; 95%CI: 0.706-0.801), WC (AUC = 0.749; 95%CI: 0.700-0.797), and fasting plasma glucose (FPG, AUC = 0.752; 95%CI: 0.705-0.799). Furthermore, combination with ABSI could improve the discriminatory power of other variables for IR. The AUC curve increased from 0.753 to 0.771for BMI, 0.749 to 0.754 for WC, 0.752 to 0.769 for FPG, respectively. Conclusions: ABSI is associated with IR in the general Chinese adults and elderly without diabetes, but the discriminatory power for IR is poor. It is recommended that ABSI be used in combination with other variables.

Resistência insulínica interfere na resposta virológica sustentada em pacientes portadores de hepatite C crônica genótipo 3 tratados com peginterferon/ribavirina? / Does insulin resistance impair the virological response to peginterferon/ribavirin in chronic hepatitis c genotype 3 patients?

ABSTRACT BACKGROUND: Insulin resistance and diabetes mellitus are common extrahepatic manifestations of chronic hepatitis C (HCV). Insulin resistance assessed by HOMA-IR is associated with low rates of sustained virological response, especially in HCV genotype 1 positive patients treated with peginterferon/ribavirin. The effect of insulin resistance on sustained virologic response in HCV genotype 3 positive patients who were treated with peginterferon/ribavirin still remains unclear. OBJECTIVE: To evaluate the impact of insulin resistance on sustained virological response in HCV genotype 3 patients treated with peginterferon/ribavirin. METHODS: A retrospective multicenter study was performed to evaluate the impact of insulin resistance on sustained virological response in non-diabetic HCV genotype 3 positive patients treated with peginterferon and ribavirin. A total of 200 HCV genotype 3 positive patients were enrolled in the study. All patients were non-diabetic. Each patient had a HOMA-IR value measured before the initiation of HCV treatment with peginterferon/ribavirin. The treatment duration was at least 24 weeks. The HOMA-IR cut-off was defined in the study as ≥2.5 due to the coefficient of correlation with sustained virological response of 0.202 (P=0.004). RESULTS: Univariate analysis showed that age, aspartate aminotransferase, platelets, stage of fibrosis and HOMA-IR were predictors of sustained virological response. However multivariate analysis showed advanced fibrosis [OR=2.01 (95%CI: 0.986-4.119) P=0.05] and age [OR=1.06 (95%CI: 1.022-1.110) P=0.002] as negative predictors of sustained virological response. CONCLUSION: In this retrospective multicenter study of non-diabetic HCV genotype 3 positive patients, insulin resistance was not associated with the sustained virological response in patients who were treated with peginterferon/ribavirin.

RESUMO CONTEXTO: A resistência insulínica e o diabetes mellitus são frequentes manifestações extra-hepáticas da hepatite C crônica. A resistência insulínica medida pelo HOMA-IR está associada a uma baixa taxa de resposta virológica sustentada, principalmente em pacientes portadores de hepatite C crônica genótipo 1 tratados com peginterferon/ribavirina. Em relação aos pacientes portadores de hepatite C crônica genótipo 3 tratados com peginterferon/ribavirina, a influência da resistência insulínica na resposta virológica sustentada ainda não está esclarecida. OBJETIVO: Avaliar a influência da resistência insulínica na resposta virológica sustentada em pacientes portadores de hepatite C crônica genótipo 3. MÉTODOS: Estudo multicêntrico retrospectivo foi realizado para avaliar a influência da resistência insulínica na resposta virológica sustentada em pacientes não-diabéticos portadores de hepatite C crônica genótipo 3 tratados com peginterferon/ribavirina. Um total de 200 pacientes portadores de hepatite C crônica genótipo 3 foi incluído no estudo. Todos os pacientes eram não diabéticos e apresentavam medida de HOMA-IR antes do início do tratamento da hepatite C crônica com peginterferon/ribavirina. A duração do tratamento foi de pelo menos 24 semanas. O cut-off de HOMA-IR foi definido para este estudo como ≥2,5 devido ao coeficiente de correlação com a resposta virológica sustentada de 0,202 (P=0,004). RESULTADOS: Na análise univariada, idade, aspartato aminotransferase, plaquetas, grau de fibrose e HOMA-IR foram preditores de resposta virológica sustentada. No entanto, na análise multivariada, apenas fibrose avançada [OR=2,01 (95%IC: 0,986-4,119) P=0,05] e idade [OR=1,06 (95%IC: 1,022-1,110) P=0,002] estavam relacionados como preditores negativo de resposta virológica sustentada. CONCLUSÃO: Neste estudo multicêntrico, retrospectivo, em pacientes não diabéticos portadores de hepatite C genótipo 3, a resistência insulínica não estava associada à resposta virológica sustentada em pacientes tratados com peginterferon/ribavirina.

Autorregulação e situação problema no jogo: estratégias para ensinar multiplicação / Self-regulation and problem situation in the game: strategies to teach multiplication / Autorregulación y situación problema en el juego: estrategias para enseñar la multiplicación

O conceito de multiplicação na matemática nem sempre é apreendido pelo aluno devido à utilização de práticas pedagógicas convencionais. A partir desta constatação, partimos da tese de que situações ativas, promotoras de autorregulação por meio da resolução de problemas presentes nos jogos, podem ser uma proposta efetiva na construção de conceitos. Nessa pespectiva nosso objetivo foi analisar as contribuições do Jogo do Resto para a compreensão do conceito de multiplicação. Trata-se de uma pesquisa qualitativa e aplicada que foi realizada em uma sala de aula com 30 alunos do quarto ano do Ensino Fundamental, na qual se utilizou como recurso o Jogo do Resto. Foi possível concluir que o jogo, pelo contexto cognitivo e afetivo que promove, foi cenário deengajamento dos alunos à ação. Os processos de autorregulação e situação problema promovidos nas intervenções envolveram os alunos em condutas de esforço e enfrentamento resultando em apropriação do conceito pretendido.

The concept of multiplication in mathematics is not always learned by the student due to the use of conventional pedagogical practices. From this observation, we started from the thesis that active situations, promoting self-regulation through the solution of problems present in the games, it can be an effective proposal in constructing concepts. In this perspective our objective was to analyze the contributions of the Game of the Rest for the understanding of the concept of multiplication. It is a qualitative and applied research that was carried out in a classroom with 30 students of the fourth year of Elementary School, in which the Game of the Rest was used as a resource. It was possible to conclude that the game, through the cognitive and affective context that it promotes, was a scenario of students' engagement with the action. The processes of self-regulation and problem situation promoted in the interventions involved the students in conducts of effort and confrontation resulting in appropriation of the intended concept.

El concepto de multiplicación en las matemáticas no siempre es aprehendido por el alumno debido a la utilización de prácticas pedagógicas convencionales. A partir de esta constatación, partimos de la tesis de que situaciones activas, promotoras de autorregulación por intermedio de la resolución de problemas presentes en los juegos, pueden ser una propuesta efectiva en la construcción de conceptos. En esa perspectiva nuestro objetivo fue analizar las contribuciones del Juego del Resto para la comprensión del concepto de multiplicación. Se trata de una investigación cualitativa y aplicada que se realizó en una sala de clase con 30 alumnos del cuarto curso de la Enseñanza Primaria, en la cual se utilizó como recurso el Juego del Resto. Fue posible concluir que el juego, por el contexto cognitivo y afectivo que promueve, fue escenario de participación de los alumnos a la acción. Los procesos de autorregulación y situación problema promovidos en las intervenciones abarcaran los alumnos en conductas de esfuerzo y enfrentamiento resultando en apropiación del concepto pretendido.

Fisiología de la perfusión medular / Physiology of spinal perfusion

Introducción: En las últimas décadas ha aumentado el interés por el estudio de la fisiología de la perfusión a nivel de la médula espinal. Muchos de los tratamientos en pacientes con lesión medular han sido basados en el paralelismo de la dinámica vascular entre el cerebro y la médula. Conocer estos aspectos así como los métodos relacionados con su monitoria resulta favorable para la adecuada intervención del paciente con lesión a nivel medular. Objetivo: Realizar una revisión en la literatura científica de los aspectos más importantes que intervienen en la perfusión de la médula espinal, los mecanismos de autorregulación y su aplicación clínica dentro del estudio de la fisiología medular. Métodos: Con las palabras claves, se realizó una revisión no sistemática en las bases de datos correspondientes a OVID, Medline/PubMed, Science Direct. Resultados y Conclusiones: El papel de la autorregulación es vital en la conservación de la integridad de la médula espinal, realizar un adecuado control de ella así como de otros factores químicos y metabólicos son determinantes en el control del flujo sanguíneo medular y minimiza el riesgo de lesión medular secundaria. Las curvas de autorregulación para el cerebro y la médula espinal son virtualmente idénticas; dentro de un rango de 60-150 mmHg.

Introduction: Over the past decades the interest in the study of the physiology of perfusion at the level of the spinal cord has increased. Many treatments in patients with spinal cord injury have been based on the parallelism of the vascular dynamics between the brain and the spinal. Knowing about these aspects and methods related to their monitoring practice is favorable for a proper intervention of the patient with spinal cord injury. Objective: To do a scientific literature review on the most important aspects involved in spinal cord perfusion, autoregulatory mechanisms and their clinical applications in the study of spinal cord physiology. Methods: Using the keywords, a non-systematic review on the OVID, Medline/PubMed and Science Direct databases, was performed. Results and Conclusion: The role of autoregulation is vital in maintaining the integrity of the spinal cord, an adequate control of it as well as other chemical and metabolic factors are important in the control of medullary blood flow and minimizes the risk of secondary spinal cord injury. The autoregulation curves for the brain and spinal cord are virtually identical, within a range of 60-150 mmHg.

Uma nova perspectiva sobre a biologia da osseointegração / A new perspective in the biology of osseointegration

O termo osseointegração refere-se à ancoragem de um implante no tecido ósseo, de forma que esse implante possa suportar carga funcional. O processo de osseointegração envolve vários mecanismos biológicos e o entendimento desses mecanismos e do papel da superfície dos implantes nesse processo, auxiliará o clínico de duas maneiras importantes: 1) na escolha dos implantes mais apropriados para os seus pacientes; e 2) no reconhecimento de problemas que possam surgir após a colocação de um implante. Nesse artigo, abordaremos uma nova perspectiva sobre a osseointegração, baseada em um trabalho recente que demonstrou que a reparação peri--implantar pode ser considerada um processo de restauração da homeostasia óssea. Esse processo representa um fenômeno universal, com vários exemplos nas ciências naturais e biológicas. O crescimento exponencial da ancoragem do implante no tecido ósseo através do tempo leva a um novo equilíbrio que pode ser representado por uma simples equação, onde dois parâmetros são importantes: 1) o valor máximo da ancoragem entre o implante e osso (novo equilíbrio tecidual)e 2) o período através do qual esse equilíbrio é adquirido. Portanto, em condições experimentais,é importante monitorar o processo de reparo por um longo período de tempo para que esse novo equilibrio seja obtido. Esse período de tempo necessário para que a hemostasia seja adquirida é descrito por um parâmetro matemático chamado “Tau”, que surge como uma maneira única de quantificar e comparar a performance do processo de osseointegração dos implantes. Essa nova perspectiva sobre a osseointegração será discutida em detalhes nesse artigo.

Osseointegration refers to the anchorage of an implant in bone, to a degree that can with stand functional loading. Osseointegration comprises several distinct biological mechanisms. An under standing these phenomena, and the role of implant surface topography in this process,will assist the clinician in two important ways: 1) It will inform their choice of the most appropriate implant designs for their patients, and 2) It will facilitate their recognition of problemsthat may arise after implant placement. We describe herein a new perspective on osseointegration.It is based on recent work that has demonstrated that peri-implant healing may beregarded as a restoration of bony homeostasis. Restoration of homeostasis is a universal phenomenon of which there are a multitude of examples in the natural and biological worlds. Applied to bone healing, the exponential rise in bone anchorage with time reaches the new equilibrium.This can be modeled using a simple equation where two important parameters emerge: 1) The ultimate value of implant/bone anchorage, which represents the new tissue equilibrium and 2)The rate at which this equilibrium is reached. Thus, experimentally, it is important to monitorhealing over a relatively long time so that the new bony equilibrium, can be achieved. However,the rate at which homeostasis is reached, described by a single mathematical parameter “tau”,emerges as a unique means by which the osseointegration performance of implants can bequantified and compared. This new perspective on osseointegration will be discussed in moredetails herein.

Papel de la leptina como señal aferente en la regulación de la homeostasis energética / Role of leptin as afferent signal of energy homeostasis regulation

La obesidad es una enfermedad crónica caracterizada por un aumento patológico de grasa corporal generado por un desbalance entre los ingresos y los egresos energéticos; este exceso de energía se almacena en el tejido adiposo, el cual no solo almacena lípidos, sino que secreta numerosas hormonas, por lo que constituye el órgano endocrino de mayor tamaño del organismo. A diferencia de otras glándulas endocrinas, su masa es variable y puede aumentar o disminuir progresivamente de tamaño dependiendo de la edad, la ingesta alimentaria, la actividad física, la programación perinatal y la predisposición genética; se destaca dentro de los factores secretados la leptina, la cual participa en la regulación del balance energético y la secreción de gonadotropinas.El objetivo de la presente revisión bibliográfica es describir el papel de la leptina como señal aferente en la regulación de la homeostasis energética, y se destaca su importancia como uno de los mecanismos implicados en la patogénesis de la obesidad.

Obesity is a chronic disease characterized by a pathological rise of body fat generated by an imbalance between energy input and output. This energy excess is stored in the adipose tissue which not only stores lipids but also secretes numerous hormones and represents the biggest endocrine organ of the human body. Unlike other endocrine glands, it has a variable mass and may gradually increase or decrease its size depending on age, food intake, physical activity, perinatal scheduling and genetic predisposition. Among the secreted factors are leptin which participates in the regulation of energy balance and the gonadotropin secretions. The objective of this literature review was to describe the role of leptin as afferent signal in the regulation of energy homeostasis; its importance as one of the mechanisms involved in obesity pathogenesis was underlined.

Lipoenxertia subcicatricial associada à rigottomy: uma análise clínica e microestrutural / Subcicatricial fat grafting associated with rigotomy: a clinical and microstructural analysis

INTRODUÇÃO: O aumento da sobrevida na fase aguda do paciente grande queimado faz também aumentar a prevalência das sequelas cicatriciais estético-funcionais. Ao pensarmos na relevância clínica da lipoenxertia subcicatricial, necessita-se da compreensão e avaliação microscópica das reais alterações após o procedimento. MÉTODOS: Foram selecionados oito pacientes, vítimas de queimadura por álcool, com tempo médio após queimadura de 12 meses (10-14 meses), sendo submetidos à lipoenxertia subcicatricial associada à Rigottomy. Foram realizadas biópsias cutâneas no pré e pós-operatório tardio com 14 semanas. Avaliados os quesitos: 1 - Melhora estético funcional da cicatriz pela escala de Vancouver; 2 - Análise quantitativa e qualitativa do colágeno cicatricial; 3 -Análise imunohistoquímica da vascularização cicatricial com anti-fator de crescimento derivado do endotélio vascular (antiVEGE). RESULTADOS: Ao compararmos o período pré e pós-lipoenxertia, pôde-se avaliar que houve melhora estético-funcional significativa e, microscopicamente, redefinição entre os limites da derme papilar e reticular; redução quantitativa e reorganização do colágeno, além do decréscimo da vascularização tecidual pela análise imunohistoquímica. CONCLUSÃO: O princípio básico de todo processo cicatricial fisiológico é reestabelecer a homeostasia local, ou seja, as etapas exageradamente intensificadas levam a alterações clínicas catastróficas. Ao realizar a lipoenxertia subcicatricial associada à Rigotomia, foi verificada, neste estudo, a melhora qualitativa e quantitativa do tecido. Sendo assim, torna-se evidente o futuro promissor deste procedimento para a complementação terapêutica das patologias cicatriciais.

INTRODUCTION: The increase in survival of large burn patients during the acute phase has also increased the prevalence of esthetic-functional scarring sequelae. With regard to the clinical relevance of subcicatricial fat grafting, the actual changes after the procedure need to be understood and microscopically evaluated. METHODS: Eight patients with alcohol burns, with an average time after burn of 12 months (10-14 months), who underwent subcicatricial fat grafting associated with rigotomy were selected. Skin biopsies were performed in before and 14 weeks after operation. The following issues were assessed: 1) esthetic-functional improvement of the scar, by using the Vancouver scar scale; 2) quantitative and qualitative analyses of cicatricial collagen; 3) immunohistochemical analysis of scar vascularization with anti-vascular endothelial growth factor (anti-VEGF) antibody. RESULTS: When comparing the pre- and post-fat grafting period, a significant esthetic-functional improvement and, microscopically, a redefinition of the boundaries of the papillary and reticular dermis were observed, as well as quantitative reduction and reorganization of collagen, in addition to the decrease of the vascularization of the tissue through immunohistochemical analysis. CONCLUSION: The basic principle of the whole physiological healing process is to reestablish local homeostasis, that is, excessively intensified steps that lead to severe clinical changes. When subcicatricial fat grafting associated with rigotomy was performed, qualitative and quantitative improvements of the tissue were verified in this study. Thus, it becomes evident that this procedure can complement the treatment of cicatricial pathologies.

Cadmium-induced apoptosis of Siberian tiger fibroblasts via disrupted intracellular homeostasis

BACKGROUND: Heavy metals can cause great harm to Siberian tigers in the natural environment. Cadmium (Cd2+) is an environmental contaminant that affects multiple cellular processes, including cell proliferation, differentiation, and survival. It has been shown to induce apoptosis in a variety of cell types and tissues. RESULTS: We investigated the apoptotic effects of Cd2+ on Siberian tiger fibroblasts in vitro. Our research revealed the typical signs of apoptosis after Cd²+ exposure. Apoptosis was dose- (0-4.8 µM) and duration-dependent (12-48 h), and proliferation was strongly inhibited. Cd²+ increased the activity of caspase-3, -8, and -9 and disrupted calcium homeostasis by causing oxidative stress and mitochondrial dysfunction. It also increased K+ efflux and altered the mRNA levels of Bax, Bcl-2, caspase-3, caspase-8, Fas, and p53. CONCLUSIONS: Our results suggest that Cd2+ triggers the apoptosis of Siberian tiger fibroblasts by disturbing intracellular homeostasis. These results will aid in our understanding of the effects of Cd2+ on Siberian tigers and in developing interventions to treat and prevent cadmium poisoning.

El papel del riñón en la homeostasis de la glucosa y drogas de acción renal en el tratamiento de la diabetes mellitus tipo 2 / Kidney role in the glucose's homeostasis and drugs of renal action in the treatment of type 2 diabetes mellitus

Los riñones contribuyen a la homeostasis de la glucosa a través de varios mecanismos, incluyendo la gluconeogénesis, utilización y reabsorción de la glucosa a partir del filtrado glomerular. Bajo condiciones fisiológicas normales, la glucosa filtrada es casi totalmente reabsorbida en el epitelio de las células tubulares; en consecuencia, no aparece glucosa en la orina. El transporte de glucosa dentro de las células epiteliales del túbulo se cumple gracias a cotransportadores activos glucosa-sodio (SGLT), una familia de proteínas dependientes de adenosin trifosfato (ATP) involucradas en el transporte de glucosa contra un gradiente de concentración con carga simultánea de sodio, igualmente en contra gradiente. La mayoría de la glucosa filtrada es reabsorbida por medio del SGLT2, un transportador de baja afinidad pero elevada capacidad localizado, predominantemente, en el segmento S1 del tubo contorneado proximal. Por largo tiempo la inhibición del SGLT2 ha sido considerada como un abordaje terapéutico potencial de la hiperglucemia en la diabetes mellitus tipo 2 (DM2), ya que al prevenir la reabsorción de glucosa por los túbulos renales promueven su excreción renal y descienden los valores de la glucemia. Los datos en humanos indican que los inhibidores de SGLT2 representan una estrategia novedosa y efectiva para controlar las cifras de glucemia en los pacientes con DM2. El recién publicado estudio EMPA-REG OUTCOME diseñado para examinar los desenlaces cardiovasculares con empagliflozina en sujetos con DM2 y enfermedad ardiovascular coexistente mostró beneficios tempranos, los cuales se mantuvieron durante el período de observación(AU)

The kidneys contribute to glucose homeostasis through several mechanisms, including gluconeogenesis, glucose use, and glucose reabsorption from the glomerular filtrate. Under normal physiological conditions, this filtered glucose is almost completely reabsorbed by renal tubular epithelial cells; thus, there is no glucose in urine. The transport of glucose into renal tubular epithelial cells is mediated by active cotransporters, the SGLT, a family of ATP-dependent proteins involved in the transport of glucose against a concentration gradient with simultaneous transport of Na+ down a concentration gradient. Most of the filtered glucose is reabsorbed through SGLT2, a low-affinity high-capacity transporter located predominantly in the S1 segment of the renal proximal tubule. Inhibition of SGLT2 has long been regarded as a potential treatment approach for hyperglycemia during T2DM, as they prevent glucose reabsorption from renal tubules, thereby promoting urinary glucose excretion and decreasing plasma glucose levels. Current data in humans indicate that SGLT2 inhibitors represent an effective and novel strategy to control the plasma glucose concentration in patients with T2DM. The recently published EMPA-REG OUTCOME trial, which assessed cardiovascular outcomes with empagliflozin therapy in persons with type 2 diabetes mellitus and coexisting cardiovascular disease showed that the benefits were noted early and continued throughout the study(AU)

Análisis de variabilidad del ritmo cardiaco y su relación con la sensibilidad insulínica en pacientes obesos y con sobrepeso / Heart rate variability and insulin resistance among obese males

Background: Heart rate variability analysis provides quantitative information about vagal and sympathetic modulation of cardiac function. Aim: To analyze the relationship between heart rate variability and insulin resistance in obese patients. Material and Methods: Male participants were studied, divided in 10 obese subjects aged 27 ± 2 years with a body mass index (BMI) of 31.2 ± 1.3 kg/m², 15 overweight subjects aged 24 ± 3 years with a BMI of 26.7 ± 1.5 kg/m² and 14 normal weight subjects aged 21 ± 2 years with a BMI of 22.5 ± 1.3 kg/m². Resting heart rate variability was measured in a period of 5 minutes. A spectral analysis was done measuring the low frequency/high frequency ratio (LF/HF). A non- linear analysis was carried out measuring the standard deviation of the instantaneous variation of RR intervals (SD1) and α-1 or a fractal analysis of RR interval complexity. A fasting blood sample was obtained to measure blood glucose and insulin and calculate the homeostasis model assessment for insulin resistance (HOMA-IR). Results: Among obese subjects HOMA-IR, LF/HF, α-1 and SD1 values were 2.6 ± 2.1, 2.4 ± 1.8, 1.2 ± 0.06 and 22.5 ± 10 respectively. The figures for normal weight subjects were 0.5 ± 0.1, 1.3 ± 0.2, 0.9 ± 0.3 and 26 ± 7.8 respectively. Conclusions: There is an association between spectral and fractal values of heart rate variability and HOMA-IR. These results may indicate a predominance of sympathetic control of heart rate among obese subjects.

The consensus sequence of FAMLF alternative splice variants is overexpressed in undifferentiated hematopoietic cells

The familial acute myeloid leukemia related factor gene (FAMLF) was previously identified from a familial AML subtractive cDNA library and shown to undergo alternative splicing. This study used real-time quantitative PCR to investigate the expression of the FAMLF alternative-splicing transcript consensus sequence (FAMLF-CS) in peripheral blood mononuclear cells (PBMCs) from 119 patients with de novo acute leukemia (AL) and 104 healthy controls, as well as in CD34+ cells from 12 AL patients and 10 healthy donors. A 429-bp fragment from a novel splicing variant of FAMLF was obtained, and a 363-bp consensus sequence was targeted to quantify total FAMLF expression. Kruskal-Wallis, Nemenyi, Spearman's correlation, and Mann-Whitney U-tests were used to analyze the data. FAMLF-CS expression in PBMCs from AL patients and CD34+ cells from AL patients and controls was significantly higher than in control PBMCs (P<0.0001). Moreover, FAMLF-CS expression in PBMCs from the AML group was positively correlated with red blood cell count (rs =0.317, P=0.006), hemoglobin levels (rs =0.210, P=0.049), and percentage of peripheral blood blasts (rs =0.256, P=0.027), but inversely correlated with hemoglobin levels in the control group (rs =–0.391, P<0.0001). AML patients with high CD34+ expression showed significantly higher FAMLF-CS expression than those with low CD34+ expression (P=0.041). Our results showed that FAMLF is highly expressed in both normal and malignant immature hematopoietic cells, but that expression is lower in normal mature PBMCs.