Bone marrow mononuclear cell transplantation rescues the glomerular filtration barrier and epithelial cellular junctions in a renovascular hypertension model.

NEW FINDINGS: What is the central question of this study? Can a single bone marrow mononuclear cell (BMMC) transplant into the subcapsular region of kidney improve cellular communication and adhesion, while restoring renal tissue cytoarchitecture and function during renovascular hypertension? What is the main finding and its importance? The BMMC transplantation restored connexin 40 expression and led to recovery of N- and E-cadherin levels within 15 days. It was observed, for the first time, that BMMC transplantation restores expression of nephrin, a component of the glomerular filtration barrier related to podocytes and the glomerular basal membrane. ABSTRACT: Stem cell therapy has emerged as a potential treatment for renal diseases owing to the regenerative potential of stem cells. However, a better understanding of the morphological and functional changes of damaged renal cells in the presence of transplanted stem cells is needed. The aim of this study was to investigate cell-cell communication and adhesion in renal parenchyma, with analysis of fibrosis, to evaluate renal morphology and function after bone marrow mononuclear cell (BMMC) transplantation in two-kidney-one-clip rats. The BMMC therapy significantly decreased blood pressure and renin expression, improved renal morphology and restored the glomerular filtration barrier, with remodelling of podocytes. In addition, there was a reduction in fibrosis, and connexin 40 and nephrin expression were significantly increased after 7 and 15 days of transplantation. Plasma creatinine, urea and total protein levels were restored, and proteinuria was reduced. Furthermore, N- and E-cadherin expression was increased soon after BMMC therapy. Green fluorescent protein-positive BMMCs were found in the renal cortex 24 and 48 h after transplantation into the renal subcapsule, and at 7 and 15 days after transplantation, these cells were observed throughout the renal medulla, indicating cellular migration. Therefore, these data suggest that transplanted BMMCs improve cell-cell communication and adhesion between damaged cells, which is accompanied by a recovery of renal morphology and function.

A naturalistic study of high-dose unilateral ECT among severely depressed inpatients: how does it work in the clinical practice?

BACKGROUND: Naturalistic studies can be useful tools to understand how an intervention works in the real clinical practice. This study aims to investigate the outcomes in a naturalistically treated depressed inpatients cohort, who were referred, or not, to unilateral ECT. METHODS: Depressed adults according to MINI admitted in a psychiatric unit were divided in unilateral ECT treated and non-ECT treated. Main outcomes were: depression improvement in Hamilton Rating Scale for Depression (HDRS-17) scores; response (HDRS-17 improvement ≥50 %); remission (HDRS-17 score ≤7); length of hospitalization. RESULTS: Forty-three patients were included in unilateral ECT group and 104 in non-ECT group. No differences of psychotic symptoms, melancholic features or past maniac episode were found between groups. Unilateral ECT group had a mean HDRS-17 score higher than non-ECT group at admission (ECT: 25.05 ± 1.03; non-ECT: 21.61 ± 0.69; p = 0.001), but no significant difference was found at discharge (ECT: 7.70 ± 0.81; non-ECT: 7.40 ± 0.51; p = 0.75). Unilateral ECT group had a larger HDRS-17 score reduction during treatment (ECT: 18.24 ± 1.18; non-ECT:14.20 ± 0.76; p = 0.004). There were no significant differences in response and remission rates between groups. Unilateral ECT group had longer mean duration of hospitalization in days (ECT: 35.48 ± 2.48; non-ECT: 24.57 ± 1.50; p < 0.001), but there were no difference in mean time of treatment (ECT group:27.66 ± 1.95; non-ECT: 24.57 ± 1.50; p = 0.25). CONCLUSIONS: Unilateral high-dose ECT is still a useful treatment option, in the real world clinical practice, to reduce the intensity of depressive symptoms in highly depressed inpatients.

Analysis of Mechanoreceptors and Free Nerve Endings of the Transverse Carpal Ligament.

Background: The treatment of carpal tunnel syndrome (CTS) by sectioning the transverse carpal ligament (TCL) is not exempt from complications. Some nerve branches may be damaged by the incision. The aim of this study is to identify and map the TCL nerve endings, serving as a guide for sectioning this structure in a zone with less nerve ending density. Methods: Ten TCLs were obtained from fresh frozen cadavers. The TCLs were measured, divided into 3 equal bands (radial, central, and ulnar), and submitted to cryostat sectioning. The sections were subjected to immunofluorescence with the protein gene product (PGP) 9.5 and confocal microscopy analysis. Results: All the specimens contained type I and type IV mechanoreceptors. Neural elements occupied 0.695 ± 0.056% of the ligament area. The density of the neural elements was greater in the radial, followed by the ulnar and central bands, with 0.730 ± 0.083%, 0.686 ± 0.009%, and 0.669 ± 0.031%, respectively. Conclusion: The present findings suggest that the region with the least potential for neural element injury during TCL release is the central third near the transition with the ulnar third. When performed distally to proximally with a slight inclination from the radial to the ulnar, this release compromises the lowest nerve element density. Topographically, the proximal limit of the release is the distal wrist crease, while the distal limit is the intersection of Kaplan cardinal line and the axis of the third webspace.

Associations of polymorphisms of folate cycle enzymes and risk of breast cancer in a Brazilian population are age dependent.

Polymorphisms in genes involved in folate metabolism have been shown to be implicated in breast cancer risk but with contradictory results. In this case-control study, we investigated the association between MTHFR C677T and A1298C, TYMS 5'-UTR, MTR A2756G and cSHMT C1420T and also the folate carrier (RFC1 G80A) and breast cancer risk in a northeastern Brazilian population. The study included 183 women diagnosed with breast cancer and 183 controls volunteers without any history of cancer. Also a significant number of healthy individuals were included for allelic frequency in the population studied. Risk of breast cancer was estimated by conditional logistic regression. An association with risk was found for women carrying the MTR A2756G polymorphic allele (AG, P = 0.0036; AG/GG, P = 0.0040), and a protective effect in carriers of the RFC1 G80A polymorphic allele (GA, P = 0.0015; AA, P = 0.0042). Stratifying the data by age (cutoff point of 50 years old), different distributions were observed for breast cancer risk. For women ≤50 years, the risk observed in the presence of the polymorphic allele MTR 2756 (AG/GG) in the general analysis was, restricted to this age group (P = 0.0118). Conversely, for women over 50, the risk of breast cancer development was statistically associated with the MTHFR 677CT genotype, but especially significant was risk associated with the presence of the polymorphic allele of cSHMT C1420T (P = 0.0120) and the protective effect associated with the RFC1 G80A polymorphism allele (P = 0.0021), was restrict to this age group. These data indicate that the cutoff age used (50 years old) was appropriate, since it was able to discriminate risk in each age group in the population studied and also to point to the importance of age in the analyses of cancer-associated polymorphisms.

Effects of mesenchymal stem cells conditioned medium treatment in mice with cholestatic liver fibrosis.

AIMS: The purpose of this work was to study the effects of mesenchymal stem cells conditioned medium (MSC CM) treatment in animals with cholestatic liver fibrosis. MATERIALS AND METHODS: We induced cholestatic liver fibrosis by bile duct ligation in C57Bl/6 mice. In the 5th and 6th days after bile duct ligation proceeding, conditioned medium obtained of cultures of mesenchymal stem cells derived from adipose tissue was injected in the animals. Blood levels of hepatic transaminases, alkaline phosphatase and albumin were measured in each group. Analysis of collagen deposition was realized by Picro Sirius red staining and cytokine profiling was performed by cytometric bead array (CBA). KEY FINDINGS: Our results showed that MSC CM treatment decreased levels of hepatic enzymes and collagen deposition in the liver. After MSC CM treatment, profibrotic IL-17A was decreased andIL-6 and IL-4 were increased. SIGNIFICANCE: In summary, MSC CM treatment demonstrated therapeutic potential to cholestatic liver fibrosis, favoring matrix remodeling and cytokine profile towards liver regeneration.

Ômega 3 na gestação e os impactos na depressão pós-parto: uma revisão narrativa / Omega 3 during pregnancy and impacts on postpartum depression: a narrative review / Omega 3 durante el embarazo e impactos en la depresión postparto: una revisión narrativa

Objetivo: Evidenciar através de uma revisão integrativa os resultados clínicos atuais do impacto do consumo de ômega 3 frente a depressão pós-parto. Método: Revisão integrativa da literatura realizada no período de Fevereiro a Julho de 2023 nas bases de dados Pubmed, LILACS, Medline e Scielo. Resultados:Foi realizada uma busca pelos descritores em saúde determinados e foram selecionadas 5 produções científicas que atenderam os critérios de inclusão. De modo geral, os trabalhos mostraram relações com a saúde do bebê e da mãe. No bebê, observou-se aumento do crescimento intrauterino, maior resposta do sistema nervoso central, melhor desenvolvimento neural, de retina, imunológico, cognitivo e físico. Já na saúde materna, observou-se aumento no processo antiinflamatório, melhor resposta imune, melhora no efeito neurotrófico do cérebro, aumento do metabolismo, melhora hormonal, menor risco cardiovascular, menores distúrbios neurológicos (incluindo a depressão) e distúrbios visuais. Conclusão:Mais estudos são necessários para elucidar os benefícios da suplementação de ômega-3 em gestantes no pós-parto

Objective: To show, through an integrative review, the current clinical results of the impact of omega 3 consumption on postpartum depression. Method:Integrative literature review carried out from February to July 2023 in the Pubmed, LILACS, Medline and Scielo databases. Results:A search was performed for specific health descriptors and 5 scientific productions that met the inclusion criteria were selected. In general, the studies showed relationships with the health of the baby and the mother. In the baby, there was an increase in intrauterine growth, greater response of the central nervous system, better neural, retinal, immunological, cognitive and physical development. In maternal health, there was an increase in the anti-inflammatory process, better immune response, improvement in the neurotrophic effect of the brain, increased metabolism, hormonal improvement, lower cardiovascular risk, lesser neurological disorders (including depression) and visual disturbances. Conclusion:More studies are needed to elucidate the benefits of omega-3 supplementation in postpartum pregnant women.

Objetivo: Mostrar, a través de una revisión integradora, los resultados clínicos actuales del impacto del consumo de omega 3 en la depresión posparto. Método:Revisión integrativa de la literatura realizada de febrero a julio de 2023 en las bases de datos Pubmed, LILACS, Medline y Scielo. Resultados:Se realizó una búsqueda de determinados descriptores de salud y se seleccionaron 5producciones científicas que cumplían con los criterios de inclusión. En general, los estudios mostraron relaciones con la salud del bebé y de la madre. En el bebé hubo un aumento del crecimiento intrauterino, mayor respuesta del sistema nervioso central,mejor desarrollo neural, retiniano, inmunológico, cognitivo y físico. En salud materna, hubo aumento del proceso antiinflamatorio, mejor respuesta inmunológica, mejora del efecto neurotrófico del cerebro, aumento del metabolismo, mejora hormonal, menor riesgo cardiovascular, menos trastornos neurológicos (incluyendo depresión) y alteraciones visuales. Conclusión:Se necesitan más estudios para dilucidar los beneficios de la suplementación con omega-3 en mujeres embarazadas posparto

Enzymology of mitochondrial DNA repair.

The mitochondrial genome encodes proteins essential for the oxidative phosphorylation and, consequently, for proper mitochondrial function. Its localization and, possibly, structural organization contribute to higher DNA damage accumulation, when compared to the nuclear genome. In addition, the mitochondrial genome mutates at rates several times higher than the nuclear, although the causal relationship between these events are not clearly established. Maintaining mitochondrial DNA stability is critical for cellular function and organismal fitness, and several pathways contribute to that, including damage tolerance and bypass, degradation of damaged genomes and DNA repair. Despite initial evidence suggesting that mitochondria lack DNA repair activities, most DNA repair pathways have been at least partially characterized in mitochondria from several model organisms, including humans. In this chapter, we review what is currently known about how the main DNA repair pathways operate in mitochondria and contribute to mitochondrial DNA stability, with focus on the enzymology of mitochondrial DNA repair.

The association of electroconvulsive therapy to pharmacological treatment and its influence on cytokines.

INTRODUCTION: A growing body of evidence shows that disturbances in the immune system are involved in the pathogenesis of depression. Although the immune-modulating effects of antidepressants have been described, few studies have addressed the functioning of the immune system in relation to electroconvulsive therapy (ECT). This study aims to investigate if the addition of ECT to pharmacotherapy is associated with changes in cytokine levels. METHODS: Adult inpatients were invited to participate in this study on admission to a psychiatric unit. Those with a diagnosis of depression by Mini-International Neuropsychiatric Interview were included. At treatment discharge, patients were retrospectively divided into those who used combined ECT and pharmacotherapy (31 subjects) and those who used only pharmacotherapy (68 subjects). Pro-inflammatory cytokines IL-2, IL-6, TNF-α, IFN-γ, and IL-17, and anti-inflammatory IL-4 and Il-10, were measured in blood samples collected at admission and discharge. A generalized estimating equation model and the post hoc Bonferroni test were performed for statistical analysis. RESULTS: The combination of ECT with pharmacotherapy was associated with a decrease of IL-6 and an increase of TNF-α. Depressive inpatients, as a whole group, had a decrease of IL-6 and an increase of IFN-γ. No significant results were found for IL-2, IL-4, Il-10 and IL-17. CONCLUSION: This study is clinically relevant because we highlight that, in agreement with the previous literature, IL-6 appears to be a useful marker in depression, and we show for the first time that its reduction is closely related to the use of ECT.

Lack of XPC leads to a shift between respiratory complexes I and II but sensitizes cells to mitochondrial stress.

Genomic instability drives tumorigenesis and DNA repair defects are associated with elevated cancer. Metabolic alterations are also observed during tumorigenesis, although a causal relationship between these has not been clearly established. Xeroderma pigmentosum (XP) is a DNA repair disease characterized by early cancer. Cells with reduced expression of the XPC protein display a metabolic shift from OXPHOS to glycolysis, which was linked to accumulation of nuclear DNA damage and oxidants generation via NOX-1. Using XP-C cells, we show that mitochondrial respiratory complex I (CI) is impaired in the absence of XPC, while complex II (CII) is upregulated in XP-C cells. The CI/CII metabolic shift was dependent on XPC, as XPC complementation reverted the phenotype. We demonstrate that mitochondria are the primary source of H2O2 and glutathione peroxidase activity is compromised. Moreover, mtDNA is irreversibly damaged and accumulates deletions. XP-C cells were more sensitive to the mitochondrial inhibitor antimycin A, an effect also prevented in XPC-corrected cells. Our results show that XPC deficiency leads to alterations in mitochondrial redox balance with a CI/CII shift as a possible adaptation to lower CI activity, but at the cost of sensitizing XP-C cells to mitochondrial oxidative stress.

Remission of depression following electroconvulsive therapy (ECT) is associated with higher levels of brain-derived neurotrophic factor (BDNF).

INTRODUCTION: Research on the association between electroconvulsive therapy (ECT) and increased brain derived neurotrophic factor (BDNF) levels has produced conflicting result. There have been few studies which have evaluated BDNF levels in clinical contexts where there was remission following treatment. The objective of this study was to investigate whether remission of depression following ECT is associated with changes in BDNF levels. METHODS: Adult inpatients in a psychiatric unit were invited to participate in this naturalistic study. Diagnoses were made using the Mini-International Neuropsychiatric Interview (MINI) and symptoms were evaluated at admission and discharge using the Hamilton Rating Scale for Depression (HDRS-17). Thirty-one patients who received a diagnosis of depression and were subjected to ECT were included retrospectively. Clinical remission was defined as a score of less than eight on the HDRS-17 at discharge. Serum BDNF levels were measured in blood samples collected at admission and discharge with a commercial kit used in accordance with the manufacturer's instructions. RESULTS: Subjects HDRS-17 scores improved following ECT (t = 13.29; p = 0.00). A generalized estimating equation (GEE) model revealed a remission × time interaction with BDNF levels as a dependent variable in a Wald chi-square test [Wald χ(2) = 5.98; p = 0.01]. A post hoc Bonferroni test revealed that non-remitters had lower BDNF levels at admission than remitters (p = 0.03), but there was no difference at discharge (p = 0.16). CONCLUSION: ECT remitters had higher serum BDNF levels at admission and the level did not vary during treatment. ECT non-remitters had lower serum BDNF levels at admission, but levels increased during treatment and were similar to those of ECT remitters at discharge.

Combining ECT with pharmacological treatment of depressed inpatients in a naturalistic study is not associated with serum BDNF level increase.

BACKGROUND: BDNF blood levels are reduced in MDD. They can be increased with pharmacologic treatment and ECT, but it is not clear whether the combination of treatments promotes an additional increase. The present study aims to evaluate whether combined treatment promotes an increase in BDNF, restoring the level to that of non-depressed controls. METHODS: Ninety-nine adult inpatients were invited to participate in this naturalistic prospective cohort study between May 2011 and April 2013. Diagnosis was made by MINI, and the symptoms were evaluated at admission and at discharge by HDRS-17. Those inpatients with a diagnosis of depression were included and divided into two groups: those who underwent combined ECT and medication (31 subjects) and those who used only pharmacotherapy (68 subjects). Serum BDNF was measured in blood samples collected at admission and discharge. One hundred healthy blood donors without any psychiatric diagnosis were included as a control group. RESULTS: There were no significant differences in serum BDNF levels between the combined and pharmacological groups at admission and at discharge, and no significant variation in BDNF occurred in any group during the treatment. There were no interactions between time and treatment groups nor significant time effects or treatment group effects for BDNF in the Generalized Estimating Equation Model (GEE). The control group had significantly higher serum BDNF levels in comparison with each of the treatment groups at admission and discharge (p = 0.00). CONCLUSION: Combination of ECT with pharmacological treatment did not result in increased serum BDNF levels and did not restore levels to that of controls.

ANÁLISE DO DESEMPENHO FÍSICO E DO EQUILÍBRIO SOB INFLUÊNCIA DA CRIOTERAPIA EM ATLETAS DE FUTSAL / PHYSICAL PERFORMANCE AND BALANCE ANALYSIS UNDER INFLUENCE OF CRYOTHERAPY IN INDOOR SOCCER ATHLETES / ANÁLISIS DEL DESEMPEÑO FÍSICO Y EQUILÍBRIO SOB INFLUENCIA DE CRIOTERAPIA EN JUGADORES DE FÚTBOL SALA

Introdução Crioterapia é a aplicação de modalidades de frio com temperatura de 0ºC a 18,3ºC, podendo interferir no desempenho físico e equilíbrio, dependendo da capacidade do indivíduo em manter a estabilização, direcionar padrões de movimentos, controlar a postura e posição articular. Objetivo Avaliar o desempenho físico, a frequência cardíaca e o equilíbrio estático com olhos abertos, em atletas de futsal (futebol de salão), antes e depois da crioimersão nos membros inferiores. Métodos Trinta e dois indivíduos do gênero masculino participaram do estudo, distribuídos aleatoriamente em dois grupos: (A) grupo controle, imersão em água a 24°C por 10 min; (B) grupo intervenção, crioimersão em água com gelo a 10°C por 10 min. Os voluntários realizavam a avaliação do equilíbrio no baropodômetro, em seguida corriam em linha reta e em ziguezague por 100 m, entravam na crioimersão, terminando com uma nova avaliação. Foram analisados o desempenho físico, através dos tempos das corridas, a frequência cardíaca, por meio de um frequencímetro e o equilíbrio, através da baropodometria e estabilometria em apoio bipodal de olhos abertos. Resultados O desempenho físico foi alterado após a crioimersão quando das análises intra e intergrupos. A frequência cardíaca apresentou diferença ao comparar-se antes e após a crio, porém sem diferenças em comparação ao controle. O equilíbrio não foi alterado após a crioimersão e nem em comparação com o grupo controle. Conclusão A crioimersão prejudicou o desempenho físico, quando a atividade foi imediatamente após a mesma, sendo desta forma o gelo não aconselhável quando se deseja desempenho na atividade desportiva. Porém não apresentou interferência na frequência cardíaca e no equilíbrio de atletas de futsal, que podem não ter sido alterados devido ao tempo da crioimersão.

Introduction Cryotherapy is the application of methods of cold temperature of 0°C to 18.3°C, which may interfere in physical performance and balance, depending on the individual's capacity of maintaining stabilization, targeting movement patterns, controlling posture and joint position. Objective To evaluate physical performance, heart rate and static balance with eyes open, in indoor soccer players before and after cold-water immersion of lower limbs. Methods Thirty-two male subjects participated in the study, being randomly divided into two groups: (A) control group, immersion in water at 24°C for 10 minutes, (B) intervention group, immersion in cold-water at 10°C for 10 minutes. The volunteers performed evaluation of balance through a baropodometer, then they ran straight and in zigzag for 100 meters, entered in cold-water immersion, ending with a new assessment. We analyzed physical performance throughout the time of race, the heart rate by means of a frequency counter, and balance through a baropodometer and stabilometry in bipedal support with their eyes open. Results The physical performance was modified after immersion in cold-water in intragroup and intergroup analysis. The heart rate showed difference when comparing before and after cryotherapy, but no differences compared to control. The balance showed no alteration after cryotherapy nor in comparison with the control group. Conclusion Cryotherapy impaired physical performance when the activity was performed immediately thereafter, therefore ice is not recommended when you want performance in sporting activities. Nevertheless, ice had no interference on heart rate and balance of indoor soccer players, which may not have been altered due to the time of immersion.

Introducción Crioterapia es la aplicación de diferentes modalidades de frio con temperatura de 0ºC a 18,3ºC, pudiendo interferir en el rendimiento físico y en el equilibrio, dependiendo de la capacidad del individuo de mantener la estabilización, direccionar padrones de movimientos, controlar la postura y posición articular. Objetivo Evaluar el rendimiento físico, la frecuencia cardíaca y el equilibrio estático con ojos abiertos, en jugadores de fútbol sala, antes y después de crioinmersión en los miembros inferiores. Métodos Treinta y dos individuos del género masculino participaron del estudio, distribuidos aleatoriamente en dos grupos: (A) grupo control, inmersión en agua a 24°C por 10 minutos; (B) grupo intervención, crioinmersión en agua con hielo a 10°C durante 10 minutos. Los voluntarios realizaban la evaluación del equilibrio en un baropodómetro, luego corrían en línea recta y en zigzag durante 100 metros, entraban en la crioinmersión, finalizando con una nueva evaluación. El rendimiento físico fue analizado a través de los tempos de carreras, la frecuencia cardíaca, por medio de un frecuencímetro cardiaco, y el equilibrio a través de baropodometría y estabilometría en apoyo bipodal con ojos abiertos. Resultados El rendimiento físico fue modificado después de la crioinmersión, tanto cuando analizados intra como intergrupal. La frecuencia cardíaca presentó diferencia significativa al comparar-se antes e después de la crioterapia, pero sin diferencias en comparación al control. El equilibrio no fue alterado después de la crioterapia ni en comparación con el grupo control. Conclusión La crioinmersión afectó negativamente el rendimiento físico, cuando la actividad fue realizada inmediatamente después de la misma, siendo de esta manera la crioinmersión no aconsejable cuando se desea incrementar el rendimiento en la actividad deportiva. Pero no presentó interferencia en la frecuencia cardíaca ni en el equilibrio en jugadores de fútbol sala, que pueden no haber sido alterados debido al tempo da crioinmersión.

Eixo XPC-P53-H202 e disfunção mitocondrial: qual é o fator central? / XPC-p53-H2O2 axis and mitochondrial disfunction: Which is the key player

A ausência de XPC, uma proteína canonicamente envolvida em reparo de DNA por excisão de nucleotídeos, está associada a vários fenótipos característicos de disfunção mitocondrial como o desequilíbrio entre os complexos da cadeia transportadora de elétrons (CTE), redução no consumo de oxigênio, maior produção de peróxido de hidrogênio, e maior sensibilidade a agentes que causam estresse mitocondrial. Contudo, uma descrição mecanística da relação entre deficiência de XPC e disfunção mitocondrial ainda não está bem estabelecida. Aqui mostramos que a deficiência de XPC está associada ao aumento na expressão do supressor de tumor p53. Essa alteração é acompanhada pelo aumento da expressão de diversas proteínas que participam em importantes funções mitocondriais. A inibição de p53 reverte a superexpressão de algumas dessas proteínas. O tratamento com o inibidor do Complexo III da CTE antimicina A induz aumento da expressão de p53 de forma mais acentuada na linhagem Xpc-/-, enquanto o tratamento com o antioxidante N-acetilcisteína diminue a produção basal de H2O2, expressão de p53 e sensibilidade aumentada ao tratamento com antimicina A. Em conjunto, nossos resultados suportam a hipótese de que o aumento da produção de H2O2 em células Xpc-/- tem um papel causal na regulação da expressão de p53 e na disfunção mitocondrial

Although XPC has been initially implicated in the nucleotide excision DNA repair pathway, its deficiency is associated with mitochondrial dysfunction, including unbalanced electron transport chain (ETC) activity, lower oxygen consumption, increased hydrogen peroxide production, and greater sensitivity to mitochondrial stress. However, a mechanistic understanding of the role of XPC in regulating mitochondrial function is still not well established. Here we show that XPC deficiency is associated with increased expression of the tumor suppressor p53, which is accompanied by increased expression of several proteins that participate in important mitochondrial functions. Inhibition of p53 reverses the overexpression of some of these proteins. In addition, treatment with the ETC inhibitor antimycin A induces p53 expression more robustly in the Xpc-/- cells, while treatment with the antioxidant N-acetylcysteine decreases basal H2O2 production, p53 expression and sensitivity to antimycin A treatment. Together, our results support a model in which increased H2O2 production in Xpc-/- causes upregulation of p53 expression and mitochondrial dysfunction

Efeitos da suplementação de creatina na captação de glicose em ratos submetidos ao exercício físico / Effects of creatine supplementation on glucose uptake in rats submitted to exercise training

Estudos recentes têm sugerido que a suplementação de creatina é capaz de modular a homeostase da glicose, aumentando sua captação pelos tecidos periféricos. O objetivo deste trabalho foi investigar o efeito da suplementação de creatina na tolerância à glicose e no conteúdo de glicogênio muscular e hepático em ratos submetidos ou não à atividade física por quatro e oito semanas. Ratos Wistar foram divididos em dois grupos: quatro e oito semanas de intervenção. Posteriormente, cada grupo foi subdividido em quatro subgrupos, de acordo com a ingestão do suplemento e o treinamento: controle cedentário, controle treinado, suplementado sedentário e suplementado treinado. Os animais tiveram livre acesso à água e ração; o grupo suplementado teve 2 por cento de sua ração sob a forma de creatina monoidratada. Os grupos exercitados nadaram 40 minutos por dia, quatro dias por semana, com carga entre 2 e 5 por cento do seu peso amarrado ao peito. Após quatro e oito semanas, o teste oral de tolerância à glicose e as dosagens de glicogênio muscular e hepático foram realizadas. Não foram observadas diferenças significativas entre os grupos no teste de tolerância oral à glicose e no conteúdo de glicogênio muscular e hepático. Este estudo mostrou que a suplementação de creatina não exerceu influência na tolerância à glicose nem nas concentrações de glicogênio em ratos submetidos ou não à atividade física por quatro ou oito semanas.

Recently, studies have suggested that creatine supplementation can modulate glucose homeostasis by increasing glucose uptake in peripheral tissues. The aim of this study was to investigate the effects of creatine supplementation on glucose tolerance, muscle and hepatic glycogen content in rats submitted or not to physical activity for four and eight weeks. Wistar rats were divided in two groups: four and eight weeks of intervention. Afterwards, each group was subdivided in four subgroups, according to supplement intake and exercise: Sedentary Control; Trained Control; Supplemented Sedentary; and Supplemented Trained. The animals had free access to water and chow and the supplemented groups had two percent of their diet as creatine monohydrated. The exercise groups swam for 40 minutes a day, four days a week, with two to five percent of their body weight attached to their chests. After four and eight weeks, oral glucose tolerance tests were performed and both hepatic and muscle glycogen were determined. No significant differences were observed between groups on glucose tolerance and glycogen content in muscle and hepatic tissue. This study shows that creatine supplementation does not influence neither glucose tolerance nor glycogen concentrations in rats submitted or not to physical activity for four and eight weeks.