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Article in English | WPRIM | ID: wpr-939848


Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6-CREB-SOD2-dependent pathway in IgG4-RS.

Cellular Senescence/genetics , Humans , Immunoglobulin G/metabolism , Interleukin-13/pharmacology , Mitochondria/metabolism , Sialadenitis/metabolism
Article in English | WPRIM | ID: wpr-939820


The negative effects of low temperature can readily induce a variety of diseases. We sought to understand the reasons why cold stress induces disease by studying the mechanisms of fine-tuning in macrophages following cold exposure. We found that cold stress triggers increased macrophage activation accompanied by metabolic reprogramming of aerobic glycolysis. The discovery, by genome-wide RNA sequencing, of defective mitochondria in mice macrophages following cold exposure indicated that mitochondrial defects may contribute to this process. In addition, changes in metabolism drive the differentiation of macrophages by affecting histone modifications. Finally, we showed that histone acetylation and lactylation are modulators of macrophage differentiation following cold exposure. Collectively, metabolism-related epigenetic modifications are essential for the differentiation of macrophages in cold-stressed mice, and the regulation of metabolism may be crucial for alleviating the harm induced by cold stress.

Acetylation , Animals , Cold-Shock Response , Epigenesis, Genetic , Macrophages/metabolism , Mice , Mitochondria/metabolism
Protein & Cell ; (12): 180-202, 2022.
Article in English | WPRIM | ID: wpr-929176


Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.

Animals , Caenorhabditis elegans/metabolism , Cation Transport Proteins/genetics , Homeostasis , Mitochondria/metabolism , Zinc/metabolism
Article in English | WPRIM | ID: wpr-928962


Alzheimer's disease (AD) is one of the most common neurodegenerative diseases among the elderly and it accounts for nearly 80% of all dementias. The pathogenesis of AD is complicated and enigmatic thus far. The mitochondrial cascade hypothesis assumes that mitochondrial damage may mediate, drive, or contribute to a variety of AD pathologies and may be the main factor in late-onset AD. Currently, there are no widely recognized drugs able to attenuate mitochondrial damage in AD. Notably, increasing evidence supports the efficacy of acupuncture for improving the mitochondrial structure and protecting mitochondrial functions in AD. This review reports the mechanisms by which acupuncture regulates mitochondrial dynamics, energy metabolism, calcium homeostasis and apoptosis. In conclusion, these findings suggest that AD mitochondrial dysfunction represents a reasonable therapeutic target and acupuncture could play a significant role in preventing and treating AD.

Acupuncture Therapy , Aged , Alzheimer Disease/drug therapy , Apoptosis , Humans , Mitochondria/metabolism
Article in Chinese | WPRIM | ID: wpr-936296


OBJECTIVE@#To explore the expression of microRNA-132 (miR-132) and its potential role in the development of atherosclerosis (AS).@*METHODS@#Thirty AS samples and 30 samples of normal peripheral vessels were collected from atherosclerotic patients undergoing peripheral angiostomy in our hospital for detecting the expression level of miR-132 using RT-qPCR. The expression of miR-132 in human umbilical vein endothelial cells (HUVEC) was up-regulated by liposome transfection, and intracellular reactive oxygen species (ROS), localization relationship between ROS and mitochondria, functional changes of mitochondrial reactive oxygen superoxide species (mtROS), mitochondrial membrane potential (MMP) and opening of mitochondrial permeability transition pore (mPTP) were analyzed by flow cytometry and laser confocal microscopy. The activity of mitochondrial redox respiratory chain complex (type I, II, III, IV and V) in HUVECs was detected using ELISA, and the expression levels of key iron death proteins were detected with Western blotting.@*RESULTS@#RT-qPCR results showed that miR-132 was significantly up-regulated in atherosclerotic plaques compared with normal vascular samples (P < 0.001). Compared with control HUVECs, HUVECs overexpressing miR-132 showed a significantly increased level of intracellular ROS (P < 0.001), and most of ROS was colocalized with mitochondria. HUVECs overexpressing miR-132 also showed significantly decreased MMP (P < 0.001) and obviously increased mtROS (P < 0.001) and opening of mPTP (P < 0.001), which led to mitochondrial REDOX respiratory chain stress disorder. The key iron death protein GPX4 was significantly down-regulated and the oxidized protein NOX4 was significantly increased in miR-132-overexpressing HUVECs (P < 0.001).@*CONCLUSION@#MiR-132 promotes atherosclerosis by inducing mitochondrial oxidative stress-mediated ferroptosis, which may serve as a promising therapeutic target for AS.

Apoptosis , Atherosclerosis/genetics , Ferroptosis , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Membrane Potential, Mitochondrial , MicroRNAs/metabolism , Mitochondria/metabolism , Oxidation-Reduction , Oxidative Stress , Reactive Oxygen Species/metabolism
Article in Chinese | WPRIM | ID: wpr-935735


Objective: To study the effects of vibration on the expression of mitochondrial fusion and fission genes and ultrastructure of skeletal muscle in rabbits. Methods: Thirty-two 3.5-month-old New Zealand rabbits were randomly divided into low-intensity group, medium-intensity group, high-intensity group and control group, with 8 rabbits in each group. The rabbits in the experimental group were subjected to hind limb vibration load test for 45 days. The vibration intensity of the high intensity group was 12.26 m/s(2), the medium intensity group was 6.13 m/s(2), and the low intensity group was 3.02 m/s(2) according to the effective value of weighted acceleration[a(hw (4))] for 4 hours of equal energy frequency. The control group was exposed to noise only in the same experimental environment as the medium-intensity group. The noise levels of each group were measured during the vibration load experiment. After the test, the mRNA expression of mitochondrial fusion gene (Mfn1/Mfn2) and fission gene (Fis1, Drp1) by RT-PCR in the skeletal muscles were measured and the ultrastructure of the skeletal muscles were observed in high intensity group. Results: The mRNA expression of mitochondrial in the skeletal muscle tissues of control group, low intensity group, medium intensity group and high intensity group were Mfn1: 3.25±1.36, 3.85±1.90, 4.53±2.31 and 11.63±7.68; Mfn2: 0.68±0.25, 1.02±0.40, 0.94±0.33 and 1.40±0.45; Fis1: 1.05±0.62, 1.15±0.59, 1.53±1.06 and 2.46±1.51 and Drp1: 3.72±1.76, 2.91±1.63, 3.27±2.01 and 4.21±2.46, respectively. Compared with the control group, the expressions of Mfn1 mRNA, Mfn2 mRNA and Fis1 mRNA in the high-intensity group increased significantly (P<0.05) , and the expressions of Mfn2 mRNA in the medium-intensity group and the low-intensity group increased significantly (P<0.05) . Compared with the control group, the ultrastructure of skeletal muscle of high intensity group showed mitochondrial focal accumulation, cristae membrane damage, vacuole-like changes; Z-line irregularity of muscle fibers, and deficiency of sarcomere. Conclusion: Vibration must be lead to the abnormal mitochondrial morphology and structure and the disorder of energy metabolism due to the expression imbalance of mitochondrial fusion and fission genes in skeletal muscles of rabbits, which may be an important target of vibration-induced skeletal muscle injury.

Animals , Hindlimb/metabolism , Mitochondria/metabolism , Mitochondrial Dynamics , Mitochondrial Proteins/pharmacology , Muscle, Skeletal , Rabbits , Vibration/adverse effects
Chinese Medical Journal ; (24): 837-848, 2022.
Article in English | WPRIM | ID: wpr-927571


BACKGROUND@#Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice.@*METHODS@#In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo.@*RESULTS@#Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway.@*CONCLUSION@#In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.

Animals , Apoptosis , Calcium/metabolism , Endothelial Cells/metabolism , Endothelium/metabolism , Hepatocyte Growth Factor/metabolism , Lipopolysaccharides/pharmacology , Mammals/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Mechanistic Target of Rapamycin Complex 2/metabolism , Mice , Mitochondria/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Respiratory Distress Syndrome, Newborn , Sirolimus/pharmacology , TOR Serine-Threonine Kinases/metabolism
Chinese Journal of Biotechnology ; (12): 2732-2740, 2020.
Article in Chinese | WPRIM | ID: wpr-878525


Dihydroorotate dehydrogenase is a flavin-dependent mitochondrial enzyme to catalyze the fourth step of the de novo synthesis of pyrimidine and to oxidize dihydroorotate to orotate. By selectively inhibiting dihydroorotate dehydrogenase, thereby inhibiting pyrimidine synthesis, the enzyme has been developed for the treatment of cancer, autoimmune diseases, bacterial or viral infections, parasitic diseases and so on. The development of inhibitory drugs requires a detailed understanding of the structural characteristics and catalytic cycle mechanism of dihydroorotate dehydrogenase. Therefore, this paper reviews these two aspects, and indicates perspectives of these inhibitors in clinical application.

Catalysis , Mitochondria/metabolism , Oxidation-Reduction , Oxidoreductases Acting on CH-CH Group Donors/metabolism
Electron. j. biotechnol ; 40: 30-39, July. 2019. ilus, graf
Article in English | LILACS | ID: biblio-1053221


Background: Myostatin (MSTN) negatively regulates muscle mass and is a potent regulator of energy metabolism. However, MSTN knockout have affect mitochondrial function. This research assessed the mitochondrial energy metabolism of Mstn−/+ KO cells, and wondered whether the mitochondria biogenesis are affected. Results: In this study, we successfully achieved Mstn knockout in skeletal muscle C2C12 cells using a CRISPR/Cas9 system and measured proliferation and differentiation using the Cell-Counting Kit-8 assay and qPCR, respectively. We found that MSTN dysfunction could promote proliferation and differentiation compared with the behaviour of wild-type cells. Moreover, Mstn KO induced an increase in KIF5B expression. The mitochondrial content was significantly increased in Mstn KO C2C12 cells, apparently associated with the increases in PGC-1α, Cox1, Cox2, ND1 and ND2 expression. However, no differences were observed in glucose consumption and lactate production. Interestingly, Mstn KO C2C12 cells showed an increase in IL6 and a decrease in TNF-1α levels. Conclusion: These findings indicate that MSTN regulates mitochondrial biogenesis and metabolism. This gene-editing cells provided favourable evidence for animal breeding and metabolic diseases.

Myostatin/genetics , Mitochondria/genetics , Mitochondria/metabolism , Organelle Biogenesis , Immunoblotting , Cell Differentiation , Muscle, Skeletal/cytology , Muscle, Skeletal/metabolism , Myoblasts/cytology , Myoblasts/metabolism , MicroRNAs , Cell Proliferation , CRISPR-Cas Systems , Flow Cytometry , Gene Editing
Rev. méd. Chile ; 146(6): 762-769, jun. 2018. graf
Article in Spanish | LILACS | ID: biblio-961457


One of the main features of cancer is the high rate of cell proliferation and growth. To do this, cancer cells need to redirect their metabolism mainly towards anaerobic glycolysis and an increased mitochondrial glutamine energy metabolism. Sirtuins are cellular proteins with regulatory functions on metabolic pathways, genomic stability, apoptosis, longevity, inflammation, energy metabolism and oxidative stress. Sirtuins have emerged recently as a potential therapeutic option to treat several chronic diseases including cancer. This review summarizes the tumor suppressor function of Sirtuin 3 (SIRT3), highlighting its repressor effect on glycolytic metabolism, promoting mitochondrial metabolism and oxidative stress reduction. SIRT3 activation by exercise is particularly described since it may represent a potent tool for several types of cancer treatment.

Humans , Exercise/physiology , Sirtuin 3/physiology , Neoplasms/metabolism , Neoplasms/therapy , Reactive Oxygen Species/metabolism , Oxidative Stress/physiology , Tumor Suppressor Proteins/physiology , Exercise Therapy/methods , Mitochondria/metabolism
Bol. méd. Hosp. Infant. Méx ; 74(3): 181-192, May.-Jun. 2017. tab, graf
Article in English | LILACS | ID: biblio-888614


Abstract: Introduction: Relapse occurs in approximately 20% of Mexican patients with childhood acute lymphoblastic leukemia (ALL). In this group, chemoresistance may be one of the biggest challenges. An overview of complex cellular processes like drug tolerance can be achieved with proteomic studies. Methods: The B-lineage pediatric ALL cell line CCRF-SB was gradually exposed to the chemotherapeutic vincristine until proliferation was observed at 6 nM, control cells were cultured in the absence of vincristine. The proteome from each group was analyzed by nanoHPLC coupled to an ESI-ion trap mass spectrometer. The identified proteins were grouped into over-represented functional categories with the PANTHER classification system. Results: We found 135 proteins exclusively expressed in the presence of vincristine. The most represented functional categories were: Toll receptor signaling pathway, Ras Pathway, B and T cell activation, CCKR signaling map, cytokine-mediated signaling pathway, and oxidative phosphorylation. Conclusions: Our study indicates that signal transduction and mitochondrial ATP production are essential during adaptation of leukemic cells to vincristine, these processes represent potential therapeutic targets.

Resumen: Introducción: Aproximadamente el 20% de los pacientes mexicanos con leucemia linfoblástica aguda (LLA) infantil presentan recaídas. En este grupo, la quimiorresistencia es uno de los principales desafíos. Los estudios proteómicos pueden dar un panorama general de procesos celulares complejos como la tolerancia a fármacos. Métodos: La línea celular de LLA de linaje B, CCRF-SB, fue expuesta de manera gradual al fármaco quimioterapéutico vincristina hasta observar proliferación celular en presencia de 6 nM, como control se cultivaron células en ausencia del fármaco. Se analizó el proteoma de cada grupo mediante nanoHPLC acoplado a un espectrómetro de masas de tipo trampa de iones. Las proteínas identificadas se agruparon en categorías funcionales sobre-representadas con el sistema de clasificación PANTHER. Resultados: Encontramos 135 proteínas expresadas exclusivamente en presencia de vincristina. Las categorías funcionales más representadas fueron la señalización asociada a los receptores tipo Toll, señalización dependiente de Ras, activación de células B y T, mapa de señalización CCKR, señalización mediada por citoquinas y la fosforilación oxidativa. Conclusiones: Nuestro estudio indica que la transducción de señales y la producción de ATP mitocondrial son procesos esenciales durante la adaptación de células leucémicas a vincristina por lo que estos procesos representan potenciales blancos terapéuticos.

Child , Humans , Vincristine/pharmacology , Proteomics/methods , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Antineoplastic Agents, Phytogenic/pharmacology , Signal Transduction/drug effects , Proteins/metabolism , Gene Expression Regulation, Leukemic , Adenosine Triphosphate/metabolism , Chromatography, High Pressure Liquid , Drug Resistance, Neoplasm , Proteome/metabolism , Spectrometry, Mass, Electrospray Ionization , Cell Line, Tumor , Cell Proliferation/drug effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Mitochondria/metabolism
Braz. j. biol ; 77(1): 43-51, Jan-Mar. 2017. tab, graf
Article in English | LILACS | ID: biblio-839155


Abstract Soil flooding is an environmental stressor for crops that can affect physiological performance and reduce crop yields. Abiotic stressors cause changes in protein synthesis, modifying the levels of a series of proteins, especially the heat shock proteins (HSP), and these proteins can help protect the plants against abiotic stress. The objective of this study was to verify if tomato plants cv. Micro-Tom from different genotypes with varying expression levels of MT-sHSP23.6 (mitochondrial small heat shock proteins) have different responses physiological to flooding. Plants from three genotypes (untransformed, MT-sHSP23.6 sense expression levels and MT-sHSP23.6 antisense expression levels) were cultivated under controlled conditions. After 50 days, the plants were flooded for 14 days. After this period half of the plants from each genotype were allowed to recover. Chlorophyll fluorescence, gas exchange, chlorophyll index, leaf area and dry matter were evaluated. Flood stress affected the photosynthetic electron transport chain, which is related to inactivation of the oxygen-evolving complex, loss of connectivity among units in photosystem II, oxidation-reduction of the plastoquinone pool and activity of photosystem I. The genotype with MT-sHSP23.6 sense expression levels was less sensitive to stress from flooding.

Resumo O alagamento do solo é um estressor ambiental para as culturas e pode afetar o desempenho fisiológico e reduzir a produtividade das culturas. Estresses abióticos causam mudanças na síntese de proteínas, modificando os níveis de uma série de proteínas, em especial as proteínas de choque térmico (HSP) e essas proteínas são conhecidas por proteger as plantas contra estresses abióticos. O objetivo deste estudo foi verificar se as plantas do tomateiro cv. Micro-Tom de distintos genótipos com diferentes níveis de expressão da MT-sHSP23.6 (proteínas mitocondriais de choque térmico com pequena massa molecular), têm diferentes respostas fisiológicas ao alagamento. As plantas de três genótipos (não-transformado, transformado com orientação antisense e transformado com orientação sense para MT-sHSP23.6) foram cultivadas sob condições controladas. Após 50 dias as plantas foram alagadas durante 14 dias. Após esse período as plantas de cada genótipo foram recuperadas. Foram avaliados fluorescência da clorofila, trocas gasosas, índice de clorofila, área foliar e massa seca. O estresse por alagamento afetou a cadeia de transporte de elétrons da fotossíntese, que está relacionado à inativação do complexo de evolução do oxigênio, perda da conectividade entre as unidades do fotossistema II, de oxidação e redução do pool de plastoquinona e atividade do fotossistema I. O genótipo com orientação sense MT-sHSP23.6 foi menos sensível ao estresse por alagamento.

Stress, Physiological , Solanum lycopersicum/physiology , Heat-Shock Proteins, Small/metabolism , Floods , Mitochondria/metabolism , Photosynthesis/physiology , Chlorophyll/metabolism , Plant Leaves/metabolism , Photosystem I Protein Complex/metabolism , Genotype
Clinics ; 70(8): 569-576, 08/2015. tab, graf
Article in English | LILACS | ID: lil-753961


OBJECTIVE: The aim of this study was to determine the in vitro effect of glutamine and insulin on apoptosis, mitochondrial membrane potential, cell permeability, and inflammatory cytokines in hyperglycemic umbilical vein endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells were grown and subjected to glutamine and insulin to examine the effects of these agents on the hyperglycemic state. Mitochondrial function and the production of inflammatory cytokines were assessed using fluorescence analysis and multiple cytotoxicity assays. Apoptosis was analyzed by the terminal deoxynucleotidyl transferase dUTP nick end-labeling assay. RESULTS: Glutamine maintains the integrity of the mitochondria by reducing the cell permeability and cytochrome c levels and increasing the mitochondrial membrane potential. The cytochrome c level was significantly (p<0.005) reduced when the cells were treated with glutamine. An apoptosis assay revealed significantly reduced apoptosis (p<0.005) in the glutamine-treated cells. Moreover, glutamine alone or in combination with insulin modulated inflammatory cytokine levels. Interleukin-10, interleukin-6, and vascular endothelial growth factor were up-regulated while tumor necrosis factor-α was down-regulated after treatment with glutamine. CONCLUSION: Glutamine, either alone or in combination with insulin, can positively modulate the mitochondrial stress and cell permeability in umbilical vein endothelial cells. Glutamine regulates the expression of inflammatory cytokines and maintains the balance of the mitochondria in a cytoprotective manner. .

Humans , Apoptosis/drug effects , Glutamine/pharmacology , Hyperglycemia/drug therapy , Mitochondria/drug effects , Oxidative Stress/drug effects , Cells, Cultured , Cell Membrane Permeability/drug effects , Cytochromes c/analysis , Cytokines/analysis , Cytokines/drug effects , Drug Combinations , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Hyperglycemia/metabolism , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Mitochondria/metabolism
Rev. latinoam. enferm ; 23(1): 130-138, Jan-Feb/2015. tab, graf
Article in English | LILACS, BDENF | ID: lil-742022


OBJECTIVE: to adapt and validate the Caregiver Burden Inventory for use with caregivers of older adults in Brazil. METHOD: methodological study involving initial translation, synthesis of translations, back translation, expert committee review, pre-testing, submission of the final version to the original authors, and assessment of the inventory's psychometric properties. The inventory assesses five dimensions of caregiver burden: time-dependence, developmental, physical, social and emotional dimensions. RESULTS: a total of 120 family caregivers took part in the study. All care-receivers were older adults dependent on assistance to perform activities of daily living, and lived in the central region of the city of Porto Alegre, RS, Brasil. Cronbach's alpha value for the inventory was 0.936, and the Pearson correlation coefficient for the relationship between the scores obtained on the Caregiver Burden Inventory and the Burden Interview was 0.814. The intraclass correlation coefficient was 0.941, and the value of Student's T-test comparing test and retest scores was 0.792. CONCLUSION: the instrument presented adequate reliability and the suitability of its items and factors was confirmed in this study. .

OBJETIVO: adaptar e validar o Inventário de Sobrecarga do Cuidador para uso em cuidadores de idosos no Brasil. MÉTODO: estudo metodológico envolvendo tradução inicial, síntese das traduções, retrotradução, revisão por comitê de especialistas, pré-teste, envio da versão final para apreciação dos autores da versão original, e avaliação de suas propriedades psicométricas. O inventário avalia cinco dimensões de sobrecarga do cuidador: tempo dependente, sobrecarga à vida pessoal, física, social e emocional. RESULTADOS: participaram do estudo 120 cuidadores familiares. Todos os indivíduos sob cuidado destes cuidadores eram idosos que dependiam de assistência para realizar atividades da vida diária e residiam na região central da cidade de Porto Alegre, RS, Brasil. O valor alfa de Cronbach encontrado para o inventário foi de 0,936 e o coeficiente de correlação Pearson para a relação entre os escores obtidos no Inventário de Sobrecarga do Cuidador e na escala Burden Interview foi de 0,814. O coeficiente de correlação intraclasse foi de 0,941 e o valor do teste t de Student que comparou os escores do teste e reteste foi de 0,792. CONCLUSÃO: o instrumento apresentou confiabilidade apropriada e a adequação de seus itens e domínios foi confirmada neste estudo. .

OBJETIVO: adaptar y validar el Inventario de Sobrecarga del Cuidador para uso en cuidadores de ancianos en Brasil. MÉTODO: estudio metodológico con traducción inicial, síntesis de las traducciones, retrotraducción, revisión por comité de especialistas, preprueba, envío de la traducción final para apreciación de los autores del instrumento original, y evaluación de sus propiedades psicométricas. El Inventario evalúa cinco dominios de sobrecarga del cuidador: tiempo dependiente, sobrecarga en la vida personal, física, social y emocional. RESULTADOS: participaron del estudio 120 cuidadores familiares. Todos los individuos bajo el cuidado de estos cuidadores eran ancianos que dependían de asistencia para realizar actividades de la vida diaria y residían en la región central de la ciudad de Porto Alegre, RS, Brasil. El valor Alfa de Cronbach encontrado para el Inventario fue 0,936 y el coeficiente de correlación de Pearson para la relación entre los puntajes obtenidos entre el Inventario de Sobrecarga del Cuidador y el Burden Interview fue 0,814. El coeficiente de correlación intraclase fue 0,941 y el valor de la prueba t de Student que comparó los puntajes de la prueba y reprueba fue de 0,792. CONCLUSIÓN: el instrumento presentó confiabilidad apropiada y la adecuación de sus ítems y dominios fue confirmada en este estudio. .

Animals , Male , /metabolism , Caloric Restriction , Circadian Rhythm , Liver/enzymology , /genetics , Blotting, Western , gamma-Aminobutyric Acid , Gene Expression Regulation, Enzymologic , Mitochondria/metabolism , Rats, Wistar , RNA, Messenger/genetics , RNA, Messenger/metabolism , Subcellular Fractions/metabolism
Rev. méd. Chile ; 143(2): 175-182, feb. 2015. tab
Article in Spanish | LILACS | ID: lil-742568


Background: In 2007, a Clinical-Case-Portfolio (CCP) was introduced as a new assessment instrument for fourth grade undergraduate medical students. Since then, several changes have been implemented such as reduction on the number of clinical cases, peer review and the introduction of virtual patient to the portfolio. Aim: To describe the virtual patient model incorporated to the CCP and assess the perception of this change and its effects on the performance of undergraduate students. Material and Methods: Virtual patients were implemented based on prototype clinical cases with specific syndromes. Students’ perceptions about CCP before and after the introduction of virtual patients were evaluated using a validated questionnaire that was answered voluntarily and anonymously. Results: Overall perception of CCP significantly improved after the incorporation of virtual patients (97.1 ± 24.9 and 111.3 ± 25.7 points; 57.8 and 66.2% respectively). The same improvements were observed for the domains “Student Learning”, “Organization and Evaluation”, “Teaching Methodology” and “Integration”. In both years, students obtained high grades in CCP evaluations. However CCP grades were not significantly correlated with integrated final grades. Conclusions: The incorporation of virtual patients improved undergraduate students’ perception of CCP.

Animals , Mice , Apoptosis , Axin Protein/metabolism , Enzyme Activation , Poly(ADP-ribose) Polymerases/metabolism , Protein Serine-Threonine Kinases/antagonists & inhibitors , Aurora Kinases , Adenosine Triphosphate/metabolism , Apoptosis Inducing Factor/genetics , Apoptosis Inducing Factor/metabolism , Cell Line , Cell Membrane/metabolism , Cell Membrane/physiology , Mitochondria/metabolism , Protein Kinase Inhibitors/pharmacology , RNA Interference , Time-Lapse Imaging
Rev. bras. cir. cardiovasc ; 30(1): 55-62, Jan-Mar/2015. tab
Article in English | LILACS | ID: lil-742887


Introduction: Complete denervation of transplanted heart exerts protective effect against postoperative atrial fibrillation; various degrees of autonomic denervation appear also after transection of ascending aorta during surgery for aortic aneurysm. Objective: This study aimed to evaluate if the level of cardiac denervation obtained by resection of ascending aorta could exert any effect on postoperative atrial fibrillation incidence. Methods: We retrospectively analysed the clinical records of 67 patients submitted to graft replacement of ascending aorta (group A) and 132 with aortic valve replacement (group B); all episodes of postoperative atrial fibrillation occurred during the 1-month follow-up have been reported. Heart Rate Variability parameters were obtained from a 24-h Holter recording; clinical, echocardiographic and treatment data were also evaluated. Results: Overall, 45% of patients (group A 43%, group B 46%) presented at least one episode of postoperative atrial fibrillation. Older age (but not gender, abnormal glucose tolerance, ejection fraction, left atrial diameter) was correlated with incidence of postoperative atrial fibrillation. Only among a subgroup of patients with aortic transection and signs of greater autonomic derangement (heart rate variability parameters below the median and mean heart rate over the 75th percentile), possibly indicating more profound autonomic denervation, a lower incidence of postoperative atrial fibrillation was observed (22% vs. 54%). Conclusion: Transection of ascending aorta for repair of an aortic aneurysm did not confer any significant protective effect from postoperative atrial fibrillation in comparison to patients with intact ascending aorta. It could be speculated that a limited and heterogeneous cardiac denervation was produced by the intervention, creating an eletrophysiological substrate for the high incidence of postoperative atrial fibrillation observed. .

Introdução: Denervação completa do coração transplantado exerce efeito protetor contra a fibrilação atrial no pós-operatório; vários graus de denervação autonômica aparecem também após a transecção da aorta ascendente durante a cirurgia de aneurisma da aorta. Objetivo: Este estudo teve como objetivo avaliar se o nível de denervação cardíaca obtida por ressecção da aorta ascendente poderia exercer algum efeito sobre a incidência de fibrilação atrial no pós-operatório. Métodos: Foram analisados retrospectivamente os prontuários de 67 pacientes submetidos a enxerto de substituição de aorta torácica (grupo A) e 132 com a substituição da valva aórtica (grupo B). Foram relatados todos os episódios de fibrilação atrial pós-operatória ocorridos durante 1 mês de seguimento. Parâmetros de variabilidade da frequência cardíaca foram obtidos a partir de 24 h de gravação do Holter; dados clínicos, ecocardiográficos e de tratamento também foram avaliados. Resultados: No geral, 45% dos pacientes (grupo A 43%, grupo B 46%) apresentaram pelo menos um episódio de fibrilação atrial no pós-operatório. Idade mais avançada (mas não gênero, tolerância à glicose anormal, fração de ejeção, diâmetro do átrio esquerdo) foi correlacionada com a incidência de fibrilação atrial pós-operatória. Apenas em um subgrupo de pacientes com transecção aórtica e sinais de maior desarranjo autonômico (parâmetros de variabilidade da frequência cardíaca abaixo da mediana e a média de frequência cardíaca acima do percentil 75), indicando possivelmente denervação autonômica mais profunda, foi observada menor incidência de fibrilação atrial pós-operatória (22% vs. 54%). Conclusão: Transecção da aorta ascendente para correção de um aneurisma da aorta não confere qualquer efeito protetor significativo de fibrilação atrial no pós-operatório em comparação com pacientes com aorta ascendente intacta. Pode-se especular que uma denervação cardíaca limitada e heterogênea foi produzida pela ...

Animals , Mice , Brain/physiology , Nerve Tissue Proteins/physiology , Poly Adenosine Diphosphate Ribose/antagonists & inhibitors , Stroke/physiopathology , Apoptosis Inducing Factor/physiology , Blotting, Northern , Calcium/metabolism , Cell Death/physiology , Glutamic Acid/drug effects , Glutamic Acid/physiology , Mitochondria/metabolism , Nerve Tissue Proteins/metabolism , Protein Binding , Poly(ADP-ribose) Polymerases/metabolism , Poly(ADP-ribose) Polymerases/physiology , Receptors, N-Methyl-D-Aspartate/drug effects
Rev. bras. cir. cardiovasc ; 30(1): 49-54, Jan-Mar/2015. tab
Article in English | LILACS | ID: lil-742891


Introduction: Perioperative myocardial infarction adversely affects the prognosis of patients undergoing coronary artery bypass graft and its diagnosis was hampered by numerous difficulties, because the pathophysiology is different from the traditional instability atherosclerotic and the clinical difficulty to be characterized. Objective: To identify the frequency of perioperative myocardial infarction and its outcome in patients undergoing coronary artery bypass graft. Methods: Retrospective cohort study performed in a tertiary hospital specialized in cardiology, from May 01, 2011 to April 30, 2012, which included all records containing coronary artery bypass graft records. To confirm the diagnosis of perioperative myocardial infarction criteria, the Third Universal Definition of Myocardial Infarction was used. Results: We analyzed 116 cases. Perioperative myocardial infarction was diagnosed in 28 patients (24.1%). Number of grafts and use and cardiopulmonary bypass time were associated with this diagnosis and the mean age was significantly higher in this group. The diagnostic criteria elevated troponin I, which was positive in 99.1% of cases regardless of diagnosis of perioperative myocardial infarction. No significant difference was found between length of hospital stay and intensive care unit in patients with and without this complication, however patients with perioperative myocardial infarction progressed with worse left ventricular function and more death cases. Conclusion: The frequency of perioperative myocardial infarction found in this study was considered high and as a consequence the same observed average higher troponin I, more cases of worsening left ventricular function and death. .

Introdução: O infarto do miocárdio perioperatório afeta negativamente o prognóstico dos pacientes submetidos à cirurgia de revascularização do miocárdio e seu diagnóstico esbarra em inúmeras dificuldades, pois a fisiopatologia é diferente da tradicional instabilidade aterosclerótica e o quadro clínico de difícil caracterização. Objetivo: Identificar a frequência de infarto do miocárdio perioperatório e seu desfecho em pacientes submetidos à cirurgia de revascularização do miocárdio. Métodos: Coorte retrospectiva realizada em hospital terciário especializado em cardiologia, de 1 de maio de 2011 a 30 de abril de 2012, que incluiu todos os prontuários contendo registros de cirurgia de revascularização do miocárdio. Para confirmação diagnóstica do infarto do miocárdio perioperatório, foram utilizados os critérios da Third Universal Definition of Myocardial Infarction Resultados: Foram analisados 116 casos. Foi diagnosticado infarto do miocárdio perioperatório em 28 pacientes (24,1%). Número de enxertos e utilização e tempo de circulação extracorpórea foram fatores associados a este diagnóstico e a média de idade foi significativamente mais elevada neste grupo. O critério diagnóstico elevação de troponina I foi positivo em 99,1% dos casos, independentemente do diagnóstico de infarto do miocárdio perioperatório. Não foi encontrada diferença significativa entre tempo de internação hospitalar e em unidade de terapia intensiva nos grupos com e sem esta complicação, porém pacientes com infarto do miocárdio perioperatório evoluíram com pior função ventricular esquerda e mais casos de óbito. Conclusão: A frequência de infarto do miocárdio perioperatório encontrada neste trabalho foi considerada alta e como consequência do mesmo observou-se média mais elevada de troponina I, mais casos de piora da função ventricular esquerda e óbito. .

Animals , Female , Male , Mice , Cell Death/physiology , Glucose/metabolism , Hypoxia-Ischemia, Brain/metabolism , Neurons/physiology , Oxygen/metabolism , Sex Characteristics , Signal Transduction/physiology , Adenosine Triphosphate/metabolism , Apoptosis Inducing Factor/metabolism , /metabolism , /metabolism , Cerebellum/cytology , Mice, Knockout , Mitochondria/metabolism , Neurons/cytology , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/metabolism
Rev. Soc. Bras. Med. Trop ; 48(1): 11-17, jan-feb/2015. tab, graf
Article in English | LILACS, SES-SP | ID: lil-742966


INTRODUCTION : Brazilian spotted fever (BSF) is a disease transmitted by ticks for which the etiological agent is Rickettsia rickettsii. The present essay evaluates the risk factors associated with the transmission of cases of BSF in the time period between 2003 and 2013 in the Piracicaba river basin, state of São Paulo. METHODS : This essay presents a retrospective study to identify the factors associated with the transmission of cases of BSF among all suspected cases identified by the System for Epidemiological Surveillance of São Paulo (CVE). After the description of temporal distribution (onset of symptoms) and the environmental and demographic variations of the confirmed and discarded cases, a multiple logistic regression model was applied. RESULTS : We searched 569 probable locations of infection (PLI) with 210 (37%) confirmed cases of BSF and 359 (63%) discarded cases. The associated variables for the confirmation of BSF in the multiple logistic model using a confidence interval (CI) of 95% were age (OR = 1.025 CI: 1.015-1.035), the presence of Amblyomma sculptum in the environment (OR = 1.629 CI: 1.097-2.439), the collection of ticks from horses (OR = 1.939 CI: 0.999-3.764), the presence of capybaras (OR = 1.467 CI: 1.009-2.138), an urban environment (OR = 1.515 CI: 1.036-2.231), and the existence of a dirty pasture (OR = 1.759 CI: 1.028-3.003). CONCLUSIONS : The factors associated with the confirmation of BSF cases included an urban environment, age, presence of the A. sculptum vector, the collection of ticks from horses, the presence of a capybara population, and a dirty pasture environment. .

Animals , Male , Rats , Apoptosis/genetics , Benzofurans/therapeutic use , Apoptosis/drug effects , Blotting, Western , Cell Line , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Electrophoresis, Gel, Two-Dimensional , Hemodynamics/drug effects , In Situ Nick-End Labeling , Microscopy, Electron, Transmission , Mitochondria/drug effects , Mitochondria/metabolism , Myocardial Infarction/metabolism , Myocardium/cytology , Myocardium/metabolism , Myocardium/ultrastructure , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , NF-kappa B/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Rats, Wistar , Signal Transduction/drug effects , Signal Transduction/genetics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Tandem Mass Spectrometry
Rev. Soc. Bras. Med. Trop ; 48(1): 50-55, jan-feb/2015. tab
Article in English | LILACS | ID: lil-742969


INTRODUCTION: Leptospirosis is a zoonosis that affects both humans and animals. Dogs may serve as sentinels and indicators of environmental contamination as well as potential carriers for Leptospira. This study aimed to evaluate the seroprevalence and seroincidence of leptospirosis infection in dogs in an urban low-income community in southern Brazil where human leptospirosis is endemic. METHODS: A prospective cohort study was designed that consisted of sampling at recruitment and four consecutive trimestral follow-up sampling trials. All households in the area were visited, and those that owned dogs were invited to participate in the study. The seroprevalence (MAT titers ≥100) of Leptospira infection in dogs was calculated for each visit, the seroincidence (seroconversion or four-fold increase in serogroup-specific MAT titer) density rate was calculated for each follow-up, and a global seroincidence density rate was calculated for the overall period. RESULTS: A total of 378 dogs and 902.7 dog-trimesters were recruited and followed, respectively. The seroprevalence of infection ranged from 9.3% (95% CI; 6.7 - 12.6) to 19% (14.1 - 25.2), the seroincidence density rate of infection ranged from 6% (3.3 - 10.6) to 15.3% (10.8 - 21.2), and the global seroincidence density rate of infection was 11% (9.1 - 13.2) per dog-trimester. Canicola and Icterohaemorraghiae were the most frequent incident serogroups observed in all follow-ups. CONCLUSIONS: Follow-ups with mean trimester intervals were incapable of detecting any increase in seroprevalence due to seroincident cases of canine leptospirosis, suggesting that antibody titers may fall within three months. Further studies on incident infections, disease burden or risk factors for incident Leptospira cases should take into account the detectable lifespan of the antibody. .

Animals , Female , Male , Mice , B-Lymphocytes/metabolism , Glycolysis , Lymphoma/metabolism , Poly(ADP-ribose) Polymerases/metabolism , AMP-Activated Protein Kinases/metabolism , Apoptosis/drug effects , B-Lymphocytes/pathology , Biological Transport/drug effects , Cells, Cultured , Enzyme Activation/drug effects , Glucose/metabolism , Glucose/pharmacokinetics , Immunoblotting , In Situ Nick-End Labeling , /pharmacology , Lymphoma/genetics , Lymphoma/pathology , Mice, Knockout , Mitochondria/drug effects , Mitochondria/metabolism , Oxidative Phosphorylation/drug effects , Poly(ADP-ribose) Polymerases/genetics , /genetics , /metabolism , Survival Analysis
Ciênc. Saúde Colet. (Impr.) ; 20(1): 193-198, jan. 2015. tab
Article in English | LILACS | ID: lil-733154


The aim of this study was to applythe Health Belief Model to explain the adherence to the recommendation not to recap needles by dentists and dental assistants of the public health system in a municipality in the State of São Paulo. A questionnaire validated and adapted for the oral health area was used, which included variables related to the frequency of recapping and health beliefs using Likert-type scales. The relationship between beliefs and adherence to the recommendation not to recap needles was obtained by regression analysis. Of all the professionals in this study (n=79), the majority (83.5%) reported recapping needles at least once in the last month. Through regression analysis, it was observed that the relationship between the beliefs described by the model and the attitude whether or not to follow the recommendation not to recap needles was explained by a lower perception of psychological barriers and a greater perception of stimuli not to recap needles. The conclusion reached is that the acceptance of recommendations to prevent working accidents with biological material was explained by some dimensions of the Health Belief Model, enabling discussion about reformulation of training offered to professionals of the public health system.

Objetivou-se neste estudo aplicar o Modelo de Crenças em Saúde a fim de explicar a adesão à recomendação de não reencapar agulhas por cirurgiões-dentistas e auxiliares de saúde bucal da rede pública de um município paulista. Utilizou-se um questionário validado e adaptado para a área de saúde bucal, que contemplava variáveis relativas à frequência do reencape e crenças em saúde, por meio de escalas tipo Likert. A relação entre as crenças e a adesão à recomendação de não reencapar agulhas foi obtida por meio da análise de regressão. Da amostra de profissionais obtida por adesão ao estudo (n = 79), a maioria (83,5%) relatou ter reencapado agulhas pelo menos alguma vez no último mês. Por meio da análise de regressão, foi observado que a relação entre as crenças descritas pelo modelo e a atitude de aderir ou não à recomendação de não reencapar agulhas foi explicada por uma menor percepção de barreiras psicológicas e por uma maior percepção de estímulos para não reencapar agulhas. Conclui-se que a aceitação das recomendações para prevenir acidentes do trabalho com material biológico foi explicado por algumas dimensões do Modelo de Crenças em Saúde, possibilitando a discussão sobre a reformulação de capacitações oferecidas para profissionais do sistema público de saúde.

Animals , Cattle , Electron Transport Complex I/metabolism , Endothelial Cells/enzymology , Hyperoxia/metabolism , Mitochondria/enzymology , Pulmonary Artery/cytology , Pulmonary Artery/enzymology , Ubiquinone/metabolism , Aerobiosis/drug effects , Benzoquinones/pharmacology , Cell Survival/drug effects , Cells, Cultured , Chromatography, High Pressure Liquid , Culture Media , Electron Transport Complex I/antagonists & inhibitors , Endothelial Cells/drug effects , Enzyme Inhibitors/pharmacology , Ferricyanides/pharmacology , L-Lactate Dehydrogenase/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Oxidation-Reduction/drug effects , Oxygen Consumption/drug effects , Pulmonary Artery/drug effects , Spectrophotometry , Tolonium Chloride/pharmacology , Ubiquinone/analysis , Ubiquinone/pharmacology