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1.
Med. clín (Ed. impr.) ; 160(6): 231-236, marzo 2023. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-217725

RESUMO

Introducción: En México la diabetes mellitus tipo 2 (DM2) presenta niveles epidemiológicos, con una tasa de prevalencia del 9,12% y con los índices de sobrepeso y obesidad más altos del mundo. Para superar esta situación se deben crear estrategias enfocadas en la identificación de sujetos en riesgo. El índice triglicéridos y glucosa (TyG) fue creado para la detección de la resistencia a la insulina, y recientemente se ha empleado en la predicción de diabetes mellitus. El objetivo del presente estudio fue determinar el poder predictivo del índice TyG en una cohorte de la Ciudad de México.MétodosSe seleccionaron 3.195 pacientes de una cohorte de pacientes del área de crónico degenerativos de los Centros de Salud de los Servicios de Salud Pública de la Ciudad de México. Se evaluó la capacidad del índice TyG en la predicción de diabetes calculado como: ln (triglicéridos en ayunas [mg/dl]×glucosa en ayunas [mg/dl]/2) después de un seguimiento de al menos 4,5 años. Se determinó una prueba Chi-squared automated interaction detector analysis, que fue corroborada por una prueba ROC.ResultadosEl valor del índice de TyG fue significativamente mayor para los pacientes que desarrollar DM2. Los valores de área bajo la curva=0,934, intervalo de confianza (IC) 95%=0,924-0,924. Obteniendo un punto de corte de 9,45 en mujeres; en hombres: DM AUC=0.824, IC 95%=0,824-0,873 punto de corte 9.12.ConclusionesEl índice TyG es un buen marcador en la predicción de DM2 respaldado por la aplicación del algoritmo CHAID como herramienta útil para la predicción de DM2. (AU)


Introduction: In Mexico, type 2 Diabetes mellitus (DM2) presents epidemiological levels with a prevalence rate of 9.12% and with the highest overweight and obesity rates worldwide. To overcome this situation, strategies must be created focused on the identification of subjects at risk. The Triglyceride and Glucose (TyG) index, was created for the detection of insulin resistance, has recently been used in the prediction of DM. The objective of the present study was to determine the predictive power of the TyG index in a cohort from Mexico City.Methods3195 patients were selected from a cohort of patients from the chronic degenerative area of the Health Centers of the Public Health Services of Mexico City. The ability of the TyG index in predicting diabetes was evaluated as: ln [Fasting triglycerides (mg/dl) x fasting glucose (mg/dl)/2]. after a follow-up of at least 4.5 years. A CHAID test was determined that was corroborated by a ROC test.Resultsthe value of the TyG index was significantly higher for patients who develop DM2. Values of AUC=0.934, 95% CI: 0.924-0.924. Obtaining a cut-off point of 9.45 in women; in men: DM2 AUC=0.824, 95% CI: 0.824-0.873, and cut-off point 9.12.ConclusionsThe TyG index is a good marker in the prediction of DM2. The CHAID determination is a useful tool in the prediction of DM2. (AU)


Assuntos
Humanos , Biomarcadores , Glucose , Diabetes Mellitus Tipo 2/diagnóstico , Resistência à Insulina , Triglicerídeos , Fatores de Risco
2.
Med Clin (Barc) ; 160(6): 231-236, 2023 03 24.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35933191

RESUMO

INTRODUCTION: In Mexico, type 2 Diabetes mellitus (DM2) presents epidemiological levels with a prevalence rate of 9.12% and with the highest overweight and obesity rates worldwide. To overcome this situation, strategies must be created focused on the identification of subjects at risk. The Triglyceride and Glucose (TyG) index, was created for the detection of insulin resistance, has recently been used in the prediction of DM. The objective of the present study was to determine the predictive power of the TyG index in a cohort from Mexico City. METHODS: 3195 patients were selected from a cohort of patients from the chronic degenerative area of the Health Centers of the Public Health Services of Mexico City. The ability of the TyG index in predicting diabetes was evaluated as: ln [Fasting triglycerides (mg/dl) x fasting glucose (mg/dl)/2]. after a follow-up of at least 4.5 years. A CHAID test was determined that was corroborated by a ROC test. RESULTS: the value of the TyG index was significantly higher for patients who develop DM2. Values of AUC=0.934, 95% CI: 0.924-0.924. Obtaining a cut-off point of 9.45 in women; in men: DM2 AUC=0.824, 95% CI: 0.824-0.873, and cut-off point 9.12. CONCLUSIONS: The TyG index is a good marker in the prediction of DM2. The CHAID determination is a useful tool in the prediction of DM2.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Masculino , Humanos , Feminino , Diabetes Mellitus Tipo 2/diagnóstico , Triglicerídeos , Glucose , Glicemia , Biomarcadores , Fatores de Risco
3.
Dent J (Basel) ; 10(12)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36547041

RESUMO

Periodontal disease (PD) and obesity are characterized by a dysregulated inflammatory state. Both conditions trigger inflammatory and immune responses with an increase in proinflammatory cytokines such as Interleukin 6 (IL-6) and the release of inflammatory mediators such as C-reactive protein (CRP). Individuals with a high body mass index (BMI) present a chronic inflammatory state. The aim of the present study was to perform a systematic review of inflammatory markers (IL-6 and CRP) in obese patients with PD and their possible relationship by analyzing the levels of these markers. A digital literature search was performed in three databases-PubMed, SciElo and Medigraphic-through an advanced search for original articles, employing IL-6 and CRP in obese patients with PD, within a publication period from 2010 to 2021. PRISMA guidelines, the JADAD scale and a qualitative analysis of scientific evidence were performed using the Cochrane collaboration method and the RoB 2 assessment tool. Ten articles were included in this analysis with the variables recorded and associated with subjects with obesity and PD. Of the ten articles included, three analyzed IL-6 and CRP, four analyzed IL-6 and three analyzed CRP. In conclusion, and based on the available evidence, the aforementioned markers of inflammation demonstrate that there is a relationship between PD and obesity.

4.
Rev. ADM ; 79(3): 165-176, mayo-jun. 2022. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-1378976

RESUMO

Introducción: El hueso, reservorio de minerales y moléculas orgánicas, es un tejido dinámico que detecta y se adapta a las cargas mecánicas de los órganos y tejidos del cuerpo, el cual mantiene la estructura ósea del esqueleto durante el crecimiento y a través de la vida del ser humano. Las células óseas son sensibles a las cargas mecánicas y microvibra- ciones que recibe el esqueleto. Objetivo: El propósito de este estudio fue realizar una revisión sistemática acerca de los efectos que ejerce la microvibración de alta frecuencia-baja intensidad, en osteocitos cultivados in vitro sobre la síntesis de factores solubles, con el propósito de entender si la microvibración tiene influencia en la aceleración del movimiento dentario. Material y métodos: Se realizó una búsqueda de artículos de revisión de osteocitos y otras células óseas in vitro, a través de la estrategia PICO (Paciente, Intervención, Comparación, Resultado [Outcome]), con el empleo de palabras clave como: «os- teocitos¼, «microvibración¼, «remodelación¼, «osteoclastogénesis¼, «citocinas¼ y «osteoblastos¼. Se estructuró por medio de PRISMA (informe de revisiones sistemáticas y meta-análisis). La captación de datos finales se hizo por medio del método de puntuación de calidad Jadad y Cochrane (modelo de correlación) como herramientas para evaluar el riesgo de sesgo de cada uno de los artículos. Se incluyeron 11 artículos con alta calidad metodológica. Resultados: La mayoría de los experimentos in vitro demostraron que la microvibración tuvo un aumento estadísticamente significativo en la proliferación y dife- renciación de las células madre mesenquimales (MSC), en osteoblastos (MC3T3-E1), en la expresión de proteínas para inducir osteogénesis y en los osteocitos (MLO-Y4). Asimismo, sobrerregularon la expresión de osteoprotegerina (OPG), prostaglandina (PGE2) y óxido nitroso (NO) al alterar y regular los factores solubles como las citocinas, factores de crecimiento y quimiocinas, de las demás células, además de mostrar una disminución en la actividad de los osteoclastos (RAW246.7) en la resorción ósea. Conclusión: La microvibración induce remodelación ósea. Los osteocitos son sensibles a los estímulos mecánicos y producen factores solubles para inducir la remodelación ósea, razón por la cual se emplea la microvibración como una terapia innovadora y prometedora, no invasiva y no farmacológica en la estimulación de la formación ósea de la superficie del hueso (AU)


Assuntos
Humanos , Osteogênese , Vibração , Remodelação Óssea , Osteócitos , Reabsorção Óssea , Análise de Variância , Citocinas , Meios de Cultura , Ligante RANK
5.
J Microsc ; 286(1): 22-30, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35092003

RESUMO

Raman spectroscopy, transmission electron microscopy (TEM) and atomic force microscopy (AFM) techniques can perform chemical analyses and acquire high-resolution images of cell samples. For this reason, in this study, semi-thin sections of a single Penicillium rubens cell were analysed by Raman enhanced surface spectroscopy. The spectra showed peaks corresponding to the macromolecules that make up the cellular components. In addition, the various organelles were analysed by TEM and AFM to observe the cellular nanostructures. With the use of these techniques, it is possible to identify molecules in semi-thin sections, which provides a wide potential for biomedical applications and for the analysis of cell dynamics. The observation of the most detailed possible structure of cells is used as a starting point in numerous studies to identify and localise some biochemical processes. Given that the function of eukaryotic cells depends on the location, shape, structure and function of the subcellular organelles (and on the interaction between them), the sum of the data obtained allows a complete analysis of what happens in the cell. This article addresses, from a multidisciplinary point of view, what happens in a single cell of a filamentous fungus (Penicillium rubens) while it is in a physiological moment (secondary metabolism) that allows the biosynthesis of an antibiotic (penicillin). For this purpose, different types of microscopies were used (TEM: transmission electron microscopy, and AFM: atomic force microscopy, which allow visualising small details in the cell) and a spectroscopy method (Raman, which allows detecting certain characteristics of the macromolecules and some stretching bonds). Regarding the results, during the synthesis of penicillin, the antibiotic-producing Penicillium rubens cells showed significant changes compared to the non-producing cells: the cell wall is observed to be significantly thickened in the production phase, organelles such as peroxisomes grow in number and size since it is known that the final route of metabolite synthesis takes place in them. When penicillin is released from peroxisomes, they must be degraded to release the load from the cell; this is done by vacuoles, which are active and engulf peroxisomes. The newly synthesised penicillin is found within secretory vesicles that travel towards the cell membrane and both membranes fuse creating ripples. On the other hand, and given that a single cell is being studied, it is essential to increase the signal to detect biomolecules employing the Raman-SERS technique, using a silver substrate to obtain the increased signal.


Assuntos
Penicilinas , Penicillium , Antibacterianos/metabolismo , Penicilinas/metabolismo , Penicillium/metabolismo , Penicillium/ultraestrutura , Análise Espectral Raman
6.
Mol Neurobiol ; 59(1): 620-642, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34750787

RESUMO

The aggregation of alpha-synuclein (α-Syn) plays a critical role in the development of Parkinson's disease (PD) and other synucleinopathies. α-Syn, which is encoded by the SNCA gene, is a lysine-rich soluble amphipathic protein normally expressed in neurons. Located in the cytosolic domain, this protein has the ability to remodel itself in plasma membranes, where it assumes an alpha-helix conformation. However, the protein can also adopt another conformation rich in cross-beta sheets, undergoing mutations and post-translational modifications, then leading the protein to an unusual aggregation in the form of Lewy bodies (LB), which are cytoplasmic inclusions constituted predominantly by α-Syn. Pathogenic mechanisms affecting the structural and functional stability of α-Syn - such as endoplasmic reticulum stress, Golgi complex fragmentation, disfunctional protein degradation systems, aberrant interactions with mitochondrial membranes and nuclear DNA, altered cytoskeleton dynamics, disrupted neuronal plasmatic membrane, dysfunctional vesicular transport, and formation of extracellular toxic aggregates - contribute all to the pathogenic progression of PD and synucleinopathies. In this review, we describe the collective knowledge on this topic and provide an update on the critical role of α-Syn aggregates, both at the cellular and molecular levels, in the deregulation of organelles affecting the cellular homeostasis and leading to neuronal cell death in PD and other synucleinopathies.


Assuntos
Encéfalo/metabolismo , Neurônios/metabolismo , Doença de Parkinson/metabolismo , Sinucleinopatias/metabolismo , alfa-Sinucleína/metabolismo , Animais , Encéfalo/patologia , Humanos , Neurônios/patologia , Doença de Parkinson/patologia , Sinucleinopatias/patologia
7.
Pharmaceuticals (Basel) ; 14(7)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202137

RESUMO

Sphaeralcea angustifolia has been widely used in inflammatory conditions such as blows, bruises, fractures, and wounds. The compounds identified as active in plants and suspension cell culture of S. angustifolia were tomentin, scopoletin, and sphaeralcic acid. To consolidate the integral use of knowledge about the S. angunstifolia and strengthen its pharmacological use in patients with knee osteoarthritis, the pharmacokinetic behavior of the active compounds was characterized. The SaTSS (S. angustifoloia standardized in Tomentin, Scopoletin, and Sphaeralcic acid) anti-ostearthritic fraction was obtained from cell suspension. The analytical method of High-Performance Liquid Chromatography (HPLC) for tomentin, scopoletin, and sphaeralcic acid were validated determining the accuracy, precision linearity, sensibility, specificity, detection limits, and quantification time-range parameters, as well as extraction efficiency and stability of compounds. The pharmacokinetic assay was performed with ICR mice strain, in which the mice were administrated with a single oral or intravenous dose (400 mg/kg with 7.1 mg/kg of scopoletin and tomentin in mixture and 34.6 mg/kg of sphaeralcic acid) of the SaTSS standardized active fraction. The results of the validated analytical methods allowed establishing, in a validated manner, that a coumarin mixture and sphaeralcic acid present in the SaTES fraction were detected in plasma. According to the values of Akaike Information Criteria (AIC), Sum of Squares (SS), Schwarz Criteria (SC), and by the determination coefficient (R2), the compounds follow a two-compartment model.

8.
J Pharm Biomed Anal ; 183: 113143, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32045824

RESUMO

Sphaeralcea angustifolia (Cav.) G. Don (Malvaceae) is a plant used in inflammatory illnesses. The scopoletin was the main responsible compound for the anti-arthritic effect in this species. The therapeutic effectiveness of a S. angustifolia dichloromethane extract gel standardized in scopoletin was confirmed in patients with osteoarthritis. Cells in suspension cultures from S. angustifolia were established for scopoletin production; in addition, tomentin, and sphaeralcic acid compounds were isolated from this culture. Tomentin and sphaeralcic acid showed also anti-inflammatory and immunomodulatory effects. Validation of HPLC quantification methods for sphaeralcic acid, and scopoletin and tomentin was performed in addition to extraction efficiency and stability of the active compounds. The pharmacokinetic parameters of scopoletin and tomentine in mixture, and sphaeralcic acid after oral administration of standardized active fraction indicated that these compounds followed a two-compartment model; they were bioavailable in plasma (absorbed) and distributed to blank organs. No products derived from their biotransformation were detected. The objective of this work was to determine the pharmacokinetic constants of urinary and fecal elimination in mice of the anti-arthritic compounds, after oral administration (400 mg / kg) of a standardized active fraction (SaTES) of S. angustifolia. It was established that the coumarin mixture (scopoletin and tomentin) were eliminated by the urine; while, sphaeralcic acid was mainly eliminated by fecal path, following both a non-compartmental behavior. No products derived from their biotransformation were detected.


Assuntos
Malvaceae/química , Escopoletina/administração & dosagem , Escopoletina/farmacocinética , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Cumarínicos/química , Feminino , Camundongos , Camundongos Endogâmicos ICR , Padrões de Referência
9.
CCH, Correo cient. Holguín ; 23(2): 647-657, abr.-jun. 2019. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1089420

RESUMO

RESUMEN La enfermedad de Stargardt y el fondo flavimaculatus son variantes de una misma entidad nosológica, que constituyen la distrofia macular juvenil más frecuente, y una causa común de pérdida de visión central en adultos menores de 50 años. Se trata de una paciente femenina de 35 años con enfermedad de Stargardt, atendida en una unidad básica avanzada en salud del municipio de Vila Nova do Piauí, Brasil, que actualmente presenta baja capacidad visual. Se presenta una lesión macular localizada en la región foveal, de aspecto bronceado y pálido en la región temporal de la papila óptica. A nivel histológico, se produce un cúmulo de material tipo lipofuscina en las células del epitelio pigmentario de la retina, por la mutación del gen ABCA4. La incidencia de la enfermedad de Stargardt se sitúa alrededor de una persona afectada entre 10 000 y suele afectar a adolescentes y adultos jóvenes.


ABSTRACT Stargardt's disease and the flavimaculatus fund are variants of the same nosological entity. They constitute the most frequent juvenile macular dystrophy and common cause of central vision loss in adults under 50 years of age. A 35-year-old female patient who was diagnosed with Stargardt's disease currently suffers from low visual capacity. We present findings of a localized macular lesion in the foveal region of the bronzed and pale aspect in the temporal region of the optic papilla. At the histological level, a cluster of lipofuscin-like material is produced in the cells of the retinal pigment epithelium by the mutation of the ABCA4 gene. The incidence of Stargardt disease is around one person affected by 10,000 people and usually affects adolescents and young adults under 20 years old.

10.
Med. clín (Ed. impr.) ; 151(12): 481-486, dic. 2018. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-182278

RESUMO

Introducción y objetivos: El péptido natriurético tipo B (BNP) es un marcador de daño a nivel de miocardio, este péptido ha sido asociado con marcadores de riesgo metabólico, aunque existe controversia en este sentido. El objetivo del presente estudio fue determinar la correlación de los valores plasmáticos del BNP y los parámetros de riesgo metabólico. Material y métodos: Estudio retrospectivo, observacional con la inclusión de 152 sujetos, los cuales fueron clasificados con base a los componentes del síndrome metabólico. Se determinó la asociación de los valores plasmáticos del BNP con los parámetros del síndrome metabólico mediante la correlación de Spearman. Resultados: Se encontró una asociación inversa significativa con el peso (r=−0,408; p<0,0001) y con el IMC (r=−0,443; p<0,001). Mientras que se observó una correlación significativa con la presión sistólica (r=0,324; p<0,001). Se determinaron los valores del BNP con respecto al número de componentes del síndrome metabólico, encontrando una disminución dependiente del número de los componentes del síndrome metabólico (p<0,05). Conclusión: Con base a los datos obtenidos en este trabajo, podemos presumir que la determinación de BNP en plasma puede ser un buen marcador de daño metabólico


Background and objective: Natriuretic peptide type B (BNP) is a marker of myocardium injury. This peptide has been associated with metabolic risk markers, although controversy exists in this regard. The aim of the present study was to determine the correlation of plasma BNP levels with metabolic risk parameters. Materials and methods: A retrospective, observational study that included 152 patients, who were classified according to their clinical diagnosis as patients with metabolic syndrome. Plasma BNP levels and clinical metabolic parameters were assessed by using Spearmańs rank correlation coefficient. Results: A significant inverse association with weight (r=−.408; p<.0001) and BMI (r=−.443; p<.001) was obtained. While a positive significant association with systolic pressure (r=.324; p<.001) was observed. A significant decrease was found in BNP levels and components of metabolic syndrome (p<.05). Conclusion: Based on the results from this study, we can conclude that BNP determination could be an adequate metabolic marker


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Insuficiência Cardíaca/sangue , Síndrome Metabólica/complicações , Obesidade/complicações , Biomarcadores/sangue , Estudos Retrospectivos , Antropometria , 28599 , Correlação de Dados
11.
J Ovarian Res ; 11(1): 84, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30241554

RESUMO

BACKGROUND: Current methods for determining superior embryo quality (morphological assessment) are unable to compensate for poor pregnancy outcomes. Due to the importance of the cumulus-oocyte complex and the value of cumulus cells (CCs) as markers of embryo health, we determined the association between the CCs gene expression of the Prostaglandin-Endoperoxide Synthase 2 (PTGS2) and Versican (VCAN) with pregnancy. METHODS: One hundred forty-nine women, suffering from infertility and undergoing IVF, were included in this study (age: 29-46 years; BMI = 25.5 ± 5.0 kg/m2). Patients underwent a standard IVF protocol. CCs were isolated during oocyte retrieval, and their RNA was isolated using Trizol. The mRNA expression of PTGS2, VCAN, and L19 was measured by qPCR. The PVL index, (PTGS2 + VCAN)*L19normalized, was determined for each oocyte. Clinical pregnancy was confirmed by ß-hCG and the presence of a fetal heartbeat. Associations were determined by ROC curves or logistic regression. RESULTS: There was no correlation between the PVL index and morphological scores. Using only single embryo transfers (SETs), we determined that the PVL index was associated with pregnancy (ß-hCG: AUC = 0.87, 95%CI: 0.74-1.00) with an optimal cutoff value of 58.2. Using the complete cohort (consisting of SETs, and patients with 2, 3, or 4 embryos transferred), the presence of at least one embryo with a PVL index score ≥ 58.2 was associated with a greater probability of achieving pregnancy (ß-hCG: odds ratio = 17.15, 95%CI: 6.82-43.18, p < 0.001). CONCLUSION: Transferring at least one embryo with a PVL index score ≥ 58.2, generates a higher chance of achieving pregnancy.


Assuntos
Células do Cúmulo/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Fertilização In Vitro/métodos , Versicanas/genética , Versicanas/metabolismo , Adulto , Feminino , Humanos , Pessoa de Meia-Idade
12.
Med Clin (Barc) ; 151(12): 481-486, 2018 12 21.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29678316

RESUMO

BACKGROUND AND OBJECTIVE: Natriuretic peptide type B (BNP) is a marker of myocardium injury. This peptide has been associated with metabolic risk markers, although controversy exists in this regard. The aim of the present study was to determine the correlation of plasma BNP levels with metabolic risk parameters. MATERIALS AND METHODS: A retrospective, observational study that included 152 patients, who were classified according to their clinical diagnosis as patients with metabolic syndrome. Plasma BNP levels and clinical metabolic parameters were assessed by using Spearmans rank correlation coefficient. RESULTS: A significant inverse association with weight (r=-.408; p<.0001) and BMI (r=-.443; p<.001) was obtained. While a positive significant association with systolic pressure (r=.324; p<.001) was observed. A significant decrease was found in BNP levels and components of metabolic syndrome. (p<.05). CONCLUSION: Based on the results from this study, we can conclude that BNP determination could be an adequate metabolic marker.


Assuntos
Síndrome Metabólica/sangue , Peptídeo Natriurético Encefálico/sangue , Biomarcadores/sangue , Pressão Sanguínea , Peso Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas
13.
Medwave ; 16(8): e6535, 2016 Sep 13.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-27690306

RESUMO

Non-alcoholic fatty liver disease refers to a disease spectrum that ranges from steatosis to non-alcoholic steatohepatitis, which leads to fibrosis, cirrhosis and hepatocellular carcinoma. Given the increasing prevalence of obesity worldwide, the incidence of non-alcoholic fatty liver disease has become a world health problem. Non-alcoholic fatty liver disease is considered to be the hepatic manifestation of metabolic syndrome associated with insulin resistance, central obesity, and type 2 diabetes mellitus. Allegedly, insulin resistance plays a pivotal role in its pathogenesis. Here we highlight non-alcoholic fatty liver disease epidemiology and pathophysiology, its progression towards steatohepatitis with particular emphasis in liver fibrosis and participation of advanced glycation end products. The different treatments reported are described here as well. We conducted a search in PubMed with the terms steatohepatitis, steatosis advanced glycation end products, liver fibrosis and adipocytokines. Articles were selected according to their relevance.


La enfermedad hepática no alcohólica se refiere a un espectro de enfermedades que va desde hígado graso, hasta esteatohepatitis y que puede cursar por fibrosis, cirrosis y hepatocarcinoma. Dado que a nivel mundial se ha incrementado la prevalencia de la obesidad, los cambios en el estilo de vida y la alimentación desbalanceada, la enfermedad hepática no alcohólica se ha convertido en un problema de salud pública. Se le considera como la manifestación hepática del síndrome metabólico, asociada a resistencia a la insulina, obesidad central, diabetes mellitus tipo 2, e hipertrigliceridemia. Se estima que la resistencia a la insulina, juega un papel detonador en la patogénesis de la enfermedad hepática no alcohólica. En este artículo se describen diferentes aspectos de la enfermedad hepática no alcohólica: la epidemiología, la patofisiología, su progresión hacia esteatohepatitis con particular énfasis en la fibrosis hepática, la participación de los productos finales de glicación avanzada, y los diferentes tratamientos reportados. Se realizó una búsqueda de artículos en la base de datos de PubMed con los términos esteatohepatitis, esteatosis, productos finales de glicación avanzada, fibrosis hepática y adipocinas. Los artículos fueron seleccionados por su relevancia en el tema.

14.
J Gastroenterol Hepatol ; 25(7): 1306-14, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20594261

RESUMO

BACKGROUND AND AIM: Development of hepatic fibrosis is a complex process that involves oxidative stress (OS) and an altered balance between pro- and anti-apoptotic molecules. Since Bcl-2 overexpression preserves viability against OS, our objective was to address the effect of Bcl-2 overexpression in the hepatic stellate cells (HSC) cell-line CFSC-2G under acetaldehyde and H(2)O(2) challenge, and explore if it protects these cells against OS, induces replicative senescence and/or modify extracellular matrix (ECM) remodeling potential. METHODS: To induce Bcl-2 overexpression, HSC cell line CFSC-2G was transfected by lipofection technique. Green fluorescent protein-only CFSC-2G cells were used as a control. Cell survival after H(2)O(2) treatment and total protein oxidation were assessed. To determine cell cycle arrest, proliferation-rate, DNA synthesis and senescence were assessed. Matrix metalloproteinases (MMP), tissue-inhibitor of MMP (TIMP), transglutaminases (TG) and smooth muscle a-actin (alpha-SMA) were evaluated by western blot in response to acetaldehyde treatment as markers of ECM remodeling capacity in addition to transforming growth factor-beta (TGF-beta) mRNA. RESULTS: Cells overexpressing Bcl-2 survived approximately 20% more than control cells when exposed to H(2)O(2) and approximately 35% proteins were protected from oxidation, but Bcl-2 did not slow proliferation or induced senescence. Bcl-2 overexpression did not change alpha-SMA levels, but it increased TIMP-1 (55%), tissue transglutaminases (tTG) (25%) and TGF-beta mRNA (49%), when exposed to acetaldehyde, while MMP-13 content decreased (47%). CONCLUSIONS: Bcl-2 overexpression protected HSC against oxidative stress but it did not induce replicative senescence. It increased TIMP-1, tTG and TGF-beta mRNA levels and decreased MMP-13 content, suggesting that Bcl-2 overexpression may play a key role in the progression of fibrosis in chronic liver diseases.


Assuntos
Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Acetaldeído/farmacologia , Actinas/metabolismo , Animais , Linhagem Celular , Proliferação de Células , Senescência Celular , Replicação do DNA , Relação Dose-Resposta a Droga , Matriz Extracelular/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/patologia , Humanos , Peróxido de Hidrogênio/farmacologia , Cirrose Hepática/genética , Cirrose Hepática/patologia , Metaloproteinase 13 da Matriz/metabolismo , Oxidantes/farmacologia , Estresse Oxidativo , Proteína 2 Glutamina gama-Glutamiltransferase , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/metabolismo , Ratos , Proteínas Recombinantes de Fusão/metabolismo , Fatores de Tempo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Transfecção , Fator de Crescimento Transformador beta/genética , Transglutaminases/metabolismo , Regulação para Cima
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