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BACKGROUND: Phase III clinical trials have documented the efficacy of the SARS-CoV-2 vaccines in preventing symptomatic COVID-19. Nonetheless, it is imperative to continue analyzing the clinical response to different vaccines in real-life studies. Our objective was to evaluate the effectiveness of five different vaccines in hospitalized patients with COVID-19 during the third COVID-19 outbreak in Mexico dominated by the Delta variant. METHODS: A test-negative case-control study was performed in nine tertiary-care hospitals for COVID-19. We estimated odds ratios (OR) adjusted by variables related a priori with the likelihood of SARS-CoV-2 infection and its severity. RESULTS: We studied 761 subjects, 371 cases, and 390 controls with a mean age of 53 years (SD, 17 years). Overall, 51% had a complete vaccination scheme, and an incomplete scheme (one dose from a scheme of two), 14%. After adjustment for age, gender, obesity, and diabetes mellitus, we found that the effectiveness of avoiding a SARS-CoV-2 infection when hospitalized with at least one vaccination dose was 71% (OR 0.29, 95% CI 0.19-0.45), that of an incomplete vaccination scheme, 67% (OR 0.33, 95% CI 0.18-0.62), and that of any complete vaccination scheme, 73% (OR 0.27, 95% CI 0.17-0.43). CONCLUSIONS: The SARS-CoV-2 vaccination program showed effectiveness in preventing SARS-CoV-2 infection in hospitalized patients during a Delta variant outbreak.
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Influenza has been a stationary disease in Mexico since 2009, and this causes a high cost for the national public health system, including its detection using RT-qPCR tests, treatments, and absenteeism in the workplace. Despite influenza's relevance, the main clinical features to detect the disease defined by international institutions like the World Health Organization (WHO) and the United States Centers for Disease Control and Prevention (CDC) do not follow the same pattern in all populations. The aim of this work is to find a machine learning method to facilitate decision making in the clinical differentiation between positive and negative influenza patients, based on their symptoms and demographic features. The research sample consisted of 15480 records, including clinical and demographic data of patients with a positive/negative RT-qPCR influenza tests, from 2010 to 2020 in the public healthcare institutions of Mexico City. The performance of the methods for classifying influenza cases were evaluated with indices like accuracy, specificity, sensitivity, precision, the f1-measure and the area under the curve (AUC). Results indicate that random forest and bagging classifiers were the best supervised methods; they showed promise in supporting clinical diagnosis, especially in places where performing molecular tests might be challenging or not feasible.
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During the second half of the last century, the prevalent knowledge recognized the voltage-gated sodium channels (VGSCs) as the proteins responsible for the generation and propagation of action potentials in excitable cells. However, over the last 25 years, new non-canonical roles of VGSCs in cancer hallmarks have been uncovered. Their dysregulated expression and activity have been associated with aggressive features and cancer progression towards metastatic stages, suggesting the potential use of VGSCs as cancer markers and prognostic factors. Recent work has elicited essential information about the signalling pathways modulated by these channels: coupling membrane activity to transcriptional regulation pathways, intracellular and extracellular pH regulation, invadopodia maturation, and proteolytic activity. In a promising scenario, the inhibition of VGSCs with FDA-approved drugs as well as with new synthetic compounds, reduces cancer cell invasion in vitro and cancer progression in vivo. The purpose of this review is to present an update regarding recent advances and ongoing efforts to have a better understanding of molecular and cellular mechanisms on the involvement of both pore-forming α and auxiliary ß subunits of VGSCs in the metastatic processes, with the aim at proposing VGSCs as new oncological markers and targets for anticancer treatments.
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Throughout the entire coronavirus disease 19 (COVID-19) pandemic, there were disruptions in the supply chain of test materials around the world, primarily in poor- and middle-income countries. The use of 3D prints is an alternative to address swab supply shortages. In this study, the feasibility of the clinical use of 3D-printed swabs for oropharyngeal and nasopharyngeal sampling for the detection of SARS-CoV-2 infection was evaluated. For that purpose, paired samples with the 3D printed and the control swabs were taken from 42 adult patients and 10 pediatric patients, and the results obtained in the detection of SARS-CoV-2 by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) were compared. Additionally, in those cases where the result was positive for SARS-CoV-2, the viral load was calculated by means of a mathematical algorithm proposed by us. For both adults and children, satisfactory results were obtained in the detection of SARS-CoV-2 by RT-qPCR; no significant differences were found in the quantification cycle values between the 3D-printed swab samples and the control samples. Furthermore, we corroborated that the 3D-printed swabs caused less discomfort and pain at the time of sampling. In conclusion, this study shows the feasibility of routinely using 3D-printed swabs for both adults and children. In this way, it is possible to maintain local and cheaper consumption along with fewer distribution difficulties.
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Hearing loss is the most frequent sensory disorder, with an incidence of 1:1500 live newborns. In more than 50% of patients, it is associated with a genetic cause, while in up to 30% of cases, it is related to syndromic entities. We performed a literature review of studies on congenital hearing loss of genetic origin in the Mexican population. We identified eight reports that showed that the pathogenic variants most frequently associated with hearing loss are related to the GJB2 gene, although in a low percentage (3%). Other mutations were identified in the GJB6, SLC26A4, or CHD23 genes. On this basis, a possible diagnostic strategy in Mexican patients with hearing loss is to consider an initial screening of these three genes. If these genes were negative for pathogenic variants, the following steps would be to consider second-generation sequencing analysis focused on panels of genes associated with hearing loss, isolated or syndromic, and if necessary, to perform exome or whole-genome analysis. Establishing an etiologic cause is critical in clinically evaluating patients with congenital hearing loss and their families. It can help determine rehabilitation strategies, such as hearing aids or cochlear implants and provide information on disease progression and genetic counseling in this population.
La pérdida auditiva es la alteración sensorial más frecuente, con una incidencia de 1:1500 recién nacidos vivos. En más del 50% de los pacientes se asocia con una causa genética, mientras que en más del 30% de los casos se asocia con entidades sindrómicas. Se llevó a cabo una revisión de la literatura de las investigaciones sobre la pérdida auditiva congénita de origen genético en la población mexicana. Se identificaron ocho reportes en los que se demostró que las variantes patogénicas más frecuentemente asociadas con pérdida auditiva se encuentran en el gen GJB2, aunque en un porcentaje bajo (3%). Se identificaron otras mutaciones en los genes GJB6, SLC26A4 o CHD23. Con base en esta información, una posible estrategia diagnóstica en pacientes mexicanos con pérdida auditiva es considerar un primer paso en el tamiz diagnóstico con los tres genes mencionados. Si estos genes fueran negativos para variantes patogénicas, el siguiente paso sería considerar el análisis por secuenciación de segunda generación enfocado en paneles de genes asociados con pérdida auditiva, tanto aislada como sindrómica, y en caso necesario, realizar el análisis del exoma o del genoma completo. Establecer una causa etiológica es un componente crítico en la evaluación clínica de los pacientes con pérdida auditiva congénita, ya que puede ayudar a determinar las estrategias de manejo y rehabilitación, como el uso de auxiliares auditivos o implantes cocleares, proporcionar información sobre la progresión de la enfermedad y dar asesoramiento genético en esta población.
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Implante Coclear , Surdez , Perda Auditiva , Conexina 26/genética , Conexinas/genética , Surdez/epidemiologia , Surdez/genética , Perda Auditiva/etiologia , Perda Auditiva/genética , Humanos , Recém-NascidoRESUMO
Abstract Hearing loss is the most frequent sensory disorder, with an incidence of 1:1500 live newborns. In more than 50% of patients, it is associated with a genetic cause, while in up to 30% of cases, it is related to syndromic entities. We performed a literature review of studies on congenital hearing loss of genetic origin in the Mexican population. We identified eight reports that showed that the pathogenic variants most frequently associated with hearing loss are related to the GJB2 gene, although in a low percentage (3%). Other mutations were identified in the GJB6, SLC26A4, or CHD23 genes. On this basis, a possible diagnostic strategy in Mexican patients with hearing loss is to consider an initial screening of these three genes. If these genes were negative for pathogenic variants, the following steps would be to consider second-generation sequencing analysis focused on panels of genes associated with hearing loss, isolated or syndromic, and if necessary, to perform exome or whole-genome analysis. Establishing an etiologic cause is critical in clinically evaluating patients with congenital hearing loss and their families. It can help determine rehabilitation strategies, such as hearing aids or cochlear implants and provide information on disease progression and genetic counseling in this population.
Resumen La pérdida auditiva es la alteración sensorial más frecuente, con una incidencia de 1:1500 recién nacidos vivos. En más del 50% de los pacientes se asocia con una causa genética, mientras que en más del 30% de los casos se asocia con entidades sindrómicas. Se llevó a cabo una revisión de la literatura de las investigaciones sobre la pérdida auditiva congénita de origen genético en la población mexicana. Se identificaron ocho reportes en los que se demostró que las variantes patogénicas más frecuentemente asociadas con pérdida auditiva se encuentran en el gen GJB2, aunque en un porcentaje bajo (3%). Se identificaron otras mutaciones en los genes GJB6, SLC26A4 o CHD23. Con base en esta información, una posible estrategia diagnóstica en pacientes mexicanos con pérdida auditiva es considerar un primer paso en el tamiz diagnóstico con los tres genes mencionados. Si estos genes fueran negativos para variantes patogénicas, el siguiente paso sería considerar el análisis por secuenciación de segunda generación enfocado en paneles de genes asociados con pérdida auditiva, tanto aislada como sindrómica, y en caso necesario, realizar el análisis del exoma o del genoma completo. Establecer una causa etiológica es un componente crítico en la evaluación clínica de los pacientes con pérdida auditiva congénita, ya que puede ayudar a determinar las estrategias de manejo y rehabilitación, como el uso de auxiliares auditivos o implantes cocleares, proporcionar información sobre la progresión de la enfermedad y dar asesoramiento genético en esta población.
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BACKGROUND: Breastfeeding education is key to undergraduate nursing, nutrition, and medicine students' study programs. All students should be prepared to support and inform mothers about the best infant feeding methods. However, students may not be receiving adequate training to provide this support during their preparation. OBJECTIVES: The objective of this study was to explore if the Learning Units of the study programs of the bachelor's degrees in medicine, nursing, and nutrition, incorporate theoretical/practical content regarding breastfeeding and to evaluate whether these contents cover requirements related to knowledge and skills in breastfeeding recommended by international organizations for student's health area. DESIGN: Descriptive. METHODS: In the study programs of the bachelor's degrees, we identified the Learning Units that described theoretical/practical contents related to the subject of breastfeeding, to later contrast this training with the objectives in knowledge and skills in breastfeeding that the students in the health area should receive during their academic education, according to international recommendations. RESULTS: The three study programs offer content on breastfeeding. The degrees in nursing and medicine manage to review a more significant number of training contents, unlike nutrition. However, the knowledge and skills targeted and identified do not seem to approach the knowledge and skills recommended by international institutions. CONCLUSIONS: Several knowledge and skills need to be addressed during the training of health students. Thematic content and educational strategies must be improved and implemented to improve their breastfeeding training.
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Bacharelado em Enfermagem , Estudantes de Enfermagem , Aleitamento Materno , Currículo , Feminino , Humanos , Lactente , MãesRESUMO
Commercialization of extra virgin olive oil (EVOO) requires a best before date recommended at up to 24 months after bottling, stored under specific conditions. Thus, it is expected that the product retains its chemical properties and preserves its 'extra virgin' category. However, inadequate storage conditions could alter the properties of EVOO. In this study, Arbequina EVOO was exposed to five storage conditions for up to one year to study the effects on the quality of the oil and the compounds responsible for flavor. Every 15 or 30 days, samples from each storage condition were analyzed, determining physicochemical parameters, the profiles of phenols, volatile compounds, α-tocopherol, and antioxidant capacity. Principal component analysis was utilized to better elucidate the relationships between the composition of EVOOs and the storage conditions. EVOOs stored at -23 and 23 °C in darkness and 23 °C with light, differed from the oils stored at 30 and 40 °C in darkness. The former was associated with a higher quantity of non-oxidized phenolic compounds and the latter with higher elenolic acid, oxidized oleuropein, and ligstroside derivatives, which also increased with storage time. (E)-2-nonenal (detected at trace levels in fresh oil) was selected as a marker of the degradation of Arbequina EVOO quality over time, with significant linear regressions identified for the storage conditions at 30 and 40 °C. Therefore, early oxidation in EVOO could be monitored by measuring (E)-2-nonenal levels.
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Diabetes mellitus is a highly prevalent disease in the world and in Mexico. Due to its chronic evolution it causes multiple sequelae, disability and mortality. An adequate control of diabetic patients based on reaching glycemic targets, maintenance of healthy weight, as well as lipid and blood pressure control is essential to reduce the risk of progression of its complications. Lifestyle changes are also key for preventing and treating the disease. Knowledge of the relationship and mechanism involved between diabetes and alterations in nutrient metabolism should be considered to provide an adequate nutritional program. This article aims to bring healthcare professionals the concepts and strategies, proposed by several scientific societies, about nutritional management of adult patients with diabetes mellitus.
La diabetes mellitus es una enfermedad altamente prevalente en el mundo y en México. Debido a su evolución crónica, es también causa de múltiples secuelas, discapacidad y mortalidad. Un adecuado control del paciente diabético que se logre a partir de metas de glucemia, mantenimiento de peso sano, así como control de lípidos y presión arterial es indispensable a fin de disminuir el riesgo de progresión de las complicaciones de la diabetes mellitus. Los cambios en el estilo de vida son clave en la prevención y el tratamiento de la enfermedad. El conocimiento de la relación y el mecanismo involucrados entre la diabetes y las alteraciones en el metabolismo de los nutrientes debe ser considerado para brindar un programa nutricional adecuado. Este artículo pretende aproximar a los profesionales de la salud los conceptos y las estrategias nutricionales actuales, propuestos por diversas sociedades científicas, para el manejo nutricional de pacientes adultos con diabetes mellitus.
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Diabetes Mellitus , Estilo de Vida , Estado Nutricional , Peso Corporal , Diabetes Mellitus/dietoterapia , Humanos , MéxicoRESUMO
BACKGROUND: Voltage-gated sodium (NaV) channels are heteromeric proteins consisting of a single pore forming α-subunit associated with one or two auxiliary ß-subunits. These channels are classically known for being responsible of action potential generation and propagation in excitable cells; but lately they have been reported as widely expressed and regulated in several human cancer types. We have previously demonstrated the overexpression of NaV1.6 channel in cervical cancer (CeCa) biopsies and primary cultures, and its contribution to cell migration and invasiveness. Here, we investigated the expression of NaV channels ß-subunits (NaVßs) in the CeCa cell lines HeLa, SiHa and CaSki, and determined their contribution to cell proliferation, migration and invasiveness. METHODS: We assessed the expression of NaVßs in CeCa cell lines by performing RT-PCR and western blotting experiments. We also evaluated CeCa cell lines proliferation, migration, and invasion by in vitro assays, both in basal conditions and after inducing changes in NaVßs levels by transfecting specific cDNAs or siRNAs. The potential role of NaVßs in modulating the expression of NaV α-subunits in the plasma membrane of CeCa cells was examined by the patch-clamp whole-cell technique. Furthermore, we investigated the role of NaVß1 on cell cycle in SiHa cells by flow cytometry. RESULTS: We found that the four NaVßs are expressed in the three CeCa cell lines, even in the absence of functional NaV α-subunit expression in the plasma membrane. Functional in vitro assays showed differential roles for NaVß1 and NaVß4, the latter as a cell invasiveness repressor and the former as a migration abolisher in CeCa cells. In silico analysis of NaVß4 expression in cervical tissues corroborated the downregulation of this protein expression in CeCa vs normal cervix, supporting the evidence of NaVß4's role as a cell invasiveness repressor. CONCLUSIONS: Our results contribute to the recent conception about NaVßs as multifunctional proteins involved in cell processes like ion channel regulation, cell adhesion and motility, and even in metastatic cell behaviors. These non-canonical functions of NaVßs are independent of the presence of functional NaV α-subunits in the plasma membrane and might represent a new therapeutic target for the treatment of cervical cancer.
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OBJECTIVE: Low voltage-activated (LVA) calcium channels are crucial for regulating oscillatory behavior in several types of neurons and other excitable cells. LVA channels dysfunction has been implicated in epilepsy, neuropathic pain, cancer, among other diseases. Unlike for High Voltage-Activated (HVA) channels, voltage-dependence and kinetics of currents carried by recombinant LVA, i.e., CaV3 channels, are quite similar to those observed in native currents. Therefore, whether these channels are regulated by HVA auxiliary subunits, remain controversial. Here, we used the α1-subunits of CaV3.1, CaV3.2, and CaV3.3 channels, together with HVA auxiliary ß-subunits to perform electrophysiological, confocal microscopy and immunoprecipitation experiments, in order to further explore this possibility. RESULTS: Functional expression of CaV3 channels is up-regulated by all four ß-subunits, although most consistent effects were observed with the ß1b-subunit. The biophysical properties of CaV3 channels were not modified by any ß-subunit. Furthermore, although ß1b-subunits increased colocalization of GFP-tagged CaV3 channels and the plasma membrane of HEK-293 cells, western blots analysis revealed the absence of physical interaction between CaV3.3 and ß1b-subunits as no co-immunoprecipitation was observed. These results provide solid evidence that the up-regulation of LVA channels in the presence of HVA-ß1b subunit is not mediated by a high affinity interaction between both proteins.
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Canais de Cálcio/metabolismo , Cálcio/metabolismo , Fenômenos Eletrofisiológicos/fisiologia , Proteínas de Fluorescência Verde/metabolismo , Animais , Canais de Cálcio/genética , Proteínas de Fluorescência Verde/genética , Células HEK293 , Humanos , Microscopia Confocal , Técnicas de Patch-Clamp , Ligação Proteica , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismoRESUMO
Introducción: La candidiasis bucal es una infección oportunista fácilmente detectable en la clínica, por lo que se ha utilizado para valorar tanto el estado inmunológico de los pacientes con VIH como la efectividad de la terapia antirretroviral, altamente efectiva debido a que se encuentra sujeta a diversos factores para lograr el éxito terapéutico. Objetivo: Determinar la frecuencia de candidiasis bucal entre indicadores asociados al éxito de la terapia antirretroviral. Material y método: Estudio transversal, analítico en donde inicialmente se realizaron grupos de acuerdo al uso o no de la terapia antirretroviral para proseguir con un interrogatorio que incluía preguntas sobre otros factores relacionados con la infección por cándida, así como la medición del flujo salival y la evaluación clínica de la cavidad bucal para determinar la frecuencia de la candidiasis. Resultados: La diferencia en la frecuencia de la candidiasis bucal entre los grupos con y sin terapia antirretroviral fue significativa, además de obtener una OR = 2,6 (1,58-4,48) y la asociación con la disminución en el conteo de linfocitos de CD4. Discusión: La resistencia a la terapia antirretroviral constituye uno de los problemas fundamentales en el éxito del tratamiento, en los pacientes infectados con virus de la inmunodeficiencia humana, al igual que las toxicidades y los problemas de adherencia. Los sensores clínicos como la candidiasis bucal son parámetros de fácil acceso para la detección temprana de falla en la terapia.
Introduction: Oral candidiasis is an opportunistic infection that is readily detectable in the clinic. It has been used to assess the immune status of HIV patients as well as the effectiveness of highly active antiretroviral therapy. Objective: To determine the frequency of oral candidiasis infection among various indicators associated with antiretroviral therapy effectiveness. Material and methods: Cross-sectional and analytical study, in which groups were initially created based on the use or not of antiretroviral therapy. Participants were subjected to questions on factors related to Candida infection, salivary flow measurements and a clinical examination of the oral cavity to determine the frequency of candidiasis Results: The difference in the frequency of oral candidiasis between groups with and without antiretroviral therapy was significant (OR 2.6 IC95% 1.5-4.4). There were also a significant association with decreased number of CD4 lymphocytes.. Discussion: Resistance to anti-retroviral therapy constitutes one of the fundamental barriers to a successful treatment in patients infected with the human immunodeficiency virus, as do toxicities and adherence problems. Clinical markers such oral candidiasis is an easily and accesible parameter for the early detection of treatment failure.
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Candidíase Bucal , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/terapiaRESUMO
El propósito del estudio fue averiguar la relación entre el sexo, edad y nivel socioeconómico de maestros de primaria, así como del grado de primaria en el que enseñaban, el tipo de escuela en la que trabajaban y el tamaño del grupo que atendían, sobre la frecuencia con la que consideraban apropiado que un niño "normal" emita las conductas características del Trastorno por Déficit de Atención e Hiperactividad (TDAH). Maestros de primaria (N = 691) señalaron la frecuencia con la que es apropiado que un niño "normal" emita en el salón de clases cada una de las 18 conductas características del TDAH. Se encontró que los maestros hombres mayores de 42 años, de nivel socioeconómico bajo, de 1º y 2º, que tenían más de 38 estudiantes en de escuelas públicas tendieron a considerar normal la emisión frecuente de las conductas del TDAH en el salón de clases, en mayor grado que sus contrapartes. Se concluyó que la tendencia de un maestro de primaria a asignar a un niño la etiqueta de TDAH dependerá de sus características sociodemográficas y de ciertas variables situacionales.
The purpose of the study was to determine the influence of sex, age and socioeconomic status of elementary school teachers, as well as the school grade and group size they taught and the kind of school (private or public) in which they worked on their judgments about the "normal" frequency of emission of attention deficit hyperactivity disorder (ADHD) behaviors by their students during class hours. Teachers (N = 691) rated the frequency which a "normal" student emitted each of the 18 ADHD characteristic behaviors during class hours. Results showed that men, teachers older than 42 years, of low socioeconomic status, teaching first and second grade, which had more than 38 students in public schools considered normal the frequent emission of the behaviors during class hours in a greater degree than their counterparts. It was concluded that the socio-demographic characteristics of elementary school teachers as well as some situational variables affect their tendency to label a student with ADHD.
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Los eventos vitales pueden tener efectos nocivos sobre la salud. La Escala de Reajuste Social es uno de los instrumentos más utilizados para medir estrés vital. Éste se ha cuantificadomediante juicios sobre la magnitud del reajuste necesario ante cada evento. Al promedio de los puntajes se le conoce como Unidad de Cambio de Vida (LCU, por sus siglas en inglés). El propósito de este estudio fue obtener una versión en español del SRRS para niños de primariay obtener los puntajes LCU. 192 maestros de escuelas primarias actuaron como jueces. Correlaciones por rangos mostraron un alto grado de acuerdo tanto entre los maestros, comorespecto a los jueces estadounidenses del estudio original de Coddington (1972) en relación con la severidad de los eventos. Comparaciones por pares mostraron que los maestros en función de sus características sociodemográficas, juzgaron ciertos eventos como más severos.
Vital stress could have noxious effects on health. The Social Readjustment Rating Scale is one of the instruments most frequently used to measure vital stress, which has been quantifiedasking judges to evaluate the magnitude of social readjustment required by a person when experiencing different events and the mean number of points assigned by the judges are knownas Life Change Units. The purpose of the present study was to translate retranslate from English to Spanish the SRRS for elementary school children and obtain the LCUs for each event.Elementary school teachers (N = 192) acted as judges. Spearman order correlations showed that Mexican teachers agreed highly in their judgments both, among themselves and with the American judges of the original study (Coddington, 1972). Mexican judges depending on their sociodemographic characteristics judged some vital events as more severe.
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Criança , Psicologia Social , Trabalho Infantil/psicologiaRESUMO
BACKGROUND & AIMS: An extrahepatic human neutrophil collagenase complementary DNA (matrix metalloprotease-8) cloned in an adenovirus vector was used as a therapeutic agent in cirrhosis. METHODS: A high titer of clinical-grade AdMMP8 was obtained. RESULTS: HeLa cells transduced with AdMMP8 expressed recombinant matrix metalloprotease-8 messenger RNA and matrix metalloprotease-8 protein. Matrix metalloprotease-8 in culture sups showed enzymatic activity against native collagen type I, which was inhibited by ethylenediaminetetraacetic acid, 1,10-phenanthroline, and tissue inhibitor of metalloprotease-1. In vivo transduction showed matrix metalloprotease-8 activity, and studies to establish the efficacy of this characterized vector were performed in CCl(4) and bile duct-ligated cirrhotic rats. Transduction with 3 x 10(11) viral particles per kilogram resulted in hepatic detection of both messenger RNA and protein matrix metalloprotease-8. A consistent response in fibrosis reversal was observed in CCl(4) rats. Liver fibrosis in bile duct-ligated cirrhotic animals was decreased in 45%, along with diminished hydroxyproline content, after AdMMP8 treatment. The expression of matrix metalloprotease-2 and matrix metalloprotease-3 was up-regulated in AdMMP8 rats. Free tissue inhibitor of metalloprotease-1, as an indirect measurement of active uncomplexed matrix metalloproteases, was also increased in the AdMMP8 groups. Transforming growth factor-beta messenger RNA was diminished, and matrix metalloprotease-9 and hepatocyte growth factor increased. Treatment in both models correlated with improvements in ascites, functional hepatic tests, and gastric varices, indicating diminished intrahepatic blood pressure in animals injected with AdMMP8. CONCLUSIONS: Therefore, therapy with the matrix metalloprotease-8 gene is promising for use in a clinical setting.
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Terapia Genética , Cirrose Hepática Experimental/terapia , Metaloproteinase 8 da Matriz/genética , Adenoviridae/genética , Animais , Tetracloreto de Carbono , Colágeno/metabolismo , Meios de Cultura , Modelos Animais de Doenças , Regulação Enzimológica da Expressão Gênica , Vetores Genéticos , Células HeLa , Humanos , Veia Ilíaca , Cirrose Hepática Experimental/induzido quimicamente , Masculino , Metaloproteinase 8 da Matriz/metabolismo , RNA Mensageiro/genética , Ratos , Ratos WistarRESUMO
BACKGROUND/AIMS: Our group has been involved in searching for different strategies to ameliorate hepatic cirrhosis. The aim of this study was to evaluate the effect of Pirfenidone in the reversion or prevention of cirrhosis experimentally induced in rats by chronic administration of CCl(4) and bile-duct ligation (BDL). METHODS: Male cirrhotic Wistar rats (8 weeks of intoxication and then hepatotoxin was discontinued) received either oral saline or Pirfenidone at 500 mg/kg per day. RESULTS: High levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase decreased significantly (P<0.001) in animals treated with Pirfenidone (n=11) with regard to saline-administrated animals (n=9). Prothrombin activity and bilirubins were also reduced. Computerized fibrosis index demonstrated a 70% decrease (P<0.001) along with less hydroxyproline content, reduction in activated HSC and higher active cell regeneration. A rearrangement of the parenchyma was also noted and gene expression of collagens I, III and IV, transforming growth factor beta-1, Smad-7, TIMP-1 and PAI-1 decreased considerably in treated animals. Cirrhotic rats in which CCl(4) was not discontinued displayed 40% liver fibrosis reduction. In a different cirrhosis model, 4-week BDL rats treated with the drug showed a significant 50% reduction in hepatic fibrosis (P<0.01). CONCLUSIONS: This new drug might be useful in healing human disease.
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Cirrose Hepática/patologia , Piridonas/farmacologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Ductos Biliares , Bilirrubina/sangue , Tetracloreto de Carbono , Hidroxiprolina/metabolismo , Ligadura , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática/sangue , Cirrose Hepática/etiologia , Cirrose Hepática/prevenção & controle , Regeneração Hepática , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Protrombina/análise , Ratos , Ratos WistarRESUMO
El objetivo es ampliar la información sobre las ONGs y servicios de salud de las Iglesias que desarrollan acciones en el ámbito territorial del Departamento de La Paz y la actualización de las que ya están incorporadas al sistema de información de las ONGs. El objetivo terminal esta destinado a movilizar recursos de cooperación externa e interna a través del diseño de proyectos de salud estratégicos.
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Organizações , Sistemas de Informação , BolíviaRESUMO
Contiene: I. Sistema de información. II. Proyectos de salud. III. Organizaciones no gubernamentales. IV. Iglesia
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Seguimentos , Organizações , Bolívia , Sistemas de InformaçãoRESUMO
El objetivo es ampliar la informacion sobre las ONGs y servicios de salud de las Iglesias que desarrollan acciones en el ambito territorial del Departamento de La Paz y la actualización de las que ya estan incorporadas al sistema de información de las ONGs. El objetivo terminal esta destinado a movilizar recursos de cooperación externa e interna a traves del diseño de proyectos de salud estratégicos.(au)