RESUMO
Beyond the problem in public health that protist-generated diseases represent, understanding the variety of mechanisms used by these parasites to interact with the human immune system is of biological and medical relevance. Giardia lamblia is an early divergent eukaryotic microorganism showing remarkable pathogenic strategies for evading the immune system of vertebrates. Among various multifunctional proteins in Giardia, arginine deiminase is considered an enzyme that plays multiple regulatory roles during the life cycle of this parasite. One of its most important roles is the crosstalk between the parasite and host. Such a molecular "chat" is mediated in human cells by membrane receptors called Toll-like receptors (TLRs). Here, we studied the importance of the 3D structure of giardial arginine deiminase (GlADI) to immunomodulate the human immune response through TLRs. We demonstrated the direct effect of GlADI on human TLR signaling. We predicted its mode of interaction with TLRs two and four by using the AlphaFold-predicted structure of GlADI and molecular docking. Furthermore, we showed that the immunomodulatory capacity of this virulent factor of Giardia depends on the maintenance of its 3D structure. Finally, we also showed the influence of this enzyme to exert specific responses on infant-like dendritic cells.
Assuntos
Giardia , Giardíase , Animais , Humanos , Hidrolases , Imunidade , Imunomodulação , Simulação de Acoplamento Molecular , Receptores Toll-LikeRESUMO
Human triosephosphate isomerase (HsTIM) is a central glycolytic enzyme and is overexpressed in cancer cells with accelerated glycolysis. Triple-negative breast cancer is highly dependent on glycolysis and is typically treated with a combination of surgery, radiation therapy, and chemotherapy. Deamidated HsTIM was recently proposed as a druggable target. Although thiol-reactive drugs affect cell growth in deamidated HsTIM-complemented cells, the role of this protein as a selective target has not been demonstrated. To delve into the usefulness of deamidated HsTIM as a selective target, we assessed its natural accumulation in breast cancer cells. We found that deamidated HsTIM accumulates in breast cancer cells but not in noncancerous cells. The cancer cells are selectively programmed to undergo cell death with thiol-reactive drugs that induced the production of methylglyoxal (MGO) and advanced glycation-end products (AGEs). In vivo, a thiol-reactive drug effectively inhibits the growth of xenograft tumors with an underlying mechanism involving deamidated HsTIM. Our findings demonstrate the usefulness of deamidated HsTIM as target to develop new therapeutic strategies for the treatment of cancers and other pathologies in which this post translationally modified protein accumulates.
Assuntos
Neoplasias da Mama , Triose-Fosfato Isomerase , Feminino , Glicólise , Humanos , Proteínas/metabolismo , Aldeído Pirúvico/metabolismo , Compostos de Sulfidrila , Triose-Fosfato Isomerase/metabolismoRESUMO
Giardiasis represents a latent problem in public health due to the exceptionally pathogenic strategies of the parasite Giardia lamblia for evading the human immune system. Strains resistant to first-line drugs are also a challenge. Therefore, new antigiardial therapies are urgently needed. Here, we tested giardial arginine deiminase (GlADI) as a target against giardiasis. GlADI belongs to an essential pathway in Giardia for the synthesis of ATP, which is absent in humans. In silico docking with six thiol-reactive compounds was performed; four of which are approved drugs for humans. Recombinant GlADI was used in enzyme inhibition assays, and computational in silico predictions and spectroscopic studies were applied to follow the enzyme's structural disturbance and identify possible effective drugs. Inhibition by modification of cysteines was corroborated using Ellman's method. The efficacy of these drugs on parasite viability was assayed on Giardia trophozoites, along with the inhibition of the endogenous GlADI. The most potent drug against GlADI was assayed on Giardia encystment. The tested drugs inhibited the recombinant GlADI by modifying its cysteines and, potentially, by altering its 3D structure. Only rabeprazole and omeprazole decreased trophozoite survival by inhibiting endogenous GlADI, while rabeprazole also decreased the Giardia encystment rate. These findings demonstrate the potential of GlADI as a target against giardiasis.
Assuntos
Giardia lamblia/efeitos dos fármacos , Giardíase/tratamento farmacológico , Hidrolases/metabolismo , Animais , Antiprotozoários/farmacologia , Simulação por Computador , Cisteína/química , Avaliação Pré-Clínica de Medicamentos/métodos , Reposicionamento de Medicamentos/métodos , Giardia lamblia/patogenicidade , Giardíase/imunologia , Tiomalato Sódico de Ouro/farmacologia , Humanos , Hidrolases/efeitos dos fármacos , Hidrolases/ultraestrutura , Omeprazol/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Rabeprazol , Tiamina/análogos & derivados , Tiamina/farmacologia , Trofozoítos/efeitos dos fármacosRESUMO
INTRODUCTION: Gestational diabetes mellitus (GDM) affects between 5 and 40% of pregnant women. Recently different interventions with nutritional supplements have been evaluated for prevention of GDM. AIM: To perform a synthesis of the evidence on the efficacy of nutritional supplements (myo-inositol, probiotics, and vitamin D) in the prevention of GDM. METHODS: A systematic search in PubMed and Cochrane library was performed, including systematic reviews of randomized clinical trials (RCTs), published in English or Spanish until May 2020, using the keywords: "prevention", "gestational diabetes", "hyperglycemia and pregnancy", "supplementation", "probiotics", "myo-inositol" and "vitamin D". RESULTS: 10 systematic reviews that met the inclusion criteria were analyzed. Myo-inositol supplementation compared to placebo decreased the incidence of GDM (RR: 0.44 [0.27-0.87]; five RCTs), low quality of evidence. Although the supplementation with vitamin D or probiotics during pregnancy could reduce the incidence of GDM the evidence is limited. CONCLUSIONS: Myo-inositol supplementation is effective for prevention of GDM in high-risk women. Supplementation with vitamin D or probiotics probably decreases the incidence of GDM.
INTRODUCTION: La diabetes mellitus gestacional (DMG) afecta a entre el 5 y el 40% de mujeres embarazadas. Recientemente se han evaluado diferentes intervenciones con suplementos nutricionales para prevenir la DMG. OBJETIVO: Realizar una síntesis de la evidencia sobre eficacia de suplementos nutricionales (mioinositol, probióticos y vitamina D) para prevenir DMG. MÉTODO: Se realizó una búsqueda sistemática en PubMed y la biblioteca Cochrane, se incluyeron revisiones sistemáticas de estudios clínicos aleatorizados (ECAs), publicados en idioma inglés o español hasta mayo de 2020; se utilizaron las palabras clave: "prevención", "diabetes gestacional", "hiperglicemia y embarazo", "suplementación", "probióticos", "mio-inositol" y "vitamina D". RESULTADOS: Se analizaron 10 revisiones sistemáticas que cumplieron los criterios de inclusión. La suplementación con mioinositol comparado con placebo disminuyó la incidencia de DMG (RR: 0.44; IC 95%: 0.27-0.87; cinco ECAs). Si bien la suplementación con vitamina D o probióticos durante el embarazo podría disminuir la incidencia de DMG, la evidencia es limitada. CONCLUSIONES: La suplementación con mioinositol es efectiva para prevenir DMG en mujeres de alto riesgo. La suplementación con vitamina D o probióticos probablemente disminuye la incidencia de DMG.
Assuntos
Diabetes Gestacional , Suplementos Nutricionais , Probióticos , Vitaminas , Diabetes Gestacional/prevenção & controle , Feminino , Humanos , Gravidez , Probióticos/uso terapêutico , Vitaminas/uso terapêuticoRESUMO
Health promotion and disease prevention are essential components of prenatal care. Maternal nutrient insufficiencies could negatively impact the morbidity and mortality of the mother-fetus pair as well as the health of the next generations. Although a healthy diet is usually sufficient to meet the increased nutrient needs, supplementation is part of routine care to ensure a healthy pregnancy and optimal fetal development. Currently, iron and folic acid supplementation is the only globally accepted recommendation for all pregnant women. However, there are vulnerable groups of women who could benefit from complementary individualized supplementation schemes. Recently, relevant information has been published related to the supplementation of single and multiple micronutrients with significant effects on maternal and fetal health, which could have implications in the clinical practice of health professionals. This review presents scientific evidence and the recommendations of different entities on the supplementation of iron, folic acid, calcium, vitamin D and multiple micronutrient supplementation during pregnancy.
La promoción de la salud y la prevención de enfermedades son componentes esenciales de la atención prenatal. Las insuficiencias de nutrimentos afectan negativamente la morbimortalidad del binomio madre-hijo, así como a la salud de las siguientes generaciones. Aunque una alimentación saludable generalmente es suficiente para cubrir las necesidades aumentadas de micronutrimentos, la suplementación es parte del cuidado habitual para garantizar un embarazo saludable y el desarrollo óptimo del producto. Actualmente la suplementación de hierro y ácido fólico es la única recomendación mundialmente aceptada para todas las mujeres embarazadas. Por otro lado, existen grupos de mujeres vulnerables que podrían beneficiarse de esquemas de suplementación individualizados complementarios. Recientemente se ha publicado información relevante relacionada con la suplementación de distintos micronutrimentos de forma individual y múltiple con efectos importantes en la salud materno-fetal, lo cual podría tener implicaciones en la práctica clínica de los profesionales de la salud. Esta revisión presenta la evidencia científica y las recomendaciones de distintos organismos sobre la suplementación de hierro, ácido fólico, calcio, vitamina D y suplementación múltiple de vitaminas y minerales durante el embarazo.
Assuntos
Suplementos Nutricionais , Promoção da Saúde , Cuidado Pré-Natal , Feminino , Humanos , Gravidez , Vitaminas/administração & dosagemRESUMO
Fetal development is characterized by great plasticity and the ability to respond to environmental factors, where DNA methylation is essential for proper embryonic development. One-carbon metabolism provides methyl groups for methylation and fetal DNA development and is highly dependent on maternal nutritional status. During pregnancy, the supply of methyl donors is critical and the demand for nutrients that support this process, such as folate and vitamin B12, is increased. Insufficiency or imbalance of these 2 micronutrients can alter epigenetic patterns, DNA synthesis and repair, and affect fetal growth and development, having negative long-term consequences on the offspring's health. Folate and vitamin B12 status have been associated with wide DNA methylation, as well as with specific genes related to neurological functions, embryonic development, energy metabolism, growth, and leptin. Furthermore, inadequate concentrations of both vitamins have been associated with an increased risk of perinatal outcomes such as neural tube defects, prematurity, low birth weight, pre-eclampsia, as well as maternal and infant obesity and insulin resistance, and decreased infant neurocognitive development. Supplementation, combined with a healthy diet, could be an essential strategy to prevent these results and improve maternal and fetal health.
El desarrollo fetal se caracteriza por una gran plasticidad y capacidad para responder a factores ambientales, donde la metilación del ADN es indispensable para el desarrollo embrionario adecuado. El metabolismo de un carbono proporciona grupos metilo para la metilación y el desarrollo del ADN fetal, y depende en gran medida del estado nutricio materno. El embarazo es una etapa donde el suministro de donantes de metilo es crítico y la demanda de nutrimentos que apoyen este proceso, como lo son el folato y la vitamina B12, está aumentada. La insuficiencia o desequilibrio de estos dos micronutrimentos puede alterar los patrones epigenéticos, la síntesis y reparación del ADN, y afectar procesos del crecimiento y desarrollo fetal, teniendo consecuencias negativas en la salud de la descendencia a largo plazo. El estado del folato y la vitamina B12 se han asociado con la metilación global del ADN, así como con genes específicos relacionados con funciones neurológicas, con el desarrollo embrionario, el metabolismo energético, el crecimiento, y con la leptina. Además, estados alterados de ambas vitaminas se han asociado con mayor riesgo de resultados perinatales como defectos del tubo neural, prematurez, bajo peso al nacer, preeclampsia, así como obesidad y resistencia a la insulina materna e infantil, y disminución del desarrollo neurocognitivo infantil. La suplementación, aunada a una dieta adecuada, podría ser una estrategia necesaria para prevenir dichos resultados y mejorar la salud maternofetal.
Assuntos
Complicações na Gravidez , Vitamina B 12 , Vitaminas , Metilação de DNA , Feminino , Desenvolvimento Fetal , Humanos , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Complicações na Gravidez/prevenção & controle , Cuidado Pré-Natal , Vitamina B 12/uso terapêutico , Vitaminas/uso terapêuticoRESUMO
Preterm labor accounts for more than 85% of perinatal morbidity, frequently requiring intensive care and presenting complications that can have consequences throughout the individual's life. More than half of preterm delivery cases have unknown causes and therefore no clear preventable etiology. From observation in epidemiological studies that demonstrated longer pregnancies in populations with high consumption of marine oils, attempts have been made to define the benefit of omega-3 polyunsaturated fatty acids (n-3 PUFA) prevention in premature childbirth through randomized clinical trials, as well as its preventive value. This review discusses the relationship between prenatal supplementation of n-3 long chain PUFA during pregnancy and the incidence of preterm delivery.
El parto prematuro protagoniza más del 85% de la morbilidad perinatal, requiere con frecuencia cuidados intensivos y presenta complicaciones que pueden tener consecuencias a lo largo de la vida del individuo. Más de la mitad de los casos de parto pretérmino tienen causas desconocidas y por lo tanto ninguna etiología clara prevenible. Desde la observación en estudios epidemiológicos que demostraron embarazos más largos en poblaciones con alto consumo de aceites marinos se ha tratado de definir por medio de ensayos clínicos aleatorizados el beneficio de suplementos de ácidos grasos poliinsaturados omega-3 (AGPI n-3) prevenir el parto prematuro, así como su valor preventivo. Esta revisión discute la relación entre la suplementación prenatal de n-3 de cadena larga durante el embarazo y la incidencia de parto prematuro.
Assuntos
Ácidos Graxos Ômega-3 , Nascimento Prematuro , Adulto , Ácidos Graxos Ômega-3/uso terapêutico , Feminino , Humanos , Gravidez , Nascimento Prematuro/prevenção & controleRESUMO
Breast milk is a complex biological fluid. Additionally to its nutritional impact, it contains diverse bioactive elements related to early metabolic programming and molecular structures, such as microRNA related to the epigenetic signaling process. Now, we know that human milk is not sterile and contains a significant diversity of microorganisms such as bacteria (bacterioma), viruses (viroma) and fungi (mycobiome), all of which integrate the concept of the human milk microbiota. Apparently the origin of this microbiota is found in the entero-mammary circulation, as well as in the retrograde circulation of the skin of the mammary gland, although it is speculated in what percentage the microbiota of the oral cavity of the infant contributes in a significant way. From a functional point of view, it has been shown the transfer of this microbiota to the infant's digestive tract, which is related to better digestive tolerance, lower frequency and intensity of dysfunctionalities of the brain-intestine-microbiota axis, and improved immunity, among others.
La leche materna es un fluido biológico complejo, ya que además de nutrir, contiene diversos elementos bioactivos relacionados con el fenómeno de programación metabólica temprana e incluso contiene estructuras moleculares relacionadas con el proceso de señalización epigenética tales como los microARN. Ahora sabemos que la leche humana no es estéril y contiene una diversidad significativa de microorganismos tales como bacterias (bacterioma), virus (viroma) y hongos (micobioma), todo lo cual integra el concepto de microbiota de leche humana. Al parecer el origen de esta microbiota se encuentra en la circulación enteromamaria, así como en la circulación retrógrada de la piel de glándula mamaria, aunque se especula en qué porcentaje la microbiota de la cavidad bucal del lactante contribuye de forma significativa. Desde el punto de vista funcional, se ha demostrado transferencia de esta microbiota hacia el tubo digestivo del lactante, lo que se relaciona con una mejor tolerancia digestiva, menor frecuencia e intensidad de disfuncionalidades del eje cerebro-intestino-microbiota, y mejora de la inmunidad, entre otras.
Assuntos
Microbiota , Leite Humano , Feminino , Humanos , Lactente , MicroRNAs , Leite Humano/microbiologia , Boca/microbiologiaRESUMO
Resumen Introducción: Se informa que la mayoría de los niños afectados por SARS-CoV-2 cursan asintomáticos y que en ellos la mortalidad por COVID-19 es baja; en México se desconoce la información al respecto en este grupo de la población. Objetivo: Evaluar los factores de riesgo asociados a mortalidad en niños mexicanos con COVID-19. Método: Análisis secundario de la base de datos de la Dirección General de Epidemiología. Se incluyeron niños menores de 19 años, en quienes se confirmó SARS-CoV-2 mediante RT-PCR. Resultados: Se incluyeron 1443 niños. La mediana de edad fue de ocho años; 3.3 % ingresó a la unidad de cuidados intensivos, 1.8 % requirió ventilación mecánica asistida y la mortalidad fue de 1.9 %. En los modelos multivariados, el desarrollo de neumonía constituyó el principal factor de riesgo de mortalidad, con razón de momios (RM) de 6.45 (IC 95 % 1.99, 20.89); los pacientes que requirieron intubación tuvieron RM de 8.75 (IC 95 % 3.23, 23.7). Conclusiones: Los niños con COVID 19 tienen alta mortalidad en México, por lo que en ellos se debe procurar evitar la neumonía, especialmente en los menores de cuatro años, con riesgo cardiovascular o inmunosupresión.
Abstract Introduction: Most children affected by SARS-CoV-2 are reported to be asymptomatic, and COVID-19-related mortality in them is low; in Mexico, there is a lack of information on the subject in this population group. Objective: To assess the risk factors associated with mortality in Mexican children with COVID-19. Method: Secondary analysis of the General Directorate of Epidemiology database. Children younger than 19 years, in whom SARS-CoV-2 infection was confirmed by RT-PCR, were included. Results: 1443 children were included. Median age was eight years; 3.3 % were admitted to the intensive care unit, 1.8 % required assisted mechanical ventilation, and mortality was 1.9 %. In multivariate models, the development of pneumonia was the main risk factor for mortality, with an odds ratio (OR) of 6.45 (95 % CI 1.99, 20.89); patients who required intubation had an OR of 8.75 (95 % CI 3.23, 23.7). Conclusions: Children with COVID-19 exhibit high mortality in Mexico, and avoiding pneumonia should therefore be tried in them, especially in children younger than four years with cardiovascular risk or immunosuppression.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Pneumonia Viral/epidemiologia , Respiração Artificial/estatística & dados numéricos , COVID-19/epidemiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Pneumonia Viral/virologia , Fatores de Risco , Fatores Etários , Reação em Cadeia da Polimerase Via Transcriptase Reversa , COVID-19/complicações , COVID-19/mortalidade , México/epidemiologiaRESUMO
Resumen En este simposio se describen las principales características de seis revistas científicas mexicanas reconocidas por el Journal Citation Reports: Archives of Medical Research, Revista de Investigación Clínica-Clinical and Translational Investigation, Gaceta Médica de México, Salud Pública de México, Cirugía y Cirujanos y Salud Mental. Se hace énfasis en sus aspectos históricos y organizacionales, así como en sus logros principales ante la comunidad científica nacional e internacional.
Abstract This symposium describes the main characteristics of six Mexican scientific journals indexed in the Journal Citation Reports: Archives of Medical Research, Revista de Investigación Clínica-Clinical and Translational Investigation, Gaceta Médica de México, Salud Pública de México, Cirugía y Cirujanos and Salud Mental. Particular emphasis is given to their historical and organizational aspects, as on well as their main achievements recognized by the national and international scientific community.
Assuntos
Humanos , História do Século XIX , História do Século XX , História do Século XXI , Publicações Periódicas como Assunto/classificação , Publicações Periódicas como Assunto/história , Pesquisa , MéxicoRESUMO
Throughout history, pandemics have had a major impact on humanity. The measures used to combat them cause collateral damage. During the COVID-19 pandemic, the actions taken to reduce the exposure, the number of infections, and the case fatality rate focus on reducing mortality, however, the collapse of the health system can cause an even greater number of deaths. At the same time, both medical personnel and patients are affected by the economic slowdown and the "effect of negativity". In this review article the different tools available for pandemic control, their development in a historical context, and how they may impact risk stratification for vulnerable patients (elderly, patients with chronic degenerative and oncological diseases) were analyzed.
A lo largo de la historia, las pandemias han tenido un gran impacto para la humanidad. Las medidas utilizadas para combatirlas causan daño colateral. En la pandemia por COVID-19, las acciones generadas para disminuir la exposición, el número de contagios y la tasa de letalidad conllevan un enfoque en la reducción de la mortalidad, sin embargo el colapso del sistema de salud puede provocar un número aún mayor de muertos. A su vez, tanto el personal médico como los pacientes se ven afectados por la desaceleración económica y el "efecto de la negatividad". En este artículo de revisión se analizaron las diferentes herramientas para el control de la pandemia, su desarrollo en un contexto histórico y como impactan en la estratificación del riesgo para pacientes vulnerables (ancianos, pacientes con enfermedades crónico degenerativas y oncológicos).
Assuntos
COVID-19/epidemiologia , COVID-19/prevenção & controle , Doença Crônica , Atenção à Saúde , SARS-CoV-2 , COVID-19/mortalidade , Doença Crônica/terapia , Recessão Econômica , Hospitalização , Humanos , Programas Nacionais de Saúde , Medição de Risco , Populações VulneráveisRESUMO
Delivery methods during childbirth and their related gut microbiota profiles have important impacts on health later in life, they can contribute to the development of diseases such as obesity, whose highest prevalence rate is found among the Mexican child population. Coincidentally, Mexico has one of the highest global average annual rate increase in cesarean births (C-section). Since Mexico leads the world in childhood obesity, studying the relationship between childbirth delivery methods and gut microbiota profiles in this vulnerable population may be used to identify early risk factors for obesity in other developed and developing countries. The objective of this study is to determine the association between child delivery method and gut microbiota profiles in healthy Mexican newborns.Fecal samples of 57 term infants who participated in a randomized clinical trial in 2013 to study the safety of Agave fructans in newborns, were used in this study. DNA samples were extracted and used to characterize the microbiota composition using high-throughput 16S rRNA gene sequencing. The samples were further divided based on childbirth delivery method, as well as early diet. Gut microbiota profiles were determined and analyzed using cluster analysis followed by multiple correspondence analysis.An unusual high abundance of Proteobacteria was found in the gut microbiota of all Mexican infants studied, regardless of delivery method. Feces from infants born by C-section had low levels of Bacteroidetes, high levels of Firmicutes, especially Clostridium and Enterococcus, and a strikingly high ratio of Firmicutes/Bacteroidetes (F:B). Profiles enriched in Bacteroidetes and low F:B ratios, were strongly associated with vaginal delivery.The profile of gut microbiota associated with feces from Mexican infants born by C-section, may be added to the list of boosting factors for the worrying obesity epidemic in Mexico.
Assuntos
Cesárea/estatística & dados numéricos , Microbioma Gastrointestinal , Obesidade/epidemiologia , Cesárea/efeitos adversos , Fezes/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , México/epidemiologia , Fatores de RiscoRESUMO
Therapeutic strategies for the treatment of any severe disease are based on the discovery and validation of druggable targets. The human genome encodes only 600-1500 targets for small-molecule drugs, but posttranslational modifications lead to a considerably larger druggable proteome. The spontaneous conversion of asparagine (Asn) residues to aspartic acid or isoaspartic acid is a frequent modification in proteins as part of the process called deamidation. Triosephosphate isomerase (TIM) is a glycolytic enzyme whose deamidation has been thoroughly studied, but the prospects of exploiting this phenomenon for drug design remain poorly understood. The purpose of this study is to demonstrate the properties of deamidated human TIM (HsTIM) as a selective molecular target. Using in silico prediction, in vitro analyses, and a bacterial model lacking the tim gene, this study analyzed the structural and functional differences between deamidated and nondeamidated HsTIM, which account for the efficacy of this protein as a druggable target. The highly increased permeability and loss of noncovalent interactions of deamidated TIM were found to play a central role in the process of selective enzyme inactivation and methylglyoxal production. This study elucidates the properties of deamidated HsTIM regarding its selective inhibition by thiol-reactive drugs and how these drugs can contribute to the development of cell-specific therapeutic strategies for a variety of diseases, such as COVID-19 and cancer.
Assuntos
Infecções por Coronavirus/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Neoplasias/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/farmacologia , Triose-Fosfato Isomerase/antagonistas & inibidores , Amidas/antagonistas & inibidores , Amidas/metabolismo , COVID-19 , Cristalografia por Raios X , Inibidores Enzimáticos/química , Humanos , Modelos Moleculares , Mutação , Pandemias , Proteoma/antagonistas & inibidores , Proteoma/genética , Proteoma/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Bibliotecas de Moléculas Pequenas/química , Triose-Fosfato Isomerase/química , Triose-Fosfato Isomerase/metabolismoAssuntos
Tomada de Decisões , Medicina Baseada em Evidências , Disseminação de Informação , Publicações Periódicas como Assunto , Pesquisa Translacional Biomédica/tendências , Academias e Institutos , Cirurgia Geral/métodos , Cirurgia Geral/tendências , Política de Saúde , Humanos , Disseminação de Informação/métodos , MéxicoRESUMO
INTRODUCTION: Most children affected by SARS-CoV-2 are reported to be asymptomatic, and COVID-19-related mortality in them is low; in Mexico, there is a lack of information on the subject in this population group. OBJECTIVE: To assess the risk factors associated with mortality in Mexican children with COVID-19. METHOD: Secondary analysis of the General Directorate of Epidemiology database. Children younger than 19 years, in whom SARS-CoV-2 infection was confirmed by RT-PCR, were included. RESULTS: 1443 children were included. Median age was eight years; 3.3 % were admitted to the intensive care unit, 1.8 % required assisted mechanical ventilation, and mortality was 1.9 %. In multivariate models, the development of pneumonia was the main risk factor for mortality, with an odds ratio (OR) of 6.45 (95 % CI: 1.99, 20.89); patients who required intubation had an OR of 8.75 (95 % CI: 3.23, 23.7). CONCLUSIONS: Children with COVID-19 exhibit high mortality in Mexico, and avoiding pneumonia should therefore be tried in them, especially in children younger than four years, with cardiovascular risk or immunosuppression. INTRODUCCIÓN: Se informa que la mayoría de los niños afectados por SARS-CoV-2 cursan asintomáticos y que en ellos la mortalidad por COVID-19 es baja; en México se desconoce la información al respecto en este grupo de la población. . OBJETIVO: Evaluar los factores de riesgo asociados a mortalidad en niños mexicanos con COVID-19. MÉTODO: Análisis secundario de la base de datos de la Dirección General de Epidemiología. Se incluyeron niños menores de 19 años, en quienes se confirmó SARS-CoV-2 mediante RT-PCR. RESULTADOS: Se incluyeron 1443 niños. La mediana de edad fue de ocho años; 3.3 % ingresó a la unidad de cuidados intensivos, 1.8 % requirió ventilación mecánica asistida y la mortalidad fue de 1.9 %. En los modelos multivariados, el desarrollo de neumonía constituyó el principal factor de riesgo de mortalidad, con razón de momios (RM) de 6.45 (IC 95 % 1.99, 20.89); los pacientes que requirieron intubación tuvieron RM de 8.75 (IC 95 % 3.23, 23.7). CONCLUSIONES: Los niños con COVID 19 tienen alta mortalidad en México, por lo que en ellos se debe procurar evitar la neumonía, especialmente en los menores de cuatro años, con riesgo cardiovascular o inmunosupresión.
Assuntos
COVID-19/epidemiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Respiração Artificial/estatística & dados numéricos , Adolescente , Fatores Etários , COVID-19/complicações , COVID-19/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , México/epidemiologia , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de RiscoRESUMO
This symposium describes the main characteristics of six Mexican scientific journals indexed in Journal Citation Reports: Archives of Medical Research, Revista de Investigación Clínica-Clinical and Translational Investigation, Gaceta Médica de México, Salud Pública de México, Cirugía y Cirujanos and Salud Mental. Particular emphasis is given to their historical and organizational aspects, as well as to their main achievements recognized by the national and international scientific community.En este simposio se describen las principales características de seis revistas científicas mexicanas reconocidas por el. Journal Citation Reports: Archives of Medical Research, Revista de Investigación Clínica-Clinical and Translational Investigation, Gaceta Médica de México, Salud Pública de México, Cirugía y Cirujanos y Salud Mental. Se hace énfasis en sus aspectos históricos y organizacionales, así como en sus logros principales ante la comunidad científica nacional e internacional.
Assuntos
Publicações Periódicas como Assunto , História do Século XIX , História do Século XX , História do Século XXI , Humanos , México , Publicações Periódicas como Assunto/classificação , Publicações Periódicas como Assunto/história , PesquisaRESUMO
Research on Giardia lamblia has accumulated large information about its molecular cell biology and infection biology. However, giardiasis is still one of the commonest parasitic diarrheal diseases affecting humans. Additionally, an alarming increase in cases refractory to conventional treatment has been reported in low prevalence settings. Consequently, efforts directed toward supporting the efficient use of alternative drugs, and the study of their molecular targets appears promising. Repurposing of proton pump inhibitors is effective in vitro against the parasite and the toxic activity is associated with the inhibition of the G. lamblia triosephosphate isomerase (GlTIM) via the formation of covalent adducts with cysteine residue at position 222. Herein, we evaluate the effectiveness of omeprazole in vitro and in situ on GlTIM mutants lacking the most superficial cysteines. We studied the influence on the glycolysis of Giardia trophozoites treated with omeprazole and characterized, for the first time, the morphological effect caused by this drug on the parasite. Our results support the effectiveness of omeprazole against GlTIM despite of the possibility to mutate the druggable amino acid targets as an adaptive response. Also, we further characterized the effect of omeprazole on trophozoites and discuss the possible mechanism involved in its antigiardial effect.
Assuntos
Antiprotozoários/farmacologia , Giardia lamblia/efeitos dos fármacos , Omeprazol/farmacologia , Animais , Inibidores Enzimáticos/farmacologia , Estabilidade Enzimática , Giardia lamblia/ultraestrutura , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Concentração Inibidora 50 , Cinética , Aldeído Pirúvico/metabolismo , Temperatura , Triose-Fosfato Isomerase/antagonistas & inibidores , Triose-Fosfato Isomerase/metabolismoRESUMO
Giardia lamblia is one of the most common protozoan infectious agents in the world and is responsible for diarrheal disease and chronic postinfectious illness. During the host-parasite interaction, proteases are important molecules related to virulence, invasion, and colonization, not only for Giardia but also for other parasites. We aimed to characterize the cysteine protease activity detected in trophozoite lysates. This proteolytic activity showed the ability to cleave NH-terminal sequences with either a recognition sequence for a viral protease or a recognition sequence for thrombin. This cleavage activity was detected in nonencysting trophozoites and increased with the progression of encystation. This activity was also detected in excretion/secretion products of axenic trophozoites and in trophozoites cocultured with differentiated Caco-2 cells. Based on size exclusion chromatography, we obtained a fraction enriched in low- to medium-molecular-weight proteins that was capable of exerting this cleavage activity and aggregating human platelets. Finally, our results suggest that this proteolytic activity is shared with other protozoan parasites.
Assuntos
Cisteína Proteases/metabolismo , Giardia lamblia/enzimologia , Proteínas de Protozoários/metabolismo , Células CACO-2 , Catepsina B/química , Catepsina B/genética , Catepsina B/metabolismo , Cisteína Proteases/química , Cisteína Proteases/genética , Giardia lamblia/química , Giardia lamblia/genética , Giardíase , Humanos , Proteólise , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , Especificidade por Substrato , Trofozoítos/química , Trofozoítos/enzimologia , Trofozoítos/genéticaRESUMO
BACKGROUND: Soy infant formulas (SIF) have long been used as an alternative for infants with special nutritional requirements. However, the medical indications for their use, their allergenicity, safety and efficacy are still controversial. OBJECTIVE: To present recommendations for the use of SIF based on the existing literature. METHODS: We consulted systematic reviews and clinical practice guides, through validated search algorithms, and systems such as Appraisal of Guidelines for REsearch and Evaluation (AGREE)II and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). For the elaboration of the clinical recommendations, the most important topics were analyzed and discussed by the responsible researchers and the group of experts in the development of a position paper. The quality of the evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: Several reports with variable quality of evidence were found. They support SIF's efficacy in the management of cow's milk allergy and infant's digestive tolerance, as well as its low cross allergy compared to cow's milk and other formulas. We also found other studies that indicate the safety of SIFs on different nutritional, immune and developmental parameters. There is also evidence that demonstrates that SIFs have important advantages in terms of cost-benefit, palatability and effects on the intestinal microbiota, compared to other formulas. CONCLUSIONS: Although evidence to recommend its use in functional digestive disorders is limited, SIFs have an adequate safety profile and are still a valid option for infant feeding.
ANTECEDENTES: Las fórmulas a base de proteína de soya (FBPS) se han utilizado desde hace tiempo como una alternativa para lactantes con requerimientos nutricionales especiales. Sin embargo, las indicaciones médicas para su uso, su alergenicidad, seguridad y eficacia aún son controvertidas. OBJETIVO: Presentar recomendaciones del uso de FBPS basadas en la literatura existente. MÉTODOS: Se realizó la consulta de revisiones sistemáticas y guías de práctica clínica, por medio de algoritmos de búsqueda validados, y sistemas como AGREE (Appraisal of Guidelines for REsearch and Evaluation) II y PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Para la elaboración de las recomendaciones clínicas se analizaron y discutieron los tópicos de mayor importancia, por parte de los investigadores responsables y el grupo de expertos del desarrollo de un documento de posición. Se evaluó la calidad de la evidencia utilizando el sistema GRADE (Grading of Recommendations, Assessment, Development and Evaluation). RESULTADOS: Se encontraron distintos reportes con calidad de evidencia variable que sustentan la eficacia de las FBPS en el manejo de la alergia a la proteína de la leche de vaca y en la tolerancia digestiva del lactante, así como su baja alergia cruzada en comparación a la leche de vaca y otras fórmulas. También se encontraron otros estudios que indican la seguridad de las FBPS sobre distintos parámetros nutricionales, inmunitarios y de desarrollo. Existe además evidencia que demuestra que las FBPS tienen ventajas importantes en cuestión de costo-beneficio, palatabilidad y efectos sobre la microbiota intestinal, en comparación con otras fórmulas. CONCLUSIONES: Aunque existe evidencia limitada para recomendar su utilización en los trastornos digestivos funcionales, las FBPS tienen un perfil de seguridad adecuado y continúan siendo una opción válida para la alimentación del lactante.
Assuntos
Glycine max/química , Fórmulas Infantis/química , Fenômenos Fisiológicos da Nutrição do Lactente , Necessidades Nutricionais , Humanos , Lactente , Hipersensibilidade a Leite/imunologia , Proteínas de Soja/químicaRESUMO
Antecedentes: Las fórmulas a base de proteína de soya (FBPS) se han utilizado desde hace tiempo como una alternativa para lactantes con requerimientos nutricionales especiales. Sin embargo, las indicaciones médicas para su uso, su alergenicidad, seguridad y eficacia aún son controvertidas. Objetivo: Presentar recomendaciones del uso de FBPS basadas en la literatura existente. Métodos: Se realizó la consulta de revisiones sistemáticas y guías de práctica clínica, por medio de algoritmos de búsqueda validados, y sistemas como AGREE (Appraisal of Guidelines for REsearch and Evaluation) II y PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Para la elaboración de las recomendaciones clínicas se analizaron y discutieron los tópicos de mayor importancia, por parte de los investigadores responsables y el grupo de expertos del desarrollo de un documento de posición. Se evaluó la calidad de la evidencia utilizando el sistema GRADE (Grading of Recommendations, Assessment, Development and Evaluation). Resultados: Se encontraron distintos reportes con calidad de evidencia variable que sustentan la eficacia de las FBPS en el manejo de la alergia a la proteína de la leche de vaca y en la tolerancia digestiva del lactante, así como su baja alergia cruzada en comparación a la leche de vaca y otras fórmulas. También se encontraron otros estudios que indican la seguridad de las FBPS sobre distintos parámetros nutricionales, inmunitarios y de desarrollo. Existe además evidencia que demuestra que las FBPS tienen ventajas importantes en cuestión de costo-beneficio, palatabilidad y efectos sobre la microbiota intestinal, en comparación con otras fórmulas. Conclusiones: Aunque existe evidencia limitada para recomendar su utilización en los trastornos digestivos funcionales, las FBPS tienen un perfil de seguridad adecuado y continúan siendo una opción válida para la alimentación del lactante.
Abstract Background: Soy infant formulas (SIF) have long been used as an alternative for infants with special nutritional requirements. However, the medical indications for their use, their allergenicity, safety and efficacy are still controversial. Objective: To present recommendations for the use of SIF based on the existing literature. Methods: We consulted systematic reviews and clinical practice guides, through validated search algorithms, and systems such as Appraisal of Guidelines for REsearch and Evaluation (AGREE)II and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). For the elaboration of the clinical recommendations, the most important topics were analyzed and discussed by the responsible researchers and the group of experts in the development of a position paper. The quality of the evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Results: Several reports with variable quality of evidence were found. They support SIFs efficacy in the management of cows milk allergy and infants digestive tolerance, as well as its low cross allergy compared to cows milk and other formulas. We also found other studies that indicate the safety of SIFs on different nutritional, immune and developmental parameters. There is also evidence that demonstrates that SIFs have important advantages in terms of cost-benefit, palatability and effects on the intestinal microbiota, compared to other formulas. Conclusions: Although evidence to recommend its use in functional digestive disorders is limited, SIFs have an adequate safety profile and are still a valid option for infant feeding.