RESUMEN
Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated response to an infection that is common among patients with moderate to severe burn injury. Previously, genomic variants in Toll-like receptor 4 (TLR4), a key innate immunity receptor, have been associated with sepsis and infection susceptibility. In this study, the association of six TLR4 SNPs with sepsis after burn injury was tested in the Mexican mestizo population. We found that the rs2737190 polymorphism is associated with sepsis after burn trauma. Interestingly, the G allele and GG genotype were associated with a lower risk of developing sepsis. Since the rs2737190 SNP is in the promoter region of the TLR4 gene, we analyzed the possibility that this polymorphism regulates the TLR4 pathway. We cultured peripheral blood mononuclear cells from different genotype carriers and found, after stimulation with LPS, that carriers of the GG genotype showed a higher expression of TLR4, IL6, and TNFα than AA genotype carriers. The results suggest that the GG genotype produces an increase in the TLR4 expression, and therefore an improvement in the immune response. We conclude that the rs2737190 polymorphism may become a useful marker for genetic studies of sepsis in patients after a burn injury.
Asunto(s)
Quemaduras , Sepsis , Quemaduras/complicaciones , Quemaduras/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Leucocitos Mononucleares , Polimorfismo de Nucleótido Simple , Sepsis/genética , Receptor Toll-Like 4/genéticaRESUMEN
INTRODUCTION: Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized mainly by skeletal muscle alterations. Although oropharyngeal dysphagia is a prominent clinical feature of DM1, it remains poorly studied in its early disease stages. METHODS: Dysphagia was investigated in 11 presymptomatic DM1 carriers, 14 patients with DM1 and 12 age-matched healthy controls, by using fiberoptic endoscopic evaluation of swallowing (FEES) and clinical scores. RESULTS: Scores for the FEES variables, delayed pharyngeal reflex, posterior pooling, and postswallow residue were significantly greater in patients with DM1 and in presymptomatic DM1 carriers than in healthy controls (P < 0.05); oropharyngeal dysfunction was more severe in patients than in presymptomatic carriers. Penetration/aspiration was found altered exclusively in patients with DM1 (P < 0.05). DISCUSSION: Swallowing dysfunction occurs in presymptomatic DM1 carriers. Timely diagnosis of dysphagia in preclinical stages of the disease will aid in the timely management of presymptomatic carriers, potentially preventing medical complications. Muscle Nerve, 2019.
Asunto(s)
Enfermedades Asintomáticas , Trastornos de Deglución/fisiopatología , Distrofia Miotónica/fisiopatología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Trastornos de Deglución/etiología , Endoscopía del Sistema Digestivo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Distrofia Miotónica/complicaciones , Distrofia Miotónica/genética , Proteína Quinasa de Distrofia Miotónica/genética , Adulto JovenRESUMEN
Sepsis is a life-threatening organ-dysfunction condition caused by a dysregulated response to an infectious condition that can cause complications in patients with major trauma. Burns are one of the most destructive forms of trauma; despite the improvements in medical care, infections remain an important cause of burn injury-related mortality and morbidity, and complicated sepsis predisposes patients to diverse complications such as organ failure, lengthening of hospital stays, and increased costs. Accurate diagnosis and early treatment of sepsis may have a beneficial impact on clinical outcome of burn-injured patients. In this review, we offer a comprehensive description of the current and traditional markers used as indicative of sepsis in burned patients. However, although these are markers of the inflammatory post-burn response, they usually fail to predict sepsis in severely burned patients due to that they do not reflect the severity of the infection. Identification and measurement of biomarkers in early stages of infection is important in order to provide timely response and effective treatment of burned patients. Therefore, we compiled important experimental evidence, demonstrating novel biomarkers, including molecular markers such as genomic DNA variations, alterations of transcriptome profiling (mRNA, miRNAs, lncRNAs and circRNAs), epigenetic markers, and advances in proteomics and metabolomics. Finally, this review summarizes next-generation technologies for the identification of markers for detection of sepsis after burn injuries.
Asunto(s)
Biomarcadores/metabolismo , Quemaduras/complicaciones , Sepsis/diagnóstico , Diagnóstico Precoz , Perfilación de la Expresión Génica , Genómica , Humanos , Pruebas en el Punto de Atención , Sepsis/complicaciones , Sepsis/genética , Sepsis/metabolismoRESUMEN
Carbon nanotubes (CNTs) consist of a family of carbon built nanoparticles, whose biological effects depend on their physical characteristics and other constitutive chemicals (impurities and functions attached). CNTs are considered the twenty first century material due to their unique physicochemical characteristics and applicability to industrial product. The use of these materials steadily increases worldwide and toxic outcomes need to be studied for each nanomaterial in depth to prevent adverse effects to humans and the environment. Entrance into the body is physical, and usually few nanoparticles enter the body; however, once there, they are persistent due to their limited metabolisms, so their removal is slow, and chronic cumulative health effects are studied. Oxidative stress is the main mechanism of toxicity but size, agglomeration, chirality as well as impurities and functionalization are some of the structural and chemical characteristic contributing to the CNTs toxicity outcomes. Among the many toxicity pathways, interference with cytoskeleton and fibrous mechanisms, cell signaling, membrane perturbations and the production of cytokines, chemokines and inflammation are some of the effects resulting from exposure to CNTs. The aim of this review is to offer an up-to-date scope of the effects of CNTs on biological systems with attention to mechanisms of toxicity.
Asunto(s)
Nanotubos de Carbono/toxicidad , Animales , Biotransformación , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Daño del ADN , Humanos , Inflamación/inducido químicamente , Inflamación/inmunología , Mediadores de Inflamación/metabolismo , Exposición por Inhalación , Estrés Oxidativo/efectos de los fármacos , Medición de Riesgo , Transducción de Señal/efectos de los fármacos , Distribución TisularRESUMEN
AKR1A1 or aldehyde reductase is a member of the aldo-keto reductases superfamily that is evolutionarily conserved among species. AKR1A1 is one of the five AKRs (AKR1A1 and 1C1-1C4) implicated in the metabolic benzo(a)pyrene (BaP) activation to reactive BaP 7,8-dione. BaP is a polycyclic aromatic hydrocarbon (PAH) widely distributed in aquatic ecosystems and its metabolic activation is necessary to produce its toxic effects. Although the presence of AKR1A1 in fish has been reported, its tissue distribution in tilapia (Oreochromis niloticus) and AKR1A1 inducibility by BaP are not known yet. Moreover, cytochrome P4501A (CYP1A) mRNA expression in fish has been used as a PAH biomarker of effect. Therefore, BaP effects on AKR1A1 and CYP1A gene expressions in tilapia, a species of commercial interest, were investigated by real-time RT-PCR. A partial AKR1A1 cDNA was identified, sequenced and compared with AKR1A1 reported sequences in the GenBank DNA database. Constitutive AKR1A1 mRNA expression was detected mainly in liver, similarly to that of CYP1A. BaP exposure resulted in statistically significant AKR1A1 and CYP1A mRNA induction in liver (20- and 120-fold, respectively) at 24 h. On the other hand, ethoxyquin (EQ) was used as control inducer for AKR1A1 mRNA. Interestingly, EQ also induced CYP1A mRNA levels in tilapia liver. Our results suggest that teleost AKR1A1, in addition to CYP1A, are inducible by BaP. The mechanism of AKR1A1 induction by BaP and its role in fish susceptibility to BaP toxic effects remains to be elucidated.
Asunto(s)
Aldehído Reductasa/genética , Benzo(a)pireno/toxicidad , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Hígado/efectos de los fármacos , ARN Mensajero/genética , Animales , Secuencia de Bases , Cartilla de ADN , ADN Complementario , Hígado/enzimología , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa , Homología de Secuencia de Ácido Nucleico , TilapiaRESUMEN
Exposure to environmental tobacco smoke (ETS) during early childhood increases the risk of developing asthma. The intention of this study was to genotype a population of children from Coahuila state in Northern Mexico and to determine whether polymorphisms of the CYP1A1, GSTP1, and IL13 genes are associated with exposure to ETS and subsequently a higher risk for asthma. IL13 plays an important role in the development of allergic response, particularly those related with airway inflammation. CYP1A1 and GSTP1 are xenobiotic-metabolizing enzymes induced by repeated exposure to toxicants. Polymorphisms of these genes have been related with ETS exposure and increased risk for asthma. To assess the effect of IL13 (-1112 C>T and Arg110Gln), GSTP1 (Ile105Val), and CYP1A1 (Ile462Val) on asthma risk and ETS exposure, we recruited 201 unrelated children and classified them into four groups: (1) control without ETS exposure; (2) control with ETS exposure; (3) with asthma and with ETS exposure and (4) with asthma and without ETS exposure. No association among ETS exposure, asthma, and the studied polymorphisms was denoted by multivariate analysis of this population.
Asunto(s)
Asma/genética , Citocromo P-450 CYP1A1/genética , Interacción Gen-Ambiente , Gutatión-S-Transferasa pi/genética , Interleucina-13/genética , Polimorfismo Genético , Contaminación por Humo de Tabaco/efectos adversos , Factores de Edad , Asma/enzimología , Asma/inmunología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Niño , Femenino , Predisposición Genética a la Enfermedad , Humanos , Modelos Logísticos , Masculino , México , Análisis Multivariante , Oportunidad Relativa , Medición de Riesgo , Factores de RiesgoRESUMEN
Occupational toxicology is of considerable concern for several world organizations including the International Labour Organization, the World Health Organization and the International Commission for Occupational Health and, in Latin America, the Pan American Health Organization. The countries of this Region, including Mexico, own manufacturing, chemical, and petrochemical industries that employ thousands workers who are continually exposed to hazardous chemicals such as solvents, particles and exhaust fumes, many of which are very complex mixtures. Traditionally, physicians have used biochemical analyses to assess the damage caused by chronic chemical exposure. Presently, recent advances in molecular biology may offer tools to perform more thorough and precise evaluations on worker health damage, risk and current health status. In this review, we present a perspective of occupational toxicology in Mexico, as an example for Latin America and developing countries. Moreover, we summarize current reports about occupational disease associated with chemical exposure, and we present an array of molecular studies proposed for the analysis and diagnosis of workers related with industry and the relevance of including molecular biology testing to complement traditional occupational medical assays in order to improve occupational health. We conclude that developing countries, e.g., Mexico, should improve work environment standards by using new technical approaches that will result in more reliable and precise data to design better health policy strategies.
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Exposición Profesional , Toxicología , México , Factores de RiesgoRESUMEN
Exposure to different substances in an occupational environment is of utmost concern to global agencies such as the World Health Organization and the International Labour Organization. Interest in improving work health conditions, particularly of those employees exposed to noxious chemicals, has increased considerably and has stimulated the search for new, more specific and selective tests. Recently, the field of molecular biology has been indicated as an alternative technique for monitoring personnel while evaluating work-related pathologies. Originally, occupational exposure to environmental toxicants was assessed using biochemical techniques to determine the presence of higher concentrations of toxic compounds in blood, urine, or other fluids or tissues; results were used to evaluate potential health risk. However, this approach only estimates the presence of a noxious chemical and its effects, but does not prevent or diminish the risk. Molecular biology methods have become very useful in occupational medicine to provide more accurate and opportune diagnostics. In this review, we discuss the role of the following common techniques: (1) Use of cell cultures; (2) evaluation of gene expression; (3) the "omic" sciences (genomics, transcriptomics, proteomics and metabolomics) and (4) bioinformatics. We suggest that molecular biology has many applications in occupational health where the data can be applied to general environmental conditions.
Asunto(s)
Monitoreo del Ambiente/métodos , Biología Molecular/métodos , Genómica/métodos , Humanos , Proteómica/métodosRESUMEN
Cilostazol, a drug commonly used in the treatment of intermittent claudication is a selective phosphodiesterase III inhibitor. It affects cell proliferation, increases cAMP levels, activates the cyclic AMP-dependent protein kinase and inhibits E2F in vascular cells. Polycystic kidney disease, a common genetic disorder, is characterized by increased cell proliferation, basement membrane abnormalities and fluid secretion. An established in vitro model of this disease is the canine Madin-Darby cell line (MDCK). In this communication, we investigated the effects of cilostazol exposure in MDCK cells. A reduced cell proliferation rate with an arrest in the G1 phase of the cell cycle was detected. Accordingly, several transcription factors associated with cell cycle control were affected by cilostazol, particularly c-myc. c-Myc DNA binding as well as its transcriptional activity was severely impaired in cilostazol-treated cells. Pharmacological tools demonstrated that besides the involvement of the cyclic AMP-dependent protein kinase, the extracellular signal-regulated kinases I/II participate in the response. These results suggest that cilostazol inhibits cell proliferation through c-myc transcriptional control, also pave the way to our better understanding of molecular transactions triggered by this drug and strengthen its potential use in other malignancies.