RESUMO
Studies of the current Chilean population performed using classical genetic markers have established that the Chilean population originated primarily from the admixture of European people, particularly Spaniards, and Amerindians. A socioeconomic-ethno-genetic cline was established soon after the conquest. Spaniards born in Spain or Chile occupied the highest Socioeconomic Strata, while Amerindians belonged to the lowest. The intermediate strata consisted of people with different degrees of ethnic admixture; the larger the European admixture, the higher the Socioeconomic Level. The present study of molecular genomic markers sought to calculate the percentage of Amerindian admixture and revealed a finer distribution of this cline, as well as differences between two Amerindian groups: Aymara and Mapuche. The use of two socioeconomic classifications - Class and Socioeconomic Level - reveals important differences. Furthermore, Self-reported Ethnicity (self-assignment to an ethnic group) and Self-reported Ancestry (self-recognition of Amerindian ancestors) show variations and differing relationships between socioeconomic classifications and genomic Amerindian Admixture. These data constitute a valuable input for the formulation of public healthcare policy and show that the notions of Ethnicity, Socioeconomic Strata and Class should always be a consideration in policy development.
Assuntos
Etnicidade , Genômica , Chile , Frequência do Gene , Marcadores Genéticos , Humanos , Indígenas Sul-Americanos/genética , EspanhaRESUMO
In vitro modeling of neurodegenerative diseases is now possible by using patient-derived induced pluripotent stem cells (iPS). Through them, it is nowadays conceivable to obtain human neurons and glia, and study diseases cellular and molecular mechanisms, an attribute that was previously unavailable to any human condition. Amyotrophic lateral sclerosis (ALS) is one of the diseases that has gained a rapid advance with iPS technology. By differentiating motor neurons from iPS cells of ALS- patients, we are studying the mechanisms underlying ALS- disease onset and progression. Here, we introduce a cellular platform to help maintain longevity of ALS iPS-motor neurons, a cellular feature relevant for most late-onset human diseases. Long term cultures of patient-derived iPS cells might prove to be critical for the development of personalized-drugs.
Actualmente es posible modelar in vitro enfermedades neurodegenerativas humanas mediante el uso de células madre pluripotentes inducidas (iPS) derivadas del paciente. A través de ellas, es hoy concebible obtener neuronas y glía humanas, y estudiar mecanismos celulares y moleculares de enfermedades, un atributo que anteriormente no era posible para ninguna condición humana. La esclerosis lateral amiotrófica (ELA) es una de las enfermedades que se ha beneficiado con la tecnología de iPS. Al diferenciar neuronas motoras de células iPS obtenidas de pacientes con ELA, hemos iniciado estudios sobre los mecanismos que subyacen a la aparición y progresión de la enfermedad. Aquí, presentamos el desarrollo de una plataforma celular que permite extender la longevidad de las neuronas motoras derivadas de iPS, una característica relevante para la mayoría de las enfermedades humanas de inicio tardío. Los cultivos a largo plazo de células iPS provenientes de pacientes pueden ser determinantes en el desarrollo de terapias asociadas a la medicina de precisión.
Assuntos
Humanos , Animais , Camundongos , Células-Tronco Pluripotentes Induzidas/citologia , Esclerose Lateral Amiotrófica/metabolismo , Imuno-Histoquímica , Linhagem Celular , Técnicas de Cocultura , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/terapiaRESUMO
BACKGROUND: Andrographis paniculata (A. paniculata), a medicinal plant, has shown anti-inflammatory, neuroprotective and antifibrotic effects in animal models as well as clinical efficacy in different studies, including an anti-fatigue effect in autoimmune diseases such as rheumatoid arthritis. In multiple sclerosis (MS), fatigue is rated as one of the most common and disabling symptoms. In the present trial, we investigated the effect of A. paniculata on relapse rate and fatigue in relapsing-remitting MS (RRMS) patients receiving interferon beta. METHODS: A randomised double-blind placebo-controlled trial assessed the effects of 170 mg of A. paniculata dried extract tablet b.i.d. p.o. on relapse rate and fatigue using the Fatigue Severity Scores (FSS) over 12 months in RRMS patients receiving interferon. The Expanded Disability Status Scale (EDSS) score, inflammatory parameters and radiological findings were also investigated. Twenty-five patients were enrolled, and twenty-two patients were ultimately analysed and randomised to the active or placebo group. RESULTS: Patients treated with A. paniculata showed a significant reduction in their FSS score as compared to the placebo, equivalent to a 44 % reduction at 12 months. No statistically significant differences were observed for relapse rate, EDSS or inflammatory parameters, with a trend in reducing new lesions among the A. paniculata group. One patient in the A. paniculata group presented with a mild and transient skin rash, which was alleviated with anti-histamine treatment for three weeks. CONCLUSION: A. paniculata was well tolerated in patients and no changes in clinical parameters were observed. A. paniculata significantly reduces fatigue in patients with RRMS receiving interferon beta in comparison to placebo and only interferon beta treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02280876 ; Trial registration date: 20.10.2014.
Assuntos
Andrographis , Fadiga/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/complicações , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Adolescente , Adulto , Animais , Método Duplo-Cego , Fadiga/etiologia , Feminino , Humanos , Interferon beta/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto JovemRESUMO
Noninvasive mechanical ventilation (NIMV) was created for patients who needed noninvasive ventilator support, this procedure decreases the complications associated with the use of endotracheal intubation (ETT). The application of NIMV has acquired major relevance in the last few years in the management of acute respiratory failure (ARF), in patients with hypoxemic and hypercapnic failure. The main advantage of NIMV as compared to invasive mechanical ventilation (IMV) is that it can be used earlier outside intensive care units (ICUs). The evidence strongly supports its use in patients with COPD exacerbation, support in weaning process in chronic obstructive pulmonary disease (COPD) patients, patients with acute cardiogenic pulmonary edema (ACPE), and Immunosuppressed patients. On the other hand, there is poor evidence that supports the use of NIMV in other pathologies such as pneumonia, acute respiratory distress syndrome (ARDS), and during procedures as bronchoscopy, where its use is still controversial because the results of these studies are inconclusive against the decrease in the rate of intubation or mortality.
RESUMO
The normal physiology of conditioning of inspired gases is altered when the patient requires an artificial airway access and an invasive mechanical ventilation (IMV). The endotracheal tube (ETT) removes the natural mechanisms of filtration, humidification and warming of inspired air. Despite the noninvasive ventilation (NIMV) in the upper airways, humidification of inspired gas may not be optimal mainly due to the high flow that is being created by the leakage compensation, among other aspects. Any moisture and heating deficit is compensated by the large airways of the tracheobronchial tree, these are poorly suited for this task, which alters mucociliary function, quality of secretions, and homeostasis gas exchange system. To avoid the occurrence of these events, external devices that provide humidification, heating and filtration have been developed, with different degrees of evidence that support their use.
RESUMO
Physiotherapist in Chile and Respiratory Therapist worldwide are the professionals who are experts in respiratory care, in mechanical ventilation (MV), pathophysiology and connection and disconnection criteria. They should be experts in every aspect of the acute respiratory failure and its management, they and are the ones who in medical units are able to resolve doubts about ventilation and the setting of the ventilator. Noninvasive mechanical ventilation should be the first-line of treatment in acute respiratory failure, and the standard of care in severe exacerbations of chronic obstructive pulmonary disease, acute cardiogenic pulmonary edema, and in immunosuppressed patients with high levels of evidence that support the work of physiotherapist. Exist other considerations where most of the time, physicians and other professionals in the critical units do not take into account when checking the patient ventilator synchrony, such as the appropriate patient selection, ventilator selection, mask selection, mode selection, and the selection of a trained team in NIMV. The physiotherapist needs to evaluate bedside; if patients are properly connected to the ventilator and in a synchronously manner. In Chile, since 2004, the physioterapist are included in the guidelines as a professional resource in the ICU organization, with the same skills and obligations as those described in the literature for respiratory therapists.
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AIM: The impetus of our study was to investigate the effects of a nutritional supplement Delphinol®, an extract of maqui berries (Aristotelia chilensis) standardised to ≥25% delphinidins and ≥35% total anthocyanins, on postprandial blood glucose and insulin levels and identify the physiologic mechanism involved. METHODS: Postprandial blood glucose and insulin were investigated in double-blind, placebo-controlled, cross-over fashion in ten volunteers with moderate glucose intolerance. Longer term effects on blood sugar levels were investigated in streptozotocin-diabetic rats over a four months period. Effects of maqui berry delphinidins on sodium-glucose symport were examined in rodent jejenum of the small intestine. RESULTS: Delphinol® intake prior to rice consumption statistical significantly lowered post prandial blood glucose and insulin as compared to placebo. We identified an inhibition of Na+-dependant glucose transport by delphinidin, the principal polyphenol to which Delphinol® is standardised. In a diabetic rat model the daily oral application of Delphinol® over a period of four months significantly lowered fasting blood glucose levels and reached values indistinguishable from healthy non-diabetic rats. CONCLUSION: Our results suggest a potential use of Delphinol® for naturally controlling post-prandial blood glucose owed to inhibition of sodium glucose co-transporter in small intestine.
Assuntos
Glicemia/efeitos dos fármacos , Elaeocarpaceae , Intolerância à Glucose/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Jejuno/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Proteínas de Transporte de Sódio-Glucose/antagonistas & inibidores , Animais , Antocianinas/análise , Antocianinas/uso terapêutico , Biomarcadores/sangue , Glicemia/metabolismo , Chile , Estudos Cross-Over , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/diagnóstico , Diabetes Mellitus Experimental/tratamento farmacológico , Método Duplo-Cego , Elaeocarpaceae/química , Feminino , Frutas , Intolerância à Glucose/sangue , Intolerância à Glucose/diagnóstico , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/química , Insulina/sangue , Jejuno/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Fitoterapia , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Plantas Medicinais , Período Pós-Prandial , Ratos , Ratos Sprague-Dawley , Proteínas de Transporte de Sódio-Glucose/metabolismo , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCCIÓN: Polimorfismos en enzimas de biotransformación hansido asociados como factores de riesgo de cáncer prostático (CaP), aunque su papel como marcadores de pronóstico no está totalmente validado. El objetivo de este trabajofue estudiar en un grupo de pacientes sometidos a tamizaje, la utilidad del polimorfismo de CYP1A1 en el diagnóstico y sobrevida de pacientes chilenos con CaP.MATERIALES Y MÉTODOS: 255 controles y 234 casos con CaP fueron incluidos en programa de tamizaje en CONAC entre1995 y 2004. De muestras de sangre periférica se obtuvo DNA genómico y determinó polimorfi smo de CYP1A1*2A. Paraanálisis de susceptibilidad se usaron modelos de regresión logística uni y multivariado. Los pacientes con CaP fueron seguidos por 8,76 años en promedio, determinando sobrevida global y cáncer específica a través de curvas de Kapplan-Meier y test de Log-rank. Se obtuvieron riesgos (Hazard Ratio) ajustados con modelo proporcional de Cox, con IC del 95%...
INTRODUCTION: Polymorphisms in biotransformation enzymes have been associated as risk factors for prostate cancer(CaP), although their role as prognostic markers is not fully validated. The aim of this work was to study in a group ofpatients undergoing screening, utility CYP1A1 polymorphism in the diagnosis and survival of Chilean patients with PCa.MATERIALS AND METHODS: 255 cases and 234 controls with CaP that were included in CONAC screening program between1995 and 2004. Genomic DNA was obtained from samples of peripheral blood and polymorphism of CYP1A1 * 2ª determined.For sensitivity analysis uni and multivariate logistic regression models were used. PCa patients were followed for8.76 years on average, determining overall and cancerspecifi c survival through Kapplan- Meier curves and log-rank test.Risks (Hazard Ratio) adjusted Cox proportional model, with 95% was obtained...
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , /genética , Estudos de Casos e Controles , Neoplasias da Próstata/genéticaRESUMO
The aim of this study was to compare the bioavailability of an oral formulation of the coumarin derivative-vitamine K antagonist acenocoumarol (Acebron™ 4 mg, Test) with the reference formulation (Neo-Sintrom™ 4 mg). We performed a single-dose, double-blind, fasting, 2-period, 2-sequence, crossover study design. Plasma concentrations of acenocoumarol were determined using a validated UPLC-MS/MS method. 24 healthy Chilean volunteers (11 male, 13 female) were enrolled and all of them completed the study. Adverse events were monitored throughout the study. The values of the pharmacokinetic parameters were (mean ± SD): AUC0-24 =1 364.38±499.26 ngxh/mL for the test and 1 328.39±429.20 ngxh/mL for the reference; AUC0-∞ =1 786.00±732.85 ngxh/mL for the test and 1 706.71±599.66 ngxh/mL for the reference; Cmax =180.69±35.11 ng/mL with a Tmax of 1.83±0.95 h for the test and 186.97±38.21 ng/mL with a Tmax of 2.19±0.83 h for the reference. Regarding half life measurements, the mean ± SD of t1/2 were 11.84±4.54 h for the test and 11.08±3.28 h for the reference. The 90% confidence intervals for the test/reference ratio using logarithmic transformed data were 97.89-100.87%, 98.62-101.99% and 98.64-102.38% for Cmax, AUC0-t(24) and AUC0-∞. There were no significant differences in pharmacokinetic parameters between groups.The results obtained in this study lead us to conclude, based on FDA criteria, that the test acenocoumarol formulation (Acebron™, 4 mg tablets) is bioequivalent to the reference product (Neo-Sintrom™, 4 mg tablets).
Assuntos
Acenocumarol/farmacocinética , Anticoagulantes/farmacocinética , Acenocumarol/administração & dosagem , Acenocumarol/química , Administração Oral , Adolescente , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/química , Química Farmacêutica , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Equivalência TerapêuticaRESUMO
El interés en el estudio del proceso de envejecimiento cerebral y los cambios comportamentales relacionados con la edad en caninos y felinos geriátricos ha aumentado en la última década (Mentzel, 2005a; Ingram & Williams, 2010). Las alteraciones del comportamiento canino que responden a cambios fisiopatológicos relacionados con la edad y que involucran distintas esferas conductuales y cognitivas, se engloban bajo la denominación de Síndrome de Disfunción Cognoscitiva (SDC) (Mentzel, 2005b). El cual fue descrito en 1997 y se observó en perros de más de 9 años (Ingram & Williams). El Síndrome de Disfunción Cognoscitivo (SDC) es también llamado Alzheimer canino por las similitudes histopatológicas cerebrales y conductuales relacionadas. En el presente estudio, los caninos geriátricos presentaron los mismos depósitos proteicos anormales presentes en la enfermedad de Alzheimer, como las placas seniles, los cuerpos ubiquitinados y la angiopatía amiloide, pero no presentaron los ovillos neurofibrilares, los cuales son los responsables de la demencia que se padece en la enfermedad. Las únicas herramientas de evaluación prácticas en clínica para esta patología son las encuestas y formularios relacionados con aspectos comportamentales. Además existen exámenes diagnósticos postmortem que permiten identificar de una manera eficaz la presencia de elementos anormales involucrados en la neuropatología, uno de ellos es la inmunohistoquímica. En este estudio se utilizaron los anticuerpos monoclonales de uso humano anti-b-amiloide, anti-proteína tau y anti-ubiquitina en muestras de cerebros de perros mayores de 10 años. El modelo canino hoy en día está constituyendo un significado indispensable para el estudio de los procesos de neurodegeneración porque ha permitido un acercamiento a la teoría del problema desde nuevas perspectivas (Dimakopoulos & Mayer, 2002).
The interest in the study of the process of cerebral aging and the changes in the behaviour related to age in geriatric canine and feline has increased in the last decade (Mentzel, 2005a; Ingram & Williams, 2010). The alterations of the canine behaviour that respond to physiopathological changes related to the age and which involve different conducts and cognitive spheres are included under the denomination of Canine Cognitive Dysfunction Syndrome (CDS) called canine Alzheimer, considering the cerebral and histopathologic behavioural similarities. In the present study the geriatric patients displayed the same abnormal protein deposits present in Alzheimer disease, such as senile plaques ubiquitinate bodies and the amyloid angiopathy. However they did not display the balls of neurofibrillary tangles which are characteristic of the disease. The only practical tools of evaluation in clinic for this pathology are the surveys and forms related to behavioural aspects. In addition there are post mortem exams such as those in inmunohistochemistry, that allow an effective identification of abnormal elements present in the neuropathology. In this study the monoclonal antibodies were used anti-b-amyloid, anti-protein tau and anti-ubiquitin in samples of brains in dogs over 10 years of age. The canine model constitutes an indispensable meaning for the study of the neurodegeneration processes because it has allowed an approach to the theory of the problem from a new perspective (Dimakopoulos & Mayer, 2002).