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1.
Biodemography Soc Biol ; 66(2): 156-171, 2021.
Article in English | MEDLINE | ID: mdl-34182852

ABSTRACT

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.


Subject(s)
Ethnicity , Genomics , Chile , Gene Frequency , Genetic Markers , Humans , Indians, South American/genetics , Spain
2.
Int. j. morphol ; 37(4): 1203-1209, Dec. 2019. graf
Article in English | LILACS | ID: biblio-1040112

ABSTRACT

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.


Subject(s)
Humans , Animals , Mice , Induced Pluripotent Stem Cells/cytology , Amyotrophic Lateral Sclerosis/metabolism , Immunohistochemistry , Cell Line , Coculture Techniques , Amyotrophic Lateral Sclerosis/pathology , Amyotrophic Lateral Sclerosis/therapy
3.
Rev Neurol ; 69(8): 323-331, 2019 Oct 16.
Article in Spanish | MEDLINE | ID: mdl-31588986

ABSTRACT

INTRODUCTION: Cognitive reserve has been shown to be a prognostic variable in cognitive recovery after brain damage. Few studies have addressed its role in the cognitive status after a sustained period of substance addiction. AIM: To analyse the modulating role of cognitive reserve in the relation between withdrawal time and the cognitive status of patients with severe substance addiction. PATIENTS AND METHODS: A total of 26 patients recovering from severe substance addiction were assessed using a neuropsychological assessment protocol and cognitive reserve questionnaires. Exploratory factor analysis is used to define the variables and linear regression analysis is employed to view the predictive relations. RESULTS: Three cognitive functioning factors are obtained: processing integrity, inhibitory control and verbal memory, as well as an overall reserve factor. In the regression models, predictive relations are found only in a model of a direct relation between withdrawal and verbal memory, and in a model of an independent relation between cognitive reserve and withdrawal time and verbal memory, but not in the modulation relationship or in other relations in the rest of the factors. CONCLUSION: The article discusses the role of the cognitive reserve as a mediator in the cognitive status of patients in a period of withdrawal after a serious addiction to substances. A relationship with memory is shown, but no modulation of the role of withdrawal time on that cognitive status is detected.


TITLE: Papel de la reserva cognitiva en la recuperacion cognitiva de pacientes que han sufrido una adiccion grave a sustancias.Introduccion. La reserva cognitiva resulta ser una variable de pronostico en la recuperacion cognitiva tras un daño cerebral. Pocos estudios han abordado su papel en el estado cognitivo tras un periodo sostenido de adiccion a sustancias. Objetivo. Analizar el papel modulador de la reserva cognitiva sobre la relacion entre el tiempo de abstinencia y el estado cognitivo de los pacientes con adiccion grave a sustancias. Pacientes y metodos. Se valora a un total de 26 pacientes en recuperacion tras una adiccion grave a sustancias con un protocolo de evaluacion neuropsicologica y cuestionarios de reserva cognitiva. Se emplea el analisis factorial exploratorio para conformar las variables y el analisis de regresion lineal para ver las relaciones predictivas. Resultados. Se obtienen tres factores de funcionamiento cognitivo: integridad de procesamiento, control inhibitorio y memoria verbal, asi como un factor global de reserva. En los modelos de regresion, solo se encuentran relaciones predictivas en un modelo de relacion directa entre la abstinencia y la memoria verbal, y en un modelo de relacion independiente entre la reserva cognitiva y el tiempo de abstinencia con la memoria verbal, pero no en la relacion de modulacion, ni en otras relaciones en el resto de los factores. Conclusion. Se debate el papel de la reserva cognitiva como mediadora en el estado cognitivo en los pacientes en periodo de abstinencia tras una adiccion grave a sustancias: muestra una relacion con la memoria, pero no una modulacion del papel del tiempo de abstinencia sobre ese estado cognitivo.


Subject(s)
Cognitive Reserve , Substance-Related Disorders/psychology , Adult , Aged , Humans , Male , Middle Aged , Neuropsychological Tests , Recovery of Function , Severity of Illness Index , Young Adult
4.
BMC Neurol ; 16: 77, 2016 May 23.
Article in English | MEDLINE | ID: mdl-27215274

ABSTRACT

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.


Subject(s)
Andrographis , Fatigue/drug therapy , Multiple Sclerosis, Relapsing-Remitting/complications , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Adolescent , Adult , Animals , Double-Blind Method , Fatigue/etiology , Female , Humans , Interferon-beta/therapeutic use , Male , Middle Aged , Pilot Projects , Young Adult
5.
Open Respir Med J ; 9: 97-103, 2015.
Article in English | MEDLINE | ID: mdl-26312101

ABSTRACT

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.

6.
Open Respir Med J ; 9: 104-11, 2015.
Article in English | MEDLINE | ID: mdl-26312102

ABSTRACT

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.

7.
Open Respir Med J ; 9: 120-6, 2015.
Article in English | MEDLINE | ID: mdl-26312104

ABSTRACT

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.

8.
Panminerva Med ; 56(2 Suppl 3): 1-7, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24861886

ABSTRACT

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.


Subject(s)
Blood Glucose/drug effects , Elaeocarpaceae , Glucose Intolerance/drug therapy , Hypoglycemic Agents/therapeutic use , Jejunum/drug effects , Plant Extracts/therapeutic use , Sodium-Glucose Transport Proteins/antagonists & inhibitors , Animals , Anthocyanins/analysis , Anthocyanins/therapeutic use , Biomarkers/blood , Blood Glucose/metabolism , Chile , Cross-Over Studies , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/diagnosis , Diabetes Mellitus, Experimental/drug therapy , Double-Blind Method , Elaeocarpaceae/chemistry , Female , Fruit , Glucose Intolerance/blood , Glucose Intolerance/diagnosis , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/chemistry , Insulin/blood , Jejunum/metabolism , Male , Mice, Inbred C57BL , Phytotherapy , Plant Extracts/adverse effects , Plant Extracts/chemistry , Plants, Medicinal , Postprandial Period , Rats , Rats, Sprague-Dawley , Sodium-Glucose Transport Proteins/metabolism , Time Factors , Treatment Outcome
9.
Rev. chil. urol ; 79(4): 14-25, 2014. tab, graf
Article in Spanish | LILACS | ID: lil-785411

ABSTRACT

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 cancer–specifi c survival through Kapplan- Meier curves and log-rank test.Risks (Hazard Ratio) adjusted Cox proportional model, with 95% was obtained...


Subject(s)
Humans , Male , Middle Aged , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/epidemiology , /genetics , Case-Control Studies , Prostatic Neoplasms/genetics
10.
Biogerontology ; 14(2): 165-76, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23559311

ABSTRACT

Aging is associated with an increased risk of depression in humans. To elucidate the underlying mechanisms of depression and its dependence on aging, here we study signs of depression in male SAMP8 mice. For this purpose, we used the forced swimming test (FST). The total floating time in the FST was greater in SAMP8 than in SAMR1 mice at 9 months of age; however, this difference was not observed in 12-month-old mice, when both strains are considered elderly. Of the two strains, only the SAMP8 animals responded to imipramine treatment. We also applied the dexamethasone suppression test (DST) and studied changes in the dopamine and serotonin (5-HT) uptake systems, the 5-HT2a/2c receptor density in the cortex, and levels of TPH2. The DST showed a significant difference between SAMR1 and SAMP8 mice at old age. SAMP8 exhibits an increase in 5-HT transporter density, with slight changes in 5-HT2a/2c receptor density. In conclusion, SAMP8 mice presented depression-like behavior that is dependent on senescence process, because it differs from SAMR1, senescence resistant strain.


Subject(s)
Aging/genetics , Aging/psychology , Behavior, Animal , Depression/epidemiology , Depression/psychology , Mice, Inbred Strains/genetics , Mice, Inbred Strains/psychology , Animals , Antidepressive Agents, Tricyclic/therapeutic use , Cerebral Cortex/metabolism , Depression/drug therapy , Disease Models, Animal , Dopamine/metabolism , Imipramine/therapeutic use , Incidence , Male , Mice , Receptors, Serotonin/metabolism , Swimming/psychology , Treatment Outcome , Tryptophan Hydroxylase/metabolism
11.
Arzneimittelforschung ; 62(8): 395-9, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22773430

ABSTRACT

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).


Subject(s)
Acenocoumarol/pharmacokinetics , Anticoagulants/pharmacokinetics , Acenocoumarol/administration & dosage , Acenocoumarol/chemistry , Administration, Oral , Adolescent , Adult , Anticoagulants/administration & dosage , Anticoagulants/chemistry , Chemistry, Pharmaceutical , Cross-Over Studies , Double-Blind Method , Female , Humans , Male , Middle Aged , Therapeutic Equivalency
12.
Int. j. morphol ; 28(4): 1255-1261, dic. 2010. ilus
Article in Spanish | LILACS | ID: lil-582920

ABSTRACT

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).


Subject(s)
Animals , Dogs , Aging , Cerebrum/pathology , Dog Diseases/pathology , Amyloid beta-Peptides/analysis , tau Proteins/analysis , Ubiquitin/analysis , Antibodies, Monoclonal , Brain Diseases/veterinary , Immunohistochemistry
13.
Int J Clin Pharmacol Ther ; 48(5): 342-8, 2010 May.
Article in English | MEDLINE | ID: mdl-20420791

ABSTRACT

Changes in bioavailability of anticonvulsant drugs such as topiramate may cause loss of or worsened seizure control. Thus, the purpose of this study was to evaluate, in a double-blind crossover design, the bioavailability between two oral formulations of topiramate in healthy volunteers after a single dose. The protocol, approved by the Institutional Committee of Ethics, consisted of administration of 1 tablet of 100 mg of topiramate of each formulation (Toprel and Topamax), to 20 healthy volunteers after a 12 h overnight fast, using an open, two-period, randomized, crossover and double-blind design. Thus, the plasma concentrations (Cp) of topiramate were measured at predetermined intervals of time, from 0 to 24 h, using a validated UPLC-MS/MS method. Based on plasma concentration-time profiles we obtained the following pharmacokinetic parameters: AUC(0-inf) 63,418.31 +/- 22,141.69 and 67,094.70 +/- 22,487.2 ngh/ml; AUC0-24: 30,421.02 +/- 9,964.0 and 30,489.35 +/- 9,407.17, ng x h/ml; tmax: 2.77 +/- 1.76 and 1.95 +/- 1.89 h; C(max): 2,143.33 +/- 724.26 and 2,262.51 +/- 751.12 ng/ml, for A (Toprel) and B (Topamax), respectively. All these differences were not statically significant with 90% confidence interval. The test of bioequivalence showed that Cmax, AUC(0-24) and AUC(0-inf) parameters are found within the range of 0.8 - 1.25 recommended by the FDA with a probability of bioequivalence of 100%. In accordance with these results, we can conclude that Toprel 100 mg, A (Test), is a bioequivalent generic and interchangeable with Topamax 100 mg, B (Reference).


Subject(s)
Anticonvulsants/pharmacokinetics , Chromatography, Liquid/methods , Fructose/analogs & derivatives , Tandem Mass Spectrometry/methods , Adult , Anticonvulsants/administration & dosage , Area Under Curve , Biological Availability , Cross-Over Studies , Double-Blind Method , Drugs, Generic/administration & dosage , Drugs, Generic/pharmacokinetics , Female , Fructose/administration & dosage , Fructose/pharmacokinetics , Humans , Male , Tablets , Therapeutic Equivalency , Topiramate , Young Adult
14.
Clín. investig. arterioscler. (Ed. impr.) ; 22(supl.1): 12-16, abr. 2010. ilus
Article in Spanish | IBECS | ID: ibc-145467

ABSTRACT

La capacidad de las lipoproteínas de alta densidad (HDL) para transportar el colesterol desde los tejidos periféricos hasta el hígado para su excreción se considera crucial para prevenir la acumulación de macrófagos “espumosos” en la íntima arterial. La adquisición del colesterol celular se inicia con la cesión de éste a la apolipoproteína (apo) A-I mediante ABCA1, generándose así pre-β HDL. La esterificación del colesterol por la lecitinacolesterol aciltransferasa promueve la formación de HDL maduras (α HDL). En humanos, prácticamente todos los ésteres de colesterol de las HDL llegan al hígado tras su transferencia a las lipoproteínas de muy baja (VLDL) y baja (LDL) densidad por la proteína transferidora de ésteres de colesterol y posterior captación mediante el receptor de LDL. Sin embargo, las HDL pueden entregar directamente colesterol libre al hígado mediante el receptor CLA-1/SR-BI, paso facilitado por la acción previa de la lipasa hepática. Estas últimas interacciones causan la liberación de HDL pequeñas y apo A-I, que adquirirán nuevamente colesterol en los tejidos periféricos (AU)


The ability of high-density lipoproteins (HDL) to transport cholesterol from peripheral tissues to the liver for excretion is considered crucial to prevent the accumulation of foamy macrophages in the arterial intima. The acquisition of cellular cholesterol is initiated by ABCA1-mediated cholesterol efflux to apolipoprotein (apo) A-I, thus generating pre-β-HDL. Cholesterol esterification by lecithin-cholesterol acyltransferase promotes the formation of mature HDL (α-HDL). In humans, practically all HDL cholesterol esters reach the liver after being transferred to very low (VLDL)- and low (LDL)-density lipoproteins by the cholesteryl ester transfer protein and subsequent uptake by the LDL receptor. However, HDL can deliver free cholesterol directly to the liver through the CLA- 1/SR-B1 receptor, a step that is aided by the prior action of hepatic lipase. These latter interactions lead to the release of small HDL particles and apo A-I, which then can newly acquire cholesterol in the peripheral tissues (AU)


Subject(s)
Female , Humans , Male , Cholesterol/blood , Phosphatidylcholine-Sterol O-Acyltransferase/administration & dosage , Protein S Deficiency/pathology , Atherosclerosis/metabolism , Liver/abnormalities , Lipase/deficiency , Bile/enzymology , Lipolysis/genetics , Cholesterol/metabolism , Phosphatidylcholine-Sterol O-Acyltransferase/metabolism , Protein S Deficiency/complications , Atherosclerosis/complications , Liver/cytology , Lipase/pharmacology , Bile/cytology , Lipolysis/physiology
15.
Clin Rheumatol ; 28(8): 931-46, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19408036

ABSTRACT

Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) possesses anti-inflammatory effects, attributed to the main constituent andrographolide proposed as alternative in the treatment of autoimmune disease. A prospective, randomized, double blind, and placebo-controlled study in patients with rheumatoid arthritis (RA) was performed. Tablets (Paractin) made of an extract of A. paniculata (30% total andrographolides) were administered three times a day for 14 weeks, after a 2-week washout period to 60 patients with active RA. The primary outcomes were pain intensity measured using a horizontal visual analog pain scale (VAPS). In addition, ACR, EULAR, and SF36 clinical parameters were recorded. The intensity of joint pain decreased in the active vs placebo group at the end of treatment, although these differences were not statistically significant. A significant diminishing for week in tender joint -0.13 95% confidence interval (CI; -0.22 to 0.06; p = 0.001), number of swollen joints -0.15 95%CI (-0.29 to -0.02; p = 0.02), total grade of swollen joint -0.27 95%CI (-0.48 to -0.07; p = 0.010), number of tender joints -0.25 95%CI (-0.48 to -0.02; p = 0.033), total grade of swollen joints -0.27 95%CI (-0.48 to -0.07; p = 0.01), total grade of tender joints -0.47 95%CI (-0.77 to -0.17; p = 0.002) and HAQ -0.52 95%CI (-0.82 to -0.21; p < 0.001) and SF36 0.02 95%CI (0.01 to 0.02; p < 0.001) health questionnaires was observed within the group with the active drug. Moreover, it was associated to a reduction of rheumatoid factor, IgA, and C4. These findings suggest that A. paniculata could be a useful "natural complement" in the treatment of AR; however, a larger trial and a more extended period of treatment is necessary in order to corroborate these results.


Subject(s)
Andrographis , Arthralgia/drug therapy , Arthritis, Rheumatoid/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Adolescent , Adult , Aged , Arsenicals , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnostic imaging , Chloroquine/therapeutic use , Double-Blind Method , Drug Therapy, Combination , Female , Glutathione/analogs & derivatives , Humans , Methotrexate/therapeutic use , Middle Aged , Placebos , Plant Leaves , Prednisone/therapeutic use , Prospective Studies , Radiography , Severity of Illness Index , Young Adult
16.
Acta Biomater ; 4(5): 1545-52, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18499544

ABSTRACT

The mechanical properties of the oxide layers developed at elevated temperature on three vanadium-free titanium alloys of interest for biomedical applications were investigated by means of the nanoindentation technique. The as-received alloys (Ti-13Nb-13Zr, Ti-15Zr-4Nb and Ti-7Nb-6Al) and their oxide scales formed by reaction with air at 750 degrees C for several oxidation times were analysed comparatively. In particular, the hardness and the Young's modulus exhibit larger values for the thermally oxidized alloys than for the untreated specimens. However, the Ti-7Nb-6Al alloy shows a different tendency to that of the TiNbZr alloys, which seems to be related to a different oxide layer growth as a function of the oxidation time.


Subject(s)
Alloys/chemistry , Biocompatible Materials/chemistry , Materials Testing , Nanostructures/chemistry , Nanostructures/ultrastructure , Titanium/chemistry , Elasticity , Hardness , Surface Properties
17.
Rev. chil. pediatr ; 74(4): 374-380, jul. 2003. tab, graf
Article in Spanish | LILACS | ID: lil-362867

ABSTRACT

Introducción: La obesidad infantil es el principal desafío nutricional actual en Chile; aún no se consigue una disminución de las tasas de obesidad y sobrepeso, tras diferentes intentos por deninir estrategias terapéuticas a largo plazo. Objetivo: Analizar factores familiares, clínicos o personales que pudieran servir como predictores de éxito terapéutico en el control ambulatorio del niño obeso. Sujetos y Métodos: Se siguió prospectivamente entre Enero y Agosto 2000, a 88 pacientes obesos de ambos sexos de 9,9 ± 3,3 años. Se realizó anamnesis general y nutricional, evaluación antropométrica ajustada por Tanner, encuesta de actividad física e ingesta, se solicitaron exámenes de laboratorio y se efectuó educación nutricional, alternando controles mensuales, grupales e individuales por nutricionista y médico. Se efectuó análisis univariado de los datos relacionando variaciones porcentuales de P/T o IMC con variables personales, familiares, antropométricas, bioquímicas y de actividad. Resultados: 48 por ciento abandonó el control antes de los 6 meses de seguimiento; de los que continuaban, 65 por ciento bajó de peso sobre 5 por ciento de su IMC o P/T inicial(34 por ciento del total). Se encontró hipercolesterolemia sobre 200 mg/dL en 15 por ciento de los niños e hipertensión (P.A. Sd sobre Pc 95) en 10 poe ciento. Sólo la edad menor a 5 años presentó mejor asociación con baja porcentual de peso -5,85 por ciento en menor de 5 años; -4,5 por ciento entre 5-10 años; -3,83 por ciento sobre los 10 años (p = 0,07), sin obtenerse asociación con otros factores estudiados: edad y educación materna, sexo, peso al nacer, tipo de familia, apreciación de obesidad y control espontáneo. Conclusiones: Este tratamiento de la obesidad infantil presenta una alta tasa de abandono y con un 34 por ciento de respuesta favorable. La edad de los niños menor a 5 años es la única variable asociada a respuesta favorable en términos de baja de peso.


Subject(s)
Humans , Child, Preschool , Child , Obesity , Infant Nutrition , Obesity
18.
Cancer Lett ; 174(1): 35-44, 2001 Dec 10.
Article in English | MEDLINE | ID: mdl-11675150

ABSTRACT

CYP1A1, CYP2E1 and GSTM1 polymorphisms were evaluated in Chilean healthy controls and lung cancer patients. In the Chilean healthy group, frequencies of CYP1A1 variant alleles for MspI (m2 or CYP1A1*2A) and ile/val (val or CYP1A1*2B) polymorphisms were 0.25 and 0.33, respectively. Frequencies of variant alleles C (CYP2E1*6) and c2 (CYP2E1*5B) for CYP2E1 were 0.21 and 0.16, respectively and frequency for GSTM1(-) was 0.24. The presence of variant alleles for GSTM1, MspI and Ile/val polymorphisms was more frequent in cases than in controls. However, frequencies for the c2 and C alleles were not significantly different in controls and in cases. The estimated relative risk for lung cancer associated to a single mutated allele in CYP1A1, CYP2E1 or GSTM1 was 2.41 for m2, 1.69 for val, 1.16 for C, 0.71 for c2 and 2.46 for GSTM1(-). The estimated relative risk was higher for individuals carrying combined CYP1A1 and GSTM1 mutated alleles (m2/val, OR=6.28; m2/GSTM1(-), OR=3.56) and lower in individuals carrying CYP1A1 and CYP2E1 mutated alleles (m2/C, OR=1.39; m2/c2, OR=2.00; val/C, OR=1.45; val/c2, OR=0.48; not significant). The OR values considering smoking were 4.37 for m2, 4.05 for val, 3.47 for GSTM1(-), 7.38 for m2/val and 3.68 for m2/GSTM1(-), higher values than those observed without any stratification by smoking. Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms could be more susceptible to lung cancer induced by environmental pollutants such as polycyclic aromatic hydrocarbons.


Subject(s)
Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP2E1/genetics , Genetic Predisposition to Disease/genetics , Glutathione Transferase/genetics , Lung Neoplasms/genetics , Polymorphism, Genetic/genetics , Chi-Square Distribution , Chile/epidemiology , Female , Gene Frequency , Genotype , Humans , Lung Neoplasms/epidemiology , Male , Middle Aged , Polymerase Chain Reaction , Sample Size , Smoking
19.
Thorax ; 56(8): 607-12, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11462062

ABSTRACT

BACKGROUND: Little is known about the associations between symptoms of asthma, pulmonary function tests, and atopy in developing countries. While asthma in children is often associated with atopy, some studies of wheezing illness have found little or no association, leading to suggestions that there are subgroups of wheezing illness. The ISAAC study recently reported that the prevalence of reported asthma symptoms in Lima, Peru was among the highest in the world, but did not report on the atopic status of the subjects. METHODS: A cross sectional survey was conducted of children aged 8-10 years who had previously participated in a cohort study of respiratory and diarrhoeal illnesses in infancy. Questionnaires were administered asking about respiratory symptoms and asthma diagnoses, pulmonary function tests were performed before and after exercise on a treadmill, and atopy was determined from skin prick tests and specific serum IgE levels. RESULTS: A total of 793 children participated in the survey. The prevalence of asthma related symptoms in the last 12 months was 23.2%, but only 3.8% of children reported a recent asthma attack. The mean differences in pretest percentage predicted forced expiratory volume in one second (FEV(1)) were 8.1% (95% CI 2.4 to 13.8) between children who did and did not report an asthma attack in the last 12 months, and 5.3% (95% CI 2.8 to 7.9) in children who did and did not report respiratory symptoms. The corresponding differences in mean percentage fall in FEV(1) after exercise were 3.1% (95% CI -1 to 7.1) and 5.1% (95% CI 3.4 to 6.8). Recent asthma or respiratory symptoms were not associated with atopy in this population (odds ratios 1.29 (95% CI 0.56 to 2.97) and 0.91 (95% CI 0.61 to 1.37), respectively). CONCLUSIONS: Most asthma in these children was unrecognised and mild. Asthma and asthma symptoms in this population do not seem to be related to atopy.


Subject(s)
Asthma/epidemiology , Hypersensitivity, Immediate/epidemiology , Respiration Disorders/epidemiology , Asthma/immunology , Asthma/physiopathology , Child , Cohort Studies , Cross-Sectional Studies , Exercise Test/methods , Forced Expiratory Volume/physiology , Humans , Hypersensitivity, Immediate/immunology , Hypersensitivity, Immediate/physiopathology , Logistic Models , Peru/epidemiology , Poverty Areas , Prevalence , Respiration Disorders/immunology , Respiration Disorders/physiopathology , Skin Tests/methods
20.
Cad Saude Publica ; 17 Suppl: 201-8, 2001.
Article in English | MEDLINE | ID: mdl-11426282

ABSTRACT

Most rural development projects include ecological considerations, and most conservation projects include some reference to sustainable development. However, conservation projects frequently fail because they do not incorporate local communities' perceptions and needs. Many development projects are also unsuccessful because they are not based on adequate ecological assessment. We focus here on the most important ecological issues to be addressed in order to place development projects in an ecosystem context. Such projects should incorporate updated and precise ecological concepts and methods. Some key ecological issues in development projects are the relationships between ecosystem functions, services, and sustainability, the concept of loose connectivity, the distinct and complementary concepts of ecosystem resistance and resilience, and the links between biodiversity and ecosystem functioning. We claim that an ecologically sound development project maximizes the preservation and improvement of ecosystem services, especially for local communities. We pose a series of questions aimed at placing rural development projects in an ecosystem context and suggest ways of organizing this information.


Subject(s)
Ecology , Program Development , Rural Health , Ecosystem , Humans
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