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5 páginas Las proteínas asociadas a la resistencia a múltiples fármacos (MRP) 1 y 2 pertenecen a los transportadores ABC (ATP-Binding Cassette). Estas proteínas de transporte intervienen en la eliminación de diversos fármacos y xenobióticos, así como en múltiples procesos fisiológicos, patológicos y farmacológicos. Existe una fuerte correlación entre los diferentes polimorfismos y su implicación clínica en la resistencia a los fármacos antiepilépticos, anticancerígenos y antiinfecciosos. En nuestro estudio, evaluamos las regiones del exón de MRP1 (ABCC1) / MRP2 (ABCC2) en una cohorte colombiana de sujetos sanos para determinar los polimorfismos de un solo nucleótido (SNP) y para determinar la frecuencia alélica y genómica. Los resultados mostraron que hay SNP en nuestra población que se han informado previamente tanto para MRP1 / ABCC1 (rs200647436, rs200624910, rs150214567) como para MRP2 / ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). Además, se identificaron 13 nuevos SNP. La evidencia también muestra una correlación clínica significativa para los polimorfismos rs3740066 y rs2273697 en el transporte de múltiples fármacos, lo que sugiere una variabilidad genética con respecto a lo reportado en otras poblaciones. Multidrug resistance-associated proteins (MRP) 1 and 2 belong to the ABC (ATP-Binding Cassette) transporters. These transport proteins are involved in the removal of various drugs and xenobiotics, as well as in multiple physiological, pathological, and pharmacological processes. There is a strong correlation between different polymorphisms and their clinical implication in resistance to antiepileptic drugs, anticancer, and anti-infective agents. In our study, we evaluated exon regions of MRP1 (ABCC1)/MRP2 (ABCC2) in a Colombian cohort of healthy subjects to determine single nucleotide polymorphisms (SNPs) and to determine the allelic and genomic frequency. Results showed there are SNPs in our population that have been previously reported for both MRP1/ABCC1 (rs200647436, rs200624910, rs150214567) and MRP2/ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). Additionally, 13 new SNPs were identified. Evidence also shows a significant clinical correlation for polymorphisms rs3740066 and rs2273697 in the transport of multiple drugs, which suggests a genetic variability in regards to that reported in other populations.

Background: A considerable proportion of contemporary youth have a high risk of obesity-related disorders such as cardiovascular disease, metabolic syndrome, or non-alcoholic fatty liver disease (NAFLD). Although there is consistent evidence for the positive effects of physical activity on several health aspects, most adolescents in Colombia are sedentary. It is, therefore, important to implement strategies that generate changes in lifestyle. The HEPAFIT study aims to examine whether a 6-month exercise program has benefits for hepatic fat content and cardiovascular health outcomes among overweight/obese adolescents from Bogotá, Colombia. Methods/design: Altogether, 100 hundred overweight/obese, sedentary adolescents (aged 11–17 years) attending two public schools in Bogotá, Colombia, will be included in a parallel-group randomized controlled trial. Adolescents will be randomly assigned to an intervention group following one of four curricula: (1) the standard physical education curriculum (60 min per week of physical activity, n = 25) at low-to-moderate intensity; (2) a high-intensity physical education curriculum (HIPE, n = 25), consisting of endurance and resistance games and non-competitive activities, such as running, gymkhanas, lifting, pushing, wrestling, or hauling, for 60-min sessions, three times per week, with an energy expenditure goal of 300 to 500 kcal/session at 75–85% maximum heart rate (HRmax); (3) a low-to-moderate intensity physical education curriculum (LIPE, n = 25) consisting of endurance and resistance games and non-competitive activities (e.g., chasing, sprinting, dribbling, or hopping) for 60-min sessions, three times per week with an energy expenditure goal of 300 kcal/session at 55–75% HRmax; and (4) a combined HIPE and LIPE curriculum (n = 25). The HIPE, LIPE, and combined interventions were performed in addition to the standard physical education curriculum. The primary outcome for effectiveness is liver fat content, as measured by the controlled attenuation parameter 1 week after the end of the intervention program. Discussion: The translational focus may be suitable for collecting new information in a school setting on the possible effects of physical activity interventions to reduce liver fat content and to improve metabolic profiles and the cardiometabolic health of overweight/obese adolescents. This may lead to the more efficient use of school physical education resources., The HEPAFIT study was carried out with the financial support of Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología “Francisco José de Caldas” COLCIENCIAS (code 59700 and no 122277757900). Katherine González-Ruíz receive a scholarship from Universidad del Rosario, Colombia, Escuela de Medicina y Ciencias de la Salud, to do a Doctorate. This article presents independent research commissioned by COLCIENCIAS under its Program Grants for Applied Research funding scheme (Convocatoria 777–2017).

The purpose of this study was to compare the neurotrophic factor response following one session of high-intensity exercise, resistance training or both in a cohort of physically inactive overweight adults aged 18-30 years old. A randomized, parallel-group clinical trial of 51 men (23.6 ± 3.5 years; 83.5 ± 7.8 kg; 28.0 ± 1.9 kg/m2) who are physically inactive (i.e., < 150 min of moderate-intensity exercise per week or IPAQ score of < 600 MET min/week for > 6 months) and are either abdominally obese (waist circumference ≥90 cm) or have a body mass index, BMI ≥25 and ≤ 30 kg/m2 were randomized to the following four exercise protocols: high-intensity exercise (4 × 4 min intervals at 85-95% maximum heart rate [HRmax] interspersed with 4 min of recovery at 75-85% HRmax) (n = 14), resistance training (12-15 repetitions per set, at 50-70% of one repetition maximum with 60 s of recovery) (n = 12), combined high-intensity and resistance exercise (n = 13), or non-exercising control (n = 12). The plasma levels of neurotrophin-3 (NT-3), neurotrophin-4 (also known as neurotrophin 4/5; NT-4 or NT-4/5), and brain-derived neurotrophic factor (BDNF) were determined before (pre-exercise) and 1-min post-exercise for each protocol session. Resistance training induced significant increases in NT-3 (+39.6 ng/mL [95% CI, 2.5-76.6; p = 0.004], and NT-4/5 (+1.3 ng/mL [95% CI, 0.3-2.3; p = 0.014]), respectively. Additionally, combined training results in favorable effects on BDNF (+22.0, 95% CI, 2.6-41.5; p = 0.029) and NT-3 (+32.9 ng/mL [95% CI, 12.3-53.4; p = 0.004]), respectively. The regression analysis revealed a significant positive relationship between changes in BDNF levels and changes in NT-4/5 levels from baseline to immediate post-exercise in the combined training group (R2 = 0.345, p = 0.034) but not the other intervention groups. The findings indicate that acute resistance training and combined exercise increase neurotrophic factors in physically inactive overweight adults. Further studies are required to determine the biological importance of changes in neurotrophic responses in overweight men and chronic effects of these exercise protocols. © 2018 Domínguez-Sanchéz, Bustos-Cruz, Velasco-Orjuela, Quintero, Tordecilla-Sanders, Correa-Bautista, Triana-Reina, García-Hermoso, González-Ruíz, Peña-Guzmán, Hernández, Peña-Ibagon, Téllez-T, Izquierdo and Ramírez-Vélez.

The use of nanotechnology in neurosciences has been evolving since new treatments, diagnoses and biomolecule monitoring are needed to find safer treatments for central nervous system diseases (CNDs). Nanotechnology employs devices that interact with biological systems allowing molecular interactions with a high degree of specificity. This review considers concepts associated with nanotechnology and leading areas of neurosciences with nanotechnology research.

Pseudomonas aeruginosa, a bacterium commonly isolated from hospital settings, exhibits intrinsic resistance to a number of antibiotics and can acquire resistance during antibiotic therapy. Resistance towards carbapenems is increasing due to its overuse in the treatment of infections caused by extended-spectrum β-lactamase (ESBL) producing organisms. Nonetheless, carbapenems are essential for the treatment of high-risk infections and are one of the remaining weapons in the fight against “extreme drug resistance” of Gram-negative/positive bacilli. Herein, we describe a case report of infections caused by P. aeruginosa strains that carry blaVIM-2 and blaKPC-2 carbapenemase genes simultaneously, identified in five patients who were admitted to a high complexity health institution in Colombia. Molecular characterization included PCR screening for blaKPC, blaGES, blaOXA-48, blaIMP, blaNDM, and blaVIM carbapenemase and other resistance genes as well as analysis of the genetic relationships by genome macro-restriction and Pulsed-Field Gel Electrophoresis (PFGE) separation. In conclusion, these infections represent a major challenge to public health due to the risk of the infection spreading compounded by the fact that limited treatment options are available, thereby increasing the risk of increased morbidity and mortality.

Diabetes mellitus (DM) is the most commonly occurring cause of neuropathy around the world and is beginning to grow in countries where there is a risk of obesity. DM Type II, (T2DM) is a common age-related disease and is a major health concern, particularly in developed countries in Europe where the population is aging. T2DM is a chronic disease which is characterised by hyperglycemia, hyperinsulinemia and insulin resistance, together with the body’s inability to use glucose as energy. Such metabolic disorder produces a chronic inflammatory state, as well as changes in lipid metabolism leading to hypertriglyceridemia, thereby producing chronic deterioration of the organs and premature morbidity and mortality. The pathology’s effects increase cerebral damage, leading to the rapid onset of neurodegenerative diseases. Hyperglycemia causes oxidative stress in tissues which are susceptible to the complications involved in diabetes, including peripheral nerves. Other additional mechanisms include activation of polyol aldose reductase signalling accompanied by protein kinase C (PKC)-ß activation, poly(ADP ribose) polymerase activation, cyclooxygenase (COX) 2 activation, endothelial dysfunction, altered Na+/K+ ATPase pump function, dyslipidaemia and perturbation of calcium balance. All the forgoing has an impact on neuron activity, mitochondrial function, membrane permeability and endothelial function. These biochemical processes directly affect the neurons and endothelial tissue, thereby accelerating cerebral aging by means of peroxidation of the polyunsaturated fatty acids and thus injuring cell membrane integrity and inducing apoptosis in the glial cells. The Central Nervous System (CNS) includes two types de glial cells: microglia and macroglia (astrocytes, oligodendrocytes and radial cells which include Bergmann cells and Müller cells). Glial cells constitute more than 90% of the CNS cell population. Human studies have shown that some oral antidiabetic drugs can improve cognition in patients suffering mild cognitive impairment (MCI) and dementia [1, 2]. While it is still unclear whether diabetes management will reduce MCI and Alzheimer’s disease (AD), incidence, emerging evidence suggests that diabetes therapies may improve cognitive function. This review focuses three aspects: the clinical manifestation of diabetes regarding glial and neuronal cells, the association between neurodegeneration and diabetes and summarises some of the pharmacogenomic data obtained from studies of T2DM treatment, focusing on polymorphisms in genes affecting pharmacokinetics, pharmacodynamics and treatment outcome of the most commonly-prescribed oral anti-diabetic drugs (OADs).

La reparación de heridas cutáneas está mediada por factores de crecimiento y citoquinas que señalizan las células de la herida y del tejido sano circundante en cada una de las fases del proceso (inflamación, proliferación y remodelación). Estudios previos han mostrado que los sustitutos artificiales de tejido que contienen células, funcionan como sistemas de liberación de factores y citoquinas que intervienen en las primeras etapas del cierre de las heridas estimulando la formación de nuevo tejido y favoreciendo la regeneración sobre la reparación. Igualmente, que tejido conectivo artificial elaborado sembrando fibroblastos aislados de mucosa oral de conejo en soportes multidireccionales y unidireccionales de colágeno I, secretan en el medio de cultivo concentraciones diferentes de factores solubles importantes en el proceso de reparación de heridas. En este trabajo se comparó el desempeño de tejido conectivo autólogo artificial obtenido sembrando fibroblastos de piel en soportes con fibras y poros orientados multidireccionalmente (MTCA) y unidireccionalmente (UTCA) en un modelo lagomorfo de herida de espesor total de 4cm2 . Igualmente, se estandarizó una metodología de cuantificación de factores de crecimiento y citoquinas en el medio de cultivo de los tejidos artificiales mencionados y en los exudados de las heridas injertadas con ellos, basada en un biosensor óptico de plasmones de resonancia (SPR) y monocapas autoensambladas (SAM) de alcanotioles. Se cuantificaron 15 factores y citoquinas en los medios de cultivo y en los exudados tomados al tercer y sexto día post- cirugía, de las heridas injertadas y de las dejadas cerrar por segunda intención (control). A pesar de la cicatrización fibrosa de las heridas de piel característica del modelo lagomorfo, fue posible evaluar el desempeño como injerto de dermis autóloga artificial multi y unidireccional en heridas de espesor total. El conjunto de resultados obtenidos soporta la hipótesis de que el tejido conectivo autólogo actúa como un sistema de entrega de señales bioactivas cuyo perfil de concentracions cambia cuando las células se cultivan en soportes con diferente orientación de fibras y poros. Las observaciones clínicas, histológicas, histomorfométricas y las cuantificaciones de factores que modulan la cicatrización indican que los injertos elaborados con soportes multidireccionales mejoran el cierre de heridas de piel de espesor total en comparación al cierre de heridas injertadas con tejidos unidireccionales o dejadas cerrar por segunda intención. Abstract: The repair of skin wounds is mediated by growth factors and cytokines that signal the cells of the blood and surrounding healthy tissue in each of the phases of the process (inflammation, proliferation and remodeling). Previous studies have shown that the artificial substitutes of the tissue whit cells, work as delivery systems of growth factors and cytokines that mediate in the early stages of wound healing, stimulating the formation of new tissues and favoring regeneration over repair. Also, the artificial connective tissue produced by seeding fibroblasts isolated from rabbit oral mucosa on multidirectional and unidirectional scaffolds of collagen I, deliver different concentrations profiles of important growth factors and cytokines for wound healing in the culture media. In this work, the performance of artificial autologous connective tissue obtained by seeding skin fibroblasts in supports with multidirectionally oriented fibers and pores (MTCA) and unidirectionally (UTCA) in a lagomorph model with a full thickness of 4cm2 wound was compared. Also, methodology to quantify growth factors and cytokines in the culture medium of the artificial tissues and in the exudates of the wounds grafted with them, based on an optical resonance plasmon biosensor (SPR) and self-assembled monolayers ( SAM) of alkanethiols. Fifteen factors and cytokines were quantified in the culture media and in the exudates taken on the third and sixth day post-surgery, of the grafted wounds and those left closed by second intention (control). In spite of the fibrous healing of the wounds of the characteristic of the lagomorph model, it was possible to evaluate the performance as an artificial and unidirectional autologous dermal graft in full thickness wounds. The set of results obtained supports the hypothesis that the autologous connective tissue acts as a delivery system of bioactive signals whose concentration profile changes when the cells are grown in supports with different orientation of fibers and pores. Clinical, histological, histomorphometric observations and quantifications of factors that modulate healing, indicate that grafts made with multidirectional supports improve the healing of total thickness skin wounds compared to the wounds grafted with unidirectional tissues or left closed by secondary intention Doctorado