A systematic review on cannabinoids for neuropathic pain administered by routes other than oral or inhalation

12 páginasThe use of cannabis and cannabinoid products for the treatment of neuropathic pain is a growing area of research. This type of pain has a high prevalence, limited response to available therapies and high social and economic costs. Systemic cannabinoid-based therapies have shown some unwanted side effects. Alternative routes of administration in the treatment of neuropathic pain may provide better acceptance for the treatment of multiple pathologies associated with neuropathic pain. To examine the efficacy, tolerability, and safety of cannabinoids (individualized formulations, phytocannabinoids, and synthetics) administered by routes other than oral or inhalation compared to placebo and/or conventional medications in the management of neuropathic pain. This systematic review of the literature reveals a lack of clinical research investigating cannabis by routes other than oral and inhalation as a potential treatment for neuropathic pain and highlights the need for further investigation with well-designed clinical trials. There is a significant lack of evidence indicating that cannabinoids administered by routes other than oral or inhaled may be an effective alternative, with better tolerance and safety in the treatment of neuropathic pain. Higher quality, long-term, randomized controlled trials are needed to examine whether cannabinoids administered by routes other than inhalation and oral routes may have a role in the treatment of neuropathic pain.Especialización en Farmacología ClínicaEspecialista en Farmacología Clínic

Effects of an exercise program on hepatic metabolism, hepatic fat, and cardiovascular health in overweight/obese adolescents from Bogotá, Colombia (the HEPAFIT study): study protocol for a randomized controlled trial

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)

Enfermedad de Alzheimer y enfermedad de Parkinson: una revisión del tratamiento actual adoptando un enfoque de nanotecnología

24 páginasNeurodegenerative disorders (NDDs) are characterized by the progressive loss of structure or neuron function, often associated with neuronal death. Treatments for neurodegenerative diseases only address symptoms without having any disease-modifying effect but serious side effects. Currently, there is no effective treatment for NDDs. This is due to the poor flow of drugs to the blood-barrier brain (BBB) which does not allow macromolecules like proteins and peptides to pass through it. Targeted drug delivery to the central nervous system (CNS) for the diagnosis and treatment of NDDs, such as Alzheimer's disease (AD), is restricted due to the limitations posed by the BBB as well as opsonization by plasma proteins in the systemic circulation and peripheral side-effects. Nanotechnology thereby presents a broad approach for transporting molecules through the BBB, thus allowing the entry of substances acting directly on the site affected by the disease. The aim of this review is to outline current strategies in nanotechnology for treating Alzheimer's and Parkinson's diseases.Los trastornos neurodegenerativos (NDD, por sus siglas en inglés) se caracterizan por la pérdida progresiva de estructura o función neuronal, a menudo asociada con la muerte neuronal. Los tratamientos para enfermedades neurodegenerativas solo abordan los síntomas sin tener ningún efecto modificador de la enfermedad, pero sí efectos secundarios graves. Actualmente, no existe un tratamiento efectivo para los NDD. Esto se debe al flujo deficiente de medicamentos hacia la barrera hematoencefálica (BBB), que no permite que macromoléculas como proteínas y péptidos pasen a través de ella. La administración dirigida de fármacos al sistema nervioso central (SNC) para el diagnóstico y tratamiento de NDD, como la enfermedad de Alzheimer (EA), está restringida debido a las limitaciones que plantea la BHE, así como a la opsonización por proteínas plasmáticas en la circulación sistémica y periférica. efectos secundarios. La nanotecnología presenta así un amplio enfoque para el transporte de moléculas a través de la BBB, permitiendo así la entrada de sustancias que actúan directamente sobre el sitio afectado por la enfermedad. El objetivo de esta revisión es delinear las estrategias actuales en nanotecnología para el tratamiento de las enfermedades de Alzheimer y Parkinson

New ABCC2 rs3740066 and rs2273697 Polymorphisms Identified in a Healthy Colombian Cohort

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

Nanotechnology in Neurosciences: An Approach

7 páginasThe 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

Diabetes-Related Neurological Implications and Pharmacogenomics

15 páginasDiabetes 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 diabetes mellitus (DM) es la causa más común de neuropatía en todo el mundo y está comenzando a crecer en países donde existe riesgo de obesidad. La DM tipo II (DM2) es una enfermedad común relacionada con la edad y es un problema de salud importante, particularmente en los países desarrollados de Europa, donde la población está envejeciendo. La DM2 es una enfermedad crónica que se caracteriza por hiperglucemia, hiperinsulinemia y resistencia a la insulina, junto con la incapacidad del organismo para utilizar la glucosa como energía. Tal trastorno metabólico produce un estado inflamatorio crónico, así como cambios en el metabolismo de los lípidos que conducen a la hipertrigliceridemia, produciendo así un deterioro crónico de los órganos y morbilidad y mortalidad prematuras. Los efectos de la patología aumentan el daño cerebral, lo que conduce a la rápida aparición de enfermedades neurodegenerativas. La hiperglucemia provoca estrés oxidativo en los tejidos que son susceptibles a las complicaciones implicadas en la diabetes, incluidos los nervios periféricos. Otros mecanismos adicionales incluyen la activación de la señalización de poliol aldosa reductasa acompañada de activación de proteína quinasa C (PKC) -ß, activación de poli (ADP ribosa) polimerasa, activación de ciclooxigenasa (COX) 2, disfunción endotelial, función alterada de la bomba de Na + / K + ATPasa, dislipidemia y perturbación del equilibrio del calcio. Todo lo anterior tiene un impacto en la actividad neuronal, la función mitocondrial, la permeabilidad de la membrana y la función endotelial. Estos procesos bioquímicos afectan directamente a las neuronas y al tejido endotelial, acelerando así el envejecimiento cerebral mediante la peroxidación de los ácidos grasos poliinsaturados y lesionando así la integridad de la membrana celular e induciendo la apoptosis en las células gliales. El Sistema Nervioso Central (SNC) incluye dos tipos de células gliales: microglia y macroglia (astrocitos, oligodendrocitos y células radiales que incluyen células de Bergmann y células de Müller). Las células gliales constituyen más del 90% de la población de células del SNC. Los estudios en humanos han demostrado que algunos fármacos antidiabéticos orales pueden mejorar la cognición en pacientes que sufren deterioro cognitivo leve (DCL) y demencia [1, 2]. Si bien aún no está claro si el manejo de la diabetes reducirá la incidencia de DCL y la enfermedad de Alzheimer (EA), la evidencia emergente sugiere que las terapias para la diabetes pueden mejorar la función cognitiva. Esta revisión se centra en tres aspectos: la manifestación clínica de la diabetes con respecto a las células gliales y neuronales, la asociación entre la neurodegeneración y la diabetes y resume algunos de los datos farmacogenómicos obtenidos de los estudios de tratamiento de la DM2

Pseudomonas aeruginosa que comparte los genes de carbapenemasa BlaKPC-2 y BlaVIM-2

12 páginasPseudomonas 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.Pseudomonas aeruginosa, una bacteria comúnmente aislada en entornos hospitalarios, exhibe resistencia intrínseca a varios antibióticos y puede adquirir resistencia durante la terapia con antibióticos. La resistencia a los carbapenémicos está aumentando debido a su uso excesivo en el tratamiento de infecciones causadas por organismos productores de β-lactamasas de espectro extendido (BLEE). No obstante, los carbapenémicos son esenciales para el tratamiento de infecciones de alto riesgo y son una de las armas que quedan en la lucha contra la “resistencia extrema a los medicamentos” de los bacilos gramnegativos y positivos. En este artículo describimos un reporte de caso de infecciones causadas por cepas de P. aeruginosa portadoras de los genes de carbapenemasa blaVIM-2 y blaKPC-2 simultáneamente, identificadas en cinco pacientes que ingresaron en una institución de salud de alta complejidad en Colombia. La caracterización molecular incluyó la detección por PCR de carbapenemasas blaKPC, blaGES, blaOXA-48, blaIMP, blaNDM y blaVIM y otros genes de resistencia, así como el análisis de las relaciones genéticas mediante macrorestricción del genoma y separación por electroforesis en gel de campo pulsado (PFGE). En conclusión, estas infecciones representan un desafío importante para la salud pública debido al riesgo de propagación de la infección, agravado por el hecho de que hay opciones de tratamiento limitadas, lo que aumenta el riesgo de mayor morbilidad y mortalidad

Ultrastructural analysis of olfactory ensheathing cells derived from olfactory bulb and nerve of neonatal and juvenile rats

8 páginasOlfactory nerve derived and olfactory bulb derived olfactory ensheathing cells (OECs) have the ability to promote axonal regeneration and remyelination, both of which are essential in a successful cell transplant. Thus, morphological identification of OECs is a key aspect to develop an applicable cell therapy for injuries to the nervous system. However, there is no clear definition regarding which developmental stage or anatomical origin of OECs is more adequate for neural repair. In the present study, an ultrastructural comparison was made between OECs recovered from primary cultures of olfactory nerve and bulb in two developmental stages. The most notorious difference between cells obtained from olfactory nerve and bulb was the presence of indented nuclei in bulb derived OECs, suggesting a greater ability for possible chemotaxis. In neonatal OECs abundant mitochondria, lipid vacuoles, and smooth endoplasmic reticulum were detected, suggesting an active lipid metabolism, probably involved in synthesis of myelin. Our results suggest that neonatal OECs obtained from olfactory bulb have microscopic properties that could make them more suitable for neural repair

STOPP-START criteria used to characterize the elderly population prone topotentially inadequate prescribing

15 páginasThe elderly has multiple comorbidities that often require treatment with multiple medications, so having strategies to lessen risks associated with pharmacological interactions and potentially inadequate prescribing (PIP) is of main importance. STOPP-START criteria are useful in identifying PIP along with other tools like LASA (Look-alike/Sound-alike) drugs and High risk medications (HRM). Objectives To characterize clinically and sociodemographically the population with PIP according to STOPP-START criteria, in hospitalized elderly patients during 6 months in a third-level hospital in Colombia, South America. Besides, to calculate the prevalence of PIP, LASA drugs and HRM and to identify other problems related with medication. Finally, to propose an algorithm for the identification of PIP in this population. Materials and methods: This was a descriptive, cross-sectional study in hospitalized patients older than 60 years during the first semester of 2021, to identify PIP according to STOPP-START criteria. An analysis of clinical and sociodemographic variables was conducted, as well as the construction of an algorithm to identify PIP in the elderly in an semiautomated way. Statistical analysis: Data was collected and analyzed using the software SPSS 2021, using descriptive statistics and measures of central tendency. Results Prevalence of PIP in the study population was 25%. 60% of patients had one problem related with medication and 27% used at least one LASA drug or HRM. Conclusions: This study allows to characterize, for the first time, the Colombian population prone to PIP, as well as the construction of an algorithm that identifies PIP in a semiautomated way.Especialización en Farmacología ClínicaEspecialista en Farmacología Clínic

Efectos de un programa de ejercicios sobre el metabolismo hepático, la grasa hepática y la salud cardiovascular en adolescentes con sobrepeso/obesidad de Bogotá, Colombia (el estudio HEPAFIT): protocolo de estudio para un ensayo controlado aleatorio

16 páginasAbstract 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.Abstracto Fondo Una proporción considerable de los jóvenes contemporáneos tiene un alto riesgo de sufrir trastornos relacionados con la obesidad, como enfermedades cardiovasculares, síndrome metabólico o enfermedad del hígado graso no alcohólico (NAFLD). Aunque existe evidencia consistente de los efectos positivos de la actividad física en varios aspectos de la salud, la mayoría de los adolescentes en Colombia son sedentarios. Es, por tanto, importante implementar estrategias que generen cambios en el estilo de vida. El estudio HEPAFIT tiene como objetivo examinar si un programa de ejercicio de 6 meses tiene beneficios para el contenido de grasa hepática y los resultados de salud cardiovascular entre adolescentes con sobrepeso u obesidad de Bogotá, Colombia. Métodos/diseño En total, 100 adolescentes sedentarios (de 11 a 17 años) con sobrepeso u obesidad que asisten a dos escuelas públicas en Bogotá, Colombia, se incluirán en un ensayo controlado aleatorio de grupos paralelos. Los adolescentes serán asignados aleatoriamente a un grupo de intervención siguiendo uno de cuatro planes de estudio: (1) el plan de estudios de educación física estándar (60 minutos por semana de actividad física, n = 25) de intensidad baja a moderada; (2) un plan de estudios de educación física de alta intensidad (HIPE, n = 25), que consiste en juegos de resistencia y resistencia y actividades no competitivas, como correr, yincanas, levantar objetos, empujar, luchar o arrastrar objetos, durante sesiones de 60 minutos , tres veces por semana, con un objetivo de gasto energético de 300 a 500 kcal/sesión al 75-85% de la frecuencia cardíaca máxima (FCmáx); (3) un plan de estudios de educación física de intensidad baja a moderada (LIPE, n = 25) que consiste en juegos de resistencia y resistencia y actividades no competitivas (por ejemplo, perseguir, correr, driblar o saltar) durante sesiones de 60 minutos, tres veces por semana con un objetivo de gasto energético de 300 kcal/sesión al 55-75% FCmáx; y (4) un plan de estudios combinado HIPE y LIPE (n = 25). Las intervenciones HIPE, LIPE y combinadas se realizaron además del plan de estudios estándar de educación física. El resultado principal de eficacia es el contenido de grasa del hígado, medido por el parámetro de atenuación controlada 1 semana después del final del programa de intervención. Discusión El enfoque traslacional puede ser adecuado para recopilar nueva información en un entorno escolar sobre los posibles efectos de las intervenciones de actividad física para reducir el contenido de grasa del hígado y mejorar los perfiles metabólicos y la salud cardiometabólica de los adolescentes con sobrepeso u obesidad. Esto puede conducir a un uso más eficiente de los recursos de educación física escolar