Motor learning impairment in rats under a high sucrose diet.

Motor learning skills are reliable indicators of behavioral acquisition and cognitive disorders. The ease with which learning skills are measured disparities the complexity of the interpretation concerning neural plasticity. Conversely, a wealth of information regarding metabolic derangements has long been reported with direct connection to high sucrose diets. However, the impact of excessive sucrose consumption on undergoing cognitive processes has been only scarcely addressed up to now. Therefore, the goal of this work was to describe the associative relationship between high sucrose consumption and changes in motor learning skills acquisition. Motor learning impairments conditioned by central alterations are hypothesized. Rotarod, elevated plus-maze and open field trials, along with metabolic and pro-inflammatory biomarkers tests in Wistar rats under a high sucrose treatment, were performed. Motor learning impairment in high sucrose diet-treated rats was found while spontaneous locomotor activity remained unchanged. Even though, no anxiety-like behavior under high sucrose diet-treatment was observed. Consistently, the worst outcome in the glucose tolerance test was developed, the worst motor learning performance was observed. Furthermore, insulin resistance correlated positively with a pro-inflammatory state and a decreased latency to fall in the rotarod test. Indeed, C-reactive protein and tumor necrosis factor-α serum levels, along with the homeostasis model assessment of insulin resistance (HOMA-IR), significantly increased in motor learning impairment. Together, these results support behavioral, metabolic and pro-inflammatory changes associated with deleterious changes in central nervous system likely involving crucial motor learning structures. Underlying pro-inflammatory-triggered processes may explain cognitive disorders in advanced states of metabolic derangements.

A Conus regularis conotoxin with a novel eight-cysteine framework inhibits CaV2.2 channels and displays an anti-nociceptive activity.

A novel peptide, RsXXIVA, was isolated from the venom duct of Conus regularis, a worm-hunting species collected in the Sea of Cortez, México. Its primary structure was determined by mass spectrometry and confirmed by automated Edman degradation. This conotoxin contains 40 amino acids and exhibits a novel arrangement of eight cysteine residues (C-C-C-C-CC-CC). Surprisingly, two loops of the novel peptide are highly identical to the amino acids sequence of ω-MVIIA. The total length and disulfide pairing of both peptides are quite different, although the two most important residues for the described function of ω-MVIIA (Lys2 and Tyr13) are also present in the peptide reported here. Electrophysiological analysis using superior cervical ganglion (SCG) neurons indicates that RsXXIVA inhibits CaV2.2 channel current in a dose-dependent manner with an EC50 of 2.8 µM, whose effect is partially reversed after washing. Furthermore, RsXXIVA was tested in hot-plate assays to measure the potential anti-nociceptive effect to an acute thermal stimulus, showing an analgesic effect in acute thermal pain at 30 and 45 min post-injection. Also, the toxin shows an anti-nociceptive effect in a formalin chronic pain test. However, the low affinity for CaV2.2 suggests that the primary target of the peptide could be different from that of ω-MVIIA.

PIP2 hydrolysis is responsible for voltage independent inhibition of CaV2.2 channels in sympathetic neurons.

GPCRs regulate Ca(V)2.2 channels through both voltage dependent and independent inhibition pathways. The aim of the present work was to assess the phosphatidylinositol-4,5-bisphosphate (PIP2) as the molecule underlying the voltage independent inhibition of Ca(V)2.2 channels in SCG neurons. We used a double pulse protocol to study the voltage independent inhibition and changed the PIP(2) concentration by means of blocking the enzyme PLC, filling the cell with a PIP(2) analogue and preventing the PIP(2) resynthesis with wortmannin. We found that voltage independent inhibition requires the activation of PLC and can be hampered by internal dialysis of exogenous PIP(2). In addition, the recovery from voltage independent inhibition is blocked by inhibition of the enzymes involved in the resynthesis of PIP(2). These results support that the hydrolysis of PIP(2) is responsible for the voltage independent inhibition of Ca(V)2.2 channels.

Construcción y validación clínica de un prototipo para el registro continuo de la presión arterial de forma no invasiva y ambulatoria / Construction and clinical validation of an automated measuring device for continuous non-invasive ambulatory blood pressure measurement

Introducción: la monitorización ambulatoria de la presión arterial con equipos biomédicos, es un método útil y confiable para el diagnóstico de la hipertensión arterial. El propósito del estudio fue validar un nuevo equipo de monitorización ambulatoria de la presión arterial de 24 horas (MAPA-FCV) de bajo costo, producido en la Fundación Cardiovascular de Colombia. Métodos: el estudio se desarrolló de acuerdo con las recomendaciones de la Sociedad Americana para el Avance de la Instrumentación Médica (AAMI, por sus siglas en Inglés) y la Sociedad Británica de Hipertensión (BHS) para validación de equipos de monitorización de presión arterial. Se incluyeron 85 sujetos sanos, en quienes, una persona previamente entrenada, obtuvo tres medidas simultáneas de presión arterial (cada 10 minutos) y se compararon con las que se obtuvieron con el equipo MAPA-FCV. Resultados: los sujetos presentaron una presión arterial sistólica de 115 ± 15 mm Hg y diastólica de 71 ± 8 mm Hg. Se encontró una diferencia media de 0,63 ± 5,94 mm Hg en la presión arterial sistólica y de 0,17 ± 5,08 mm Hg en la diastólica entre el equipo y el observador entrenado. Así mismo, se observó que más de 93% de las mediciones simultáneas de presión arterial, presentaron una diferencia menor a 10 mm Hg. Conclusiones: en el estudio el monitor MAPA-FCV alcanzó altos grados de concordancia con los valores de presión arterial que obtuvo el personal capacitado; adicionalmente el equipo cumplió con los criterios de validación de la AAMI y BHS, lo que hace posible su recomendación para uso clínico en población adulta.

Introduction: ambulatory arterial pressure monitoring with biomedical devices is a useful and reliable method to diagnose hypertension. The aim of this study was to validate a new low cost Holter blood pressure monitor (MAPA-FCV) produced at the Fundación Cardiovascular de Colombia. Methods: the study was developed according to the guidelines for validation of automated blood pressure measuring devices of the Association for the Advancement of Medical Instrumentation (AAMI) and the British Hypertension Society (BHS). Three blood pressure measurements were taken in 85 healthy subjects in a 30 minutes period (every 10 minutes). Measurements were taken by one observer trained to measure blood pressure with a mercury column device, and were compared with those obtained with the automatic device. Results: mean systolic blood pressure obtained in the subjects was 115 ± 15 mmHg, and mean diastolic blood pressure was 71 ± 8 mmHg. The mean and standard deviation of the differences between the measurements obtained by the observer and those obtained with the automatic device were 0.63 ± 5.94 mmHg for systolic pressure and 0.17 ± 5.08 mmHg for diastolic pressure. In addition, about 93% of the differences between the ascultatory and MAPA-FCV were within 10 mmHg. Conclusions: in the present study a close agreement between systolic and diastolic pressure measurements obtained by the auscultatory method and the MAPA-FCV device was found. The data obtained show that the MAPA-FCV can be recommended for clinical use according to the guidelines of international entities.

Accumulation of hypoxia-inducible factor-1alpha through a novel electrophilic, thiol antioxidant-sensitive mechanism.

15-deoxy-Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2)) is a peroxisome-activated proliferator receptor-gamma (PPARgamma) agonist which contains an alpha,beta-unsaturated electrophilic ketone involved in nucleophilic addition reactions to thiols. Here we studied its effect on hypoxia-inducible factor-1alpha (HIF-1alpha) in human proximal tubular cells HK-2. 15d-PGJ(2) induced stabilization of HIF-1alpha protein, without affecting HIF-1alpha mRNA levels or proteasome activity, leading to its nuclear accumulation and activation of HIF-induced transcription. Accumulation of HIF-1alpha was unaffected by selective PPARgamma blockade nor mimicked by the PPARgamma agonists ciglitazone and 9,10-dihydro-15d-PGJ(2). N-acetylcysteine, reduced glutathione (GSH) or dithiothreitol (i.e. agents that act as thiol reducing agents and/or increase the GSH content), but not reactive oxygen species (ROS) scavengers, prevented 15d-PGJ(2)-induced HIF-1alpha accumulation whereas the inhibitor of GSH synthesis buthionine sulfoximine cooperated with 15d-PGJ(2) to accumulate HIF-1alpha. Finally, HIF-1alpha expression was increased by the electrophilic alpha,beta-unsaturated compounds acrolein and PGA(2), but not by 9,10-dihydro-15d-PGJ(2), which lacks the electrophilic cyclopentenone moiety. Taken together, these results point out to a new mechanism to increase pharmacologically the cell levels of HIF-1alpha through the electrophilic reaction of alpha,beta-unsaturated ketones with thiol groups.

La importancia de la rehabilitación cardiovascular: experiencia en la Fundación Cardiovascular de Colombia / Importance of cardiovascular rehabilitation: experience in the Colombian Cardiovascular Foundation

Introducción: los programas de rehabilitación cardiovascular constituyen una herramienta fundamental en el manejo integral de los pacientes con enfermedades cardiovasculares. Se presentan los datos históricos relevantes del programa de Rehabilitación de la Fundación Cardiovascular de Colombia y los resultados obtenidos durante su existencia, comparándolos con otros programas a nivel nacional e internacional.Resultados: se confirman los beneficios de los programas de rehabilitación cardiovascular a nivel de control de factores de riesgo, mejoría en la tolerancia al ejercicio, mejoría en la calidad de vida y reducción de la morbimortalidad. Conclusiones: los programas de rehabilitación cardiovascular apoyados por un equipo multidisciplinario, influyen de manera positiva en el mejoramiento de la calidad de vida de los pacientes que han presentado un evento cardiovascular y han sido manejados a través de medio médicos o quirúrgicos.

Introduction: the programs of cardiovascular rehabilitation constitute a fundamental tool in the integral treatment of patients with cardiovascular disease. Historical relevant data from the Colombian Cardiovascular Foundation Rehabilitation program, as well as the results obtained during its existence, are presented, comparing them to those of other national and international programs. Results: the benefits of the cardiovascular rehabilitation programs referring to the control of risk factors, improvement to exercise tolerance, improvement in the quality of life and morbid-mortality reduction, are confirmed. Conclusions: cardiovascular rehabilitation programs supported by a multidisciplinary team have a positive influence in the improvement of the quality of life of patients who have had a cardiovascular event and have been treated by medical or surgical means.