Metallothionein expression in the central nervous system in response to chronic heavy metal exposure: possible neuroprotective mechanism.

It has been reported that volcanoes release several tonnes of mercury per year among other heavy metals through eruptions, fumaroles, or diffuse soil degassing. Since a high percentage of the world's population lives in the vicinity of an active volcano, the aim of this study is to evaluate the accumulation of these metals in the central nervous system and the presence of cellular mechanisms of heavy metal detoxification such as metallothioneins. To carry out this study, wild mice (Mus musculus) chronically exposed to an active volcanic environment were captured in Furnas village (Azores, Portugal) and compared with those trapped in a reference area (Rabo de Peixe, Azores, Portugal). On the one hand, the heavy metal load has been evaluated by analyzing brain and cerebellum using ICP-MS and a mercury analyzer and on the other hand, the presence of metallothionein 2A has been studied by immunofluorescence assays. Our results show a higher load of metals such as mercury, cadmium and lead in the central nervous system of exposed mice compared to non-exposed individuals and, in addition, a higher immunoreactivity for metallothionein 2A in different areas of the cerebrum and cerebellum indicating a possible neuroprotection process.

Risk factors for anastomotic leakage following total or subtotal colectomy

Introduction: A higher rate of anastomotic leakage (AL) is reported after ileosigmoid anastomosis (ISA) or ileorectal anastomosis (IRA) in total or subtotal colectomy (TSC) compared with colonic or colorectal anastomosis. Themain aimof the present studywas to assess potential risk factors for AL after ISA or IRA and to investigate determinants of morbidity. Methods: We identified 180 consecutive patients in a prospective referral, single center database, in which 83 of the patients underwent TSC with ISA or IRA. Data regarding the clinical characteristics, surgical treatment, and outcome were assessed to determine their association with the cumulative incidence of AL and surgical morbidity. Results: Ileosigmoid anastomosis was performed in 51 of the patients (61.5%) and IRA in 32 patients (38.6%). The cumulative incidence of ALwas 15.6% (13 of 83 patients). A higher AL rate was found in patients under 50 years-old (p=0.038), in the electivelaparoscopic approach subgroup (p=0.049), and patients in the inflammatory bowel disease (IBD) subgroup (p=0.009). Furthermore, 14 patients (16.9%) had morbidity classified as Clavien-Dindo ≥ IIIA. Discussion: A relatively high incidence of AL after TSC was observed in a relatively safe surgical procedure. Our findings suggest that the risk of AL may be higher in IBD patients. According to our results, identifying risk factors prior to surgerymay improve short-term outcomes. (AU)

The Health Hazards of Volcanoes: First Evidence of Neuroinflammation in the Hippocampus of Mice Exposed to Active Volcanic Surroundings.

Neuroinflammation is a process related to the onset of neurodegenerative diseases; one of the hallmarks of this process is microglial reactivation and the secretion by these cells of proinflammatory cytokines such as TNFα. Numerous studies report the relationship between neuroinflammatory processes and exposure to anthropogenic air pollutants, but few refer to natural pollutants. Volcanoes are highly inhabited natural sources of environmental pollution that induce changes in the nervous system, such as reactive astrogliosis or the blood-brain barrier breakdown in exposed individuals; however, no neuroinflammatory event has been yet defined. To this purpose, we studied resting microglia, reactive microglia, and TNFα production in the brains of mice chronically exposed to an active volcanic environment on the island of São Miguel (Azores, Portugal). For the first time, we demonstrate a proliferation of microglial cells and an increase in reactive microglia, as well an increase in TNFα secretion, in the central nervous system of individuals exposed to volcanogenic pollutants.

Correction to: BRG1 regulation by miR-155 in human leukemia and lymphoma cell lines.

Following the publication of the original article the author listed as Antonio Herrera contacted the Publisher to state that his correct and full name is Antonio Herrera-Merchan. Antonio Herrera-Merchan has agreed to the publication of this erratum.

BRG1 regulation by miR-155 in human leukemia and lymphoma cell lines

Introduction/purpose. BRG1 is a key regulator of leukemia stem cells. Indeed, it has been observed that this type of cells is unable to divide, survive and develop new tumors when BRG1 is down-regulated. Materials and methods. We assessed BRG1 and miR-155 expression in 23 leukemia cell lines, and two no pathological lymphocyte samples using qPCR. MiR-155 transfection and western blot were used to analyze the relationship between miR-155 and its validated target, BRG1, by measuring protein expression levels. The effect of miR-155 on cell proliferation and prednisolone sensitivity were studied with resazurin assay. Results. BRG1 expression levels could correlate negatively with miR-155 expression levels, at least in Burkitt’s lymphoma and diffuse large B cell lymphoma (DLBCL) cell lines. To clarify the role of miR-155 in the regulation of BRG1 expression, we administrated miR-155 mimics in different leukemia/lymphoma cell lines. Our results suggest that miR-155 regulate negatively and significantly the BRG1 expression at least in the MOLT4 cell line. Conclusion. Our study revealed a previously unknown miR-155 heterogeneity that could result in differences in the treatment with miRNAs in our attempt to inhibit BRG1. However, the expression levels of BRG1 and miR-155, before prednisolone treatment were not statistically significantly associated prednisolone sensitive leukemia cells (AU)

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BRG1 regulation by miR-155 in human leukemia and lymphoma cell lines.

INTRODUCTION/PURPOSE: BRG1 is a key regulator of leukemia stem cells. Indeed, it has been observed that this type of cells is unable to divide, survive and develop new tumors when BRG1 is down-regulated. MATERIALS AND METHODS: We assessed BRG1 and miR-155 expression in 23 leukemia cell lines, and two no pathological lymphocyte samples using qPCR. MiR-155 transfection and western blot were used to analyze the relationship between miR-155 and its validated target, BRG1, by measuring protein expression levels. The effect of miR-155 on cell proliferation and prednisolone sensitivity were studied with resazurin assay. RESULTS: BRG1 expression levels could correlate negatively with miR-155 expression levels, at least in Burkitt's lymphoma and diffuse large B cell lymphoma (DLBCL) cell lines. To clarify the role of miR-155 in the regulation of BRG1 expression, we administrated miR-155 mimics in different leukemia/lymphoma cell lines. Our results suggest that miR-155 regulate negatively and significantly the BRG1 expression at least in the MOLT4 cell line. CONCLUSION: Our study revealed a previously unknown miR-155 heterogeneity that could result in differences in the treatment with miRNAs in our attempt to inhibit BRG1. However, the expression levels of BRG1 and miR-155, before prednisolone treatment were not statistically significantly associated prednisolone sensitive leukemia cells.

Effects of pomegranate juice in circulating parameters, cytokines, and oxidative stress markers in endurance-based athletes: A randomized controlled trial.

OBJECTIVE: The aim of the present study was to assess the effects of pomegranate juice on the level of oxidative stress in the blood of endurance-based athletes. Pomegranate juice is rich in polyphenols, conferring it a higher antioxidant capacity than other beverages with polyphenolic antioxidants. METHODS: A randomized double-blind, multicenter trial was performed in athletes from three different sport clubs located in southeastern of Spain. Plasma oxidative stress markers (protein carbonyls and malondialdehyde [MDA]) as well as C-reactive protein and sE-selectin were measured. Thirty-one athletes participated in the study. Participants were divided into three groups. The first group was supplemented with 200 mL/d pomegranate juice (PJ; n = 10) over a 21-d period, the second with 200 mL/d pomegranate juice diluted 1:1 with water (PJD; n = 11), and a control group that did not consume pomegranate juice (C; n = 10). Nine athletes were excluded due to protocol violations (n = 4 in the PJ group and n = 5 in the PJD group) because they did not observe the 24 h of rest before the last blood test. RESULTS: The control group increased levels of carbonyls (+0.7 ± 0.3 nmols/mg protein) and MDA (+3.2 ± 1.0 nmols/g protein), whereas the PJ and PJD groups maintained or decreased their levels, respectively. On the other hand, lactate levels increased in the PJ group (from 10.3 at day 0 to 21.2 mg/dL at day 22). A nonsignificant decrease was detected in sE-selectin and C-reactive protein in the groups consuming pomegranate juice. CONCLUSION: Consumption of pomegranate juice over a 21-d period improved MDA levels and carbonyls, and thus decreased the oxidative damage caused by exercise.

Importance of exercise in the control of metabolic and inflammatory parameters at the moment of onset in type 1 diabetic subjects.

The onset of type 1 diabetes coincides with the final phase of ß-cell destruction. In some cases, this period is characterized by the presence of a functional reserve of ß-cells, favouring an adequate metabolic control (honeymoon phase). Therefore, the extension of this situation could have evident benefits in subsequent diabetes management. We aimed to study the influence of regular physical activity before and after the onset of the disease. We did an observational study of 2 groups of type 1 diabetic patients from onset to a 2-year period. One group (n = 8) exercised regularly (5 or more hours/week) before onset and continued doing so with the same regularity. The second group (n = 11) either did not perform physical activity or did so sporadically. Circulating glycated haemoglobin (HbA1c), C-peptide, protein carbonyls and basal cytokine levels were determined at the beginning and at the end of the 1(st) and 2(nd) year. The more active group debuted with and maintained significantly lower HbA(1c) levels and insulin requirements compared to the more sedentary group. C-peptide levels were only significantly higher in the active group at the moment of onset compared to the sedentary group. In addition, determination of basal circulating cytokines revealed a large variability between individuals but no significant differences when comparing the groups. Altogether, the obtained results seem to indicate that physical activity allows a better control at the moment of onset regarding glycaemic control, residual endocrine pancreatic mass and subsequent insulin requirements.

Single cell-derived clones from human adipose stem cells present different immunomodulatory properties.

Human adipose mesenchymal stem cells are a heterogeneous population, where cell cultures derived from single-cell-expanded clones present varying degrees of differential plasticity. This work focuses on the immunomodulatory/anti-inflammatory properties of these cells. To this end, five single-cell clones were isolated (generally called 1.X and 3.X) from two volunteers. Regarding the expression level of the lineage-characteristic surface antigens, clones 1·10 and 1·22 expressed the lowest amounts, while clones 3·10 and 3·5 expressed more CD105 than the rest and clone 1·7 expressed higher amounts of CD73 and CD44. Regarding cytokine secretion, all clones were capable of spontaneously releasing high levels of interleukin (IL)-6 and low to moderate levels of IL-8. These differences can be explained in part by the distinct methylation profile exhibited by the clones. Furthermore, and after lipopolysaccharide stimulation, clone 3.X produced the highest amounts of proinflammatory cytokines such as IL-1ß, while clones 1·10 and 1·22 highly expressed IL-4 and IL-5. In co-culture experiments, clones 1.X are, together, more potent inhibitors than clones 3.X for proliferation of total, CD3(+) T, CD4(+) T and CD8(+) T lymphocytes and natural killer (NK) cells. The results of this work indicate that the adipose stem cell population is heterogeneous in cytokine production profile, and that isolation, characterization and selection of the appropriate cell clone is a more exact method for the possible treatment of different patients or pathologies.

Cardiac adaptation to training and decreased training loads in endurance athletes: a systematic review.

INTRODUCTION: Changes in echocardiographic standard measurements as a consequence of training and detraining in elite or subelite athletes have not been comprehensively studied. METHODS: We identified 200 potentially relevant studies from 1966 to June 2006 and eliminated 187 studies that did not fulfil the objectives of the study. We identified 13 studies with echocardiographic assessment of heart adaptation following variation in training loads in elite or subelite endurance-trained athletes. We performed a meta-analysis by studying the changes in the left ventricular end-diastolic (LVEDD), left ventricular end-systolic (LVESD), left ventricular posterior wall (LVPW) and interventricular septum thickness (IVST) dimensions induced by training. RESULTS: A significant positive overall effect size on echocardiographic outcomes was found following training, using the fixed effect model on LVPW, LVEDD, LVESD and IVST. LVPW and LVEDD were significantly higher following training. CONCLUSION: Studies reported an increase in LVEDD and LVPW, following endurance training. However, the heterogeneity of the studies and the sensitivity of echocardiography technique can be two reasons, for which the results do not allow to state unequivocally that the adaptation to endurance training of highly trained hearts stems from increments of diastolic diameter of the left ventricle and lateral wall of the left ventricle (LVPW).

Determinación de la transición aeróbica-anaeróbica mediante parámetros del modelo respiratorio / Determination of the aerobic-anaerobic transition by means of the breathing parameters

El objetivo de este trabajo ha sido analizar la relación entre determinados parámetros del modelo respiratorio y la transición aeróbica-anaeróbica. Veintidós varones (24.9 +/- 4.1) años (Media +/- SD) y 11 mujeres (21.7 +/- 2.1) años, realizaron una prueba de esfuerzo máxima. La transición aeróbica-anaeróbica fue analizada mediante dos métodos: 1º el método ventilatorio y 2º el cambio de los tiempos respiratorios y sus inversos. Los criterios para la determinación de los umbrales ventilatorios por ambos métodos fue llevado a cabo por 4 observadores, 2 sin experiencia y 2 con experiencia. La correlación de Pearson para los valores medios de los 4 observadores fue: r= 0.55 +/- 0.23 para VT1 (ventilatory threshold 1) en los varones y r=0.71 +/- 0.09 para el VT1 en las mujeres. La correlación más alta se observó para VT2 (ventilatory threshold 2): r= 0.78 +/- 0.04 (varones) y r= 0.79+/- 0.07 (mujeres). Los resultados muestran evidencia de la actividad central inspiratoria durante la transición aeróbica-anaeróbica, sugiriendo la validez del método propuesto (AU)

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Adaptación del sistema nervioso alentrenamiento / Biological adaptation to endurance training

Cuando se piensa en las modificaciones que pueden producirse en organismos altamente entrenados, indudablemente se dirige el pensamiento hacia el sistema nervioso. Músculo y nervio son unidades indivisibles del movimiento. Es objeto de este trabajo de revisión, analizar la adaptación del sistema neuromuscular al entrenamiento de resistencia. En los últimos 30 años mucho se ha avanzado sobre la modificación, a consecuencia del entrenamiento de resistencia, de las caracteristicas morfológicas y fisiológicas de las fibras musculares, de la placa motora y de las relaciones entre las aferencias (AU)

Análisis de las pruebas de ergoespirometría en fase estable (Revisión) / Analysis of the ergoespirometric tests in steady state (A review)

El estudio de la resistencia en el laboratorio de fisiología es objeto de debate en relación al tipo de pruebas que mejor pueden valorarla. Algunos investigadores opinan que son las pruebas máximas las idóneas, mientras otros señalan que deben ser las pruebas a carga constante. El objetivo de este trabajo es revisar los estudios realizados en el laboratorio a carga constante, denominados en fase estable. Las pruebas en fase estable se basan en el principio de estabilidad fisiológica que permite mantener el esfuerzo durante un periodo de tiempo prolongado. Uno de estos parámetros es el ácido láctico, cuya máxima expresión es el concepto de “Máximo Estado Estable de Lactato”. La discusión relativa al concepto de este término ha sido en delimitar la oscilación permitida de la concentración de este metabolito (0,5 a 1 mM/L) y la duración del ejercicio (20 a 30 min) para considerar fase estable. La dificultad del término de máximo estado estable implica los problemas metodológicos discutidos en la literatura científica existente. A pesar de esta dificultad se hace necesario la aplicación de este tipo de pruebas para valorar el estado de entrenamiento con mayor rigor (AU)

Aplicación práctica de las pruebas de esfuerzo / Practical applications of stress test

Las pruebas de esfuerzo realizadas con análisis de gases forman parte de las “herramientas” de valoración del médico deportivo. Sin embargo, hasta hace poco tiempo este tipo de pruebas se centraban en la parte fisiológica, dejando de un lado su utilidad en el diagnóstico de ciertas patologías. Es objetivo de este trabajo presentar las aplicaciones prácticas, principalmente las fisiológicas, de esta herramienta fundamental para el médico deportivo (AU)

La recuperación de la frecuencia cardíaca en deportistas de fondo: triatletas, atletas, ciclistas y nadadores' / Heart rate recovery in endurance sportsmen triathletes, athletes, cyclists and swimmers

El objetivo del presente estudio es por un lado el de comparar la respuesta de la FC durante 4 minutos tras una prueba de esfuerzo (FC recuperación rápida y lenta) en 4 grupos de atletas de élite: nadadores, atletas, triatletas y ciclistas, incluidos todos ellos en pruebas de fondo; y por otro lado sacar datos de índices de recuperación que puedan ser orientativos para realizar comparaciones con otros atletas de dichos grupos.La hipótesis inicial que proponemos es que la curva de FC de recuperación en los cuatro grupos de sujetos no debe poseer diferencias significativas en cuanto a su variación en el tiempo, ya que suponemos que las variaciones en el entrenamiento de unos y otros no son suficientes para provocar ajustes tan sensibles en los mecanismos de control de FC.Se han estudiado 61 atletas varones federados de nivel nacional divididos en los cuatro grupos mencionados según el deporte practicado. La fecuencia cardíaca se registró durante los 4 primeros minutos de la recuperación, determinándose el índice de recuperación para cada uno de los 4 minutos.Se efectuó un test de multivarianza con un nivel de significación de 0.05.Los resultados obtenidos verifican la hipótesis inicial ya que nos muestran como a pesar que existir diferencias cuantitativas entre las 4 curvas de recuperación (una para cada deporte), la forma de las curvas en el tiempo es similar, por lo que estadísticamente no se encuentran diferencias significativas en la forma de recuperar entre los grupos de deportistas. Sí observamos, sin embargo, que a nivel cuantitativo, los nadadores parten de mayores FC finales de ejercicio y terminan también con mayor FC tras cuatro minutos de recuperación, mientras que los triatletas parten con las FC más bajas), son los que presentan las FCR menores para los cuatro minutos (AU)

Ergoespirometría: paradigma del análisis de la respuesta integrada al ejercicio dinámico / Ergoespirometry: paradigm of the analysis of the integrated answer to the dynamic exercise

El ejercicio físico dinámico constituye una fuente fundamental de conocimiento de la fisiología pues compromete al organismo de forma absoluta, no sólo a los órganos implicados directamente, sino a aquellos aparentemente no funcionales, como por ejemplo, el aparato digestivo y el riñón. Es decir, el organismo responde de forma integrada.La ergoespirometría, que de forma rutinaria se utiliza en los laboratorios de fisiología, aporta una gran cantidad de información, precisamente, sobre la respuesta integrada del organismo al ejercicio dinámico. Por ello, el objetivo de este trabajo es presentar las bases fisiológicas por las que la ergoespirometría es una forma de analizar la respuesta y adaptación integrada del organismo a una situación de estrés como es el ejercicio. Además, al objeto de que el lector no tenga una información meramente teórica, se presentan las aplicaciones prácticas que se pueden denominar, fisiológica y patológica.La ergoespirometría permite cuantificar de forma bastante, fiable la capacidad máxima y submáxima del ejercicio, permitiendo caracterizar fisiológicamente a cualquier persona interesada en realizar y controlar su estado físico. La rutina de interpretación es valorar el VO2 máximo, como parámetro máximo y la transición aeróbica-anaeróbica, con los dos valores umbral: aeróbico y anaeróbico. Si interesante es la valoración fisiológica, más lo es aún, la aplicación de la ergoespirornetría al diagnóstico y valoración de patología cardiorrespiratoria. Sin embargo, es la menos desarrollada en nuestro país. Por ello, el objetivo de este trabajo es estimular el interés del médico deportivo por la utilidad de esta "herramienta" diagnóstica (AU)

Effect of amphotericin B on dopachrome tautomerase activity and other melanogenic parameters in cultured B16/F10 melanoma cells.

The antifungal reagent Fungizone (amphotericin B and deoxycholate) caused an activation in dopachrome tautomerase and dopa oxidase activities of B16/F10 melanoma cells at the routine concentration (2.5 micrograms/ml) used for preventing molds and yeast growth in cultures of animal cells. However, higher amphotericin B concentrations caused a significant cell death and the inhibition of enzymatic activities. At the optimal concentration of Fungizone, the enzymatic activities and melanin content were augmented as incubation time increased. The detergent sodium deoxycholate alone exerted no effect on these melanogenic parameters, eliminating the possibility that this detergent was partially responsible for melanogenic modifications produced by Fungizone. After withdrawal of Fungizone from the reaction medium, the recovery of melanogenic parameters to normal values was slower for DCT than for tyrosinase. The behavior of dopa oxidase was very similar to that reported by Johnson and Bagnara (Pigment Cell Res. 3, 173-175) for tyrosine hydroxylase.