Injuries according to the percentage of adult height in an elite soccer academy.

OBJECTIVES: This study aimed to ascertain if there is a defined pattern of injury related to the percentage of attained adult height and classify injuries according to maturity status bands. DESIGN: Prospective cohort study. METHODS: From 1998-2019, 63 elite male soccer players of at least the U12 category from a Spanish LaLiga club's academy were followed until reaching their final height. Medical staff recorded injuries following the FIFA consensus and measured height 2-3 times per season. The percentage of adult height at which each injury occurred was calculated using the player's closest height to the injury and his final adult height. Injuries were classified in maturity bands, pre-peak-height-velocity (PHV) <88%, circa-PHV 88%-96%, and post-PHV >96%. RESULTS: There were 509 injuries among the 63 players. Growth-related injuries occurred at a median (IQR) of 91.2% (86.7%-95.2%) of adult height, predominating in pre-PHV and PHV bands. Muscle injuries predominantly occurred at post-PHV, with 77.78% of those conditions occurring within that time frame and at 98.7% (96%-99.5%) of adult height. Likewise, knee and ankle joint/ligament injuries predominated at post-PHV (87% and 65% of total cases, respectively) occurring at 99.0% (97.9%-99.9%) and 98.4% (89.2%-99.4%) of adult height, respectively. CONCLUSIONS: Injuries follow a specific pattern according to the percentage of adult height.

Contribution of dopamine to mitochondrial complex I inhibition and dopaminergic deficits caused by methylenedioxymethamphetamine in mice.

Methylenedioxymethamphetamine (MDMA) causes a persistent loss of dopaminergic cell bodies in the substantia nigra of mice. Current evidence indicates that MDMA-induced neurotoxicity is mediated by oxidative stress probably due to the inhibition of mitochondrial complex I activity. In this study we investigated the contribution of dopamine (DA) to such effects. For this, we modulated the dopaminergic system of mice at the synthesis, uptake or metabolism levels. Striatal mitochondrial complex I activity was decreased 1 h after MDMA; an effect not observed in the striatum of DA depleted mice or in the hippocampus, a dopamine spare region. The DA precursor, L-dopa, caused a significant reduction of mitochondrial complex I activity by itself and exacerbated the dopaminergic deficits when combined with systemic MDMA. By contrast, no damage was observed when L-dopa was combined with intrastriatal injections of MDMA. On the other hand, dopamine uptake blockade using GBR 12909, inhibited both, the acute inhibition of complex I activity and the long-term dopaminergic toxicity caused by MDMA. Moreover, the inhibition of DA metabolism with the monoamine oxidase (MAO) inhibitor, pargyline, afforded a significant protection against MDMA-induced complex I inhibition and neurotoxicity. Taken together, these findings point to the formation of hydrogen peroxide subsequent to DA metabolism by MAO, rather than a direct DA-mediated mitochondrial complex I inhibition, and the contribution of a peripheral metabolite of MDMA, as the key steps in the chain of biochemical events leading to DA neurotoxicity caused by MDMA in mice.

Effects of antalarmin and nadolol on the relationship between social stress and pulmonary metastasis development in male OF1 mice.

It has been found that acute social stress in male OF1 mice produced a general immunosuppression and increased B16F10 tumor development. This study examined the effects of blocking either the hypothalamic-pituitary-adrenocortical (HPA) axis or the sympathetic adrenomedullary (SAM) system on the impact of such stress on tumor development. Naive male OF1 mice were individually housed for 12 days before being inoculated with tumor cells or vehicle. Six days later, tumor-bearing mice were inoculated with antalarmin (a corticotropin-releasing factor receptor antagonist), nadolol (a beta-adrenergic antagonist) or vehicle. All these mice were subjected to social stress by pairing them for 24h with counterparts selected for their high and homogeneous levels of aggressiveness. The pairs were only in physical contact for three 5-min periods, being in sensory contact for the rest of this period. One hour after social stress, serum corticosterone and IFN-gamma levels were analyzed in each experimental group. Fifteen days later, lungs were removed to determine the number of metastatic foci with their areas, and blood samples were taken to assess serum titers of corticosterone and IFN-gamma. Both antalarmin and nadolol-treated mice developed significantly fewer metastatic foci with smaller areas than vehicle-treated subjects although only the group treated with antalarmin had reduced corticosterone levels. This study confirms that social stress has complex effects on immune system and tumor development that are not simply linked to corticosterone titers.

Competencias para el desarrollo de la atención farmacéutica / Competencies required for the practice of pharmaceutical care

Objetivo: Elaborar y consensuar una propuesta de competencias genéricas y específicas para dirigir el aprendizaje en atención farmacéutica en la asignatura Estancias. Método: Partiendo del «Libro blanco del título de grado en Farmacia», se elaboró una propuesta de competencias que se sometió a análisis mediante entrevistas individuales a cinco profesionales farmacéuticos. Posteriormente, se realizó una consulta mediante cuestionarios a 47 farmacéuticos tutores de Estancias, referida a su grado de acuerdo con cada una de las competencias definidas y al grado de incidencia de actividades realizadas en el centro, dirigidas a su adquisición. Resultados: Se elaboró una propuesta de 17 competencias genéricas y 14 específicas. Respondió al cuestionario el 65,95 % de los tutores. Las competencias genéricas que alcanzaron el máximo grado de acuerdo entre los tutores fueron: «preocuparse por la calidad» (78,6%) y «manejar los conocimientos básicos de la profesión» (78,6%). De las específicas destacaron: «manejar la receta/orden médica» (76,7%), el «conocimiento y habilidades que garanticen el uso seguro del medicamento» (70%) y «comunicarse con pacientes/profesionales» (70%). Entre las competencias específicas, los valores inferiores en el porcentaje de máximo grado de acuerdo correspondieron a «utilizar y elaborar protocolos para la dispensación» (40%) y «asumir responsabilidad del seguimiento farmacoterapéutico/resultados de salud» (46,7%). Se encontró una correlación positiva entre el grado de acuerdo con las competencias propuestas y el grado de incidencia en la realización de actividades dirigidas a su adquisición en 29 de las 31 competencias. Conclusiones: Las competencias genéricas y específicas valoradas proporcionan una herramienta docente válida para dirigir el aprendizaje en atención farmacéutica durante las Estancias (AU)

Objective: To develop and reach a consensus on a proposal for generic and specific competencies for students receiving practical training in pharmaceutical care. Method: A proposal concerning competencies was developed within the framework of the White Book on Pharmacy Education. This proposal was discussed during individual interviews with five pharmacy professionals. Later, an assessment questionnaire was sent to 47 tutors in pharmacy training, asking them about their level of agreement with each of the competencies defined and the activities carried out in their practice center to help students to achieve each competency. Results: A proposal including 17 generic and 14 specific competencies was prepared. Thirty-one pharmacy tutors (65.95%) responded to the questionnaire. The highest rated generic competencies according to the maximum level of agreement were: concern for quality (78.6%) and management of the basic knowledge of the profession (78.6%). Among the specific competencies that stood out were: management of doctors’ prescriptions (76.7%), knowledge and skills that guarantee the safe use of drugs (70%) and communication with patients/ other professionals (70%). Among the specific competencies that received the lowest scores in terms of the level of agreement were: management and development of protocols for dispensing drugs (40%) and assumption of responsibility for drug therapy follow-up and health outcomes (46.7%). A positive correlation between the level of agreement with the competencies and the activities carried out to help students to achieve them was found in 29 out of the 31 competencies. Conclusion: The generic and specific competencies assessed provide a valid educational tool for guiding pharmaceutical care education in the student receiving practical pharmaceutical training (AU)

Time-dependent behavioral, neurochemical, and immune consequences of repeated experiences of social defeat stress in male mice and the ameliorative effects of fluoxetine.

This study attempted to determine whether differing numbers of days of repeated defeat experience altered behavior, immune measures, and neuroendocrine mediators in mice. OF1 male mice were socially stressed by repeated experiences of defeat in a sensorial contact model. Subjects exposed to nine defeats showed more stretch-attend postures and fewer active defense elements than counterparts exposed to 23 defeats. Submissive subjects with nine experiences of defeat also had a lower splenocyte proliferative response than unmanipulated controls. The proliferation index progressively increased but at a higher rate in manipulated controls than in socially stressed subjects, resulting in a significant immunosuppressive effect after 23 days of exposure to social stressors. Nine days of such exposure resulted in higher hypothalamic ratios of serotonin and dopamine to their major metabolites than in unmanipulated or manipulated controls and subjects socially stressed for 23 days. The data generally indicate that the acute social stressors (such as nine defeats) produce a profile of behavioral and physiological variables characteristic of a state of anxiety. The proliferation index was also lower after 52 days of social stress than in manipulated controls. Fluoxetine treatment appeared to have an anxiolytic effect, reducing immobility, and even seemed to protect subjects from the immune impairment and endocrine alteration caused by social stressors. The results generally provide clues that improve our knowledge of the consequences of social stressors and their possible treatment.

Behavioral and neurochemical responses in mice bearing tumors submitted to social stress.

Through the proinflammatory cytokines secreted in response to inflammation or injury, the immune system produces physiological and behavioral alterations. This study analyzes the effects on behavior, mononuclear proliferative response and central monoamine activity in response to the inoculation of tumor cells in mice submitted to social stress. Two groups of male OF1 mice were used, one of which was inoculated with B16 melanoma cells. Both groups were subdivided into two new groups, with one being submitted to social stress through sensory contact model with a selected aggressive subject, and the other being handled without social interaction. Subjects were exposed to social stress for a 24-h period, with three 5 min intervals of direct physical interaction, where the behavior was recorded and assessed. One hour after the stress and/or handling, they were put down and samples taken for physiological assessment. Significant behavioral changes were found in subjects with implanted tumors, mainly characterized by an increase in avoidance behavior and a decrease in immobility, defense-submission and non-social exploration behavior, coupled with an increase in the spleen mononuclear cell proliferative response. Similarly, an increase was observed in the density of dopamine(2) (D(2))-receptors in the striatum (SRT) and an increase in dopaminergic (DOPAC/DA) and serotonergic (5HIAA/5HT) turnover in the hypothalamus. The increase in the density of D(2)-receptors in the SRT coincides with the decrease in some behaviors with a predominant motor component. The results indicate significant changes in the defensive strategy used to cope with situations of intense social stress in mice bearing tumors.

Ecstasy-induced toxicity in rat liver.

BACKGROUND/AIMS: The aim of the present study was to examine the effects of single and repeated administration of 3,4-methylenedioxyme-thamphetamine (MDMA, "ecstasy") on rat liver. METHODS: Animals were given an acute (20 mg/kg) and repeated (20 mg/kg, b.i.d., for 4 consecutive days) intraperitoneal dose of MDMA, and at various times after administration the hepatic and serum determinations were made. RESULTS: The effect of acute MDMA administration included increased triglyceride and cholesterol levels and an increase in all enzyme activities 6 h post administration. The toxic effect of MDMA was also observed in other hepatic processes. Glycogen content showed a marked decrease, which was accompanied by a decrease in serum glucose levels. No significant changes in lipid peroxidation and hepatic GSH content were observed. In contrast, multiple MDMA administration produced some evidence of oxidative stress, namely, increased MDA content and decreased GSH content, a small decrease in liver glycogen at 3 h recovering 6 h post dose, no effect on blood glucose and increased AST and ALP activities but no effects on ALT activity. Seven days after the last MDMA injection a tendency towards recovery was shown. CONCLUSION: Our results show that the liver toxicity caused by MDMA administration involves several mechanisms.

3,4-Methylenedioxymethamphetamine (ecstasy)-induced hepatotoxicity: effect on cytosolic calcium signals in isolated hepatocytes.

AIMS/BACKGROUND: Hepatocellular damage has been reported as a consequence of 3,4-methylenedioxymethamphetamine (MDMA) intake. However, little is known about the cellular mechanisms involved. The present study was undertaken to evaluate the effects of MDMA on cell viability as well as free calcium levels ([Ca2+]i) in short-term cultured hepatocytes. Reduced glutathione (GSH), adenosine-5'-triphosphate (ATP) and lipid peroxidation were investigated to evaluate the toxic effect of MDMA, in vitro, using freshly isolated rat hepatocytes. METHODS: In order to measure cytosolic free Ca2+ concentrations ([Ca2+]i), rat hepatocytes were loaded with the Ca2+ indicator fura-2-acetoxymethylester (fura-2-AM). RESULTS: A sustained rise of ([Ca2+]i) after incubation with MDMA was the most noteworthy finding. In Ca2+-free medium, MDMA caused a reduced increase of ([Ca2+]i). On the other hand, MDMA (0.1-5 mM) induced a concentration-dependent and time exposure-dependent GSH and ATP depletion. Although it did not reach statistical significance, GSH deficits were accompanied by a tendency to increase lipid peroxidation 3 h after MDMA incubation. CONCLUSIONS: The above data suggest that the marked rise of ([Ca2+]i) and subsequent ATP and GSH depletion can lead to a rapid decrease in cell viability.

3,4-methylenedioxymethamphetamine ("Ecstasy") stimulates the expression of alpha1(I) procollagen mRNA in hepatic stellate cells.

3,4-Methylenedioxymethamphetamine, MDMA ("Ecstasy"), has been previously shown to produce cell necrosis and fibrosis in the liver. Our aim was to study the effect of MDMA on the type I collagen production by a cell line of hepatic stellate cells (HSC), the cell type mainly responsible for collagen synthesis in the liver. We demonstrated that MDMA increases alpha1(I) procollagen mRNA levels and that this increase correlates with glutathione depletion and enhanced hydrogen peroxide production by HSC. Pre-treatment with either glutathione monoethyl ester or deferoxamine prevents the MDMA-induced alpha1(I) procollagen mRNA expression, indicating oxidative stress to be a mediator of this effect. Lipid peroxidation was not detected in MDMA-treated cells and therefore does not seem to be involved in the pro-fibrogenic action of MDMA on HSC.

Effects of chronic mild stress (CMS) and imipramine administration, on spleen mononuclear cell proliferative response, serum corticosterone level and brain norepinephrine content in male mice.

There is increasing evidence that stress and emotional reactions produce changes in various immune processes. These changes may be due to alterations of the stress responses endocrine and for autonomic mediating mechanisms. In order to study such effects, the impact of chronic mild stress (CMS) application, and of subsequent imipramine administration were studied on the spleen mononuclear cell proliferative response period. OFI strain male mice were subjected to 4 or 7 weeks of CMS. The effects of these treatments on serum corticosterone levels and hypothalamic and hippocampal norepinephrine (NE) contents were also assessed. Subjects submitted to CMS had a higher spleen mononuclear cell proliferative response after either treatment duration. Imipramine treatment diminished this response enhancement in CMS exposed animals, but did not alter the proliferative responses of control subjects. Serum corticosterone levels, as well as hypothalamic and hippocampal nonrepinephrine contents did not significantly vary between groups. Taken together, these results suggest that CMSs effects on immune reactivity are not related to serum glucocorticoids or NE changes in these locations associated with the hypothalamic-pituitary- adrenocortical (HPA) axis.