Impacto del estrés oxidativo sobre las lesiones cutáneas causadas por radiaciones ionizantes

RESUMEN Los efectos inducidos por exposición de manera accidental o terapéutica a dosis de radiaciones ionizantes inducen varios eventos celulares que afectan el proceso de cicatrización de la piel, y tiene gran impacto en la prognosis y supervivencia de individuos afectados. La información existente sobre los efectos nocivos por altas exposiciones a radiaciones proviene a partir de los accidentes ocurridos por las bombas atómicas en Hiroshima y Nagasaki produciendo problemas de salud por leucemias y linfomas en los sobrevivientes. El síndrome de radiación aguda (SRA) generalmente inicia durante las dos horas inmediatas posteriores a la exposición, y la severidad de las lesiones depende de la dosis y del tiempo de exposición. El desarrollo de las lesiones por el daño como efectos tardíos a exposiciones por radiaciones es más complejo y determina no únicamente el daño al parénquima celular sino también se presentan daños en el tejido vascular y en otros tejidos de soporte. Al menos parcialmente estos eventos se presentan a consecuencia del estrés oxidativo generado por el excesivo incremento de especies reactivas del oxígeno (EROs). Se han estado estudiando componentes comerciales como blancos potenciales para la prevención de los daños causados por radiaciones en piel que tienen una amplia actividad contra múltiples citocinas involucradas en los procesos de la lesión cutánea y por otro lado se están estudiando fármacos que reaccionan con los radicales libres o indirectamente inhiben la expresión de las enzimas que generan la producción de EROs o bien aumentan la expresión de enzimas antioxidantes intracelulares

Micronutrient fortification of food and its impact on woman and child health: A systematic review

Background: Vitamins and minerals are essential for growth and metabolism. The World Health Organization estimates that more than 2 billion people are deficient in key vitamins and minerals. Groups most vulnerable to these micronutrient deficiencies are pregnant and lactating women and young children, given their increased demands. Food fortification is one of the strategies that has been used safely and effectively to prevent vitamin and mineral deficiencies.Methods: A comprehensive search was done to identify all available evidence for the impact of fortification interventions. Studies were included if food was fortified with a single, dual or multiple micronutrients and impact of fortification was analyzed on the health outcomes and relevant biochemical indicators of women and children. We performed a meta-analysis of outcomes using Review Manager Software version 5.1.Results: Our systematic review identified 201 studies that we reviewed for outcomes of relevance. Fortification for children showed significant impacts on increasing serum micronutrient concentrations. Hematologic markers also improved, including hemoglobin concentrations, which showed a significant rise when food was fortified with vitamin A, iron and multiple micronutrients. Fortification with zinc had no significant adverse impact on hemoglobin levels. Multiple micronutrient fortification showed non-significant impacts on height for age, weight for age and weight for height Z-scores, although they showed positive trends. The results for fortification in women showed that calcium and vitamin D fortification had significant impacts in the post-menopausal age group. Iron fortification led to a significant increase in serum ferritin and hemoglobin levels in women of reproductive age and pregnant women. Folate fortification significantly reduced the incidence of congenital abnormalities like neural tube defects without increasing the incidence of twinning. The number of studies pooled for zinc and multiple micronutrients for women were few, though the evidence suggested benefit. There was a dearth of evidence for the impact of fortification strategies on morbidity and mortality outcomes in women and children.Conclusion: Fortification is potentially an effective strategy but evidence from the developing world is scarce. Programs need to assess the direct impact of fortification on morbidity and mortality

A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial

BACKGROUND: Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, phisical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms. Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment. Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children–Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. METHODS/DESIGN: A phase II randomized, double-blind pilot clinical trial. Scope: male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. Instrumentation: clinical data, blood analysis, Wechsler Intelligence Scale for Children–Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. DISCUSSION: A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and α-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01329770 (29 March 2011

Characteristics of children with acute lymphoblastic leukemia presenting with arthropathy

Acute lymphoblastic leukemia (ALL) is the most common childhood neoplasia and may present with arthralgia and arthritis, with the risk of misdiagnosis and diagnostic delay. We describe in detail arthropathy (arthritis/arthralgia) among children with leukemia as the children's laboratory results, misdiagnosis, and treatment before the diagnosis of ALL and the diagnostic delay. In this retrospective cohort study, we reviewed records of 286 children aged 1-15 years diagnosed with ALL from January 1992 to March 2013. We identified 26 children with arthralgia and 27 children with arthritis. The majority of the children had one or two joints involved (arthralgia 72%, arthritis 42%), and most often hips and knees. Morning stiffness was not reported. Imaging of affected joints was included in the initial workup of 77% of children with ALL and arthropathy, and 66% was abnormal. Misdiagnosis as JIA occurred in 26% and 71% of these children received treatment with intraarticular corticosteroids. The diagnostic delay was 3 weeks longer for the children with arthritis than those with arthralgia (median 54 vs 36 days), primarily as a consequence of a longer first doctor's delay. Compared to the children with arthralgia, the children with arthritis were more often misdiagnosed and treated with intraarticular steroid before the diagnosis of ALL. They also had longer diagnostic delay, primarily as a consequence of a longer first doctor's delay.</p

Tracking of autologous VSOP-labeled mesenchymal stem cells in the sheep brain using 3.0 T MRI

Assessment of biodistribution and monitoring of cell migration processes in vivo are essential for the safety of novel cell-based therapies for ischemic stroke and early-stage clinical trials, but are mainly lacking investigation in large animal models which are closer to the situation found in human patients. This chapter reports a series of experiments which establish a MRI-sensitive labeling procedure for autologous ovine mesenchymal stem cells (MSC) and the assessment of in vivo and in vitro detection limits of the cells at 3.0 T. Cell migration was monitored after intravenous transplantation following experimental stroke in sheep. Cell detection was feasible at 3.0 T with detection limits defined at 500 cells in vitro and 1,000 cells after local stereotaxic administration in vivo. No signs for MSC homing toward the ischemic lesion were observed after systemic cell delivery. Iron-containing cells were identified in the lung and skin wounds, but not in brain parenchyma after intravenous cell delivery. These findings are in contrast to results obtained in small animal models and may indicate significant differences of MSC behavior in large organisms. They also revealed the necessity for sensitivity-enhanced MRI sequences for improved cell detection in large animals