Mast Cell Changes the Phenotype of Microglia via Histamine and ATP.

BACKGROUND/AIMS: Microglia are the dynamic motile phagocytes of the brain considered the first line of defense against threats or disturbances to the Central Nervous System (CNS). Microglia help orchestrate the immunological response by interacting with others immune cells. Mast cells (MCs) are effector cells of the innate immune system distributed in all organs and vascularized tissues, brain included. Several molecular mechanisms for potential interactions between MCs and microglia have been determined. However, the effect of MCs on regulated exocytosis and phagocytic clearance in microglia has not been explored. METHODS: Cocktails of MCs mediators (MCM) obtained at 37°C and 53°C were used to induce microglia activation. Changes in intracellular calcium [Ca2+]i and ATP release were studied by calcium and quinacrine fluorescence imaging. Fluorescent latex beads were used to assay phagocytosis in microglia after MCM treatment and compared to that measured in the presence of histamine, ATP and lipopolysaccharide (LPS). Iba-1 expression and area were quantified by immunofluorescence and histamine levels evaluated by ELISA techniques. RESULTS: Local application onto microglia of the MC mediator cocktail elicited Ca2+ transients and exocytotic release associated with quinacrine dye de-staining. Ca2+ signals were mimicked by histamine and blocked by the H1 receptor (H1R) antagonist, cetirizine. Hydrolysis of ATP by apyrase also affected Ca2+ transients to a lesser extent. Iba-1 fluorescence, cell area and phagocytosis were enhanced by histamine through H1R. However, ATP prevented iba-1 expression and microglial phagocytosis. MCM showed combined effects of histamine and ATP, increasing the number of internalized microbeads per cell and area without raising iba1 expression. CONCLUSION: Our results highlight the relevance of MC-derived histamine and ATP in the modulation of secretory and phagocytic activities that would explain the heterogeneity of microglial responses in different pathological contexts.

Utero-ovarian anastomoses and their influence on uterine fibroid embolization.

PURPOSE: To correlate clinical outcomes after uterine artery embolization (UAE) performed to treat uterine fibroids with the presence of varying types of utero-ovarian anastomoses (UOA). MATERIALS AND METHODS: A retrospective analysis was performed of all uterine angiograms from 202 patients (mean age 42 y, range 28-54 y) who underwent UAE because of heavy menstrual bleeding, dysmenorrhea, or anemia or a combination of these symptoms. UOA were classified as absent or present, unilateral or bilateral. The effects of UOA on long-term outcomes (clinical endpoints such as control of bleeding and pain) and complications (amenorrhea) were assessed statistically using Kaplan-Meier curves and χ(2) and log-rank tests. RESULTS: Of the UOA in 104 women, 38 anastomoses were bilateral, and 66 were unilateral. Type III was the most common type of anastomosis (66 cases) followed by type Ia (22 cases) and type Ib (18 cases); there were no type II anastomoses. Amenorrhea was reported in 27 (14%) women at 5-year follow-up after UAE (only 3% in women < 45 y old). There were 10 cases of clinical failure with a median follow-up of > 4 years. Bilateral or unilateral presence of UOA had no statistically significant effect on outcomes or on complications. CONCLUSIONS: Recurrence rates, clinical failure, and amenorrhea after UAE do not seem to be influenced by the presence or absence of UOA. However, further studies are needed to confirm these findings.

Pharmacological utility of melatonin in the treatment of septic shock: experimental and clinical evidence.

Sepsis is a major cause of mortality in critically ill patients and develops as a result of the host response to infection. In recent years, important advances have been made in understanding the pathophysiology and treatment of sepsis. Mitochondria play a central role in the intracellular events associated with inflammation and septic shock. One of the current hypotheses for the molecular mechanisms of sepsis is that the enhanced nitric oxide (NO) production by mitochondrial nitric oxide synthase (mtNOS) leads to excessive peroxynitrite (ONOO-) production and protein nitration, impairing mitochondrial function. Despite the advances in understanding of its pathophysiology, therapy for septic shock remains largely symptomatic and supportive. Melatonin has well documented protective effects against the symptoms of severe sepsis/shock in both animals and in humans; its use for this condition significantly improves survival. Melatonin administration counteracts mtNOS induction and respiratory chain failure, restores cellular and mitochondrial redox status, and reduces proinflammatory cytokines. Melatonin clearly prevents multiple organ failure, circulatory failure, and mitochondrial damage in experimental sepsis, and reduces lipid peroxidation, indices of inflammation and mortality in septic human newborns. Considering these effects of melatonin and its virtual absence of toxicity, the use of melatonin (along with conventional therapy) to preserve mitochondrial bioenergetics as well as to limit inflammatory responses and oxidative damage should be seriously considered as a treatment option in both septic newborn and adult patients. This review summarizes the data that provides a rationale for using melatonin in septic shock patients.

Estudio Transversal Hispano-Ecuatoriano: Discapacidades derivadas de Ictus cerebral / Hispano- Ecuadorian Cross-Sectional Study: Disabilities derived from cerebral stroke

INTRODUCCIÓN: En la actualidad el ictus es considerado una de las principales causas de discapacidad en el mundo. Globalmente 5 millones de personas adquieren discapacidad permanente cada año por esta causa; hasta el 30% de los pacientes afectados padecen algún tipo de discapacidad. El manejo temprano del paciente puede disminuir las secuelas derivadas de las lesiones. El objetivo de este estudio es conocer si existen diferencias en las discapacidades derivadas de ictus entre las ciudades de Madrid (España) y Cuenca (Ecuador), en relación a una atención temprana programada. MATERIALES Y MÉTODOS: El presente, es un estudio observacional, descriptivo, de corte transversal, multicéntrico. La muestra estuvo conformada por 40 pacientes diagnosticados de ACV, 20 pertenecientes al Grupo Cuencano, de Ecuador (GC) y 20 al Grupo Matritense, de España (GM). Los datos fueron obtenidos de las historias clínicas. Se compararon ambos grupos mediante la prueba Chi-cuadrado (X2) de Pearson para cada variable estudiada. RESULTADOS: En el GM el 80% de los ACV fueron de origen isquémico, en el GC fueron el 90%, sin asociación significativa. En los dos grupos el mayor porcentaje de secuelas se dieron por afectación del territorio de la arteria cerebral media (ACM). No se evidenció diferencia significativa en el porcentaje de discapacidades derivadas de ictus entre los grupos, el grupo matritense de España presentó una menor tasa de discapacidades derivadas que fue del 45%, frente al grupo cuencano de Ecuador que tuvo un 76% de capacidades derivadas, pero la diferencia no fue significativa (p=0.069); sin embargo la asociación entre el porcentaje de exitus entre los grupos si tuvo asociación estadísticamente significativa (p=0.003). CONCLUSIÓN: No se encontró asociación significativa en cuanto a etiología, factores de riesgos y características clínicas del Ictus entre los grupos. No hay diferencias significativas en las secuelas derivadas de ictus entre los grupos, pero si hay diferencias significativas en relación al porcentaje de exitus con la aplicación de un programa tipo "Código Ictus".

BACKGROUND: Currently, stroke is one of the main causes of disability in the world. Globally 5 million people acquire permanent disability each year for this cause; up to 30% of affected patients suffer from some type of disability. Early management of the patient can reduce the sequelae derived from the injury. The aim of this study is to find out if there are differences in disabilities derived from strokes, between the cities of Madrid (Spain) and Cuenca (Ecuador), in association with programmed early patient care. METHODS: This is an observational, descriptive, cross-sectional, multicenter study. The sample consisted of 40 patients diagnosed with stroke, 20 from Cuenca, Ecuador, and 20 from Madrid, Spain. Data was obtained from the patient's medical records. Both groups were compared using Pearson's Chi-square test (Χ2) for each studied variable. RESULTS: in the Madrid Group 80% of the strokes were ischemic, in the Cuenca Group 90% of the strokes were ischemic, there is not significant association. In both groups the highest percentage of sequelae occurred due to injury of the middle cerebral artery (MCA). There was no significant difference in the percentage of disabilities derived from stroke between the groups, the Madrid Group had a lower rate of derived disabilities (45%), compared to Cuenca Group (76%), but the differences was not significant (p=0.069); however, the association between the death percentage among the groups was statistically significant (p=0.003). CONCLUSION: No significant association was found in terms of etiology, risk factors and clinical characteristics of stroke between the groups. There are no significant differences in the sequelae derived from stroke between the groups, but there is significant difference in terms of death percentage between the groups, with the application of "Código Ictus" type of program.

Melatonin as pharmacologic support in burn patients: a proposed solution to thermal injury-related lymphocytopenia and oxidative damage.

OBJECTIVE: To review the data that support the clinical use of melatonin in the treatment of burn patients, with special emphasis on the stimulation of the oxidative defense system, the immune system, circadian rhythm of sleep/wakefulness, and the reduction in the toxicity of therapeutic agents used in the treatment of burn victims. DATA SOURCE: A MEDLINE/PubMed search from 1975 to July 2006 was conducted. STUDY SELECTION: The screening of the literature was examined using the key words: burn patients, lymphocytopenia, skin oxidative stress, antioxidant, melatonin, and free radicals. DATA EXTRACTION AND SYNTHESIS: Thermal injury often causes damage to multiple organs remote from the original burn wound and may lead to multiple organ failure. Animal models and burn patients exhibit elevated free radical generation that may be causative in the local wound response and in the development of burn shock and distant organ injury. The suppression of nonspecific resistance and the disturbance in the adaptive immune system makes burn patients vulnerable to infections. Moreover, there is loss of sleep and the toxicity produced by drugs habitually used in the clinic for burn patients. Melatonin is a powerful antioxidant and is a potent protective agent against damage after experimental thermal injury. Some actions of melatonin as a potential supportive pharmacologic agent in burn patients include its: role as a scavenger of both oxygen and nitrogen-based reactants, stimulation of the activities of a variety of antioxidative enzymes, reduction in proinflammatory cytokines, inhibition of adhesion molecules, chronobiotic effects, and reduction in the toxicity of the drugs used in protocols to treat thermal injury patients. CONCLUSIONS: These combined actions of melatonin, along with its low toxicity and its ability to penetrate all morphophysiologic membranes, could make it a ubiquitously acting and highly beneficial molecule in burn patients.