Gelatinasas como marcadores de consumo crônico de álcool: Um estúdio piloto em Urugua

El consumo crónico de alcohol en Uruguay es un problemacreciente, sin embargo, las determinaciones de biomarcadoresconsensuados no se realizan sistemáticamente ni se investiganotros marcadores potenciales. Para validar la hipótesis de quelas metaloproteinasas de matriz con actividad gelatinasa sonbiomarcadores de consumo crónico de alcohol, se evaluaronmuestras de sangre de 100 alcohólicos que comenzaron aatenderse en la Unidad de Trastornos Relacionados con el Alcoholy de 50 donantes sanos no alcohólicos. Las muestras de alcohólicospresentaron actividad de gelatinasas que triplicaron la de loscontroles y aumentos pequeños pero significativos en los niveles degama-glutamil transferasa, aspartato-aminotransferasa y volumencorpuscular medio. Los valores de transferrina deficiente encarbohidratos fueron menores en alcohólicos que en controles. Estosresultados permiten proponer a las gelatinasas como los indicadoresmás sensibles del consumo sostenido de alcohol en la poblaciónanalizada ya que las enzimas hepáticas y el volumen corpuscularmedio muestran una tendencia acorde con la literatura pero noalcanzaron valores asociados a la patología. Dado que la transferrinadeficiente en carbohidratos es considerada el biomarcador indirectomás sensible y específico de consumo crónico de alcohol, los valoresmenores obtenidos en alcohólicos respecto de controles sugierenproblemas metodológicos que podrían subsanarse aplicando otrastécnicas de medida o la presencia de interferencias que deben seridentificadas. Finalmente, estos hallazgos justifican una extensiónde este trabajo piloto, así como estudios adicionales centrados enla participación de las metaloproteinasas de matriz con actividadgelatinasa en las cascadas de daño asociadas al consumo crónicode alcohol.Chronic alcohol consumption in Uruguay is a growing problem, however, determinations of consensual biomarker are not performed systematically neither potential markers are explored. To validate the hypothesis that matrix metalloproteinases with gelatinase activity are biomarkers of chronic alcohol consumption, blood samples of 100 alcoholics that began medical treatment at the Unidad de Trastornos Relacionados con el Alcohol and 50 healthy non-alcoholic donors were evaluated. Alcoholic samples showed gelatinase activity that tripled that of controls and small but significant increases in levels of gamma-glutamyl transferase, aspartate-aminotransferase and mean cellular volume. Carbohydrate deficient transferrin values were lower in alcoholics than in controls. These results allow proposing gelatinases as the most sensitive indicators of sustained alcohol consumption in the population analyzed since hepatic enzymes and mean cellular volume showed a tendency consistent with the literature but did not reach values associated with the pathology. Since carbohydrate-deficient transferrin is considered the most sensitive and specific indirect biomarker of chronic alcohol consumption, lower values in alcoholics related to controls suggest methodological problems that could be solved by applying other measurement techniques or the presence of yet unknown interferences. Finally, these findings justify an extension of this pilot work, as well as additional studies focused on the participation of matrix metalloproteinases with gelatinase activity in the cascades of damage associated with chronic alcohol consumption.O consumo crônico de álcool no Uruguai é um problema crescente, no entanto, as determinações consensuais de biomarcadores não são realizadas sistematicamente ou os potenciais marcadores são explorados. Para validar a hipótese de que as metaloproteinases de matriz com atividade gelatinase são biomarcadores do consumo crônico de álcool, foram avaliadas amostras de sangue cd 100 alcoólatras que começaram a ser tratadas na Unidad de Trastornos Relacionados con el Alcohol e 50 doadores não-alcoólatras saudáveis. As amostras alcoólicas apresentaram atividade de gelatinase que triplicou a dos controles e pequenos más significativos aumentos nos níveis de gama-glutamil transferase, aspartato-aminotransferase e volume médio celular. Os valores de transferrina deficientes em carboidratos foram menores nos alcoolistas que nos controles. Esses resultados permitem que as gelatinases sejam propostas como os indicadores mais sensíveis do consumo sustentado de álcool na população analisada, uma vez que as enzimas hepáticas e o volume celular médio apresentam uma tendência consistente com a literatura, mas não alcançaram valores associados à patologia. Como a transferrina deficiente em carboidratos é considerada o biomarcador indireto mais sensível e específico do consumo crônico de álcool, os valores mais baixos em alcoólatras do que em controles sugerem problemas metodológicos que poderiam ser sanados pela aplicação de outras técnicas de mensuração a presença de interferências que deben identificadas. Finalmente, esses achados justificam uma extensão deste trabalho piloto, bem como estudos adicionais voltados para a participação de metaloproteinases de matriz com atividade de gelatinase nas cascatas de danos associados ao consumo crônico de álcool.Fil: Marco, Marta. Universidad de la República. Facultad de Química; UruguayFil: Boragno, Daniela. Universidad de la República. Facultad de Química; UruguayFil: Rodriguez, Paola. Universidad de la República. Facultad de Química; UruguayFil: Mestre Cordero, Victoria Evangelina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiología Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Pereira, Natalia Romina. Universidad de la República. Facultad de Química; UruguayFil: Berasain, Patricia. Universidad de la Republica. Facultad de Medicina. Hospital de Clínicas "dr. Manuel Quintela".; UruguayFil: Cadenas, Florencia. Universidad de la Republica. Facultad de Medicina. Hospital de Clínicas "dr. Manuel Quintela".; UruguayFil: Rodriguez, Cecilia. Universidad de la Republica. Facultad de Medicina. Hospital de Clínicas "dr. Manuel Quintela".; UruguayFil: Moreira, Alejandra. Universidad de la Republica. Facultad de Medicina. Hospital de Clínicas "dr. Manuel Quintela".; UruguayFil: Simoff, Ximena. Universidad de la Republica. Facultad de Medicina. Hospital de Clínicas "dr. Manuel Quintela".; UruguayFil: Bianchi, Virginia. Universidad de la Republica. Facultad de Medicina. Hospital de Clínicas "dr. Manuel Quintela".; UruguayFil: Barindelli, Anna. Universidad de la Republica. Facultad de Medicina. Hospital de Clínicas "dr. Manuel Quintela".; UruguayFil: Fielitz, Pablo. Universidad de la Republica. Facultad de Medicina. Hospital de Clínicas "dr. Manuel Quintela".; UruguayFil: Olivera Bravo, Silvia. Universidad de la República. Facultad de Química; Urugua

Neuroprotective effects of violacein in a model of inherited amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive death of motor neurons and muscle atrophy, with defective neuron-glia interplay and emergence of aberrant glial phenotypes having a role in disease pathology. Here, we have studied if the pigment violacein with several reported protective/antiproliferative properties may control highly neurotoxic astrocytes (AbAs) obtained from spinal cord cultures of symptomatic hSOD1G93A rats, and if it could be neuroprotective in this ALS experimental model. At concentrations lower than those reported as protective, violacein selectively killed aberrant astrocytes. Treatment of hSOD1G93A rats with doses equivalent to the concentrations that killed AbAs caused a marginally significant delay in survival, partially preserved the body weight and soleus muscle mass and improved the integrity of the neuromuscular junction. Reduced motor neuron death and glial reactivity was also found and likely related to decreased inflammation and matrix metalloproteinase-2 and -9. Thus, in spite that new experimental designs aimed at extending the lifespan of hSOD1G93A rats are needed, improvements observed upon violacein treatment suggest a significant therapeutic potential that deserves further studies.IIBCE (MEC), PEDECIBA y ANII

Attitude towards Intranasal Vaccines and Psychological Determinants: Effects on the General Population in Northern Italy

Little is known about the use of intranasal vaccines, but some studies have shown that this innovative way of administration is preferred over needle injection as it is considered both less painful and intrusive to the body, equally effective, and associated with fewer side effects. This study aimed to investigate specific psychological determinants (intolerance of uncertainty, persecutory ideation, perceived control, vaccine hesitancy) of attitude toward nasal vaccine delivery. A convenience sample including 700 Italian participants took part in this cross-sectional study and completed an online questionnaire. A structural equation model with a latent variable was performed to study the relationship between psychological variables, vaccine hesitancy, and attitude toward nasal vaccine delivery. The results indicate that both a hesitant attitude toward vaccination (β = 0.20, p = 0.000) and low perceived control (β = −0.20, p = 0.005) may directly increase preference for nasal administration; furthermore, high levels of persecutory ideation may indirectly influence the propensity for intranasal vaccine. These findings suggest that pharmaceutical companies could implement nasal vaccines and provide detailed information on these vaccines through informational campaigns. Hesitant individuals with low levels of perceived control could more easily comply with these types of vaccines