ABSTRACT
Alzheimer's disease (AD) is a neurodegenerative disorder caused by accumulation of amyloid-ß oligomers (AßO) in the brain, neuroinflammation, oxidative stress, and cognitive decline. Grandisin, a tetrahydrofuran neolignan, exhibits relevant anti-inflammatory and antioxidant properties. Interestingly, grandisin-based compounds were shown to prevent AßO-induced neuronal death in vitro. However, no study has assessed the effect of these compounds on the AD animal model. This study focuses on a triazole grandisin analogue (TGA) synthesized using simplification and bioisosteric drug design, which resulted in improved potency and solubility compared with the parent compound. This study aimed to investigate the possible in vivo effects of TGA against AßO-induced AD. Male C57/Bl6 mice underwent stereotaxic intracerebroventricular AßO (90 µM) or vehicle injections. 24 h after surgery, animals received intraperitoneal treatment with TGA (1 mg/kg) or vehicle, administered on a 14 day schedule. One day after treatment completion, a novel object recognition task (NORT) was performed. Memantine (10 mg/kg) was administered as a positive control. NORT retention sessions were performed on days 8 and 16 after AßO injection. Immediately after retention sessions, animals were euthanized for cortex and hippocampus collection. Specimens were subjected to oxidative stress and cytokine analyses. TGA reduced the level of cortex/hippocampus lipoperoxidation and prevented cognitive impairment in AßO-injected mice. Additionally, TGA reduced tumor necrosis factor (TNF) and interferon-γ (IFN-γ) levels in the hippocampus. By contrast, memantine failed to prevent cortex/hippocampus lipid peroxidation, recognition memory decline, and AßO-induced increases in TNF and IFN-γ levels in the hippocampus. Thus, memantine was unable to avoid the AßO-induced persistent cognitive impairment. The results showed that TGA may prevent memory impairment by exerting antioxidant and anti-inflammatory effects in AßO-injected mice. Moreover, TGA exhibited a persistent neuroprotective effect compared to memantine, reflecting an innovative profile of this promising agent against neurodegenerative diseases, such as AD.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Lignans , Neuroprotective Agents , Mice , Male , Animals , Amyloid beta-Peptides/metabolism , Memantine/pharmacology , Antioxidants/pharmacology , Alzheimer Disease/pathology , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Lignans/pharmacology , Furans/pharmacology , Anti-Inflammatory Agents/pharmacology , Neuroprotective Agents/pharmacology , Hippocampus/metabolismABSTRACT
Coronavirus disease (COVID-19) is an acute respiratory disease caused by the new coronavirus (SARS-CoV-2) that has spread throughout the world causing millions of deaths. COVID-19 promotes excessive release of pro-inflammatory cytokines leading to acute lung injury and death. Reactive oxygen species (ROS) and oxidative stress (OS) may also play a role in the pathophysiology of COVID-19. The present study investigated levels of inflammatory cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-12) and OS biomarkers (MPO, SOD, CAT, GST enzymes and contents of GSH, TBARS and PC) in patients with SARS-CoV-2 infection, which were correlated with disease severity. Patients with SARS significantly increased IL-1ß levels, while IL-6 levels were elevated in both groups of SARS-CoV-2 positive patients. The most severe patients showed increased levels of IL-8 and IL-10, while subjects without SARS showed lower values. MPO activity were higher in both groups of SARS-CoV-2 positive patients, while SOD and CAT activity were decreased in both groups. Compared to controls, GGT was elevated only in the SARS patient group, while GST values were increased in the group of positive patients in SARS-CoV-2 without SARS and were decreased in patients with SARS. GSH and UA contents decreased in SARS-CoV-2 positive subjects, whereas TBARS and PC contents increased in both groups of SARS-CoV-2 positive patients, particularly in the SARS patient group. In addition, several important correlations were found between cytokines and the different OS parameters suggesting some inter-relationship in the complex antioxidant system of the patients. In general, patients with SARS-CoV-2 infection showed higher levels of OS biomarkers, and also elevated contents of IL-6 and IL-10, probably worsening the damage caused by SARS-CoV-2 infection. This damage may contribute to the severity of the disease and its complications, as well as a prognosis for SARS-CoV-2 patients.
Subject(s)
COVID-19 , Humans , Interleukin-10 , SARS-CoV-2/metabolism , Interleukin-6 , Thiobarbituric Acid Reactive Substances , Interleukin-8 , Inflammation , Cytokines , Oxidative Stress , Biomarkers , Prognosis , Superoxide Dismutase/metabolismABSTRACT
La maduración visomotora es una función universal, todos los niños a medida que aumenta su edad cronológica adquieren mayor maduración viso motora y, a su vez, se caracteriza por la diversidad, influida por el contexto. Objetivos: a) describir el nivel de madurez visomotora de niños y adolescentes escolarizados del Gran San Miguel de Tucumán, según edad y nivel socioeconómico (NSE), b) generar normas actualizadas del Test guestáltico visomotor de Bender y c) comparar los baremos obtenidos en la actualidad con los de 1995 para población de Tucumán. Participantes: 945 sujetos del Gran San Miguel de Tucumán, entre 5 y 12 años. Se trata de un estudio cuantitativo, comparativo, transversal, con muestreo no probabilístico intencional. Se realizaron análisis descriptivos del puntaje error y análisis univariados considerando edad y NSE. Se halló que la cantidad de errores tendían a disminuir a medida que aumentaba la edad y se encontraron diferencias estadísticas significativas en la combinación NSE y edad. Se establecieron percentiles para toda la muestra. Se efectuaron prueba t de Student para muestras independientes para comparar puntajes error del baremo Tucumán 1995 y los del presente estudio. Este trabajo aporta información valiosa al diagnóstico de la evaluación psicológica infantojuvenil.
Visuomotor maturation is a universal function. As children's chronological age advances so does their visuomotor maturation. Such maturation is characterized by diversity, which is, in turn, influenced by context. Objectives: a) to describe the level of visuomotor maturity of children schooled at San Miguel de Tucuman, taking into consideration age and socioeconomic status (NSE), b) to set updated norms on Bender Gestalt Test and c) to compare the recently obtained scale with that of the year 1995 for the population in Tucumán. Participants: 945 subjects from San Miguel de Tucuman, aged 5 12. This is a quantitative, comparative, cross-sectional, non-probability sampling based study. A descriptive analysis of the error score and a univariate analysis considering the informants' age and socioeconomic status were carried out. Findings showed that the older the children were, the less mistakes they tended to make. Additionally, meaningful statistical differences were found when both factors namely, age and socioeconomic status, were considered. Percentiles weree stablish ed for the whole sample. Student's t-tests for independent samples were performed so as to compare error scores from the scale Tucuman 1995 with those of the current study. This piece of research offers valuable information for the diagnosis of child and adolescent psychological assessment.
Subject(s)
Child , Adolescent , Bender-Gestalt Test , Child , Psychomotor Performance , AdolescentABSTRACT
Se estudia la modificabilidad cognitiva de niños que viven bajo condiciones de pobreza de Tucumán, Argentina. Se enfoca la Evaluación Psicológica de las habilidades cognitivas desde una metodología Test-Intervención-Postest. Los objetivos fueron describir y comparar las habilidades cognitivas en las fases Test y Postest a partir del rendimiento en las pruebas administradas, en los grupos clínico y control. Los instrumentos utilizados fueron los subtests Analogías y Construcción con Cubos de la Escala de Inteligencia de Wechsler para niños, tercera edición (WISC-III), y una Encuesta sociodemográfica. Al contrastar los resultados de fases Test y Postest, entre ambos grupos, se hallaron diferencias significativas en las pruebas administradas que permiten inferir que la Intervención favoreció la modificabilidad cognitiva en los niños del grupo clínico.(AU)
Subject(s)
Humans , Child , Wechsler Scales , Cognition , Cultural Deprivation , Poverty , ArgentinaABSTRACT
Se estudia la modificabilidad cognitiva de niños que viven bajo condiciones de pobreza de Tucumán, Argentina. Se enfoca la Evaluación Psicológica de las habilidades cognitivas desde una metodología Test-Intervención-Postest. Los objetivos fueron describir y comparar las habilidades cognitivas en las fases Test y Postest a partir del rendimiento en las pruebas administradas, en los grupos clínico y control. Los instrumentos utilizados fueron los subtests Analogías y Construcción con Cubos de la Escala de Inteligencia de Wechsler para niños, tercera edición (WISC-III), y una Encuesta sociodemográfica. Al contrastar los resultados de fases Test y Postest, entre ambos grupos, se hallaron diferencias significativas en las pruebas administradas que permiten inferir que la Intervención favoreció la modificabilidad cognitiva en los niños del grupo clínico.
