ABSTRACT
Lipopolysaccharide (LPS)-induced endotoxemia triggers the secretion of proinflammatory cytokines and can cause acute lung injury (ALI). The high mobility group box 1 (HMGB1) protein plays an important role as a late mediator of sepsis and ALI. Galantamine (GAL) is a central acetylcholinesterase inhibitor that inhibits the expression of HMGB1. This study evaluated the effects of GAL by measuring levels of inflammatory mediators and observing histopathological features associated with LPS-induced ALI. Sixty 8-10 week old male Sprague-Dawley rats (200-240 g) were randomized into three groups as follows: control group, LPS group (7.5 mg/kg LPS), and LPS+GAL group (5 mg/kg GAL before LPS administration). Histopathological examination of lung specimens obtained 12 h after LPS administration was performed to analyze changes in wet-to-dry (W/D) weight ratio, myeloperoxidase (MPO) activity, and HMGB1 expression level. Additionally, plasma concentrations of tumor necrosis factor-α, interleukin-6, and HMGB1 were measured using an enzyme-linked immunosorbent assay at 0 (baseline), 3, 6, 9, and 12 h after LPS administration. Mortality in the three groups was recorded at 72 h. LPS-induced ALI was characterized by distortion of pulmonary architecture and elevation of MPO activity, W/D weight ratio, and levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, and HMGB1. Pretreatment with GAL significantly reduced the LPS-induced lung pathological changes, W/D weight ratio, levels of pro-inflammatory cytokines and MPO activity (ANOVA). Moreover, GAL treatment significantly decreased the mortality rate (ANOVA). In conclusion, we demonstrated that GAL exerted a protective effect on LPS-induced ALI in rats.
Subject(s)
Animals , Male , Acute Lung Injury/drug therapy , Cholinesterase Inhibitors/therapeutic use , Galantamine/therapeutic use , HMGB1 Protein/metabolism , Analysis of Variance , Acute Lung Injury/chemically induced , Acute Lung Injury/mortality , Acute Lung Injury/pathology , Enzyme-Linked Immunosorbent Assay , HMGB1 Protein/antagonists & inhibitors , /blood , Lipopolysaccharides , Lung/drug effects , Lung/metabolism , Lung/pathology , Mortality , Organ Size , Peroxidase/metabolism , Protective Agents/therapeutic use , Random Allocation , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/bloodABSTRACT
Los costos originados por trastornos cognitivos y demencias son significativos para los sistemas de salud. Según guías nacionales e internacionales, los fármacos recomendados para su tratamiento son inhibidores de colinesterasa (donepecilo, galantamina y rivastigmina) y memantina. En la Argentina también son utilizados otros nootrópicos, galantamina, rivastigmina, vasodilatadores, vitaminas y antioxidantes. El objetivo del presente estudio es describir y comparar el patrón de prescripción de drogas para el tratamiento de trastornos cognitivos y demencias en las distintas regiones del país. Se realizó un estudio observacional retrospectivo a partir de las prescripciones (1 814 108 envases) realizadas en la práctica clínica habitual durante el segundo semestre del 2008 y el primer y segundo semestre del 2009. El trabajo fue realizado sobre la población total del Instituto Nacional de Servicios Sociales para Jubilados y Pensionados. Se analizaron variables demográficas, cantidad y tasa de prescripciones, presentaciones y dosis utilizadas por regiones. Considerando todo el país, memantina fue la droga más prescripta en esos períodos, con un total de 570 893 envases. Memantina, donepecilo, rivastigmina e idebenona presentaron un incremento en las tasas de prescripción 2008-2009. Analizando los cambios regionales en tasas de prescripción, la memantina aumentó en el Noroeste y Noreste argentino, la idebenona en el Noroeste y la Patagonia y el donepecilo en el Noreste. Grupos de fármacos no recomendados fueron altamente prescriptos en todas las regiones del país. Algunos fueron indicados en adultos jóvenes o de mediana edad.
Cognitive impairment and dementia treatment costs are significant for health systems. According to national and international guidelines, recommended drugs for treatment of dementias are cholinesterase inhibitors (donepezil, galantamine, rivastigmine) and memantine. Despite these guidelines recommendations, other nootropics, vasodilators and antioxidants are often used in Argentina. The purpose of this study was to describe and compare the prescription pattern of commonly used drugs for the treatment of cognitive disorders and dementia in different regions of Argentina. An observational, retrospective study of 1 814 108 recipes prescribed to National Institute of Social Services for Retired and Pensioners outpatients during the during the second half of 2008 and the first and second half of 2009 was performed, taking in count the whole country and also different Argentina´s regions. Demographic variables, quantity and rate of prescriptions, dosage forms and strengths were analyzed. Considering the entire country, memantine was the most prescribed drug in these periods (570 893 packages). An increase in the memantine, donepezil, rivastigmine and idebenone rates of prescription was observed. Prescription rate of memantine increased in the North-West and North-East regions, that of idebenone in the North-East region and Patagonia and donepezil in the North-East region. Non recommended drugs were highly prescribed in all the analyzed regions. Some of them were indicated to young and middle-aged patients.