Asunto(s)
Glaucoma de Ángulo Abierto/inducido químicamente , Glucosamina/efectos adversos , Presión Intraocular/efectos de los fármacos , Administración Oral , Anciano , Anciano de 80 o más Años , Suplementos Dietéticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Hipertensión Ocular/inducido químicamente , Osteoartritis/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
Primary alkyl aryl sulfones are converted to the corresponding carboxylic acids in fair to excellent yield through double deprotonation and exposure to atmospheric oxygen. The methodology allows for the convenient synthesis of (13)C labeled carboxylic acids.
Asunto(s)
Ácidos Carboxílicos/síntesis química , Sulfonas/química , Ácidos Carboxílicos/química , Estructura Molecular , Oxidación-Reducción , Oxígeno/químicaRESUMEN
In this article, a novel delivery system for the anticancer drug, arsenic trioxide (ATO), is characterized. The release of ATO from DPPC liposomes with MPPC lysolipid incorporated into the bilayer was measured. Upon heating the liposomes to 37°C, there was a 15-25% release over 24 hours. The ATO release from the DPPC and DPPC:MPPC (5%) systems leveled off after 10 hours at 37°C, whereas the DPPC:MPPC (10%) liposomes continue to release ATO over the 24-hour time span. Upon heating the liposomes rapidly to 42°C, the release rate was substantially increased. The systems containing lysolipids exhibited a very rapid release of a significant amount of arsenic in the first hour. In the first hour, the DPPC:MPPC (5%) liposomes released 40% of the arsenic and the DPPC:MPPC (10%) liposomes released 55% of the arsenic. Arsenic release from pure DPPC liposomes was comparable at 37 and 42°C, indicating that the presence of a lysolipid is necessary for a significant enhancement of the release rate. A coarse-grained molecular dynamics (CGMD) model was used to investigate the enhanced permeability of lysolipid-incorporated liposomes and lipid bilayers. The CG liposomes did not form a gel phase when cooled due to the high curvature; however, permeability was still significantly lower below the liquid-to-gel phase-transition temperature. Simulations of flat DPPC:MPPC bilayers revealed that a peak in the permeability did coincide with the phase transition from the gel to LC state when the lysolipid, MPPC, was present. No pores were observed in the simulations, so it is unlikely this was the permeability-enhancing mechanism.
Asunto(s)
Arsenicales/metabolismo , Membrana Dobles de Lípidos/química , Liposomas/química , Liposomas/metabolismo , Óxidos/metabolismo , Temperatura de Transición , 1,2-Dipalmitoilfosfatidilcolina/química , Trióxido de Arsénico , Arsenicales/uso terapéutico , Rastreo Diferencial de Calorimetría , Geles/química , Geles/metabolismo , Humanos , Membrana Dobles de Lípidos/metabolismo , Simulación de Dinámica Molecular , Neoplasias/tratamiento farmacológico , Óxidos/uso terapéutico , Permeabilidad , Transición de Fase , Fosfatidilcolinas/químicaRESUMEN
Human papillomavirus causes anal condylomata, high-grade anal intraepithelial neoplasia, and anal squamous cell cancer. We found high-grade intraepithelial neoplasia or squamous cell cancer in 75 (47%) of 159 HIV-seropositive men who have sex with men (MSM) and in 42 (26%) of 160 HIV-seronegative MSM with anal condylomata meriting surgery (P<.001, determined by use of the chi(2) test). Anal condylomata in MSM often harbor high-grade intraepithelial neoplasia and squamous cell cancer.