RESUMEN
We previously demonstrated that stimulation of nicotinic acetylcholine receptors (nAChRs) increases amyloid-ß (Aß) phagocytosis in rat microglia and is closely associated with the decrease of brain Aß and amelioration of memory dysfunction in a transgenic mouse model of Alzheimer's disease (AD). Here, we examined the subtypes of nAChRs involved in these beneficial effects. In primary cultures of rat microglia, the α7 nAChR selective agonist 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride (DMXBA) promoted Aß and fluorescent latex bead phagocytosis, whereas selective α7 nAChR antagonists suppressed the enhanced Aß phagocytosis. In a transgenic mouse model of AD, administration of DMXBA attenuated brain Aß burden and memory dysfunction. Moreover, DMXBA suppressed γ-secretase activity in solubilized fractions of human neuroblastoma cells and transgenic mouse brain. These results suggested that selective activation of α7 nAChRs promoted microglial Aß phagocytosis and suppressed neuronal γ-secretase activity to contribute to the attenuation of the brain Aß burden and cognitive impairment. Thus, we propose neuronal and microglial α7 nAChRs as new therapeutic targets in the treatment of AD.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Péptidos beta-Amiloides/inmunología , Péptidos beta-Amiloides/metabolismo , Compuestos de Bencilideno/farmacología , Compuestos de Bencilideno/uso terapéutico , Encéfalo/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Microglía/inmunología , Fagocitosis/efectos de los fármacos , Fagocitosis/inmunología , Piridinas/farmacología , Piridinas/uso terapéutico , Receptor Nicotínico de Acetilcolina alfa 7/agonistas , Enfermedad de Alzheimer/complicaciones , Animales , Células Cultivadas , Disfunción Cognitiva/etiología , Modelos Animales de Enfermedad , Humanos , Ratones Transgénicos , Neuroblastoma/metabolismo , Ratas , Células Tumorales CultivadasRESUMEN
BACKGROUND: Japan has not succeeded in reducing the annual number of new HIV-infected patients, although the prevalence of HIV infection is low (0.02%). METHODS: A single-center observational study was conducted at the largest HIV clinic in Tokyo, which treats 15% of the total patients in Japan, to determine the reasons for having diagnostic tests in newly infected individuals. HIV-infected patients who visited our clinic for the first time between 2011 and 2014 were analyzed. RESULTS: The 598 study patients comprised one-third of the total reported number of new patients in Tokyo during the study period. 76% were Japanese MSM. The reasons for being tested which led to the diagnosis was voluntary testing in 32%, existing diseases in 53% (AIDS-defining diseases in 22%, sexually transmitted infections (STI) in 8%, diseases other than AIDS or STIs in 23%) and routine pre-surgery or on admission screening in 15%. 52% and 74% of the study patients and patients presented with AIDS, respectively, had never been tested. The median CD4 count in patients with history of previous testing (315/µL) was significantly higher than that of patients who had never been tested (203/µL, p<0.001). CONCLUSIONS: Only 32% of the newly HIV diagnosed patients were diagnosed because of voluntary testing, and 53% were diagnosed due to presence of other diseases. These results remain unchanged from our previous report 10 years earlier (2000-2004) on newly diagnosed patients at the same clinic. HIV testing has not been widely used by newly diagnosed patients in the Tokyo metropolitan area.
Asunto(s)
Infecciones por VIH/epidemiología , Conocimientos, Actitudes y Práctica en Salud , Aceptación de la Atención de Salud , Adulto , Recuento de Linfocito CD4 , Comorbilidad , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Tokio/epidemiología , Adulto JovenRESUMEN
PURPOSE: This retrospective cohort study was conducted to demonstrate how allocation of nurses specialized in HIV care influences clinical outcomes of antiretroviral therapy (ART) for people living with HIV (PLWH). METHODS: The medical records of 116 PLWH who started ART between January 2002 and December 2004 were analyzed. Occurrence of viral suppression and viral relapse after suppression achievement and their time from baseline were observed as clinical outcomes related to ART. Clinical outcomes were obtained from medical records between January 2002 and December 2006. PLWH were classified into two groups according to allocation (n = 95, nurse allocated group) or nonallocation (n =21, nurse nonallocated group) of nurses specialized in HIV. RESULTS: Survival analysis showed that HIV viral load was suppressed more rapidly and continuously in nurse allocated group than nonallocated group (p < .0001). Viral relapse after suppression achievement occurred easily in nurse nonallocated group than allocated group (p = .003). CONCLUSIONS: The present findings demonstrated that the role of specialized nurses is critically important from the viewpoint of clinical outcome.