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1.
J Appl Toxicol ; 37(8): 943-953, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28138993

RESUMEN

Lipid profiling has emerged as an effective approach to not only screen disease and drug toxicity biomarkers but also understand their underlying mechanisms of action. Tamoxifen, a widely used antiestrogenic agent for adjuvant therapy against estrogen-positive breast cancer, possesses side effects such as hepatic steatosis and phospholipidosis (PLD). In the present study, we administered tamoxifen to Sprague-Dawley rats and used lipidomics to reveal tamoxifen-induced alteration of the hepatic lipid profile and its association with the plasma lipid profile. Treatment with tamoxifen for 28 days caused hepatic PLD in rats. We compared the plasma and liver lipid profiles in treated vs. untreated rats using a multivariate analysis to determine differences between the two groups. In total, 25 plasma and 45 liver lipids were identified and altered in the tamoxifen-treated group. Of these lipids, arachidonic acid (AA)-containing phosphatidylcholines (PCs), such as PC (17:0/20:4) and PC (18:1/20:4), were commonly reduced in both plasma and liver. Conversely, tamoxifen increased other phosphoglycerolipids in the liver, such as phosphatidylethanolamine (18:1/18:1) and phosphatidylinositol (18:0/18:2). We also examined alteration of AA-containing PCs and some phosphoglycerolipids in the pre-PLD stage and found that these lipid alterations were initiated before pathological alteration in the liver. In addition, changes in plasma and liver levels of AA-containing PCs were linearly associated. Moreover, levels of free AA and mRNA levels of AA-synthesizing enzymes, such as fatty acid desaturase 1 and 2, were decreased by tamoxifen treatment. Therefore, our study demonstrated that AA-containing PCs might have potential utility as novel and predictive biomarkers for tamoxifen-induced PLD. Copyright © 2017 John Wiley & Sons, Ltd.


Asunto(s)
Ácido Araquidónico/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Lipidosis/metabolismo , Hígado/metabolismo , Fosfatidilcolinas/sangre , Tamoxifeno/toxicidad , Animales , Ácido Araquidónico/metabolismo , Biomarcadores/sangre , Biomarcadores/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Relación Dosis-Respuesta a Droga , Metabolismo de los Lípidos/efectos de los fármacos , Lipidosis/inducido químicamente , Hígado/efectos de los fármacos , Masculino , Fosfatidilcolinas/metabolismo , Ratas Sprague-Dawley
2.
Gerodontology ; 34(1): 129-134, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27207609

RESUMEN

OBJECTIVE: This study was performed to determine the prevalence of oral health conditions unnoticed by doctors and ward staff that may increase risk of incidents and/or accidents in hospitalised patients with moderate-severe dementia. BACKGROUND DATA DISCUSSING THE PRESENT STATUS OF THE FIELD: Dementia patients may not recognise risks in the mouth, such as tooth mobility or ill-fitting dental prostheses and/or dentures. In addition to the risk of choking, injury by sharp edges of collapsed teeth or prosthodontics could pose risks. However, many previous publications were limited to case reports or series. MATERIALS AND METHODS: Ninety-two consecutive hospitalised dementia patients (M: 52, F: 40, median age: 82.5 years, range: 62-99 years, from 2011 to 2014), referred for dentistry for dysphagia rehabilitation, were enrolled in this study. Participants referred for dental treatment with dental problems detected by ward staff were excluded. All participants had a Global Clinical Dementia Rating Score >2. Their dental records were evaluated retrospectively for issues that may cause incidents and/or accidents. RESULTS: Problems in the mouth, for example tooth stumps, dental caries, and ill-fitting dentures, were detected in 51.1% of participants (47/92). Furthermore, 23.9% (22/92) showed risk factors that could lead to incidents and/or accidents, for example falling out of teeth and/or prosthodontics or injury by sharp edges of teeth and/or prosthodontics. CONCLUSIONS: Hospitalised moderate-severe dementia patients had a high prevalence of oral health conditions unnoticed by doctors and ward staff that may increase risk of incidents and/or accidents.


Asunto(s)
Accidentes , Demencia/complicaciones , Enfermedades de la Boca/complicaciones , Accidentes/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Boca/epidemiología , Prevalencia , Factores de Riesgo
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