RESUMEN
A metabolomic approach was applied to a mouse model of starvation-induced hepatic steatosis. After 24 h of fasting it appears that starvation reduced the phospholipids (PL), free cholesterol (FC), and cholesterol esters (CE) content of low-density lipoproteins (LDL). In liver lipid profiles major changes were observed using different techniques. High performance thin layer chromatography (HPTLC)-measurements of liver-homogenates indicated a significant rise of FC with 192%, triacylglycerols (TG) with 456% and cholesterol esters (CE) with 268% after 24 h of starvation in comparison with the control group. Reversed phase liquid chromatography coupled to mass spectrometry measurements (LC-MS) of liver homogenate indicated that the intensity of Phosphatidylcholine (PC) in the 24-h starvation group dropped to 90% of the value in the control group while the intensity of CE and TG increased to 157% and 331%, respectively, of the control group. Interestingly, a 49:4-TG with an odd number of C atoms appeared during starvation. This unique triacylglycerol has all characteristics of a biomarker for detection of hepatic steatosis. These observations indicate that in mammals liver lipid profiles are a dynamic system which are readily modulated by environmental factors like starvation.
Asunto(s)
Sangre/metabolismo , Hígado Graso/metabolismo , Hígado/metabolismo , Animales , Ésteres del Colesterol/metabolismo , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Privación de Alimentos , Lipoproteínas LDL/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Fosfatidilcolinas/metabolismo , Fosfolípidos/metabolismo , Triglicéridos/metabolismoRESUMEN
BACKGROUND: Treatment with interferon-alpha has been shown to be effective in one-third of hepatitis B e antigen-positive chronic hepatitis B patients, but is clinically associated with relevant adverse events. AIM: To investigate the safety of pegylated interferon alpha-2b in 300 hepatitis B e antigen-positive patients with compensated liver disease. METHODS: Patients were treated with pegylated interferon alpha-2b for 52 weeks combined with either lamivudine 100 mg/day or placebo. Pegylated interferon alpha-2b was administered for 100 microg once a week for 32 weeks; thereafter, the dose was reduced to 50 microg once a week. Adverse events and their effect on study medication were reported at monthly visits in a standardized way. RESULTS: The most frequently reported side-effects were flu-like syndrome (68%), headache (40%), fatigue (39%), myalgia (29%) and local reaction at the injection site (29%). These symptoms typically occurred within the first month of therapy and subsided during the course of therapy. Neutropenia and thrombocytopenia induced by pegylated interferon alpha-2b increased the risk of infections and bleeding complications, but these complications were rare and mild. The frequency of all side-effects was not different between patients treated with pegylated interferon alpha-2b combined with lamivudine or placebo. In 69 (22%) patients the dose of pegylated interferon alpha-2b was reduced prematurely. Of these dose reductions, 36 (52%) were because of neutropenia. Therapy was discontinued in 28 (8%) patients. The most frequent reasons for early discontinuation were psychiatric side-effects (depression, psychosis) and flu-like symptoms. Multivariate Cox regression analysis showed that low neutrophil count at baseline and cirrhosis were independent predictors of dose reduction or therapy discontinuation. CONCLUSION: We conclude that in patients with chronic hepatitis B and compensated liver disease prolonged pegylated interferon alpha-2b therapy is safe, and that pre-existent cirrhosis and neutropenia are the most important predictors of dose reduction or early treatment discontinuation.
Asunto(s)
Antivirales/efectos adversos , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/efectos adversos , Adulto , Antivirales/administración & dosificación , Infecciones Bacterianas/complicaciones , Método Doble Ciego , Femenino , Hemorragia/etiología , Hepatitis B Crónica/complicaciones , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Masculino , Polietilenglicoles , Proteínas Recombinantes , Factores de RiesgoRESUMEN
A suspension culture of TABERNAEMONTANA ELEGANS was characterized on growth, nutrient uptake (carbohydrate, nitrogen, and phosphate), and on accumulation of indole alkaloids. Besides tryptamine seven indole alkaloids were isolated and identified: vobasine, vobasinol, perivine, isositsirikine, apparicine, tubotaiwine, and O-acetylvallesamine. In spite of the presence of vobasinol as major product, only trace amounts of dimeric indole alkaloids could be detected. Alkaloid formation started at the early stationary phase.