RESUMEN
OBJECTIVE: Patients with schizophrenia have a higher prevalence of metabolic syndrome (MetS) than the general population. Minimizing weight gain and metabolic abnormalities in a population with an already high prevalence of obesity is of clinical and social importance. This randomized controlled trial investigated the effect of monthly nutritional education on weight change and metabolic abnormalities among patients with schizophrenia in Japan. METHODS: From July 2014 to December 2014, we recruited 265 obese patients who had a DSM-IV diagnosis of schizophrenia or schizoaffective disorder. Participants were randomly assigned to a standard care (A), doctor's weight loss advice (B), or an individual nutritional education group (C) for 12 months. The prevalence of MetS and body weight were measured at baseline and 12 months. RESULTS: After the 12-month treatment, 189 patients were evaluated, and the prevalence of MetS based on the ATP III-A definition in groups A, B, and C was 68.9%, 67.2%, and 47.5%, respectively. Group C showed increased weight loss (3.2 ± 4.5 kg) over the 12-month study period, and the change in weight differed significantly from that of group A; additionally, 26.2% of the participants in group C lost 7% or more of their initial weight, compared with 8.2% of those in group A. CONCLUSION: Individual nutrition education provided by a dietitian was highly successful in reducing obesity in patients with schizophrenia and could be the first choice to address both weight gain and metabolic abnormalities induced by antipsychotic medications.
Asunto(s)
Antipsicóticos/uso terapéutico , Síndrome Metabólico/dietoterapia , Obesidad/dietoterapia , Evaluación de Resultado en la Atención de Salud , Educación del Paciente como Asunto/métodos , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Pérdida de Peso , Adulto , Antipsicóticos/efectos adversos , Femenino , Humanos , Japón , Masculino , Síndrome Metabólico/inducido químicamente , Persona de Mediana Edad , Obesidad/inducido químicamenteRESUMEN
The anti-tumor properties of novel derivatives prepared from Aconitum C(20)-diterpenoid alkaloid, which show the least toxicity among the Aconitum alkaloids, were investigated in the Non-Hodgkin's lymphoma cell line Raji cells. Two novel Aconitum C(20)-diterpenoid alkaloid derivatives, 11-m-Trifluorometylbenzoyl (Mb)-pseudokobuisne and 11-Anisoyl (As)-pseudokobusine, showed significant suppressive effects and their 50% inhibitory concentrations were 2.2 µg/ml and 2.4 µg/ml against Raji cells, respectively. Both compounds have the same structure except for a functional group in the C-11 position. One of the active compounds, 11-Mb-pseudokobusine, clearly inhibited the phosphorylation of extracellular signal-regulated kinase, induced enhanced phosphoinositide 3 kinase phosphorylation and led to the subsequent accumulation of G1 and/or sub G1 phase in Raji cells. In addition, no significant suppressive effects on the growth of human CD34(+) hematopoietic stem/progenitor cells (HSPC) were observed by 11-Mb-pseudokobusine which showed a strong suppressive activity on the growth of Raji cells, whereas 11-As-pseudokobusine also a showed significantly suppressive effect on the growth of HSPC. Therefore, the atisine type structure characteristic of C(20)-diterpenoid alkaloids plays a very important role in the pharmacological properties. In particular, the C-11 residues are an important component for the anti-tumor properties and for the lower toxicity to hematopoiesis.
Asunto(s)
Aconitum/química , Alcaloides/química , Alcaloides/farmacología , Diterpenos/química , Diterpenos/farmacología , Células Madre Hematopoyéticas/citología , Linfoma no Hodgkin/patología , Western Blotting , Hidrocarburos Aromáticos con Puentes/farmacología , Butadienos/farmacología , Carbono , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Quinasa 2 Dependiente de la Ciclina/metabolismo , Diterpenos/uso terapéutico , Activación Enzimática/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Fase G1/efectos de los fármacos , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/enzimología , Nitrilos/farmacología , Fenantrenos/farmacología , Fitoterapia , Relación Estructura-ActividadRESUMEN
The cytotoxicity of three alkaloids from the roots of Aconitum yesoense var. macroyesoense as well as 36 semi-synthetic C(20)-diterpenoid atisine-type alkaloid derivatives against A549 human lung carcinoma cells was examined. Ten acylated alkaloid derivatives, pseudokobusine 11-veratroate (9), 11-anisoate (12), 6,11-dianisoate (14), 11-p-nitrobenzoate (18), 11,15-di-p-nitrobenzoate (22), 11-cinnamate (25) and 11-m-trifluoromethylbenzoate (27), and kobusine 11-p-trifluoromethylbenzoate (35), 11-m-trifluoromethylbenzoate (36) and 11,15-di-p-nitrobenzoate (39), exhibited cytotoxic activity, and 11,15-dianisoylpseudokobusine (16) was found to be the most potent cytotoxic agent. Their IC(50) values against A549 cells ranged from 1.72 to 5.44 µM. In the occurrence of cytotoxic effects of atisine-type alkaloids, replacement by an acyl group at both C-11 and C-15 resulted in the enhancement of activity of the parent alkaloids compared to that from having hydroxy groups at this position, and the presence of a hydroxy group at the C-6 position was required for the cytotoxic effects. These acylated alkaloid derivatives inhibit cell growth through G1 arrest.
Asunto(s)
Alcaloides/química , Alcaloides/farmacología , Diterpenos/química , Diterpenos/farmacología , Hidrocarburos Aromáticos con Puentes/química , Hidrocarburos Aromáticos con Puentes/farmacología , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citometría de Flujo , Humanos , Estructura Molecular , Fenantrenos/química , Fenantrenos/farmacología , Relación Estructura-ActividadRESUMEN
Little information has so far been reported regarding the antiproliferative properties of Aconitum alkaloids against human tumor cells despite of their intense toxicities. In the present study, the antitumor properties and radiation sensitizing effects were investigated by various types of novel derivatives prepared from Aconitum alkaloids. The antitumor properties were investigated against human tumor cell lines, A172, A549, HeLa and Raji, respectively, by a cell growth, a clonogenic assay, cell cycle distribution, cell cycle related molecules and gammaH2AX expression. The novel compounds derived from C(20)-diterupenoid alkaloids showed a significantly suppressive effect in all cell lines. In contrast, natural C(19)-norditerpenoid alkaloids and their derivatives showed either no effect or only a slight effect. One of the compounds also showed radiosensitizing properties on A549 cells. These effects are not related to either the cell cycle distribution, the enhancement of apoptosis or the gammaH2AX expression. Novel derivatives prepared from Aconitum alkaloids, not but natural alkaloids, clearly showed anti-proliferative activity in human tumor cell lines.
Asunto(s)
Aconitum/química , Alcaloides/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Preparaciones de Plantas/análogos & derivados , Preparaciones de Plantas/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Alcaloides/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Ciclo Celular/efectos de los fármacos , Ciclo Celular/efectos de la radiación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Terapia Combinada , Ensayos de Selección de Medicamentos Antitumorales , Histonas/metabolismo , Humanos , Preparaciones de Plantas/química , Raíces de Plantas , Fármacos Sensibilizantes a Radiaciones/químicaRESUMEN
The cytotoxicity against A172 human malignant glioma cells was examined for 14 alkaloids from the roots of Aconitum yesoense var. macroyesoense and of Aconitum japonicum and from the seeds of Delphinium elatum as well as for 25 semisynthetic derivatives. The major alkaloid constituents of A. yesoense var. macroyesoense, kobusine (2) and pseudokobusine (3), a minor alkaloid constituent of A. japonicum, aljesaconitine A (5), and six alkaloid derivatives, N-deethyldelcosine (10), N-deethyldelsoline (11), 12-benzoylluciculine (18), 12-anisoylluciculine (19), 6,11-dibenzoylpseudokobusine (28), and 6-veratroylpseudokobusine (29), had only very weak activity. Four acylated alkaloid derivatives, 12-acetylluciculine (23), 11-veratroylpseudokobusine (30), 11-(m-trifluoromethylbenzoyl)pseudokobusine (32), and 11-(m-trifluoromethylbenzoyl)kobusine (39), exhibited more potent activity, while pseudokobusine 11-cinnamoate (31), 11-anisoate (33), and 11-p-nitrobenzoate (34) were found to be the most potent cytotoxic agents.
Asunto(s)
Aconitum/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Plantas Medicinales/química , Alcaloides/química , Antineoplásicos Fitogénicos/química , Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/química , Hidrocarburos Aromáticos con Puentes/farmacología , Diterpenos/síntesis química , Diterpenos/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Raíces de Plantas/química , Compuestos Policíclicos/síntesis química , Compuestos Policíclicos/química , Compuestos Policíclicos/farmacología , Semillas/químicaRESUMEN
Epigallocatechin-3-gallate (EGCg) has been widely recognized as a powerful antioxidant and free radical scavenger. The effects of EGCg on the proliferation and differentiation of X-irradiated megakaryocytic progenitor cells (colony-forming unit-megakaryocyte, CFU-Meg) using CD34+ cells prepared from human placental and umbilical cord blood have been shown. In the absence of exogenous thrombopoietin (TPO), no colonies are observed in cultures containing or lacking EGCg (1 nM-100 microM). In the presence of TPO, in contrast, EGCg significantly promotes CFU-Meg-derived colony formations within the 10-100-nM range. A 1.5-fold increase in the total number of CFU-Meg has been counted compared with the control. These favorable effects of EGCg are also observed in the culture of CD34+ cells before and after X irradiation with 2 Gy. Moreover, in order to investigate the function of EGCg promoting megakaryocytopoiesis and thrombopoiesis in ex vivo cultures, both non-irradiated and X-irradiated CD34+ cells are grown in liquid cultures supplemented with TPO. In both cultures, EGCg increases the total number of cells and megakaryocytes. It has been suggested that the favorable effects of EGCg reduce the risk factor from radiation damage in megakaryocytopoiesis.
Asunto(s)
Catequina/análogos & derivados , Megacariocitos/efectos de los fármacos , Megacariocitos/efectos de la radiación , Células Madre/efectos de los fármacos , Células Madre/efectos de la radiación , Catequina/administración & dosificación , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/efectos de la radiación , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Células Cultivadas , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Humanos , Megacariocitos/citología , Dosis de Radiación , Protectores contra Radiación/administración & dosificación , Células Madre/citologíaRESUMEN
Administration of 50 microg of bisphenol A (BPA) for the first 5 days after birth resulted in a decrease in the percentage of moving sperm, and an increase in the incidence of malformed sperm, in the epididymides of mice at 10 weeks of age, although no marked changes were found in the testicular histology between BPA-treated and vehicle-treated control mice. The deteriorating effects of 50 microg of BPA were ameliorated by the concurrent administration of 100 IU of retinol acetate (RA). Neonatal treatment with 0.5 microg of BPA for 5 days resulted in an increase in the incidence of malformed sperm, whereas the BPA effect became more severe in mice nursed by mothers fed a vitamin A-deficient (VAD) diet only a few days before and after parturition. On the other hand, neonatal treatment with 20 microg of estrogen for the first 5 days after birth resulted in an increase in the number of estrogen receptor alpha (ERalpha)-positive cells in the epithelium of the vas deferens, whereas only a few epithelial cells showed weak ERalpha-positive signals in the vehicle-treated control mice at 18 days after birth. This increase, however, was suppressed by the concurrent administration of RA. Although five daily treatments with 50 microg BPA led to no significant increase in the number of ERalpha-positive cells, it may have been due to the weak estrogenic activity of BPA, as discussed. These findings clearly showed that in mice, neonatal exposure to a relatively large dose of BPA causes damage to the motility and morphology of sperm, but the BPA effect is, to some extent, inhibited by a supplement of VA, and enhanced under a VAD condition.