RESUMO
OBJECTIVES: We tested the hypothesis that a common functional variant in brain-derived neurotrophic factor (BDNF), Val66Met, which has been shown to be associated with increased body mass index (BMI) in schizophrenia (SCZ) and schizoaffective disorder (SAD), is also associated with antipsychotic-induced weight gain in bipolar disorder (BPD). Association of Val66Met with other metabolic measures, including high- and low-density cholesterol, triglycerides, total cholesterol, fasting blood glucose, and hemoglobin A1c, was also tested. METHODS: This was a 12-month, prospective, randomized trial of two atypical antipsychotic drugs (APDs) with moderate (risperidone) or high (olanzapine) risk to cause weight gain. Subjects were diagnosed as having BPD (n = 90) and SCZ or SAD (n = 76). RESULTS: BMI was significantly greater in all diagnoses for Met66 allele carriers at six months (p = 0.01). Met66 carriers with BPD showed a greater increase in the triglycerides/high-density (HDL) cholesterol ratio (p = 0.01), a key marker for metabolic syndrome related to insulin resistance, and log-triglycerides (p = 0.04), after three or six months of treatment. Met66 carriers had the greatest increase in log-triglycerides (p = 0.03) and triglycerides/HDL cholesterol ratio after three months of treatment with risperidone (p = 0.003), and the highest BMI at six months (p = 0.01). CONCLUSIONS: The positive association of BNDF Val66Met with high BMI values replicates previous findings in patients with SCZ and indicates the BDNF Val66Met genotype as a potential risk factor for obesity and insulin resistance measures in patients with BPD receiving antipsychotics as well.
Assuntos
Antipsicóticos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/genética , Resistência à Insulina/genética , Obesidade/genética , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Adulto , Alelos , Benzodiazepinas/efeitos adversos , Glicemia/metabolismo , Índice de Massa Corporal , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Dislipidemias/induzido quimicamente , Dislipidemias/genética , Dislipidemias/metabolismo , Feminino , Genótipo , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/induzido quimicamente , Obesidade/metabolismo , Olanzapina , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fatores de Risco , Risperidona/efeitos adversos , Triglicerídeos/metabolismoRESUMO
The ecological restoration of rare earth mines and the management of rare earth tailings have consistently posed global challenges, constraining the development of the rare earth industry. In this study, Zeolite A is efficiently prepared from the tailings of an ion-type rare earth mine in the southern Jiangxi Province of China. The resulting Zeolite A boasts exceptional qualities, including high crystallinity, a substantial specific surface area, and robust thermal stability. The optimum conditions for Zeolite synthesis are experimental determination and the adsorption properties of Zeolite A for typical pollutants (Cd2+, Cu2+, NH4+, PO43- and F-) in rare earth mines. The synthesised Zeolite A material is found to have strong adsorption properties. The adsorption mechanism is mainly cation exchange, and the priority of adsorption of pollutants is Cu2+> Cd2+ > NH4+ > PO43- > F-. Notably, the sodium Zeolite A material synthesized at room temperature can be effectively recycled multiple times. In summary, we propose a method to synthesise low cost and high adsorption zeolites using rare earth tailings. This will facilitate the reduction of rare earth tailings and the rehabilitation of rare earth mines. Our method has great potential as a rehabilitation technology for rare earth mines.
RESUMO
The aim of the study is to investigate the radioprotective effect of polysaccharide extract from Sipunculus nudus (SNP). Beagle dogs were randomly divided into the following six groups. Group-1: Un-treated and un-irradiated controls. Group-2: Exposed to a single acute dose of 2 Gy γ-radiation alone. Groups-3, 4 and 5: Oral administration of SNP at 50, 100 or 200 mg/kg body weight once a day for 7 days followed by a single acute whole body exposure to 2 Gy γ-radiation. The same doses of SNP were administered for further 27 days. Group-6: Positive controls treated with 1.6 mg/kg Nilestriol by gavage after radiation. Blood parameters including white/red cells and platelet counts, as well as hemoglobin level, were assessed every other day for 34 days (7 days before and 27 days of experiment). Serum separated from aliquots of the same blood sample was used to estimate enzyme activity of antioxidant superoxide-dismutase, and to determine levels of free radical, nitric oxide, hydroxyl and superoxide anion. At the end of the experiment, all dogs were euthanized to weigh the organs for organ co-efficient calculation. Pathological changes were assessed in the bone marrow. The results showed that the dogs exposed to γ-radiation alone exhibited a typical hematopoietic syndrome. In contrast, at the end of 27 days experiment, dogs received oral administration of SNP+γ-radiation showed: (i) a much improved blood picture as indicated by shorter duration of leucopenia, neutropenia, thrombocytopenia (platelet counts), as well as hemoglobin levels, (ii) significantly improved hematopoietic activity in the bone marrow, (iii) substantial decrease in nitric oxide levels, and notable increase in activity of antioxidant superoxide dismutase. The results suggested that oral administration of SNP in Beagle dogs was effective in facilitating the recovery of hematopoietic bone marrow damage induced by γ-radiation.
Assuntos
Raios gama , Poliquetos/química , Polissacarídeos/farmacologia , Protetores contra Radiação/farmacologia , Animais , Medula Óssea/patologia , Medula Óssea/efeitos da radiação , Cães , Radicais Livres/metabolismo , Hematopoese/efeitos da radiação , Hiperplasia , Contagem de Leucócitos , Leucócitos/patologia , Leucócitos/efeitos da radiação , Masculino , Tamanho do Órgão/efeitos da radiação , Polissacarídeos/química , Superóxido Dismutase/metabolismoRESUMO
We studied the effects of switching antipsychotic drug-treated patients with schizophrenia or bipolar disorder who evidenced adverse metabolic side effects as indicated by a triglyceride/high-density lipoprotein ratio (TG/HDL) ≥ 3.5 to aripiprazole (ARIP; 5-30 mg/day, n = 24) or ziprasidone (ZIP; 40-160 mg/day, n = 28). Anthropometric and metabolic measures, psychopathology, quality of life and motor adverse effects were assessed over a 52-week period with evaluations at baseline, 6, 12, 26 and 52 weeks. There were statistically significant improvements in body weight, body mass index (BMI), TG, HDL and TG/HDL which did not differ between treatments. However, numerous secondary measures including weight and BMI, and the proportion of patients who lost ≥ 7% or who no longer met criteria for obesity, favored ZIP over ARIP. Decreases in total cholesterol and increases in HDL-cholesterol also favored ZIP. On the other hand, decreases in TG/HDL ratio and reduction in HgbA1c favored ARIP. There were no significant time or group × time interaction effects for most psychopathology measures; however, Global Assessment of Functioning Scores favored ARIP at 6 and 12 months. We conclude that switching patients with evidence of metabolic side effects to either ARIP or ZIP may be beneficial for some, but not all metabolic measures, with minimal risk of worsening of psychopathology and possibly some benefit in that regard as well.
Assuntos
Antipsicóticos/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Dislipidemias/prevenção & controle , Piperazinas/uso terapêutico , Transtornos Psicóticos/tratamento farmacológico , Quinolonas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tiazóis/uso terapêutico , Adulto , Antipsicóticos/efeitos adversos , Aripiprazol , Aterosclerose/epidemiologia , Aterosclerose/prevenção & controle , Transtorno Bipolar/sangue , Transtorno Bipolar/complicações , Transtorno Bipolar/fisiopatologia , Estudos de Coortes , Manual Diagnóstico e Estatístico de Transtornos Mentais , Monitoramento de Medicamentos , Dislipidemias/induzido quimicamente , Dislipidemias/complicações , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Pacientes Desistentes do Tratamento , Piperazinas/efeitos adversos , Transtornos Psicóticos/sangue , Transtornos Psicóticos/complicações , Transtornos Psicóticos/fisiopatologia , Quinolonas/efeitos adversos , Fatores de Risco , Esquizofrenia/sangue , Esquizofrenia/complicações , Esquizofrenia/fisiopatologia , Índice de Gravidade de Doença , Tiazóis/efeitos adversos , Redução de Peso/efeitos dos fármacosRESUMO
OBJECTIVE: Longitudinal data comparing the metabolic effects of olanzapine and risperidone with or without valproic acid supplementation in schizophrenic and bipolar patients are lacking. METHOD: This study compares the metabolic effects of olanzapine and risperidone in a prospective, randomized, open-label trial in 160 patients with DSM-IV-TR schizophrenia, schizoaffective disorder, or bipolar disorder after 1, 3, 6, and 12 months' treatment. The study was conducted between 2000 and 2006. The primary analysis compared all patients randomized to olanzapine or risperidone; the primary outcome measure was changes in triglycerides (TG), and TG/high density lipoprotein cholesterol (HDL-C) ratio, a risk factor for ischemic cardiovascular disease. Secondary analyses included the effect of concomitant valproic acid. RESULTS: Significantly greater increases in weight (F(4,434) = 4.7), body mass index (BMI) (F(4,424) = 5.1), glycosylated hemoglobin (HgbA1c) (F(4,427) = 4.3), total cholesterol (F(4,429) = 4.4), TG (F(4,426) = 5.9), and TG/HDL-C ratio (F(4,426) = 4.3) (P < .005 for all drug × time interaction effects) were observed at all but the initial time points in the olanzapine- compared to the risperidone patients. Olanzapine/+valproic acid produced significantly greater increases in HgbA1c, BMI, weight, TG, and TG/HDL-C than olanzapine/-valproic acid at 3 and 6 months, while risperidone/+valproic acid produced significantly smaller increases in HgbA1c, BMI, and weight at 1, 3, and 6 months than risperidone/-valproic acid. The olanzapine/+valproic acid group had significantly greater BMI, and weight at 1, 3, and 6 months, and greater HgbA1c at 3 and 6 months, compared with the risperidone/+valproic acid group. There were too few patients treated with mood stabilizers other than valproic acid to analyze effects of any other mood stabilizer separately. Metabolic effects did not differ significantly by diagnostic category (schizophrenia/schizoaffective disorder vs bipolar disorder). CONCLUSION: Further study of the metabolic effects of adjunctive valproic acid is indicated, as valproic acid may produce markedly different metabolic effects when combined with various antipsychotic drugs. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00179062.
Assuntos
Antipsicóticos/farmacocinética , Benzodiazepinas/farmacocinética , GABAérgicos/farmacocinética , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/metabolismo , Risperidona/farmacocinética , Ácido Valproico/farmacocinética , Adolescente , Adulto , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina , Estudos Prospectivos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Clozapine, despite its side-effect burden, has been considered to be the drug of choice for patients with schizophrenia whose psychotic symptoms fail to respond adequately to other anti-psychotic drugs. There are conflicting data concerning the potential utility of olanzapine in treatment-resistant schizophrenia at doses beyond the 10- to 20-mg/day range that has proven to be effective for most nonrefractory patients with schizophrenia. OBJECTIVE: The main objective of this study was to compare the efficacy and tolerability of high-dose olanzapine (target dose, 25-45 mg/day) and clozapine (300-900 mg/day) in patients with schizophrenia or schizoaffective disorder who had failed to respond adequately to prior treatment with other antipsychotic drugs. STUDY DESIGN/METHOD: This 6-month, randomized, double-blind, parallel-group study compared the efficacy and tolerability of olanzapine (mean dose, 34 mg/day; N = 19) or clozapine (mean dose, 564 mg/day; N = 21) in patients with treatment-resistant schizophrenia or schizoaffective disorder, diagnosed according to DSM-IV criteria. Outcome measures included psychopathology, cognitive performance (as assessed with a comprehensive neuropsychological test battery), and tolerability. The study was conducted between May 2000 and December 2003. RESULTS: Robust and significant (mostly p < .001) improvement in multiple measures of psychopathology, mainly between 6 weeks and 6 months of treatment, was found in both treatment groups, with no significant difference between the 2 treatments except for the Global Assessment of Functioning score, which favored clozapine (p = .01). Improvement in some domains of cognition was significant-and equivalent for both drugs, as well. Nonsignificantly different improvement in Verbal List Learning-Immediate Recall (p < .05), Controlled Word Association Test (p < .05), and Digit Symbol Substitution Test (p < .001) was found. There were no significant differences in extrapyramidal symptoms. Weight gain was significantly (p = .01) greater with olanzapine. CONCLUSIONS: Olanzapine, at higher than customary doses, demonstrated similar efficacy to clozapine in treatment-resistant schizophrenia and schizoaffective disorder in this study. However, the small sample size precludes definitively concluding that the 2 treatments are equivalent, at these doses, in treatment-resistant schizophrenia. The metabolic side effects of olanzapine are a limitation in its use. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00179231.