RESUMO
Gender-specific relationships between diabetes mellitus (DM) and schizophrenia have previously received little systematic study. The results showed that the overall DM prevalence was 20% with rates of 17% (58/343) in males and 27% (46/172) in females (p<0.01). Furthermore, increased body mass index (BMI), abdominal obesity and antipsychotic types were predictors of diabetes in these chronic schizophrenic patients.
Assuntos
Antipsicóticos/uso terapêutico , Diabetes Mellitus/epidemiologia , Hospitalização/estatística & dados numéricos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Caracteres Sexuais , Adulto , Idoso , Antropometria/métodos , Glicemia/fisiologia , Distribuição de Qui-Quadrado , Fast Foods , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
Chemodynamic therapy (CDT) is widely explored for tumor-specific therapy by converting endogenous H2O2 to lethal ·OH to destroy cancer cells. However, ·OH scavenging by glutathione (GSH) and insufficient intratumoral H2O2 levels seriously hinder the application of CDT. Herein, we reported the fabrication of copper ion-doped ZIF-8 loaded with gold nanozymes and doxorubicin hydrochloride (DOX) for the chemotherapy and CDT synergistic treatment of tumors with the assistance of tumor microenvironment (TME)-activated fluorescence imaging. The Cu2+-doped ZIF-8 shell was gradually degraded to release DOX and gold nanoclusters responding to the acidic TME. The fluorescence signal of the tumor region was acquired after the quenched fluorescence of the gold nanoclusters by Cu2+ and DOX by aggregation-induced quenching was turned on because of the interaction of GSH with Cu2+ and the release of free DOX. The Cu2+ ions could deplete the GSH via redox reactions and the generated Cu+ could convert internal H2O2 to ·OH for tumor CDT. The chemotherapeutic effect of DOX was strengthened through drug efflux inhibition and drug sensitivity increase due to the consumption of GSH and ·OH burst. Moreover, DOX could raise the level of H2O2 and augment the effect of CDT. In addition, the fluorescent gold nanoclusters not only served as a peroxidase to convert H2O2 to ·OH but also employed as an oxidase to consume GSH, resulting in the amplification of chemotherapy and CDT. This work presents an approach to construct tumor microenvironment-activated theranostic probes without external stimuli and to achieve the tumor elimination through cascade reactions and synergistic treatment.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Imagem Óptica , Nanomedicina Teranóstica , Microambiente Tumoral/efeitos dos fármacos , Animais , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Terapia Fototérmica , Propriedades de SuperfícieRESUMO
A new indole alkaloid, 17-oxo-19-(Z)-naucline, and six known alkaloids 2-7 were isolated from the branches of Nauclea officinalis. The structure of the new compound 1 was characterised mainly by analysing its physical data including IR, 1 D, 2 D NMR, and HR-ESI-MS. Other compounds were identified by comparisons their data with those reported in the literature. Compound1, 4, 5, 6, 7 showed in vitro anti-inflammatory activity decrease the LPS-stimulated production of nitric oxide in RAW264.7 cell, while all compounds exhibited weak cytotoxicity against human tumour cell lines (LOVO, A549 and HepG2).
Assuntos
Anti-Inflamatórios/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Alcaloides Indólicos/farmacologia , Rubiaceae/química , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Células RAW 264.7RESUMO
Recent evidence suggests that centrally released brain-derived neurotrophic factor (BDNF) modulates eating behavior and metabolism that is responsible for body weight fluctuation. BDNF also may play an important role in the therapeutic action of antipsychotic medications. We investigated whether the Val66Met polymorphism of the BDNF gene affected weight gain after long-term antipsychotic treatment in schizophrenia. The polymorphism was genotyped in 196 Chinese patients with schizophrenia on long-term antipsychotic medication. Serum BDNF was measured in all patients and 50 normal controls. Mean body mass index (BMI) change was evaluated retrospectively by means of clinical records. The results showed that there was a significant relationship between the three BDNF Val/Met genotypes and mean BMI gain, with genotype having a strong effect on BMI gain in male but not female patients. BDNF levels were significantly lower in patients than normal controls, and negatively correlated with BMI gain in female but not male patients. Our results suggest that variation in the BDNF gene may be a risk factor for weight gain in male patients with schizophrenia on long-term antipsychotic treatment, and decreased BDNF levels may be associated with weight gain in females.
Assuntos
Antipsicóticos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Esquizofrenia/genética , Esquizofrenia/fisiopatologia , Aumento de Peso/efeitos dos fármacos , Análise de Variância , Antipsicóticos/uso terapêutico , Índice de Massa Corporal , Fator Neurotrófico Derivado do Encéfalo/sangue , Doença Crônica , Feminino , Genótipo , Humanos , Pacientes Internados , Masculino , Metionina/genética , Polimorfismo Genético/genética , Escalas de Graduação Psiquiátrica , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Fatores Sexuais , Valina/genética , Aumento de Peso/genéticaRESUMO
OBJECTIVE: Schizophrenia is associated with various abnormalities in the immune system. Suppression of inflammatory cytokines by cigarette smoke is well-established. The purpose of this study was to determine any differences in cytokine profiles in smokers and nonsmokers with schizophrenia and whether there were any relationships among altered cytokine profiles and psychopathological symptoms. MATERIALS AND METHODS: Serum interleukin (IL)-2, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha levels were measured in 96 male inpatients with DSM-IV schizophrenia: 66 smokers and 30 nonsmokers. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). RESULTS: The positive PANSS symptoms were lower in smokers than nonsmokers, while the negative symptoms were lower in those who smoked more cigarettes. Cytokine levels were positively correlated: IL-2 level with IL-6 and IL-6 with both IL-8 and TNF-alpha. Both IL-2 and IL-6, but not IL-8 or TNF-alpha, were significantly lower in smokers than nonsmokers (p < 0.002; p < 0.01). Lower IL-2 levels correlated with fewer negative symptoms and with smoking more cigarettes. CONCLUSIONS: The fewer positive symptoms in smokers and fewer negative symptoms in those who smoked more cigarettes may be associated with nicotine-induced suppression of some inflammatory cytokines.
Assuntos
Antipsicóticos/uso terapêutico , Interleucinas/sangue , Interleucinas/química , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Fumar/sangue , Fator de Necrose Tumoral alfa/sangue , Fatores Etários , Doença Crônica , Clozapina/sangue , Clozapina/uso terapêutico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico , Abandono do Hábito de Fumar/psicologia , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/químicaRESUMO
Schizophrenia has been observed to be associated with various abnormalities in cytokines and cytokine receptors. Three very recent reports showed the evidence that the IL3 gene, colony stimulating factor 2 receptor alpha (CSF2RA), beta (CSF2RB) and IL-3 receptor alpha (IL3RA), the IL-specific receptor subunits for CSF2 and IL3, respectively, are associated with schizophrenia. To examine the association of the IL3RA polymorphism (rs6603272) with schizophrenia in a Chinese population, 310 physically healthy patients with schizophrenia were compared with 330 age-, sex- matched normal controls. Statistically significant differences were observed in both allelic and genotypic frequencies of the rs6603272 polymorphism (Allele, chi2=6.24, d.f.=1, p=0.013, odds ratio (OR)=1.35, 95% CI 1.07-1.71; Genotype, chi2=6.85, d.f.=2, p=0.033). Our results indicate a small but significant contribution of the IL3RA polymorphism to susceptibility to schizophrenia, suggesting that the IL3 pathway may be involved in schizophrenia.
Assuntos
Predisposição Genética para Doença , Subunidade alfa de Receptor de Interleucina-3/genética , Polimorfismo Genético/genética , Receptores de Interleucina-3/genética , Esquizofrenia/genética , Alelos , Povo Asiático , Feminino , Frequência do Gene , Humanos , MasculinoRESUMO
The high rate of smoking in schizophrenia may reflect patients' attempts to reduce the side effects of antipsychotic medications, and one mechanism for this reduction may be a reduction in oxidative stress and free radical-mediated brain damage that may contribute to schizophrenic symptoms and to complications of its treatment. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS), side effects were assessed with the Simpson and Angus Rating Scale (SAS), and malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured in plasma. All of these measures were compared in 130 male inpatients with DSM-IV schizophrenia: 104 smokers and 26 non-smokers. The results showed that the positive PANSS symptoms were lower in smokers than non-smokers (14.5 vs 17.5), while the negative symptoms were lower in those who smoked more cigarettes (r=-0.23). The SAS showed no differences. The CAT activity was correlated with both GSH-Px and SOD activities. Of the three enzymes only the CAT activity was significantly higher in smokers than non-smokers (2.9 vs 1.6 U/ml), but greater SOD activity correlated more cigarettes smoked (r=0.24). Consistent with some protection against oxidative stress, MDA also was significantly lower in smokers than non-smokers (9.2 vs 14.4 nmol/ml). The fewer positive symptoms in smokers and fewer negative symptoms in those who smoked more cigarettes may be a selection bias, but appears to be associated with decreased oxidative stress and lipid peroxidation in schizophrenics who smoke tobacco.
Assuntos
Estresse Oxidativo/fisiologia , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Tabagismo/complicações , Adulto , Análise de Variância , Sintomas Comportamentais , Catalase/metabolismo , Distribuição de Qui-Quadrado , Glutationa Peroxidase , Humanos , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Esquizofrenia/sangue , Superóxido Dismutase/metabolismo , Tabagismo/sangueRESUMO
RATIONALE: Catechol-O-methyltransferase (COMT) is an enzyme involved in the degradation and inactivation of the neurotransmitter dopamine, which is important in mediating drug reward such as nicotine in tobacco smoke. Different COMT alleles encode enzyme whose activity varies from three- to fourfold that may affect dopamine levels and alter subjective effects of nicotine. Recent evidence also suggests that a COMT polymorphism may be especially important in determining an individual's predisposition to developing nicotine dependence. SUBJECTS AND METHODS: We studied the COMT Val108Met polymorphism in a male population of 203 current smokers, 66 former smokers, and 102 non-smokers. The age-adjusted odds ratios were estimated by multiple logistic regression models. RESULTS: The results showed no significant association of the COMT Val108Met with initiation, persistent smoking, or smoking cessation. However, current smokers with the Met allele had significantly higher Fagerstrom Test for Nicotine Dependence scores (7.5 +/- 2.1 vs 6.8 +/- 1.8, p = 0.018) and started smoking significantly earlier (18.4 +/- 4.9 vs 20.1 +/- 5.9 years, p = 0.036). CONCLUSIONS: These results suggest that the COMT Val108Met polymorphism may not influence smoking status in a Chinese male population but may influence the age at which smoking started and smoking severity among smokers. However, the findings must be regarded as preliminary because of the relatively small sample size and marginal associations and should be replicated in a larger cohort.
Assuntos
Povo Asiático/genética , Catecol O-Metiltransferase/genética , Polimorfismo Genético , Fumar/genética , Tabagismo/genética , Adulto , Fatores Etários , Idoso , China , Estudos de Coortes , Predisposição Genética para Doença , Genótipo , Humanos , Modelos Logísticos , Masculino , Metionina , Pessoa de Meia-Idade , Razão de Chances , Fumar/metabolismo , Abandono do Hábito de Fumar , Tabagismo/enzimologia , ValinaRESUMO
Several lines of evidence suggest that central brain-derived neurotrophic factor (BDNF) modulates food intake, metabolism, and increases in body weight. Reports have also shown that serum BDNF is altered in schizophrenic patients treated with antipsychotics. This study aimed to determine if there was a relationship between BDNF and antipsychotic-induced weight gain in patients with chronic schizophrenia. Serum BDNF was measured in 124 schizophrenia patients chronically treated with clozapine (n=57), risperidone (n=23) or typical antipsychotics (n=44) and 50 healthy control subjects. To further assess group differences in serum BDNF, additional analyses were performed in a subset of patients and controls individually matched for body mass index (BMI). BDNF levels were lower in patients with schizophrenia than normal controls. However, this difference was not present when controlling for current BMI. In the individually BMI-matched sample, no differences in serum BDNF levels were observed in schizophrenic patients compared to BMI-matched healthy controls. BDNF levels negatively correlated with BMI gain in female but not in male patients when gender was considered. Antipsychotic class exerted differential effects over BDNF levels and BMI gain. Our findings suggest that decreased BDNF levels may be associated with weight gain in female schizophrenic patients on long-term antipsychotic treatment.
Assuntos
Antipsicóticos/efeitos adversos , Fator Neurotrófico Derivado do Encéfalo/sangue , Esquizofrenia/tratamento farmacológico , Aumento de Peso , Antipsicóticos/uso terapêutico , Doença Crônica , Clozapina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risperidona/uso terapêutico , Esquizofrenia/fisiopatologia , SoroRESUMO
OBJECTIVE: To investigate the effects of Ginkgo biloba extract (EGb) administration on T lymphocyte subsets and superoxide dismutase (SOD) levels in schizophrenia. METHODS: One hundred and nine schizophrenic inpatients were randomly assigned to 12 weeks of treatment with 360 mg/day of EGb plus a stable dose of 0.25 mg kg(-1) day(-1) of haloperidol and placebo plus the same dose of haloperidol using a double-blind design. Clinical efficacy was determined using the Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Positive Symptoms, and Scale for Assessment of Negative Symptoms. T lymphocytes (CD3+), T helper cells (CD4+), T suppressor cells (CD8+), and IL-2-secreting cells were measured using the alkaline phosphatase/antialkaline phosphatase technique; and SOD levels were measured by radioimmunometric assay at baseline and at posttreatment, as compared to 30 sex- and age-matched normal subjects. RESULTS: Patients demonstrated significantly lower CD3+, CD4+, and IL-2-secreting cells, together with CD4/CD8 ratio, and significantly higher blood SOD levels than did healthy controls at baseline. There was a significantly negative relationship between SOD and CD4+ cells in the schizophrenic group at baseline. After a 12-week treatment, CD3+, CD4+, and IL-2-secreting cells, together with CD4/CD8 ratio, showed a significant increase, but a significant decrease in SOD levels in the EGb group. There was only a significant increase in CD4+ cells but no change in SOD levels in the placebo group. There was a significant correlation between the change in CD4+ cells at posttreatment vs pretreatment and a reduction of BPRS total score in the whole patient group. CONCLUSIONS: EGb may improve the decreased peripheral immune functions in schizophrenia. The beneficial effects of EGb on the immune systems and the improvement of schizophrenic symptoms may be medicated through its antioxidant activity.
Assuntos
Antioxidantes/uso terapêutico , Antipsicóticos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Ginkgo biloba , Haloperidol/uso terapêutico , Esquizofrenia/tratamento farmacológico , Subpopulações de Linfócitos T/efeitos dos fármacos , Adulto , Antioxidantes/farmacologia , Antipsicóticos/farmacologia , Escalas de Graduação Psiquiátrica Breve , Complexo CD3/análise , Contagem de Linfócito CD4 , Relação CD4-CD8 , Doença Crônica , Método Duplo-Cego , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Haloperidol/farmacologia , Humanos , Interleucina-2/metabolismo , Masculino , Pessoa de Meia-Idade , Esquizofrenia/enzimologia , Esquizofrenia/imunologia , Psicologia do Esquizofrênico , Superóxido Dismutase/sangue , Fatores de Tempo , Resultado do TratamentoRESUMO
There is accumulating evidence of altered antioxidant enzyme activities and increased levels of lipid peroxidation in schizophrenia. Free radical-mediated abnormalities may contribute to specific aspects of schizophrenic symptomatology and complications of its treatment. However, few studies have evaluated both antioxidant enzymes and lipid peroxidation in the same schizophrenic patient groups treated with typical or atypical antipsychotics. Plasma malondialdehyde (MDA) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were analyzed using established procedures in 92 medicated schizophrenia including paranoid (n=34), disorganized (n=18) and residual subtypes (n=40), as well as in control subjects (n=50). The results showed that activities of SOD and GSH-Px were decreased but levels of MDA were elevated in patients with a chronic form of schizophrenia as compared with normal controls. SOD and GSH-Px activities were found to be significantly lower in paranoid and residual subtypes compared to both disorganized subtype and the control group. MDA levels were significantly higher in all subtypes compared to the control group. There were no significant differences in any parameters measured among all three subgroups treated with clozapine (n=44), risperidone (n=20) and typical antipsychotics (n=28). Additionally, a significantly higher MDA levels, but a significantly lower CAT activity was noted in female than male patients. These results suggest that oxidative stress may be implicated in the pathophysiology of all subtypes of schizophrenia, which may contribute to the increased membrane lipid peroxidation. Long-term treatments with typical and atypical antipsychotics may produce the similar effects on the antioxidant enzymes and lipid peroxidation.
Assuntos
Antipsicóticos/uso terapêutico , Catalase/sangue , Glutationa Peroxidase/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/sangue , Esquizofrenia/tratamento farmacológico , Superóxido Dismutase/sangue , Adulto , Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Clozapina/uso terapêutico , Feminino , Radicais Livres , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Risperidona/efeitos adversos , Risperidona/uso terapêutico , Esquizofrenia/enzimologiaRESUMO
The bilateral communication between the immune and neuroendocrine systems plays an essential role in modulating the adequate response of the hypothalamic-pituitary-adrenal (HPA) axis to the stimulatory influence of cytokines and stress-related mediators. Growing evidence suggests that neuro-immune-endocrine crosstalk may be impaired in schizophrenia. We determined the relationship between cortisol, cytokines interleukin-2 (IL-2) and interleukin-6 (IL-6), and symptoms in schizophrenia during treatment with typical and atypical antipsychotic drugs. Subjects included 30 healthy controls (HC) and 78 schizophrenic (SCH) in-patients. SCH were randomly assigned to 12-week treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol using a double-blind design. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS). Serum cortisol and IL-2 levels were assayed by radioimmunometric assay, and serum IL-6 levels by quantitative enzyme-linked immunosorbent assay. Following a 2-week washout period, serum levels of cortisol, IL-2, and IL-6 were increased in patients with schizophrenia compared to HC. Elevations in cortisol were associated with increase in both IL-2 and IL-6 in SCH. Moreover, elevations in cortisol were associated with negative symptoms and IL-2 with positive symptoms. In all, 12 weeks of risperidone treatment significantly decreased elevated cortisol and improved negative symptoms, but produced similar effects on IL-2 and IL-6 as well as on positive symptoms compared to haloperidol. The improvement of negative symptoms was related to the change in cortisol. Our results suggest that the imbalance in the HPA axis and cytokine system in patients with SCH is implicated in clinical symptoms, and is improved with atypical antipsychotic treatment.
Assuntos
Resistência a Medicamentos/fisiologia , Hidrocortisona/sangue , Interleucina-2/sangue , Interleucina-6/sangue , Esquizofrenia/sangue , Adulto , Antipsicóticos/uso terapêutico , Estudos de Casos e Controles , Método Duplo-Cego , Resistência a Medicamentos/efeitos dos fármacos , Feminino , Haloperidol/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Radioimunoensaio/métodos , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Fatores de Tempo , Resultado do TratamentoRESUMO
RATIONALE: There are few data from systematic, double-blind clinical trials that have compared the effect of the typical and the atypical antipsychotics on serum prolactin (PRL) levels in patients with schizophrenia. OBJECTIVES: The goal of this study was to compare the effect of risperidone and haloperidol on serum PRL and investigate the relationship between serum PRL levels and clinical response in patients with schizophrenia. METHODS: Seventy-eight inpatients with a diagnosis of schizophrenia (according to DSM-III-R) were randomly assigned to 12 weeks of treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol after a 2-week washout period, using a randomized, double-blind design. Clinical efficacy was determined using the positive and negative syndrome scale (PANSS). Their serum PRL was assayed by means of radioimmunometric assay (RIA) between pre-treatment and post-treatment, and compared with 30 sex-matched and age-matched normal subjects. RESULTS: Both risperidone and haloperidol treatment significantly increased serum PRL levels in drug-free chronic schizophrenia patients (both P<0.001). Hyperprolactinemia induced by risperidone 6 mg/kg was comparable to levels produced by haloperidol 20 mg/day. Considering dose-adjusted serum PRL levels, risperidone treatment induced a significant elevation of PRL levels compared with haloperidol treatment at the haloperidol equivalent (P<0.001). Change in PRL levels at pre-treatment and post-treatment were related to positive symptom improvement seen in the risperidone group (r=0.51, P=0.016), but not in the haloperidol group (P>0.05). Female patients showed both a higher baseline and post-treatment PRL level and a greater increase in PRL than men (all P<0.05). CONCLUSIONS: Risperidone is associated with a robust effect on prolactin secretion in contrast to the conventional antipsychotic haloperidol. Prolactin monitoring during risperidone treatment should be performed.
Assuntos
Antipsicóticos/efeitos adversos , Haloperidol/efeitos adversos , Prolactina/sangue , Risperidona/efeitos adversos , Esquizofrenia/tratamento farmacológico , Adulto , Método Duplo-Cego , Feminino , Humanos , Hiperprolactinemia/induzido quimicamente , Masculino , Prolactina/metabolismo , RadioimunoensaioRESUMO
OBJECTIVE: To investigate the disease burden of drug-resistant and drug-sensitive tuberculosis (TB) patients in Guangdong and Zhejiang provinces. METHODS: Three hundred and two patients with TB, who had been involved in the project for drug resistance surveillance and completed the full course of treatment, were enrolled for this study. The proportion method for drug susceptibility was used. The method of disability adjusted life year (DALY) was applied to assess the disease burden of TB patients. RESULTS: The average DALYs of initial cases with drug-sensitive and drug-resistant TB, and retreated cases with drug-sensitive and drug-resistant TB, were 0.26, 0.68, 0.49, and 1.04, respectively. The average DALY loss of drug-resistant TB patients was 0.86 and that of drug-sensitive TB patients was 0.44. CONCLUSIONS: The values of DALY for initial and retreated cases with drug-resistant TB were 2 times higher than those for patients with drug-sensitive TB, indicating the higher disease burden in drug-resistant TB patients. Therefore, to reduce the disease burden of patients with drug-resistant TB, standardized protocols must be applied in the treatment of TB.
Assuntos
Efeitos Psicossociais da Doença , Tuberculose Resistente a Múltiplos Medicamentos/economia , Tuberculose Pulmonar/economia , Antituberculosos/farmacologia , China/epidemiologia , Humanos , Estudos de Amostragem , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologiaRESUMO
BACKGROUND: Many studies have indicated that immune cytokines may be involved in the pathophysiology of schizophrenia. Recently, there have been reports that typical and atypical antipsychotic drugs may influence the levels of cytokines or cytokine receptors. The aim of this study was to compare the effect of typical and atypical antipsychotic drugs on serum interleukin-2 (IL-2), interleukin-6 (IL-6), and interleukin-8 (IL-8) and to investigate the relationship between the changes in cytokines and the therapeutic outcome in schizophrenia. METHOD: From April 1996 to August 1997, seventy-eight inpatients with a diagnosis of chronic schizophrenia (DSM-III-R) were randomly assigned to 12 weeks of treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol. Clinical efficacy was determined using the Positive and Negative Syndrome Scale. Serum IL-2 was assayed by radioimmunometric assay, and serum IL-6 and IL-8 concentrations were measured by quantitative enzyme-linked immunosorbent assay in patients and 30 sex- and age-matched normal subjects. RESULTS: Both risperidone and haloperidol reduced the elevated serum IL-2 concentrations in schizophrenia, and no significant difference was noted in the reduction of serum IL-2 concentrations between risperidone and haloperidol treatment. Neither risperidone nor haloperidol showed significant influence on the higher serum IL-6 or IL-8 concentrations in schizophrenia. Correlations between serum IL-2 or IL-8 concentrations at baseline and the therapeutic outcome were observed, demonstrating that patients presenting with low concentrations of serum IL-2 or IL-8 at baseline showed greater improvement and patients presenting with higher serum IL-2 or IL-8 concentrations at baseline showed less improvement after treatment. CONCLUSIONS: Both typical and atypical anti-psychotic drugs may at least partially normalize abnormal immune alterations in schizophrenia. Some immune parameters at baseline may be useful for predicting the neuroleptic response of schizophrenic patients.
Assuntos
Antipsicóticos/uso terapêutico , Haloperidol/uso terapêutico , Interleucina-2/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Risperidona/uso terapêutico , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/farmacologia , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Haloperidol/farmacologia , Hospitalização , Humanos , Imunidade Celular/efeitos dos fármacos , Interleucina-2/imunologia , Interleucina-6/imunologia , Interleucina-8/imunologia , Masculino , Radioimunoensaio , Risperidona/farmacologia , Esquizofrenia/imunologia , Resultado do TratamentoRESUMO
Free radicals may be involved in the pathogenesis of tardive dyskinesia (TD). Superoxide dismutase (SOD), a critical enzyme in the detoxification of superoxide radicals, was found to be abnormal in TD. To examine the blood SOD levels in schizophrenic patients with and without TD, and the relationships between SOD levels and tardive dyskinesia symptoms in TD patients, 45 physically healthy patients with TD who met DSM-III-R criteria for schizophrenia were compared with 45 schizophrenic patients without TD, as well as with 50 age-, sex- and smoking-matched normal controls. The severity of TD was assessed using the abnormal involuntary movement scale (AIMS). The psychopathology of patients were assessed by the Positive and Negative Syndrome Scale (PANSS). Blood SOD levels were measured by radioimmunometric assay (RIA). The results showed that the patients with TD had lower concentrations of blood SOD than those without TD, but had higher blood SOD levels than the normal controls. In the patients with TD, AIMS total score was inversely correlated with SOD levels. Our data support the view that free radicals may be involved in the pathophysiology of TD. There may exist a relationship between the free radical metabolism and the severity of dyskinesia of TD patients.
Assuntos
Antipsicóticos/efeitos adversos , Discinesia Induzida por Medicamentos/enzimologia , Discinesia Induzida por Medicamentos/etiologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/enzimologia , Superóxido Dismutase/sangue , Adulto , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Esquizofrenia/diagnóstico , Índice de Gravidade de DoençaRESUMO
Cytokines have been one of the recent focal points of immunological research in schizophrenia. The present study was to assess the serum levels of some of interleukins in schizophrenia and their relationships with the psychopathological parameters. Seventy physically healthy Chinese patients, who met DSM-III-R criteria for schizophrenia and who were drug-free for at least 2 weeks, were compared with 30 age- and sex-matched Chinese normal controls. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Serum levels of IL-6 and IL-8 were measured by sandwich enzyme-linked immunosorbent assay (ELISA), and serum IL-2 level was assayed by radioimmunometric assay (RIA). Serum levels of IL-2, IL-6 and IL-8 were significantly elevated in patients with a chronic form of schizophrenia (all p<0.05). There was a significant inverse relationship between IL-2 level and the PANSS positive subscale P (r=-0.31, p=0.006) and a significant positive correlation between IL-8 level and PANSS negative subscale N (r=0.25, p=0.036) in schizophrenic patients. In control subjects, a significant and positive relationship between serum IL-2 and IL-6 (r=0.513, p=0.004) was noted, whereas, there was a significant and negative relationship between IL-2 and IL-8 in schizophrenic patients (r=-0.28, p=0.02). Our data confirms and supports the view that immune disturbance is involved in schizophrenia, which is compatible with the possibility that Chinese schizophrenic patients have an ongoing autoimmune process. This immune disturbance is related to the subgroup of schizophrenic patients with characteristic clinical variables. The dysfunction of interaction or inter-adjustment between different cytokines may exist in schizophrenic patients.
Assuntos
Interleucina-2/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Esquizofrenia/imunologia , Psicologia do Esquizofrênico , Adulto , Análise de Variância , Estudos de Casos e Controles , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Estatísticas não ParamétricasRESUMO
There are a number of indications that schizophrenia is associated with changes in the immune system. Although functional studies have mostly demonstrated decreased in vitro production of IL-2 by peripheral blood mononuclear cells (PBMCs) stimulated with mitogen, the reason is unclear. The aim of the study was to explore the relationship between IL-2 production and CD4+ cells which mainly secret IL-2 in non-Caucasian patients with schizophrenia. Blood CD4+ cells and mitogen-stimulated IL-2 secreting cells identified by an immunohistochemical study with the alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique, and in vitro IL-2 production with radioimmunometric assay (RIA) were measured in 30 schizophrenic patients and 30 normal control subjects matched for sex, age and race. The results showed that blood CD4+ cells and mitogen-induced IL-2 secreting cells and IL-2 production were significantly lower in schizophrenic subjects than in the normal controls. There was significantly positive correlation between CD4+ cells and IL-2 production in normal controls but not in patients. These findings suggest that immune disturbance may be present in schizophrenic patients. The lower in vitro IL-2 production is probably related to the decreased number of T-cells that secret IL-2, as well as to the intrinsic disorder of the patients' T cells.
Assuntos
Antígenos CD4/biossíntese , Antígenos CD4/imunologia , Interleucina-2/biossíntese , Interleucina-2/imunologia , Esquizofrenia/imunologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RadioimunoensaioRESUMO
Blood levels of superoxide dismutase (SOD), measured by radioimmunometric assay, were compared in 68 patients with chronic schizophrenia and 50 normal control subjects. Psychopathology in the patients was assessed with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Scale for the Assessment of Negative Symptoms. Blood SOD levels were significantly elevated in schizophrenia compared with control values. SOD levels showed a positive relationship with the BRPS and the SAPS total score in patients.
Assuntos
Delusões/fisiopatologia , Alucinações/fisiopatologia , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Superóxido Dismutase/sangue , Adulto , Doença Crônica , Delusões/diagnóstico , Feminino , Radicais Livres/metabolismo , Alucinações/diagnóstico , Humanos , Peroxidação de Lipídeos/fisiologia , Masculino , Pessoa de Meia-Idade , Valores de Referência , Esquizofrenia/diagnósticoRESUMO
The elevation in serum prolactin (PRL) concentration in schizophrenic patients treated with typical antipsychotic drugs is well documented. Recently, increased prolactin levels have been reported in patients taking risperidone. The purpose of this study was to explore the effect of the atypical antipsychotic drug risperidone on serum prolactin, and to investigate the relationship between the change in PRL and the therapeutic outcome. In this study, 30 male inpatients with a diagnosis of chronic schizophrenia (DSM-III-R) were assigned to 12 weeks of treatment with risperidone after a 2-week washout period. The risperidone dose was fixed at 6 mg/day. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS). Serum PRL was assayed in serum by radioimmunometric assay in schizophrenic patients before and after 12-week treatment, as compared to 30 age-matched normal male subjects. The results showed that risperidone treatment significantly increased the serum PRL. A significant and positive relationship between the change in PRL at pre- and post-treatment and the reduction rate of PANSS positive subscore was observed. Risperidone treatment significantly increased the serum PRL levels of schizophrenic patients. There was a close relationship between the improvement in positive symptoms and the change of serum PRL level before and after risperidone treatment. The serum PRL levels at baseline could be used to predict the responses of schizophrenic patients to risperidone.