Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
1.
One Health ; 18: 100743, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38725962

RESUMO

Background: In December 2015, the World Health Organization, the World Animal Health Organization, and the Food and Agriculture Organization of the United Nations convened the International Congress on the elimination of rabies in Geneva. How to use epidemiological factors of post-exposure prophylaxis to prevent rabies has become the focus of attention. Objective: To analyze the epidemiological characteristics of 9772 patients with rabies in a four-year period in one hospital, to clarify the outbreak law of rabies and to explore the corresponding prevention and control strategies. Methods: The epidemiological data of rabies patients were collected from the infectious disease reporting information management system of the hospital from July 2018 to June 2022. The distributional characteristics of 13 influencing factors were analyzed using the chi-square test and linear regression. Results: There was a significant correlation between the number of wounds and age, and the numbers of female and male patients were close. People over the age of 44 were more likely to get bites or scratches on their lower extremity (P<0.0001). There was a greater possibility for elderly people to be bitten by dogs (P<0.0001). Dogs preferred to bite or scratch lower limbs (P<0.0001), while cats upper limbs (P<0.0001). Upper limbs were more possibly attacked by animals at home (P<0.0001). There were significant correlations among exposure grade, wound treatment and number of wounds. Conclusions: Lower extremity protection is needed for the elderly and when encountering dogs, and more attention needs to be paid to the upper extremities when encountering cats and household pets, as well as pets that are cute but need to be protected from bites or scratches.

2.
J Transl Med ; 19(1): 289, 2021 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217302

RESUMO

BACKGROUND: We performed a prospective multicentre diagnostic study to evaluate the combined interferon-γ (IFN-γ) and interleukin-2 (IL-2) release assay for detect active pulmonary tuberculosis (TB) in China. METHODS: Adult patients presenting symptoms suggestive of pulmonary TB were consecutively enrolled in three TB-specialized hospitals. Sputum specimens and blood sample and were collected from each participant at enrolment. The levels of Mycobacterium tuberculosis (MTB)-specific antigen-stimulated IFN-γ and IL-2 were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: Between July 2017 and December 2018, a total of 3245 patients with symptoms suggestive of pulmonary TB were included in final analysis. Of 3245 patients, 2536 were diagnosed as active TB, consisting of 1092 definite TB and 1444 clinically diagnosed TB. The overall sensitivity and specificity of IFN-γ were 83.8% and 81.5%, respectively. In addition, compared with IFN-γ, the specificity of IL-2 increased to 94.3%, while the sensitivity decreased to 72.6%. In addition, the highest sensitivity was achieved with parallel combination of IFN-γ/IL-2, with a sensitivity of 87.9%, and its overall specificity was 79.8%. The sensitivity of series combination test was 68.5%. Notably, the sensitivity of series combination test in definite TB (72.1%) was significantly higher than that in clinically diagnosed TB (65.8%). CONCLUSION: In conclusion, we develop a new immunological method that can differentiate between active TB and other pulmonary diseases. Our data demonstrates that the various IFN-γ/IL-2 combinations provides promising alternatives for diagnosing active TB cases in different settings. Additionally, the diagnostic accuracy of series combination correlates with severity of disease in our cohort.


Assuntos
Mycobacterium tuberculosis , Tuberculose Pulmonar , Adulto , Antígenos de Bactérias , China , Ensaio de Imunoadsorção Enzimática , Humanos , Interferon gama , Testes de Liberação de Interferon-gama , Interleucina-2 , Estudos Prospectivos , Tuberculose Pulmonar/diagnóstico
3.
J Clin Pharm Ther ; 46(6): 1600-1605, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34293194

RESUMO

WHAT IS KNOWN AND OBJECTIVE: This study was aimed at comparing the adverse drug reactions (ADRs) arising from the use of iodinated contrast medium (ICM) and gadolinium-based contrast media (GBCM), and to provide a basis for the clinical selection of contrast media. METHODS: Retrospective data for ADR cases occurring from the use of ICM or GBCM during enhanced scanning in computed tomography and magnetic resonance imaging were collected between June/2013 and May/2020 from Wenling Hospital of Traditional Chinese Medicine. Chi-square tests were performed based on the characteristics of patients and the classification of contrast medium. Bonferroni correction was applied to the statistical analyses with multiple comparisons of proportions. RESULTS: Among 27,328 patients who were subjected to enhanced CT scanning, 207 cases (0.76%) showed ICM-related ADRs. Among 16,381 patients who were subjected to enhanced MRI scanning, 25 cases (0.15%) showed ADRs related to GBCM. The incidence of ADR induced by GBCM was significantly lower than ICM-induced ADR (p < 0.01). There were no significant differences in the incidence among different types of ICM, including ioversol and iodixanol, as well as iodixanol from different manufacturers (p > 0.05). Interestingly, the ADR incidence of ICM seemed to be associated with gender, with a significantly higher incidence in females than in male patients, and it was also associated with the age, with a lower occurrence in older (>44 years) compared to younger patients. WHAT IS NEW AND CONCLUSION: With respect to ADR incidence, the safety profile of ICM of different types and different manufacturers was found to be similar in clinical use, warranting no need of specifically choosing imported or more expensive products. While choosing contrast medium type for clinical use, attention should be paid to certain populations, especially to younger and female patients when the patients are about to undergo a contrast-enhanced examination.


Assuntos
Meios de Contraste/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Gadolínio/efeitos adversos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Tomografia Computadorizada por Raios X/métodos , Ácidos Tri-Iodobenzoicos/administração & dosagem , Ácidos Tri-Iodobenzoicos/efeitos adversos , Adulto Jovem
4.
Tuberculosis (Edinb) ; 128: 102063, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33713970

RESUMO

Xinjiang is a unique region of Central Asian part of China. It is widely noted for high tuberculosis burden and particularly for growing prevalence of drug resistance. Understanding genotypic distribution of Mycobacterium tuberculosis could help clarify unknown causes for the spread of drug-resistant strains. We analyzed 986 M. tuberculosis isolates collected from Xinjiang. Two genotyping schemes, i.e., spoligotyping and multiple-locus variable number tandem repeats (VNTR), were used to determine the phylogenetic lineages and their association with drug-resistances. The M. tuberculosis isolates studied displayed wide distribution of spoligotypic lineages, including Beijing, T, CAS, Ural, LAM, MANU, H, X, EAI, S, Microti, and BOV. The dominant Beijing lineage showed statistical difference from non-Beijing lineages in patients ages (P < 0.001), ethnic groups (P < 0.001) and resistance of three or more drugs (P = 0.008). Further analysis of the year of 2017 subset (n = 257) using VNTR scheme revealed an extremely high discrimination power (Hunter-Gaston discriminatory index = 0.9994). Cluster analysis showed a much lower recent transmission index (7.93%), indicating that the high drug-resistant tuberculosis in this region was mainly caused by reactivation or inappropriate therapy rather than by recent transmission. These data would be valuable for making and implementing policies for improving tuberculosis treatment and care in Xinjiang.


Assuntos
Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Técnicas de Tipagem Bacteriana , China , Feminino , Genótipo , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Repetições Minissatélites , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/efeitos dos fármacos , Adulto Jovem
5.
J Colloid Interface Sci ; 575: 443-451, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32388290

RESUMO

As for photocatalytic oxidation of nitric oxide (NO), the low NO oxidation activity and generation of by-products (cf. NO2) are the urgent challenge. To tackle these issues, a simple in-situ growing stragegy was employed to constructe Ti3C2/g-C3N4 system. The fabricated Ti3C2/g-C3N4 composite (TC-CN) presented enhanced photocatalytic NO removal efficiency and inhibited toxic NO2 generation. Density functional theory (DFT) calculations and experimental characterizations were combined to demonstrate the presence of strong interface effect between Ti3C2 and g-C3N4, which could greatly improve photo-generated charge carrier separation via the construction of electron transfer channels, and further activate oxygen molecules adsorbed on the side of Ti3C2 layer. As a result, nitrite and nitrate instead of NO2 were the final products during the photocatalytic reaction process through the monitoring by in situ diffuse reflectance infrared spectroscopy (DRIFTS).

6.
Stud Health Technol Inform ; 264: 1449-1450, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438175

RESUMO

Terminology facilitates consistent use and semantic integration of heterogeneous, multimodal data within and across domains. This paper presents TBench (Termilology Workbench) for multilingual terminology editing and development within a distributed environment. TBench is a web-service Java tool consisting of two main functionalities that are knowledge construction (i.e.extended model based on ISO25964, batch reusing and constructing multilingual concept hierarchy and relationships) and collaborative control in order to achieve custom extensions, reuse, multilingual alignment, integration and refactoring.


Assuntos
Multilinguismo , Semântica , Software , Vocabulário Controlado
7.
Stud Health Technol Inform ; 264: 1598-1599, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438250

RESUMO

This work describes the design and building of a Chinese clinical terminology (called CCTS). The terminology is similar to an ontology, and will promote the use of Chinese clinical data, such as indexing, retrieval and exchange. The terminology is a TOPL concept framework, which integrates hierarchical structures of Chinese and interenational reference terminology standards for health. Our framework includes 14 subtrees, 2286 classes and 65 relationships.


Assuntos
Vocabulário Controlado , Padrões de Referência
8.
J Clin Microbiol ; 57(1)2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30333128

RESUMO

The sustained increase in the incidence of nontuberculous mycobacterial (NTM) infection and the difficulty in distinguishing these infections from tuberculosis constitute an urgent need for NTM species-level identification. The MeltPro Myco assay is the first diagnostic system that identifies 19 clinically relevant mycobacteria in a single reaction based on multicolor melting curve analysis run on a real-time PCR platform. The assay was comprehensively evaluated regarding its analytical and clinical performances. The MeltPro Myco assay accurately identified 51 reference mycobacterial strains to the species/genus level and showed no cross-reactivity with 16 nonmycobacterial strains. The limit of detection was 300 bacilli/ml, and 1% of the minor species was detected in the case of mixed infections. Clinical studies using 1,163 isolates collected from five geographically distinct health care units showed that the MeltPro Myco assay correctly identified 1,159 (99.7%) samples. Further testing with 94 smear-positive sputum samples showed that all samples were correctly identified. Additionally, the entire assay can be performed within 3 h. The results of this study confirmed the efficacy of this assay in the reliable identification of mycobacteria, suggesting that it might potentially be used as a screening tool in regions endemic for tuberculosis.


Assuntos
Técnicas Microbiológicas/métodos , Técnicas de Diagnóstico Molecular/métodos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Micobactérias não Tuberculosas/isolamento & purificação , Coinfecção/diagnóstico , Coinfecção/microbiologia , DNA Bacteriano/genética , DNA Espaçador Ribossômico/genética , Humanos , Técnicas Microbiológicas/normas , Técnicas de Diagnóstico Molecular/normas , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/genética , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Análise de Sequência de DNA , Escarro/microbiologia , Fatores de Tempo , Tuberculose/diagnóstico , Tuberculose/microbiologia
9.
Eur Respir J ; 53(3)2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30578402

RESUMO

The current treatment for multidrug-resistant tuberculosis (MDR-TB) takes a lengthy period of 18-24 months and has a poor cure rate of 50-60%. A multicenter, prospective cohort study was conducted to assess the role of testing for molecular susceptibility to pyrazinamide (PZA) in optimising treatment for MDR-TB.We assigned 76 patients to an optimised molecular susceptibility group and 159 patients to a regular treatment group where PZA susceptibility was not determined. Of these patients, 152 were matched after propensity score matching (76 in the optimised group and 76 in the regular group). Treatment success rate was measured in the propensity-matched cohort as the primary outcome.Patients in the optimised group achieved a higher treatment success rate than those in the regular group (76.3% versus 55.3%, p=0.006). Of 51 patients with isolates that were susceptible to PZA and who were receiving a 12-month regimen, 42 (82.4%) were treated successfully. The optimised group showed faster culture conversion than the regular group (p=0.024). After exclusion of pre-extensively drug-resistant TB (pre-XDR-TB), the treatment outcome in the optimised group was still better than the regular group (83.1% versus 62.1%, p=0.009).Introducing molecular susceptibility testing for PZA improved the treatment outcomes for MDR-TB without the use of new drugs. Introducing PZA for patients with PZA-susceptible (PZA-S) MDR-TB allows the current regimen to be shortened to 12 months with comparable success rates to the World Health Organization (WHO) recommended shorter regimen.


Assuntos
Mycobacterium tuberculosis/efeitos dos fármacos , Pirazinamida/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Amidoidrolases/genética , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , China , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Modelos Logísticos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Estudos Prospectivos , Pirazinamida/uso terapêutico , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
10.
J Clin Lab Anal ; 32(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28670691

RESUMO

BACKGROUND: T-cell Xtend (TCX) was introduced to extend the blood storage time for T-SPOT.TB test, a widely used commercial interferon gamma release assay (IGRA) for rapid in vitro tuberculosis. METHODS: A total of 99 Uyghur suspected tuberculosis patients were recruited in this study. T-SPOT.TB test was performed with fresh blood (controls), 36 hours delayed blood and delayed and TCX-treated (at 36 hours) blood from each patient, respectively. RESULTS: White blood cells and lymphocytes proportion in peripheral blood mononuclear cells s and spot-forming cells in positive control wells decreased significantly in delayed blood samples when compared with controls, while this decrease was not detected in TCX-treated group. In the 58 patients with paired T-SPOT.TB results of three groups of samples, a higher positive rate was observed in TCX-treated group than both in controls and untreated group (41.4% vs 37.9% and 25.9%). The concordance of T-SPOT.TB results between the treated group and controls was 0.856, whereas the agreement between controls and untreated group was unsatisfactory (0.649). In the 23 elderly patients (>70 years old) with paired T-SPOT.TB results of controls and TCX group, treated group showed a non-significant trend toward higher positive rate than controls (43.5% vs 26.1%, P=.22). Meanwhile, TCX treatment reduced the risk of false negative T-SPOT.TB results in the elderly population. CONCLUSION: Deterioration of blood sample caused by long storage time can be neutralized by TCX treatment. The results provide data for the utility of TCX in a novel population and in Asian region, and reveal the potential of TCX to improve the accuracy of T-SPOT.TB test in elderly population.


Assuntos
Preservação de Sangue , Testes de Liberação de Interferon-gama , Adulto , Preservação de Sangue/normas , Preservação de Sangue/estatística & dados numéricos , Estudos de Casos e Controles , Feminino , Humanos , Testes de Liberação de Interferon-gama/normas , Testes de Liberação de Interferon-gama/estatística & dados numéricos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Tuberculose/diagnóstico
11.
Biomed Res Int ; 2017: 3179535, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28337447

RESUMO

Objectives. We studied the genetic diversity of clinical isolates from patients with tuberculosis in the multiethnic area of Xinjiang autonomous region in China. A total of 311 clinical M. tuberculosis isolates were collected in 2006 and 2011 and genotyped by two genotyping methods. All isolates were grouped into 68 distinct spoligotypes using the spoligotyping method. The Beijing family was dominant, followed by T1 and CAS. MIRU-VNTR results showed that a total of 195 different VNTR types were identified. Ten of the 15 loci were highly or moderately discriminant according to their HGDI scores, and 13 loci had good discriminatory power in non-Beijing family strains, whereas only two loci had good discriminatory power in Beijing family strains. Chi-square tests demonstrated that there were no correlations between four characteristics (sex, age, type of case, and treatment history) and the Beijing family. In summary, Beijing family strains were predominant in Xinjiang, and the VNTR-15China locus-set was suitable for genotyping all Xinjiang strains, but not for the Beijing family strains. Thus, these data suggested that different genotype distributions may exist in different regions; MLVA locus-sets should be adjusted accordingly, with newly added loci to increase resolution if necessary.


Assuntos
Variação Genética , Mycobacterium tuberculosis/genética , Tuberculose/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas de Tipagem Bacteriana , China , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Mycobacterium tuberculosis/patogenicidade , Tuberculose/microbiologia
12.
Stud Health Technol Inform ; 245: 1338, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29295419

RESUMO

To handle differences in affiliation names submitted with biomedical journal articles, we build an affiliation knowledge base named Authority File for Affiliations (AFA) based on ontology principles. There are currently 113,700 affiliation concepts with about 583,700 affiliation names. The AFA becomes an essential tool in managing citation information and data analysis.


Assuntos
Autoria , Bases de Dados Factuais , Bases de Conhecimento , Metadados , Ontologias Biológicas
13.
PLoS One ; 10(2): e0117777, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25679504

RESUMO

OBJECTIVE: To assess associations between the aqueous humour concentration of interleukin IL-1ß, IL-6, IL-8, IL-10 and IL-12p, tumor necrosis factor α (TNF-α) and vascular endothelial growth factor (VEGF) and axial length in eyes with cataract. METHODS: The hospital-based investigation included patients who underwent cataract surgery between March 2014 and April 2014. Using aqueous humour collected at the start of cataract surgery, the interleukins IL-1ß, IL-6, IL-8, IL-10 and IL-12p, TNF-α and VEGF were examined using a cytometric bead array. Axial length was determined by partial coherence laser interferometry (IOL Master). RESULTS: The study included 33 patients with cataract (33 eyes) with a mean age of 69.2±10.8 years (range: 50-87 years) and a mean axial length of 24.7±1.9 mm (range: 22.6-31.5 mm). Lower aqueous concentration of VEGF was significantly associated with longer axial length (VEGF concentration (pg/mL) = -5.12 x Axial Length (mm) + 163; correlation coefficient r = -0.41; P<0.001) and more myopic refractive error (VEGF concentration (pg/mL) = 1.27 x spherical equivalent (diopters) + 44.8; r = 0.383; P = 0.002). The aqueous concentrations of all other substances were not significantly (all P>0.10) associated with axial length or refractive error. CONCLUSIONS: Higher intravitreal concentrations of VEGF were measured in eyes with a longer axial length, while the intraocular concentrations of IL-1ß, IL-6, IL-8, IL-10, IL-12p and TNF-α were not correlated with axial length. The lower concentration of VEGF in axially elongated eyes may be one of the reasons for the lower prevalence of age-related macular degeneration and diabetic retinopathy in myopic eyes.


Assuntos
Humor Aquoso/metabolismo , Catarata/metabolismo , Catarata/patologia , Citocinas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Catarata/diagnóstico , Catarata/terapia , Extração de Catarata , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
J Neurol Sci ; 343(1-2): 69-75, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24952673

RESUMO

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases characterized by the immune-mediated demyelination and neurodegeneration of the CNS. Our previous studies showed that Rho kinase inhibitor Fasudil can delay onset, and ameliorate severity of EAE, accompanied by the improvement in myelination and the inhibition of inflammatory responses in the CNS. In this study, we found that Fasudil inhibited the migration of T cells indirectly by affecting the production of inflammatory factors and the expression of chemokines in astrocytes functions, indicating that Fasudil treatment reduced inflammatory cytokines such as TNF-α and IL-6, reactive oxygen species (NO) and chemokines like MIP-3α (CCL-20), RANTES (CCL5), MIP-1α (CCL-3) and MCP-1 (CCL2) in vitro, and blocked the chemotaxis of reactive mononuclear cells in EAE mice. Further studies found that Fasudil treatment reduced the infiltration and accumulation of pathogenic T cells into the CNS. Astrocytes expressing GFAP and CCL-20 were inhibited in Fasudil-treated EAE compared with control mice. These results demonstrate that Fasudil alleviates the pathogenesis of EAE possibly by blocking astrocyte-derived chemokine-mediated migration of inflammatory macrophages and pathogenic T cells, and might be used to treat MS.


Assuntos
Astrócitos/metabolismo , Movimento Celular/fisiologia , Citocinas/metabolismo , Regulação da Expressão Gênica/fisiologia , Quinases Associadas a rho/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Animais Recém-Nascidos , Astrócitos/efeitos dos fármacos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/genética , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/patologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Glicoproteína Mielina-Oligodendrócito/toxicidade , Nitritos/sangue , Fragmentos de Peptídeos/toxicidade , Inibidores de Proteínas Quinases/farmacologia , Espécies Reativas de Oxigênio/metabolismo
15.
Immunology ; 143(2): 219-29, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24749492

RESUMO

Viewing multiple sclerosis (MS) as both neuroinflammation and neurodegeneration has major implications for therapy, with neuroprotection and neurorepair needed in addition to controlling neuroinflammation in the central nervous system (CNS). While Fasudil, an inhibitor of Rho kinase (ROCK), is known to suppress experimental autoimmune encephalomyelitis (EAE), an animal model of MS, it relies on multiple, short-term injections, with a narrow safety window. In this study, we explored the therapeutic effect of a novel ROCK inhibitor FSD-C10, a Fasudil derivative, on EAE. An important advantage of this derivative is that it can be used via non-injection routes; intranasal delivery is the preferred route because of its efficient CNS delivery and the much lower dose compared with oral delivery. Our results showed that intranasal delivery of FSD-C10 effectively ameliorated the clinical severity of EAE and CNS inflammatory infiltration and promoted neuroprotection. FSD-C10 effectively induced CNS production of the immunoregulatory cytokine interleukin-10 and boosted expression of nerve growth factor and brain-derived neurotrophic factor proteins, while inhibiting activation of p-nuclear factor-κB/p65 on astrocytes and production of multiple pro-inflammatory cytokines. In addition, FSD-C10 treatment effectively induced CD4(+) CD25(+) , CD4(+) FOXP3(+) regulatory T cells. Together, our results demonstrate that intranasal delivery of the novel ROCK inhibitor FSD-C10 has therapeutic potential in EAE, through mechanisms that possibly involve both inhibiting CNS inflammation and promoting neuroprotection.


Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Anti-Inflamatórios/administração & dosagem , Sistema Nervoso Central/efeitos dos fármacos , Encefalomielite Autoimune Experimental/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Quinases Associadas a rho/antagonistas & inibidores , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/administração & dosagem , Administração Intranasal , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/enzimologia , Linfócitos T CD4-Positivos/imunologia , Sistema Nervoso Central/enzimologia , Sistema Nervoso Central/imunologia , Proteínas de Ligação a DNA , Encefalomielite Autoimune Experimental/enzimologia , Encefalomielite Autoimune Experimental/imunologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-10/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator de Crescimento Neural/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/metabolismo , Índice de Gravidade de Doença , Baço/efeitos dos fármacos , Baço/enzimologia , Baço/imunologia , Fatores de Tempo , Fator de Transcrição RelA/metabolismo , Quinases Associadas a rho/metabolismo
16.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 30(4): 346-50, 2014 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-24721398

RESUMO

OBJECTIVE: To investigate the effects of lipoic acid (LA) on the release of TNF-α, IL-1ß, IL-6, IL-10 and the expressions of chemokines in astrocytes stimulated with lipopolysaccharide (LPS). METHODS: Astrocytes were separated from the cerebral cortex of newly-born C57BL/6 mice (within 48 h after birth). After identification and purification, the second-generation astrocytes were stimulated with LPS (1 µg/mL), and then treated with LA (100 µg/mL). The production of nitric oxide (NO) was assayed by Griess assay. The levels of TNF-α, IL-1ß, IL-6 and IL-10 in supernatants were quantified by ELISA. The expressions of CC chemokine ligand-20 (CCL20), monocyte chemoattractive protein 1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) mRNAs were detected using reverse transcription-PCR. RESULTS: Compared with PBS control, LPS significantly increased the production of TNF-α, IL-1ß and IL-6, but decreased the level of IL-10 in cultured astrocytes (P<0.05). LA treatment inhibited LPS-induced NO, TNF-α, IL-1ß and IL-6 production, and enhanced IL-10 secretion, and compared with LPS stimulation alone, the differences were statistically significant (P<0.05). In addition, LA treatment also suppressed the expressions of CCL20, MCP-1 and MIP-1α mRNA in astrocytes stimulated with LPS. CONCLUSION: LA inhibits neuroinflammatory response in LPS-activated astrocytes. The neuroprotection of LA is partly due to the inhibition of pro-inflammatory cytokines and chemokines derived from astrocytes.


Assuntos
Antioxidantes/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Quimiocinas/metabolismo , Lipopolissacarídeos/farmacologia , Ácido Tióctico/farmacologia , Animais , Quimiocinas/genética , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 30(1): 11-4, 2014 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-24405591

RESUMO

OBJECTIVE: To evaluate the effects of Fasudil on the production of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells. METHODS: The BV-2 cells cultured in vitro were divided into PBS control group, LPS stimulation group and LPS plus Fasudil group. The production of TNF-α and IL-1ß was measured by ELISA. The release of NO was checked by Griess reagent assay. Toll-like receptor 2 (TLR2) and TLR4 expressions were determined by flow cytometry. RESULTS: The stimulation of LPS significantly increased the production of TNF-α, IL-1ß and NO as well as TLR4 protein expression in BV-2 cells. Fasudil attenuated NO production, and reduced the release of TNF-α and IL-1ß in LPS-stimulated BV-2 cells. Interestingly, Fasudil also decreased TLR4 expression. CONCLUSION: Fasudil can suppress the production of TNF-α, IL-1ß and NO of microglia cells induced by LPS, which may be associated with the down-regulation of TLR4 pathway.


Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Microglia/citologia , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico/metabolismo , Receptor 2 Toll-Like/metabolismo
18.
PLoS One ; 7(2): e32103, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22384153

RESUMO

BACKGROUND: The multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has emerged as a global threat. Xinjiang is a multi-ethnic region and suffered second highest incidence of TB in China. However, epidemiological information on MDR and XDR TB is scarcely investigated. METHODOLOGY/PRINCIPAL FINDINGS: A prospective study was conducted to analyze the prevalence of MDR and XDR TB and the differences of drug resistance TB between Chinese Han and other nationalities population at Chest Hospital of Xinjiang Uygur Autonomous Region, China. We performed in vitro drug susceptibility testing of Mycobacterium tuberculosis to first- and second-line anti-tuberculosis drugs for all 1893 culture confirmed positive TB cases that were diagnosed between June 2009 and June 2011. Totally 1117 (59.0%, 95% CI, 56.8%-61.2%) clinical isolates were resistant to ≥1 first-line drugs; the prevalence of MDR TB was 13.2% (95% CI, 11.7%-14.7%), of which, 77 (30.8%; 95% CI, 25.0%-36.6%) and 31 (12.8%; 95% CI, 8.6%-17.0%) isolates were pre-XDR and XDR TB respectively. Among the MDR/XDR TB, Chinese Han patients were significantly less likely to be younger with an odds ratio 0.42 for age 20-29 years and 0.52 for age 40-49 years; P(trend) = 0.004), and Chinese Han patients has a lower prevalence of XDR TB (9.6%) than all the other nationality (14.9%). CONCLUSIONS/SIGNIFICANCE: The burden of drug resistance TB cases is sizeable, which highlights an urgent need to reinforce the control, detection and treatment strategies for drug resistance TB. However, the difference of MDR and XDR TB between Chinese Han and other nationalities was not observed.


Assuntos
Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adolescente , Adulto , Idoso , Antituberculosos/farmacologia , Povo Asiático , China , Etnicidade , Tuberculose Extensivamente Resistente a Medicamentos/etnologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Estudos Prospectivos , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/etnologia
19.
PLoS One ; 6(8): e24069, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21886847

RESUMO

BACKGROUND: Susceptibility to tuberculosis is not only determined by Mycobacterium tuberculosis infection, but also by the genetic component of the host. Macrophage receptor with a collagenous structure (MARCO) is essential components required for toll like receptor-signaling in macrophage response to Mycobacterium tuberculosis, which may contribute to tuberculosis risk. PRINCIPAL FINDINGS: To specifically investigated whether single nucleotide polymorphisms (SNPs) in MARCO gene are associated with pulmonary tuberculosis in Chinese Han population. By selecting tagging SNPs in MARCO gene, 17 tag SNPs were identified and genotyped in 923 pulmonary tuberculosis patients and 1033 healthy control subjects using a hospital based case-control association study. Single-point and haplotype analysis revealed an association in intron and exon region of MARCO gene. One SNP (rs17009726) was associated with susceptibility to pulmonary tuberculosis, where the carriers of the G allele had a 1.65 fold (95% CI = 1.32-2.05, p(corrected) = 9.27E-5) increased risk of pulmonary tuberculosis. Haplotype analysis revealed that haplotype GC containing G allele of 17009726 and haplotype TGCC (rs17795618T/A, rs1371562G/T, rs6761637T/C, rs2011839C/T) were also associated with susceptibility to pulmonary tuberculosis (p(corrected) = 0.0001 and 0.029, respectively). CONCLUSIONS: Our study suggested that genetic variants in MARCO gene were associated with pulmonary tuberculosis susceptibility in Chinese Han population, and the findings emphasize the importance of MARCO mediated immune responses in the pathogenesis of tuberculosis.


Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptores Imunológicos/genética , Tuberculose Pulmonar/genética , Adulto , Estudos de Casos e Controles , China/epidemiologia , China/etnologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Fatores de Risco , Receptores Toll-Like , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...