RESUMO
BACKGROUND: Some gastrointestinal disorders may be associated with Helicobacter pylori infection, which not only affect maternal health, but may also lead to adverse pregnancy outcomes. We aim to explore the association between H. pylori and gastrointestinal disorders in pregnant women. MATERIALS AND METHODS: In total, 503 patients were retrospectively analyzed and divided into the H. pylori-uninfected group, the H. pylori-infected group, or the H. pylori-eradicated group. We analyzed the influence of H. pylori on gastrointestinal diseases during pregnancy among the groups, as well as the severity, symptoms, laboratory tests of the H. pylori-related diseases. RESULTS: Pregnant women with H. pylori infection had higher risk of nausea and vomiting of pregnancy (NVP) (p < 0.001), severe NVP(p = 0.012), hyperemesis gravidarum (p = 0.027), hematemesis (p = 0.018), hyponatremia (p = 0.033), as well as functional dyspepsia symptoms including epigastric pain (p = 0.004), bloating (p = 0.024), and feeling full quickly in a meal (p = 0.031) compared with those without H. pylori infection. While the prevalence of NVP (p = 0.024), severe NVP (p = 0.009), epigastric pain (p = 0.037), and bloating (p = 0.032) were lower in H. pylori-eradicated pregnant women than in H. pylori-infected women. In addition, pregnant women with H. pylori infection had higher risk of spontaneous preterm birth than whom without H. pylori infection (p = 0.033). CONCLUSIONS: Helicobacter pylori infection was associated with higher risks of NVP, severe NVP, hyperemesis gravidarum, functional dyspepsia, and spontaneous preterm birth in pregnant women.
Assuntos
Dispepsia , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Hiperêmese Gravídica , Complicações Infecciosas na Gravidez , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Hiperêmese Gravídica/complicações , Hiperêmese Gravídica/epidemiologia , Estudos Retrospectivos , Dispepsia/epidemiologia , Dispepsia/complicações , Gastrite/complicações , Dor/complicaçõesRESUMO
AIMS: To evaluate the impact of SARS-CoV-2 vaccine on IBD activity. METHODS: Adult IBD patients from five large IBD centers in China were enrolled and followed up for 6 months. Patients were divided into vaccinated and unvaccinated groups according to vaccination status. Demographic and clinical data were collected. RESULTS: A total of 280 individuals (213 UC and 67 CD patients) were enrolled in the study. The unvaccinated and vaccinated groups of UC patients were comparable for basic characteristics, including age (t = - 0.8, p = 0.425), sex (χ2 = 0.980, p = 0.322), course of disease (z = - 0.513, p = 0.608), surgical conditions (χ2 = 1.042, p = 0.838), disease extent (χ2 = 4.853, p = 0.088), or baseline drug therapy (χ2 = 7.784, p = 0.064). In the subgroup of UC patients, there was no association between vaccination and disease activities, according to the medium disease activity scores for two groups: unvaccinated patients having scores (IQR) 1(2.75), 1(2), 1(2), and 1(2) at baseline, 1, 3, and 6 months, respectively, whereas vaccinated patients having scores (IQR) 1(2), 1(2), 1(2), and 1(2). Similar conclusions were also derived in the subgroup of CD patients. There were also no statistically significant differences in age (t = - 1.48, p = 0.144), sex (χ2 = 0.003, p = 0.957), course of disease (z = - 0.074, p = 0.941), surgical conditions (χ2 = 0.613, p = 0.594), localization (χ2 = 6.261, p = 0.199), or baseline drug therapy (χ2 = 5.881, p = 0.114) between 2 groups of CD patients. The medium disease activity scores (IQR) of the unvaccinated group at baseline, 1, 3, and 6 months were 1(4), 1(3), 1(3), and 1(3), respectively, whereas those of vaccinated group were 2.5(3.75), 2.5(3.75), 3(2), and 2(2), respectively. Overall, very few participants in this study described worsening IBD disease activity requiring a change or addition of medication. CONCLUSIONS: SARS-CoV-2 vaccine has no adverse effect on disease activity in IBD population. IBD patients should be recommended to receive SARS-CoV-2 vaccine in time.
Assuntos
COVID-19 , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adulto , Chlorocebus aethiops , Animais , Humanos , Doença de Crohn/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Vacinas contra COVID-19/uso terapêutico , Células Vero , COVID-19/prevenção & controle , SARS-CoV-2 , Doenças Inflamatórias Intestinais/tratamento farmacológico , China/epidemiologiaRESUMO
Isoflavone is one of the phytoestrogens that have estrogenic effects, so it is usually served as an active ingredient for quality control of traditional Chinese medicines rich in isoflavones. Nine isoflavones commonly found in traditional Chinese medicines were separated in 30 min using mixed micellar liquid chromatography. The mobile phase consisted of 0.08 M sodium dodecylsulfate and 6.05 mM ß-cyclodextrin:methanol (87:13, v/v) at pH 3 and eluted isocratically at 1 mL/min through a C18 column. In this study, we systematically optimized the chromatographic conditions including the pH, the composition and concentration of surfactants, the type and ratio of organic solvents, and column temperature. The method was validated according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use guidelines. There is no report using micellar liquid chromatography to detect isoflavones, and the optimized method has been successfully applied to quantify isoflavones in red clover and Radix Puerariae. This method is efficient, cheap, and convenient. Finally, we verified the existence of supramolecular amphiphilic vesicles in the mobile phase by transmission electron microscopy to explain the increased chromatographic efficiency.
Assuntos
Medicamentos de Ervas Chinesas/análise , Isoflavonas/análise , Dodecilsulfato de Sódio/química , beta-Ciclodextrinas/química , Cromatografia Líquida , Concentração de Íons de Hidrogênio , Substâncias Macromoleculares/química , Medicina Tradicional Chinesa , MicelasRESUMO
AIMS: To investigate control measures for COVID-19 pandemic in GIE centers in China. METHODS: This is a retrospective multi-center research, including seven centers. Data collection was from 1 February to 31 March 2020 and the same period in 2019. RESULTS: There were a total of 28 COVID-19 definite cases in these hospitals. Six out of seven GIE centers were arranged to shut down on 1 February, with a mean number of shutdown days of 23.6 ± 5.3. The actual workloads were only 10.3%-62.9% compared to those last year. All centers had a preoperative COVID-19 screening process. Epidemiological questionnaire, temperature taking and QR-code of journey were conducted. Chest CT scan was conducted during the shutdown period and continued in five centers after return to work. Antibody and nucleic acid test were applied in one to three centers. All endoscopists had advanced PPE. Five centers used surgical mask and the rest used N95 mask. Six centers used goggles or face shield. Five centers selected isolation gowns and the rest selected protective suits. The change frequency of these PPE was 4 h. Sterilizing measures were improved in six centers. Five centers utilized ultraviolet and six centers strengthened natural ventilation. Four and six centers used peracetic acid during the period of shutdown and return to work, alone or matched with OPA or acidified water. CONCLUSIONS: Many effective control measures were conducted in GIE centers during the outbreak, including patients' volume limitation, preoperative COVID-19 screening, advanced PPE and disinfection methods.
Assuntos
COVID-19/prevenção & controle , Endoscopia Gastrointestinal , Controle de Infecções/normas , COVID-19/epidemiologia , China/epidemiologia , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Pandemias , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND: Neuromyelitis optica spectrum disorder (herein called NMO) is an inflammatory demyelinating disease that can be initiated by binding of immunoglobulin G autoantibodies (AQP4-IgG) to aquaporin-4 on astrocytes, causing complement-dependent cytotoxicity (CDC) and downstream inflammation. The increased NMO pathology in rodents deficient in complement regulator protein CD59 following passive transfer of AQP4-IgG has suggested the potential therapeutic utility of increasing the expression of complement regulator proteins. METHODS: A cell-based ELISA was developed to screen for pharmacological upregulators of endogenous CD55 and CD59 in a human astrocyte cell line. A statin identified from the screen was characterized in cell culture models and rodents for its action on complement regulator protein expression and its efficacy in models of seropositive NMO. RESULTS: Screening of ~ 11,500 approved and investigational drugs and nutraceuticals identified transcriptional upregulators of CD55 but not of CD59. Several statins, including atorvastatin, simvastatin, lovastatin, and fluvastatin, increased CD55 protein expression in astrocytes, including primary cultures, by three- to four-fold at 24 h, conferring significant protection against AQP4-IgG-induced CDC. Mechanistic studies revealed that CD55 upregulation involves inhibition of the geranylgeranyl transferase pathway rather than inhibition of cholesterol biosynthesis. Oral atorvastatin at 10-20 mg/kg/day for 3 days strongly increased CD55 immunofluorescence in mouse brain and spinal cord and reduced NMO pathology following intracerebral AQP4-IgG injection. CONCLUSION: Atorvastatin or other statins may thus have therapeutic benefit in AQP4-IgG seropositive NMO by increasing CD55 expression, in addition to their previously described anti-inflammatory and immunomodulatory actions.
Assuntos
Aquaporina 4/imunologia , Astrócitos/metabolismo , Antígenos CD55/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Imunoglobulina G/administração & dosagem , Neuromielite Óptica/tratamento farmacológico , Regulação para Cima/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Linhagem Celular Transformada , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Interações Medicamentosas , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Camundongos , Neuromielite Óptica/metabolismo , Neuromielite Óptica/patologia , RNA Mensageiro/metabolismo , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Ativação Transcricional/efeitos dos fármacos , Receptor fas/metabolismoRESUMO
BACKGROUND: Aquaporin-4-immunoglobulin G (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (herein called NMO) is an autoimmune disease of the central nervous system in which AQP4-IgG binding to AQP4 on astrocytes results in complement-dependent astrocyte injury and secondary inflammation, demyelination, and neuron loss. We previously reported evidence for a complement bystander mechanism for early oligodendrocyte injury in NMO. Herein, we tested the hypothesis that complement bystander injury, which involves diffusion to nearby cells of activated soluble complement components from complement-injured astrocytes, is a general phenomenon that may contribute to neuronal injury in NMO. METHODS: Primary cocultures of rat astrocytes and cortical neurons were established to study complement-dependent cell death after exposure to AQP4-IgG and complement. In animal experiments, AQP4-IgG was delivered to adult rats by intracerebral injection. Cell cultures and rat brain were studied by immunofluorescence. RESULTS: In primary astrocyte-neuron cocultures, addition of AQP4-IgG and complement resulted in death of neurons nearby astrocytes. Deposition of complement membrane attack complex C5b-9 was seen on neurons nearby astrocytes, whereas C1q, the initiating protein in the complement pathway, was seen only on astrocytes. Neuron death was not seen with a complement inhibitor, with C1q- or C6-depleted complement, in pure neuron cultures exposed to AQP4-IgG and complement or in cocultures exposed to an astrocyte toxin. Intracerebral injection in rats of AQP4-IgG and a fixable dead cell fluorescent marker produced death of neurons near astrocytes, with C5b-9 deposition. Neuron death was not seen in rats receiving a complement inhibitor or in AQP4-IgG-injected AQP4 knockout rats. CONCLUSION: These results support a novel mechanism for early neuron injury in NMO and provide evidence that complement bystander injury may be a general phenomenon for brain cell injury following AQP4-IgG-targeted astrocyte death.
Assuntos
Aquaporina 4/imunologia , Complemento C1q/metabolismo , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Complexo de Ataque à Membrana do Sistema Complemento/toxicidade , Imunoglobulina G/sangue , Neuromielite Óptica/sangue , Neurônios/efeitos dos fármacos , Animais , Aquaporina 4/deficiência , Astrócitos/efeitos dos fármacos , Antígenos CD59/metabolismo , Células Cultivadas , Córtex Cerebral/citologia , Técnicas de Cocultura , Complemento C1q/toxicidade , Meios de Cultivo Condicionados/farmacologia , Modelos Animais de Doenças , Embrião de Mamíferos , Regulação da Expressão Gênica/efeitos dos fármacos , Imunoglobulina G/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Neuromielite Óptica/induzido quimicamente , Ratos , Ratos Transgênicos , Fatores de TempoRESUMO
OBJECTIVE: To evaluate the impact of RA on work capacity and identify factors related to work capacity impairment in patients with RA. METHODS: A cross-sectional multicentre study was performed in 21 tertiary care hospitals across China. A consecutive sample of 846 patients with RA was recruited, of which 589 patients of working age at disease onset constituted the study population. Information on the socio-demographic, clinical, working and financial conditions of the patients was collected. Logistic regression analyses were used to identify factors associated with work capacity impairment. RESULTS: The rate of work capacity impairment was 48.0% in RA patients with a mean disease duration of 60 months (interquartile range 14-134 months), including 11.7% leaving the labour force early, 33.6% working reduced hours and 2.7% changing job. Multivariable logistic regression analysis showed that reduced working hours was significantly related to current smoking [odds ratio (OR) 2.07 (95% CI 1.08, 3.97)], no insurance [OR 1.94 (95% CI 1.20, 3.12)], in manual labour [OR 2.66 (95% CI 1.68, 4.20)] and higher HAQ score [OR 2.22 (95% CI 1.36, 3.60)]. There was an association of current smoking [OR 3.75 (95% CI 1.54, 9.15)], in manual labour [OR 2.33 (95% CI 1.17, 4.64)], longer disease duration [OR 1.01 (95% CI 1.00, 1.01)] and lower BMI [OR 0.90 (95% CI 0.82, 0.99)] with leaving the labour force early. CONCLUSION: There is a substantial impact of RA on the work capacity of patients in China. Social-demographic, disease- and work-related factors are all associated with work capacity impairment.
Assuntos
Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Povo Asiático , Avaliação do Impacto na Saúde , Avaliação da Capacidade de Trabalho , Absenteísmo , Adulto , Idade de Início , Idoso , Artrite Reumatoide/etnologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Regressão , Fatores SocioeconômicosRESUMO
OBJECTIVE: The objective of this study is to explore the clinicopathological characteristics of gastric cancer and precancerous conditions in patients with primary gastric lymphoma. METHODS: We analyzed 474 cases of primary gastric lymphoma, mainly DLBCL and MALT, from three clinical centres retrospectively, and compared the clinicopathological parameters of primary gastric lymphoma patients complicated with gastric cancer, precancerous conditions, or with no complications. RESULTS: A total of 5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer, including metachronous gastric adenocarcinoma (3.2%) and synchronous gastric adenocarcinoma (1.9%). Of the patients with gastric lymphoma, 14.6% had precancerous conditions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%). Primary gastric lymphoma patients with an ulcerative type (p = 0.009) and Lugano classification stage IIE + IV (p < 0.001) lymphoma had a higher risk of complicating with gastric cancers or precancerous conditions. The rate of infection of Helicobacter pylori (Hp) was 68.4% in patients with primary gastric lymphoma, which was higher in patients with MALT lymphoma (p < 0.001), Lugano classification stage I + II (p < 0.001), and patients complicated with precancerous conditions and gastric cancer (p < 0.001), especially gastric cancer of the intestinal type (p = 0.04). Gastric cancer (95.8%) and precancerous conditions (91.3%) occurred mostly in Hp-infected primary gastric lymphoma patients, with a minor subset of Hp-eradicated patients. Primary gastric lymphoma patients had a higher detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population. CONCLUSIONS: Patients with primary gastric lymphoma have a high risk of developing gastric cancer and precancerous conditions, and this risk may be related to Helicobacter pylori infection. Follow-up of primary gastric lymphoma provides an opportunity for the detection of early gastric cancer.Key messages5.1% of the patients with primary gastric lymphoma were diagnosed with gastric cancer.14.6% of the patients with gastric lymphoma had premalignant lesions including atrophy (14.6%), intestinal metaplasia (8.9%), and low-grade intraepithelial neoplasia (1.9%).Primary gastric lymphoma patients complicating with gastric cancer had a higher infection rate of Helicobacter pylori (100.0%), a detection rate of early gastric cancer (25.0%) and a five-year survival rate (40.0%) than the general Chinese population.
Assuntos
Adenocarcinoma , Infecções por Helicobacter , Helicobacter pylori , Linfoma de Zona Marginal Tipo Células B , Lesões Pré-Cancerosas , Neoplasias Gástricas , Humanos , Linfoma de Zona Marginal Tipo Células B/epidemiologia , Linfoma de Zona Marginal Tipo Células B/complicações , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/complicações , Estudos Retrospectivos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Atrofia/complicações , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/complicações , Lesões Pré-Cancerosas/patologia , Metaplasia/epidemiologia , Metaplasia/complicaçõesRESUMO
OBJECTIVE: To learn about the prevalence and risk factors of coronary artery disease (CAD) in rheumatoid arthritis (RA). METHODS: Data were obtained from a 12-month retrospective investigation of the patients with RA, randomly selected from Departments of Rheumatology and Immunology in 21 big hospitals in China. The data were collected about their social conditions, clinical conditions, medications associated with RA, such as disease modifying anti-rheumatic drugs (DMARDs), non steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, biologic agents. A nonparameter test and multivariate logistic regression analysis were performed. RESULTS: In the study, 960 patients were enrolled. The prevalence of CAD was 3.5% in China, which was obviously higher than that of normal people. The prevalence of overweight and obesity, smoking, hypertension, diabetes mellitus, hypercholesterolemia and cerebrovascular disease were 35.1%, 12.3%, 17.0%, 7.7%, 0.4% and 3.0%, respectively. Compared with the control group, the CAD group had higher age [(64.7±9.3) years vs. (52.3±14.0) years,P<0.001], more rheumatoid nodules (14.7% vs. 3.1%,P=0.005), lower rate of hydroxychloroquine (HCQ) use (5.9% vs. 22.6%,P=0.021), higher prevalence rates of lung interstitial disease (17.5% vs. 7.0%,P<0.001), diabetes mellitus and hypertension (29.4% vs. 7.0%,P<0.001; 38.2% vs. 16.2%,P=0.001). There was no obvious correlation of CAD in RA with joint deformity, rheumatoid factor (RF) titer, glucocorticoid use, hypercholesterolemia and body mass index (BMI). Multivariate analysis showed higher age, diabetes mellitus and hypertension were independent predictors of CAD, and the use of HCQ was a protective factor of CAD. CONCLUSION: The prevalence of CAD is 3.5%. Higher age, diabetes mellitus and hypertension are independent predictors of CAD, and the use of HCQ is a protective factor of CAD.
Assuntos
Artrite Reumatoide/complicações , Doença da Artéria Coronariana/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVE: To investigate the current status of tumor necrosis factor (TNF) inhibitors application in rheumatoid arthritis (RA) patients in China and to analyze the related factors. METHODS: A retrospective survey was conducted in 21 hospitals from different parts of China. The patients with RA were randomly enrolled. Data of their social backgrounds, clinical conditions, usage and adverse effects of TNF inhibitors were collected. The costs of TNF inhibitors and the indirect costs of the disease were calculated. A multivariate Logistic regression analysis was performed to analyze the factors related to TNF inhibitors application. RESULTS: In the study, 1 095 RA patients from July 2009 to November 2010 were enrolled, of whom 112 had received TNF inhibitors, representing 10.2% of the total patients. The patients who received etanercept and infliximab were 7.4% (86/1 095) of the patients and 2.4% (26/1 095), respectively. There were 0.5% of the patients (5/1 095) who had received both of the TNF inhibitors. The patients who had accepted etanercept and treatment duration for less than 3 months and 3-6 months accounted for 38.5% and 25.0% respectively, while those treated with Infliximab were 38.1%. Their health assessment questionnaire (HAQ) scores were 1.1, 0.5 and 0.1, corresponding to treatment duration of infliximab for less than 3, 3-6 and 6-9 months and those were 1.3, 1.0, 0.3 corresponding to treatment duration of etanercept, respectively. Infliximab costs were RMB 24 525.0, 69 300.0 and 96 800.0 Yuan and etanercept costs were RMB 7 394.8, 9 158.6, 54 910.9 Yuan, respectively. Indirect costs for RA patients who accepted infliximab for less than 3, 3-6 and 6-9 months were RMB 365.6, 0 and 158.9 Yuan and those who accepted etanercept were RMB 2 158.4, 288.5 and 180.1 Yuan, respectively. Allergy and infection were the main side-effects of etanercept and both happened in 3.5% of all the patients. Liver damage happened in 2.3% of all the patients, while allergy and infection happened in 6.5% of all the patients who accepted infliximab. Logistic regression analysis showed that patients with higher education experience increased the odds of entering the TNF inhibitors group (OR: 1.292, 95%CI: 1.132-1.473, P=0.000). CONCLUSION: About one-tenth of RA patients in China have accepted TNF inhibitors. Higher education experience is the key factor for using TNF inhibitors.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Honorários por Prescrição de Medicamentos/estatística & dados numéricos , Inibidores do Fator de Necrose Tumoral , Adulto , Idoso , Anti-Inflamatórios não Esteroides/economia , Anticorpos Monoclonais/economia , Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/economia , China , Etanercepte , Feminino , Humanos , Imunoglobulina G/economia , Imunoglobulina G/uso terapêutico , Imunossupressores/economia , Imunossupressores/uso terapêutico , Infliximab , Masculino , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral/uso terapêutico , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To investigate the medication status of rheumatoid arthritis (RA) patients and to analyze the clinical use of sulphasalazine (SSZ) and the adverse effect. METHODS: A total of 1 096 outpatients and inpatients diagnosed with RA were investigated in 21 hospitals all over China from July 2009 to December 2010, including gender, age of onset, clinical manifestations, as well as the clinical characteristics and medication status of 160 RA patients who received SSZ therapy. RESULTS: In the group of 160 patients who received SSZ, the male-to-female ratio was 1:7, The average age at onset was (46.1±15.0) years, while the average course was (9.9±7.8) years. The average dose of sulphasalazine was (1.87±0.52) g/d for a mean duration of (26.3± 14.6) months. Only 17% (27/160) of the patients received SSZ monotherapy. Methotrexate (63.1%), leflunomide (36.2%) and hydroxychloroquine (18.1%) were most commonly used combination drugs. And 36.2% (58/160) of the patients used the two-drug combination of methotrexate plus sulphasalazine .In this group, 41.9% (67/160) once used SSZ but withdrew for adverse events and other reasons, while 17.5% (28/160) withdrew for adverse events, of which the most common were gastrointestinal (8.8%), skin (3.8%) and liver toxicity (3.1%). CONCLUSION: Sulphaszlazine is not a common choice in the RA therapeutics in China, and the average dose of SSZ is lower than the standard dose of 2 to 3 g/d . The adverse events of SSZ are common; however, there are few severe adverse events or threat to life,SSZ is relatively safe in clinical practice.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Sulfassalazina/administração & dosagem , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Antirreumáticos/uso terapêutico , China , Estudos Transversais , Quimioterapia Combinada , Feminino , Humanos , Isoxazóis/administração & dosagem , Leflunomida , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Sulfassalazina/efeitos adversos , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: This study investigates the effects and mechanisms of intestinal microbiota transplantation on cerebral ischemia reperfusion injury in aged mice. METHODS: We constructed a middle cerebral artery occlusion model after fecal microbiota transplantation from young C57 mice to aged C57 mice for 30 consecutive days via enema. The neurological deficit score, cerebral infarction volume, fecal flora composition, and IL-17 levels in the colon, brain, and serum were evaluated in young mice, aged mice, and aged mice that received fecal microbiota transplantation. Moreover, we administered rIL-17A through caudal vein injection to verify its effect on cerebral ischemia reperfusion injury in aged mice. RESULTS: We find that aged mice exhibited larger cerebral infarction volume and more severe neurological deficit than young mice after middle cerebral artery occlusion. Bacteroidetes increased and firmicutes decreased significantly in the feces of aged mice after microbiota transplantation. Furthermore, the transplanted mice showed improved neurological function and reduced infarction volume after middle cerebral artery occlusion compared with the control aged mice. We also find that the neuroprotective effect of the microbiota transplantation was reversed by pre-treatment of rIL-17A. CONCLUSION: In summary, intestinal microbiota transplantation can alleviate cerebral ischemia reperfusion injury in aged mice by restoring their microbiota environment and inhibiting IL-17 in the gut, serum, and brain tissue.
Assuntos
Fármacos Neuroprotetores , Traumatismo por Reperfusão , Animais , Transplante de Microbiota Fecal , Infarto da Artéria Cerebral Média/terapia , Interleucina-17 , Camundongos , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/terapiaRESUMO
Neuromyelitis optica spectrum disorders (NMOSD) is a heterogeneous group of neuroinflammatory conditions associated with demyelination primarily in spinal cord and optic nerve, and to a lesser extent in brain. Most NMOSD patients are seropositive for IgG autoantibodies against aquaporin-4 (AQP4-IgG), the principal water channel in astrocytes. There has been interest in establishing experimental animal models of seropositive NMOSD (herein referred to as NMO) in order to elucidate NMO pathogenesis mechanisms and to evaluate drug candidates. An important outcome of early NMO animal models was evidence for a pathogenic role of AQP4-IgG. However, available animal models of NMO, based largely on passive transfer to rodents of AQP4-IgG or transfer of AQP4-sensitized T cells, often together with pro-inflammatory maneuvers, only partially recapitulate the clinical and pathological features of human NMO, and are inherently biased toward humoral or cellular immune mechanisms. This review summarizes current progress and shortcomings in experimental animal models of seropositive NMOSD, and opines on the import of advancing animal models.
Assuntos
Aquaporina 4/imunologia , Neuromielite Óptica/metabolismo , Neuromielite Óptica/patologia , Animais , Aquaporina 4/metabolismo , Aquaporina 4/fisiologia , Astrócitos/patologia , Autoanticorpos/imunologia , Encéfalo/patologia , Modelos Animais de Doenças , Humanos , Imunoglobulina G/imunologia , Neuromielite Óptica/genética , Nervo Óptico/metabolismo , Nervo Óptico/patologia , Medula Espinal/patologiaRESUMO
Pathogenesis in seropositive neuromyelitis optica spectrum disorders (herein called NMO) involves binding of IgG1 autoantibodies to aquaporin-4 (AQP4) on astrocytes in the central nervous system, which initiates complement and cellular injury. We previously developed an antibody blocking approach for potential therapy of NMO in which an engineered, monoclonal, anti-AQP4 antibody lacking cytotoxicity effector functions (called aquaporumab) blocked binding of NMO autoantibodies to astrocyte AQP4 (Tradtrantip et al. Ann. Neurol. 71, 314-322, 2012). Here, a high-affinity aquaporumab, which was generated by affinity maturation using saturation mutagenesis, was shown to block cellular injury caused by NMO patient sera. Anti-AQP4 antibody rAb-53, a fully human antibody with effector function neutralizing Fc mutations L234A/L235A and affinity-enhancing Fab mutations Y50R/S56R, called AQmabAM, bound to AQP4 in cell cultures with Kd ~ 18 ng/ml (~0.12 nM), ~8-fold greater affinity than the original antibody. AQmabAM, but without L234A/L235A Fc mutations, produced complement-dependent cytotoxicity (CDC) with EC50 ~ 82 ng/ml. AQmabAM prevented CDC produced by sera from eight NMO patients with IC50 ranging from 40 to 80 ng/ml, and similarly prevented antibody-dependent cellular cytotoxicity (ADCC). Mechanistic studies demonstrated that AQmabAM blocked binding of serum NMO autoantibodies to AQP4. AQmabAM offers a targeted, non-immunosuppressive approach for therapy of seropositive NMO. Autoantibody blocking may be a useful therapeutic strategy for other autoimmune diseases as well.
Assuntos
Anticorpos Bloqueadores/farmacologia , Afinidade de Anticorpos/efeitos dos fármacos , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Aquaporina 4/imunologia , Autoanticorpos/imunologia , Imunoglobulina G/farmacologia , Neuromielite Óptica/tratamento farmacológico , Proteínas Recombinantes/farmacologia , Animais , Anticorpos Bloqueadores/uso terapêutico , Anticorpos Monoclonais , Afinidade de Anticorpos/genética , Citotoxicidade Celular Dependente de Anticorpos/genética , Ligação Competitiva , Células CHO , Sobrevivência Celular/efeitos dos fármacos , Proteínas do Sistema Complemento/imunologia , Cricetulus , Testes Imunológicos de Citotoxicidade , Humanos , Imunoglobulina G/genética , Células Matadoras Naturais , Mutagênese , Neuromielite Óptica/imunologia , SoroRESUMO
Redistribution of the water channel aquaporin-4 (AQP4) away from astrocyte endfeet and into parenchymal processes is a striking histological feature in mouse models of Alzheimer's disease (AD) and other neurological conditions with prominent astrogliosis. AQP4 redistribution has been proposed to impair bulk Aß clearance in AD, resulting in increased amyloid deposition in the brain; however, this finding is controversial. Here, we provide evidence in support of a different and novel role of AQP4 in AD. We found that Aqp4 deletion significantly increased amyloid deposition in cerebral cortex of 5xFAD mice, with an increase in the relative number of fibrillar vs. dense core plaques. AQP4 deficient 5xFAD mice also showed a significant reduction in the density of GFAP labeled peri-plaque astrocyte processes. Microglial plaque coverage was also significantly reduced, suggesting astrocyte involvement in organizing the peri-plaque glial response. The alterations in peri-plaque glial structure were accompanied by increased neuronal uptake of Aß and an increase in the number of dystrophic neurites surrounding plaques. On the basis of these findings, we propose that redistribution of AQP4 into the parenchymal processes facilitates astrocyte structural plasticity and the formation of a reactive glial net around plaques that protects neurons from the deleterious effects of Aß aggregates. AQP4 redistribution may thus facilitate plaque containment and reduce neuropathology in AD.
Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Aquaporina 4/metabolismo , Astrócitos/metabolismo , Astrócitos/patologia , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/metabolismo , Animais , Aquaporina 4/genética , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/metabolismo , Microglia/patologia , Neurônios/metabolismoRESUMO
Cellular injury in AQP4-IgG seropositive neuromyelitis spectrum disorder (herein called NMO) involves AQP4-IgG binding to astrocytes, resulting in astrocyte injury by complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) mechanisms. The rapid disease progression, severe tissue damage, and abundant leukocyte infiltration seen in some NMO patients suggest a more direct mechanism for demyelination and neurologic deficit than secondary injury from astrocyte loss. Here, we report evidence for an 'ADCC bystander mechanism' in NMO involving injury to nearby cells by leukocytes following their activation by AQP4-bound AQP4-IgG on astrocytes. In model cocultures containing AQP4-expressing and null CHO cells, AQP4-IgG and complement killed bystander null cells to ~ 100 µm away from AQP4-expressing cells; AQP4-IgG and NK cells produced bystander killing to ~ 300 µm, with perforin deposition seen on injured null cells. Bystander cytotoxicity was also seen with neutrophil-mediated ADCC and in astrocyte-neuron cocultures. Mechanistic studies, including real-time imaging, suggested that leukocytes activated by an AQP4-dependent ADCC mechanism injure bystander cells by direct targeted exocytosis on neighboring cells and not by diffusion of soluble granule contents. In support of this conclusion, ADCC bystander injury was preferentially reduced by an RGDS peptide that inhibits integrin adhesion. Evidence for ADCC bystander injury to oligodendrocytes and neurons was also found in mice following intracerebral injection of AQP4-IgG and NK cells, which was inhibited by RGDS peptide. These results establish a novel cellular pathogenesis mechanism in AQP4-IgG seropositive NMO and provide evidence that inflammatory mechanisms can cause widespread tissue damage in NMO independently of the secondary effects from astrocyte loss.
Assuntos
Citotoxicidade Celular Dependente de Anticorpos/fisiologia , Aquaporina 4/sangue , Efeito Espectador/fisiologia , Proteínas do Sistema Complemento/metabolismo , Imunoglobulina G/sangue , Neuromielite Óptica/sangue , Animais , Aquaporina 4/imunologia , Células CHO , Técnicas de Cocultura , Proteínas do Sistema Complemento/imunologia , Cricetinae , Cricetulus , Humanos , Imunoglobulina G/imunologia , Camundongos , Camundongos Knockout , Neuromielite Óptica/imunologiaRESUMO
AIM: Fibromyalgia (FM) is a chronic disorder characterized by widespread musculoskeletal pain and fatigue. It is a less frequently diagnosed disease in China, thus Chinese rheumatologists may have lower awareness of FM compared with colleagues in Western countries. The aim of this study is to investigate the perceptions of FM in Chinese rheumatologists and analyze their therapeutic approach in clinical practice. METHOD: An anonymous questionnaire survey was conducted among a nationwide sample of Chinese rheumatologists at the 15th National Rheumatology Conference in 2010. The 20-question survey included questions regarding background, work experience, perceptions of diagnosis and behaviors of treatment related to FM. Continuing medical education (CME) information was also collected in the survey. RESULTS: Seven hundred and seven rheumatologists responded to the questionnaire, a response rate of 60%. Less than one-fifth of the respondents were experienced in dealing with FM. Although most of the respondents regarded FM as a distinct pathological entity, nearly 30% of Chinese rheumatologists believed that FM was only a psychological disorder. The respondents recognized some of the FM-related symptoms, but had limited knowledge on the diagnostic criteria. Eighty percent of the respondents declared they had difficulties in treating FM patients. However, nearly all (90.8%) respondents believed that the prognosis of FM patients was usually benign. Our data also showed that most Chinese rheumatologists were eager for CME on FM. CONCLUSION: The awareness and perception of FM are still low among Chinese rheumatologists. CME on FM is needed for improving the quality of health care in China.