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OBJECTIVES: To update evidence on the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) and provide information to the taskforce for the 2024 update of the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA). METHODS: We searched various databases for randomised controlled trials on RA published until June 2022, with no language restriction. For each of the 15 clinical questions, 2 independent reviewers screened the articles, evaluated the core outcomes, and performed meta-analyses. RESULTS: Subcutaneous injection of methotrexate (MTX) showed similar efficacy to oral MTX in MTX-naïve RA patients. Ozoralizumab combined with MTX improved drug efficacy compared to the placebo in RA patients with inadequate response (IR) to csDMARD. Rituximab with and without concomitant csDMARDs showed similar efficacy to other bDMARDs in bDMARD-IR RA patients. Combined Janus kinase inhibitors and MTX achieved similar clinical responses and equal safety during a 4-year period compared to tumour necrosis factor inhibitors in MTX-IR RA patients. Biosimilars showed efficacy equivalent to that of the original bDMARDs in csDMARD-IR and bDMARD-IR RA patients. CONCLUSION: This systematic review provides latest evidence for the 2024 update of the JCR CPG for RA management.
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OBJECTIVE: We compared the accuracy of C-arm fluoroscopy versus O-arm-assisted pedicle screw (PS) placement in the cervicothoracic spinal junction (CTSJ). METHODS: Patients who underwent PS placement in the CTSJ (C7-T4) at our hospital were included in this study. Of 37 patients who underwent PS placement in the CTSJ, 20 underwent intraoperative C-arm fluoroscopy-assisted surgery (C Group) and 17 underwent intraoperative O-arm-assisted surgery (O Group). In total, 159 PSs were placed-73 in the C Group and 86 in the O Group. The accuracy of PS placement was compared between the C Group and O Group using the classification proposed by Gertzbein and Robbins to analyze pedicle violation. RESULTS: PS accuracy was higher in the O Group than C Group; PS placement evaluated as grade A, representing no perforation, was 95.3% (82/86) for the O Group, whereas it was 78.1% (57/73) for the C Group. There was a clear statistically significant difference in accuracy of PS placement between the groups (P = 0.0013). CONCLUSIONS: O-arm-assisted surgery improved the accuracy of PS placement in the CTSJ.
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Parafusos Pediculares , Fusão Vertebral , Cirurgia Assistida por Computador , Fluoroscopia , Humanos , Imageamento Tridimensional , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Eosinophilic fasciitis (EF) is a rare connective tissue disease that causes inflammation and fibrosis of the fascia, inducing pain and motor dysfunction. Characteristic skin manifestations, such as edema, erythema, induration, peau d'orange appearance, and the groove sign, are of diagnostic significance and observed in the majority of patients with EF. We herein report a case of EF without these characteristic skin manifestations. A 66-year-old Japanese woman developed progressive limb pain and motor dysfunction. No skin changes were observed. We diagnosed the patient with EF based on the clinical course, magnetic resonance imaging, and en bloc biopsy containing fascia and muscle. Oral prednisolone therapy markedly attenuated limb pain and motor dysfunctions. Through a systemic search of the medical literature, we retrieved 4 juvenile cases and 8 adult cases of EF without characteristic skin manifestations during the clinical course. We herein present a systemic review on EF without skin manifestations and discuss differences between the two proposed sets of diagnostic criteria of EF.
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Eosinofilia , Fasciite , Adulto , Idoso , Eosinofilia/complicações , Eosinofilia/tratamento farmacológico , Fasciite/complicações , Fasciite/diagnóstico , Fasciite/tratamento farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética , Prednisolona/uso terapêuticoRESUMO
BACKGROUND: Existing reviews of screening tools for Autism Spectrum Disorder (ASD) focus on young children, and not all screening tools have been examined against validated diagnostic procedures. AIMS: To examine the validity of screening tools for ASD in non-young children and adults to provide clinical recommendations about the use of these tools in a variety of clinical settings. METHODS AND PROCEDURES: Electronic databases, including MEDLINE, EMBASE, PsychINFO, Cochrane Library and CINAHL, were searched through March 2017. Studies examining the validity of ASD screening tools against the Autism Diagnostic Observation Schedule and/or the Autism Diagnostic Interview - Revised in non-young children (age 4 or above) and adults were included. Three authors independently reviewed each article for data extraction and quality assessment. OUTCOMES AND RESULTS: 14 studies met the inclusion criteria, of which 11 studies were with children (4-18 years of age) and 3 studies included adults only (19 years of age and above). Included studies were conducted in a general population/low-risk sample (Nâ¯=â¯3) and a clinically referred/high-risk sample (Nâ¯=â¯11). In total 11 tools were included. CONCLUSIONS AND IMPLICATIONS: Only three screening tools (the Autism-Spectrum Quotient, the Social Communication Questionnaire, and the Social Responsiveness Scale) were examined in more than 2 studies. These tools may assist in differentiating ASD from other neurodevelopmental and psychiatric disorders or typically developed children. In young adult populations, the paucity of the existing research in this group limits definitive conclusion and recommendations.
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Transtorno do Espectro Autista/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Programas de Rastreamento , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Hemophagocytic syndrome (HPS) associated with systemic lupus erythematosus (SLE), dubbed acute lupus hemophagocytic syndrome (ALHS), is an intractable complication of SLE. A 24-year-old man who had been diagnosed with SLE three months previously, presented with fever, rash, hallucination, and pancytopenia accompanied with hyperferritinemia and bone marrow hemophagocytosis. He was diagnosed with ALHS and neuropsychiatric (NP)-SLE. Although 4 courses of methylprednisolone pulse therapy and 1 course of intravenous cyclophosphamide (IVCY) improved his NP-SLE, his ALHS did not respond. However, the addition of cyclosporine A (CsA) led to a rapid remission from ALHS. This suggests the usefulness of CsA in the treatment of intractable, corticosteroid- and IVCY-resistant ALHS.
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Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Administração Intravenosa , Corticosteroides/uso terapêutico , Ciclofosfamida/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Humanos , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Masculino , Metilprednisolona/uso terapêutico , Adulto JovemRESUMO
Kikuchi-Fujimoto disease (KFD) is a benign disease of unknown etiology characterized by lymphadenopathy and a fever. For the majority of patients with KFD, the course is self-limited; however, the optimum method of managing recurrent cases has not yet been established. We herein report a case of a 42-year-old Japanese woman with KFD (confirmed by a lymph node biopsy). Although high-dose prednisolone (PSL) rapidly induced remission, she experienced four recurrences on treatment tapering. Concomitant use of hydroxychloroquine (HCQ) with low-dose PSL induced continuous remission. This is the first case to suggest the effectiveness of HCQ for recurrent KFD in a Japanese patient.
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Linfadenite Histiocítica Necrosante/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Prednisolona/uso terapêutico , Adulto , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Imunossupressores/administração & dosagem , Prednisolona/administração & dosagem , RecidivaRESUMO
OBJECTIVE: To investigate the effects and mechanisms of transgenic rice seeds expressing the altered peptide ligand (APL) of human glucose-6-phosphate-isomerase (hGPI325-339) in mice model of GPI induced arthritis (GIA). METHODS: We generated transgenic rice expressing APL12 which was analog peptide of hGPI325-339. The transgenic rice seeds were orally administered prophylactically before the induction of GIA. The severity of arthritis and titers of serum anti-GPI antibodies were evaluated. We examined IL-17 production from splenocytes and inguinal lymph node (iLN) and mesenteric lymph nodes (mLN) cells and analyzed the expression levels of functional molecules from splenocytes and iLN cells. RESULTS: Prophylactic treatment of GIA mice with APL12 transgenic rice seeds (APL12-TG) significantly improved the severity of arthritis, histopathological arthritis scores, and decreased titers of serum anti-GPI antibodies, BAFF mRNA in iLN cells, IL-17 production in splenocytes and iLN cells compared with non-transgenic rice-treated mice. APL12-TG-treated GIA mice showed upregulation of Foxp3 and GITR protein in CD4+CD25+ cells in the spleen. CONCLUSION: APL12-TG improved the severity of GIA through a decrease in production of IL-17 and anti-GPI antibodies via upregulation of Foxp3 and GITR expression on regulatory T cells in spleen.
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Artrite Reumatoide/imunologia , Artrite Reumatoide/prevenção & controle , Glucose-6-Fosfato Isomerase/imunologia , Oryza/genética , Peptídeos/administração & dosagem , Plantas Geneticamente Modificadas , Sementes , Administração Oral , Sequência de Aminoácidos , Animais , Anticorpos/sangue , Artrite Reumatoide/terapia , Modelos Animais de Doenças , Interleucina-17/sangue , Ligantes , Camundongos Endogâmicos DBA , Peptídeos/química , Fitoterapia , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To investigate the effects of transgenic rice seeds expressing the altered peptide ligand (APL) of human glucose-6-phosphate-isomerase (hGPI325-339) in mice model of GPI-induced arthritis (GIA). METHODS: We generated transgenic rice expressing T-cell epitope of hGPI325-339 and APL12 contained in the seed endosperm. The transgenic rice seeds were orally administered prophylactically before the induction of GIA. The severity of arthritis and titers of serum anti-GPI antibodies were evaluated. We examined for IL-17 production in splenocytes and inguinal lymph node (iLN) cells, and analyzed the expression levels of functional molecules in splenocytes. RESULTS: Prophylactic treatment of GIA mice with APL12 transgenic (APL12-TG) rice seeds significantly reduced the severity of arthritis and titers of serum anti-GPI antibodies compared with non-transgenic (Non-TG) rice-treated mice. APL12-TG and hGPI325-339 transgenic (hGPI325-339-TG) rice seeds improved the histopathological arthritis scores and decreased IL-17 production compared with non-TG rice-treated mice. APL12-TG rice-treated GIA mice showed upregulation of Foxp3 and GITR protein in CD4 + CD25 + Foxp3+ cells in the spleen compared with non-TG rice- and hGPI325-339-TG rice-treated mice. CONCLUSION: APL12-TG rice seeds improved the severity of GIA through a decrease in production of IL-17 and anti-GPI antibodies via upregulation of Foxp3 and GITR expression on Treg cells in spleen.
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Artrite/terapia , Glucose-6-Fosfato Isomerase/metabolismo , Oryza/metabolismo , Peptídeos/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Sementes/metabolismo , Administração Oral , Animais , Citocinas/química , Citocinas/metabolismo , Citocinas/toxicidade , Glucose-6-Fosfato Isomerase/química , Glucose-6-Fosfato Isomerase/toxicidade , Humanos , Ligantes , Camundongos , Camundongos Endogâmicos DBA , Oryza/genética , Peptídeos/administração & dosagem , Peptídeos/genética , Peptídeos/uso terapêutico , Plantas Geneticamente Modificadas/genética , Ligação Proteica , Sementes/genéticaRESUMO
OBJECTIVE: To clarify the efficacy and safety of abatacept for secondary Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). METHODS: The primary endpoint of this open-labeled, prospective, observational multicenter study for secondary SS with RA was the remission rate of Simplified Disease Activity Index (SDAI) at 52 weeks after initiation of abatacept. The secondary endpoints included Saxon's test and Schirmer's test. Adverse events and adherence rate during the study period were also analyzed. RESULTS: Thirty-six patients (all females) were enrolled in this study. The mean SDAI decreased significantly from 20.6 ± 11.2 (±SD) at baseline to 10.0 ± 10.5 at 52 weeks (p < 0.05). Patients with SDAI remission increased from 0 (0 week) to 12 patients (33.3%) at 52 weeks. Saliva volume assessed by Saxon's test increased significantly from 2136 ± 1809 (0 week) to 2397 ± 1878 (24 weeks) mg/2 min (n = 34, p < 0.05). Saliva volume increased significantly from 2945 ± 2090 (0 week) to 3419 ± 2121 (24 weeks) mg/2 min in 11 patients with Greenspan grade 1 or 2 of labial salivary gland biopsy (p < 0.05), but no change was noted in 18 patients with Greenspan grade 3 or 4. Tear volume by Schirmer's test increased significantly from 4.2 ± 4.8 (0 week) to 6.4 ± 7.8 (24 weeks) mm/5 min (n = 30, p < 0.05). The adherence rate to abatacept was 80.6% (29/36) over the 52-week period. Twelve adverse events occurred in 10 of the 36 patients, and 7 of these events were infections. CONCLUSION: Abatacept seems to be effective for both RA and SS related manifestations.
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Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Síndrome de Sjogren/tratamento farmacológico , Abatacepte/administração & dosagem , Abatacepte/efeitos adversos , Adulto , Idoso , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/etiologiaRESUMO
OBJECTIVE: To compare the effectiveness of three different biologics in anti-Ro/SSA antibody-positive and antibody-negative patients with rheumatoid arthritis (RA). METHODS: The study subjects were 110 biologics naïve patients with RA who started treatment with biologics and examined for anti-Ro/SSA antibody between December 2003 and March 2014. For patients treated with intravenous infliximab (IFX), tocilizumab (TCZ), or abatacept (ABT), we compared the clinical characteristics and changes in composite disease activity index, such as DAS28, SDAI, and CDAI, for 12 months in anti-Ro/SSA antibody-positive and antibody-negative patients. RESULTS: We examined 59 patients (nine were positive and 50 were negative for anti-Ro/SSA antibody) treated with IFX, 27 patients (5 positive and 22 negative) treated with TCZ, and 24 patients (13 positive and 11 negative) treated with ABT. For patients treated with IFX, parameters of disease activity did not change significantly from baseline in anti-Ro/SSA antibody-positive patients, whereas they improved in antibody-negative patients. On the other hand, treatment with TCZ and ABT significantly decreased disease activity, relative to baseline, in both anti-Ro/SSA antibody-positive and antibody-negative patients. Anti-Ro/SSA antibody-positive patients treated with IFX showed higher frequency of HACA and seroconversion of ANA, and lower serum TGF-ß levels. CONCLUSIONS: Positivity to anti-Ro/SSA in RA seems to confer resistance to IFX via production of HACA and ANA, and low serum TGF-ß levels, but not to TCZ and ABT.
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Anticorpos Antinucleares/sangue , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Produtos Biológicos/uso terapêutico , Abatacepte/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVES: To compare MRI findings in rheumatoid arthritis (RA) patients treated with biologic disease-modifying anti-rheumatic drugs (DMARDs). METHODS: The study subjects were 43 RA patients treated with biologic DMARDs (13 with infliximab, 15 with tocilizumab, and 15 with abatacept). They were evaluated using Simplified Disease Activity Index (SDAI) and low-field extremity MRI at baseline, and at 24 weeks and 52 weeks of treatment. RESULTS: Synovitis scores were significantly lower by 24 weeks in all groups, compared with baseline (P < 0.05). Significant improvement in bone marrow edema (BME) scores were noted from baseline to 24 weeks in infliximab and abatacept groups (P < 0.05), but from 24 weeks to 52 weeks in tocilizumab group (P < 0.01). No significant change was found in erosion score. The synovitis score at baseline correlated significantly with SDAI at 24 weeks (P < 0.05), and the score at 24 weeks correlated significantly with SDAI at 52 weeks (P < 0.05). CONCLUSIONS: The results suggest that the inflammatory improvement by infliximab and abatacept may express earlier than those by tocilizumab, despite similar improvement in SDAI. MRI-detected synovitis could be a useful predictor of SDAI at 24 weeks of treatment. The MRI remains the best tool to detect and assess the effects of biologic DMARDs in RA.
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Abatacepte/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medula Óssea/patologia , Infliximab/uso terapêutico , Adulto , Idoso , Artrite Reumatoide/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoAssuntos
Hiperplasia Angiolinfoide com Eosinofilia/diagnóstico , Hiperplasia Angiolinfoide com Eosinofilia/tratamento farmacológico , Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Mucosa Bucal/patologia , Adulto , Biópsia , Ciclosporina/administração & dosagem , Citocinas/sangue , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunossupressores/administração & dosagem , Imageamento por Ressonância Magnética , Masculino , Resultado do TratamentoRESUMO
OBJECTIVE: Autoreactive CD4+ T cells are involved in the pathogenesis of Sjögren's syndrome (SS). The aim of the present study was to clarify the dominant T cell epitopes of M3 muscarinic acetylcholine receptor (M3R) and to establish a new antigen-specific therapy for SS using an experimental mouse model. METHODS: Production of cytokines from M3R-reactive CD4+ T cells, after culture with various M3R peptides, was analyzed by enzyme-linked immunosorbent assay. Adoptive cell transfer was performed using splenocytes from M3R(-/-) mice that were immunized with M3R peptides or phosphate buffered saline plus H37Ra as a control. Rag1(-/-) mice were inoculated with the splenocytes and examined for the development of sialadenitis. Altered peptide ligands (APLs) of the T cell epitopes, with substitutions in amino acid residues at T cell receptor contact sites, were synthesized, and the ability of the APLs to suppress sialadenitis was evaluated. The mechanisms underlying such effects were assessed. RESULTS: CD4+ M3R-reactive T cells produced interleukin-17 (IL-17) and interferon-γ (IFNγ) in response to the N-terminal 1 (N1) and 1st extracellular loop peptides of M3R, and Rag1(-/-) mice that received N1- and/or 1st peptide-immunized splenocytes developed sialadenitis. Among the designed APLs, N1-APL7 (NâS at amino acid 15) significantly suppressed IFNγ production in vitro, and also suppressed sialadenitis in vivo. Levels of early growth response 2 in CD4+ T cells from the cervical lymph nodes of N1-APL7-treated mice were significantly higher than those of control mice, and cell proliferation was reversed by administration of exogenous IL-2. Levels of the anergy-related molecules itchy homolog E3 ubiquitin-protein ligase, Casitas B-lineage lymphoma b, gene related to anergy in lymphocytes, and Deltex-1 were significantly higher in CD4+ T cells cultured with N1-APL7. CONCLUSION: The major T cell epitopes were from the N1 and 1st peptide regions. Moreover, N1-APL7, selected as the antagonistic APL in vitro, also suppressed sialadenitis through the induction of anergy. This is a potentially useful strategy for regulating pathogenic T cell infiltration in SS.
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Linfócitos T CD4-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Receptor Muscarínico M3/imunologia , Sialadenite/imunologia , Síndrome de Sjogren/imunologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Transferência Adotiva , Animais , Anergia Clonal/imunologia , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Proteínas de Homeodomínio/genética , Interferon gama/metabolismo , Interleucina-17/metabolismo , Interleucina-2/farmacologia , Ligantes , Camundongos , Camundongos Knockout , Proteínas Proto-Oncogênicas c-cbl/metabolismo , Receptor Muscarínico M3/genética , Baço/citologia , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Abstract Objective. To assess the efficacy and safety of abatacept for secondary Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA). Methods. The primary endpoint of this 1-year, open-labeled, prospective, observational multicenter study of RA-associated secondary SS was the rate of SDAI remission at 52 weeks after initiation of abatacept therapy. The secondary endpoints included that of Saxson's test and Schirmer's test. Adverse events during the study period were also analyzed. Results. Thirty-two patients (all females) were enrolled in this study. Interim analysis at 24 weeks included assessment of efficacy (n = 31) and safety (n = 32). The mean SDAI decreased from 19.8 ± 11.0 (± SD) at baseline to 9.9 ± 9.9 at 24 weeks (P < 0.05). Patients with clinical remission, as assessed by SDAI, increased from 0 patient (0 week) to 8 patients (25.8%) at 24 weeks. Saliva volume (assessed by Saxson's test) increased slightly from 2232 ± 1908 (0 week) to 2424 ± 2004 (24 weeks) mg/2 min (n = 29). In 11 patients with Greenspan grading 1/2 of labial salivary glands biopsy, saliva volume increased from 2945 ± 2090 (0 week) to 3419 ± 2121 (24 weeks) mg/2 min (P < 0.05). Schirmer's test for tear volume showed increase from 3.6 ± 4.6 (0 week) to 5.5 ± 7.1 (24 weeks) mm/5 min (n = 25; P < 0.05). Five adverse events occurred in five of 32 patients (15.6%), and three of these events were infections. Conclusion. Abatacept seems to be effective for both RA and RA-related secondary SS.
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Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Síndrome de Sjogren/tratamento farmacológico , Abatacepte/efeitos adversos , Adulto , Antirreumáticos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Síndrome de Sjogren/etiologia , Resultado do TratamentoRESUMO
Reported here are 2 patients with connective tissue disease who developed pulmonary nocardiosis. Case 1 involved a 73-year-old man with malignant rheumatoid arthritis treated with prednisolone 25 mg/day. Chest X-rays revealed a pulmonary cavity and bronchoscopy detected Nocardia species. The patient was successfully treated with trimethoprim/sulfamethoxazole. Case 2 involved a 41-year-old woman with systemic lupus erythematosus. The patient received remission induction therapy with 50 mg/day of prednisolone and tacrolimus. Six weeks later, a chest CT scan revealed a pulmonary cavity; bronchoscopy resulted in a diagnosis of pulmonary nocardiosis. The patient had difficulty tolerating trimethoprim/sulfamethoxazole, so she was switched to and successfully treated with imipenem/cilastatin and amikacin.
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Rheumatoid arthritis is an autoimmune disease associated with the recognition of self proteins secluded in arthritic joints. We generated transgenic rice seeds expressing three types of altered peptide ligands (APL) and the T cell epitope of type II collagen (CII256-271). When these transgenic rice and non-transgenic rice seeds were orally administrated to DBA/1 J mice once a day for 14 days, followed by immunization with CII, the clinical score of collagen-induced arthritis (CIA) was reduced and inflammation and erosion in the joints were prevented in mice fed APL7 transgenic rice only. IL-10 production against the CII antigen significantly increased in the splenocytes and iLN of CIA mice immunized with the CII antigen, whereas IFN-γ, IL-17, and IL-2 levels were not altered. These results suggest that IL-10-mediated immune suppression is involved in the prophylactic effects caused by transgenic rice expressing APL7.
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Artrite Experimental/prevenção & controle , Colágeno Tipo II/imunologia , Oryza/genética , Peptídeos/administração & dosagem , Peptídeos/farmacologia , Sementes/genética , Administração Oral , Sequência de Aminoácidos , Animais , Artrite Experimental/imunologia , Ligantes , Camundongos , Dados de Sequência Molecular , Peptídeos/genética , Peptídeos/imunologia , Plantas Geneticamente Modificadas , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologiaRESUMO
Rheumatoid arthritis (RA) is an autoimmune disease associated with the recognition of self proteins secluded in arthritic joints. We previously reported that altered peptide ligands (APLs) of type II collagen (CII256-271) suppress the development of collagen-induced arthritis (CIA). In this study, we generated transgenic rice expressing CII256-271 and APL6 contained in fusion proteins with the rice storage protein glutelin in the seed endosperm. These transgene products successfully and stably accumulated at high levels (7-24 mg/g seeds) in protein storage vacuoles (PB-II) of mature seeds. We examined the efficacy of these transgenic rice seeds by performing oral administration of the seeds to CIA model mice that had been immunized with CII. Treatment with APL6 transgenic rice for 14 days significantly inhibited the development of arthritis (based on clinical score) and delayed disease onset during the early phase of arthritis. These effects were mediated by the induction of IL-10 from CD4(+ ) CD25(-) T cells against CII antigen in splenocytes and inguinal lymph nodes (iLNs), and treatment of APL had no effect on the production of IFN-γ, IL-17, IL-2 or Foxp3(+) Treg cells. These findings suggest that abnormal immune suppressive mechanisms are involved in the therapeutic effect of rice-based oral vaccine expressing high levels of APLs of type II collagen on the autoimmune disease CIA, suggesting that the seed-based mucosal vaccine against CIA functions via a unique mechanism.
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Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Colágeno Tipo II/uso terapêutico , Oryza/metabolismo , Peptídeos/imunologia , Administração Oral , Animais , Artrite Experimental/induzido quimicamente , Artrite Reumatoide/induzido quimicamente , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Ligantes , Camundongos , Camundongos Endogâmicos DBA , Oryza/genética , Peptídeos/genética , Peptídeos/metabolismo , Plantas Geneticamente ModificadasRESUMO
IRAS 04368+2557 is a solar-type (low-mass) protostar embedded in a protostellar core (L1527) in the Taurus molecular cloud, which is only 140 parsecs away from Earth, making it the closest large star-forming region. The protostellar envelope has a flattened shape with a diameter of a thousand astronomical units (1 AU is the distance from Earth to the Sun), and is infalling and rotating. It also has a protostellar disk with a radius of 90 AU (ref. 6), from which a planetary system is expected to form. The interstellar gas, mainly consisting of hydrogen molecules, undergoes a change in density of about three orders of magnitude as it collapses from the envelope into the disk, while being heated from 10 kelvin to over 100 kelvin in the mid-plane, but it has hitherto not been possible to explore changes in chemical composition associated with this collapse. Here we report that the unsaturated hydrocarbon molecule cyclic-C3H2 resides in the infalling rotating envelope, whereas sulphur monoxide (SO) is enhanced in the transition zone at the radius of the centrifugal barrier (100 ± 20 AU), which is the radius at which the kinetic energy of the infalling gas is converted to rotational energy. Such a drastic change in chemistry at the centrifugal barrier was not anticipated, but is probably caused by the discontinuous infalling motion at the centrifugal barrier and local heating processes there.
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OBJECTIVE: IgG4-related disease (IgG4-RD) is characterized by IgG4-positive plasmacytic infiltration and fibrosis in various organs. Orbital involvement in IgG4-RD includes lacrimal glands, extra-ocular muscles, trigeminal nerve and other parts of the orbit. Immunohistochemical staining is used to diagnose IgG4-RD in patients with orbital inflammation. The purpose of this retrospective study was to clarify the clinicopathological features of IgG4-RD complicated with orbital involvement. METHODS: We examined the clinical features, pathological findings and response to treatment in nine patients with IgG4-RD who underwent orbital tissue biopsy between April 2010 and August 2012 at the University of Tsukuba Hospital. RESULTS: Among the nine patients, eight had dacryoadenitis, one had infraorbital nerve swelling, and another one had IgG4-related orbital inflammation. Involvement of other organs was identified in all patients, including involvement of the salivary glands, lymph nodes, lung, kidney and para-aorta. In all patients, biopsy samples from orbital tissues showed lymphoplasmacytic infiltration and fibrosis, and IgG4-positive/IgG-positive plasmacyte ratio of > 40%. All patients were treated with prednisolone (0.6 mg/kg/day) and responded well in early phase, although relapse was noted in two patients following tapering of prednisolone, evident by swelling of lacrimal glands. CONCLUSION: Patients with IgG4-RD complicated with orbital involvement often present with involvement of other organs. The histopathological findings of orbital tissue match the characteristic features of IgG4-RD. Corticosteroid is effective for orbital and systemic involvement in IgG4-RD.
Assuntos
Doenças Autoimunes/diagnóstico , Oftalmopatias/diagnóstico , Imunoglobulina G/sangue , Órbita/patologia , Idoso , Doenças Autoimunes/sangue , Doenças Autoimunes/patologia , Oftalmopatias/sangue , Oftalmopatias/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: Adenosine has been reported to interact with dopamine and glutamate of which are currently central pathophysiology of schizophrenia. Further, there have been emerging reports that patients with bipolar disorder (BD) have pathophysiological changes of the purinergic system. Thus, we performed a systematic review and meta-analysis of adenosine modulators in these disorders. METHOD: We searched PubMed, EMBASE, the Cochrane Library databases, CINAHL, and PsycINFO up to April 25, 2013. Randomized controlled trials comparing adenosine modulator adjuvant therapy with placebo in patients with schizophrenia and BD were included. Primary outcome measures were Positive and Negative Syndrome Scale (PANSS) and Young Mania Rating Scales (YMRS). The risk ratio, 95% confidence interval, and standardized mean differences (SMD) were used. RESULTS: Nine studies, including six studies in schizophrenia (total n=457) and three studies in BD (total n=289) were included. Overall, adenosine modulators were superior to placebo in PANSS total scores (SMD=-1.07, p=0.01) and positive and general but not negative symptom subscale scores in schizophrenia. Individually, allopurinol failed to show its superiority to placebo in all primary outcome measures in schizophrenia. In BD, data from pooled adenosine modulators indicated significant reduction of YMRS scores in comparison to placebo (SMD=-0.39, p=0.004). CONCLUSIONS: Our results suggest that adenosine modulator adjuvant therapy is more beneficial in overall psychopathology (especially positive symptoms) in schizophrenia and in treating mania episodes of BD in comparison to placebo. The limited sample size of available studies suggests that more research should be done to evaluate both efficacy and tolerability of these medications.