RESUMO
OBJECTIVES: To investigate the protective effect of osteoporosis medications on the risk of developing rheumatoid arthritis (RA) in patients with osteoporosis. METHODS: We conducted a retrospective cohort study from 1 January, 2011 to 31 March, 2023. There was a total of 971901 patients from a hospital-based population in Taiwan. In this cohort, there was a total of 17065 osteoporosis patients with or without pathological fracture. In these patients, 7180 patients were osteoporosis medication users, and 9605 patients were non-osteoporosis medication users, after exclusion of previous RA. The risk of RA in the patients with osteoporosis medications was assessed, and stratified by sex and different medications, including bisphosphonates, denosumab, raloxifene and teriparatide. RESULTS: Patients with osteoporosis medication use had a reduced risk of RA compared with non-osteoporosis medication users [adjusted hazard ratio (aHR)=0.484, 95%CI: 0.270-0.867, p<0.05), after adjusting for age, comorbidites and medications. Specifically, patients with ever use of bisphosphonates (n=2069) or denosumab (n=4510) had a reduced risk of RA (aHR=0.405, 95%CI: 0.173-0.951, p<0.05, and aHR=0.394, 95%CI: 0.192-0.809, p<0.05, respectively). Notably, patients that only used denosumab (n=2938) had a further reduced risk of RA (aHR=0.32, 95%CI: 0.12-0.83, p<0.05), particularly in female patients (aHR=0.26, 95%CI: 0.09-0.74, p<0.05). Patients taking raloxifene or teriparatide did not have a significantly reduced risk of RA. CONCLUSIONS: Denosumab use reduces the risk of RA in patients with osteoporosis. Receptor activator of nuclear factor kappa B ligand (RANKL) mediated osteoclast joint damage may be involved in the pathogenesis of RA during the preclinical stage.
Assuntos
Artrite Reumatoide , Conservadores da Densidade Óssea , Denosumab , Osteoporose , Humanos , Denosumab/uso terapêutico , Denosumab/efeitos adversos , Feminino , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Masculino , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Osteoporose/prevenção & controle , Estudos Retrospectivos , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Pessoa de Meia-Idade , Taiwan/epidemiologia , Fatores de Risco , Medição de Risco , Resultado do Tratamento , Fatores de Proteção , Difosfonatos/uso terapêuticoRESUMO
OBJECTIVES: To investigate the association of hydroxychloroquine (HCQ) with the risk of cardiovascular disease (CVD) events in patients with traditional risk factors, hypertension (HTN) or diabetes mellitus (DM). METHODS: We conducted a retrospective cohort study from 1 January, 2010 to 30 September, 2022. There was a total of 1007585 patients from a hospital-based population. In this cohort, 146862 patients had newly diagnosed HTN or DM. Among these patients, 1903 patients had HCQ exposure and 136396 patients had no HCQ exposure after exclusion of previous CVD events or invasive cardiovascular procedures. The risk of developing CVD events, a composite of acute myocardial infarction (AMI) and ischaemic stroke was evaluated. RESULTS: The patients with HCQ exposure had reduced risk of CVD events [HR (hazard ratio)=0.67 95%CI: 0.55-0.83], AMI (HR=0.61, 95%CI: 0.41-0.90) and ischaemic stroke (HR=0.74, 95%CI:0.59-0.93), when compared with non-HCQ exposure, after adjusting for age, sex, rheumatic diseases, comorbidities and medications. Specifically, reduced risk for CVD events (HR=0.67, 95%CI: 0.54-0.83), including AMI (HR=0.67, 95%CI: 0.44-1.00) and ischaemic stroke (HR=0.71, 95%CI: 0.55-0.90) were observed in older patients (age ≥50 yrs) with HCQ exposure, and reduced risk for AMI also observed in younger patients (age <50 yrs) (HR=0.28, 95%CI: 0.08-0.97). Reduced risk for CVD events (HR=0.63, 95%CI: 0.48-0.82) and ischaemic stroke (HR=0.63, 95%CI: 0.47-0.85) were observed particularly in female patients with HCQ exposure. Reduced risk for AMI was observed particularly in male patients with HCQ exposure (HR=0.44, 95%CI: 0.22-0.87). CONCLUSIONS: HCQ has protective effect on CVD events, including both AMI and ischaemic stroke in the patients with traditional risk factors. The protective effect of HCQ on CVD events is prominent in older patients.
Assuntos
Isquemia Encefálica , Doenças Cardiovasculares , Diabetes Mellitus , Hipertensão , AVC Isquêmico , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Hidroxicloroquina/efeitos adversos , Estudos Retrospectivos , Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Fatores de Risco , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Doenças Cardiovasculares/epidemiologia , AVC Isquêmico/tratamento farmacológicoRESUMO
Background and Objective: The International Map of Axial Spondyloarthritis (IMAS) explores the physical, psychological, and social experiences of patients with axial spondyloarthritis (axSpA). This initiative is now being expanded to Taiwan as the Taiwanese Map of Axial Spondyloarthritis (TMAS). We aim to provide rheumatologists with insights into the perspectives of Taiwanese patients, enabling physicians to better understand the unmet needs of these patients and optimize their management. Materials and Methods: The TMAS is a cross-sectional study gathering data through an online survey of axSpA patients, promoted by the Ankylosing Spondylitis Caring Society of R.O.C. (ASCARES), conducted from July 2017 to March 2018 by Ipsos, and analyzed by the Health & Territory Research (HTR) group of the University of Seville. The questionnaire includes 99 questions that cover domains such as patient profile, diagnosis, habits/lifestyle, employment status, physical/psychological health status, social support, use of healthcare services, and treatments. Results: A total of 112 axSpA patients were included in this survey. The mean age was 38.6 years and 75.0% were male. The average diagnostic delay was 3 years, and 19.6% reported extra-articular manifestations. Out of the 49 respondents who reported HLA-B27 information, 35 were HLA-B27-positive. The disease burden was high, with a mean BASDAI score of 4.9 and 75.9% having a mild to moderate degree of spinal stiffness. Furthermore, they were socially and psychologically burdened, with 88.4% experiencing work-related issues and 25.9% suffering from anxiety. Conclusions: The TMAS sheds light on the overall perspective of axSpA patients in Taiwan. The TMAS shows shorter diagnostic delay compared to patients from the EMAS. However, high disease activity and significant psychological distress still trouble the patients, causing functional impairments and even leading to career failures. Understanding the perspective of axSpA patients can help rheumatologists adjust treatment strategies to their unmet needs and improve their disease outcomes.
Assuntos
Espondilartrite , Espondilite Anquilosante , Humanos , Masculino , Adulto , Feminino , Espondilartrite/diagnóstico , Espondilartrite/psicologia , Antígeno HLA-B27 , Estudos Transversais , Diagnóstico TardioRESUMO
The importance of social interactions has been reported in a variety of animal species. In human and rodent models, social isolation is known to alter social behaviors and change anxiety or depression levels. During the coronavirus pandemic, although people could communicate with each other through other sensory cues, social touch was mostly prohibited under different levels of physical distancing policies. These social restrictions inspired us to explore the necessity of physical contact, which has rarely been investigated in previous studies on mouse social interactions. We first conducted a long-term observation to show that pair-housed mice in a standard laboratory cage spent nearly half the day in direct physical contact with each other. Furthermore, we designed a split-housing condition to demonstrate that even with free access to visual, auditory, and olfactory social signals, the lack of social touch significantly increased anxiety-like behaviors and changed social behaviors. There were correspondingly higher levels of the pro-inflammatory cytokine interleukin-6 in the hippocampus in mice with no access to physical contact. Our study demonstrated the necessity of social touch for the maintenance of mental health in mice and could have important implications for human social interactions.
Assuntos
Abrigo para Animais , Tato , Animais , Ansiedade/psicologia , Comportamento Animal , Masculino , Camundongos , Comportamento Social , Isolamento Social/psicologia , Estresse PsicológicoRESUMO
BACKGROUND: Nonradiographic axial spondyloarthropathies (nr-axSpA) are diagnosed by the absence of radiographic sacroiliitis and the presence of bone marrow edema (BME) on magnetic resonance imaging (MRI). According to the classification criteria of the international Assessment of Spondyloarthritis Society (ASAS), structural changes to sacroiliac joints (SIJs) on MRI cannot be used as criteria in the absence of BME. However, less than half the Asian patients with clinically active axSpA show BME. The incidence of human leukocyte antigen (HLA)-B27 is low in Asian populations, which makes it more difficult to identify nr-axSpA. We used MRI to evaluate the structural damage to SIJs in patients with nr-axSpA with and without BME with the aim of identifying the best methodology for accurate diagnosis, especially in populations with less common BME and HLA-B27. METHODS: One hundred three patients with inflammatory back pain were included in this prospective study. No patient's radiograph met the definition of positive modified New York criteria. BME and structural damage to SIJ including sclerosis and erosion were assessed independently on coronal and axial short-tau inversion recovery and T1-weighted spin echo MRI scans by two well-trained musculoskeletal radiologists using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Demographics of patients were collected. Disease characteristics and structural damage were analyzed in patients with and without BME on SIJ MRI. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of structural damage. RESULTS: All individuals in the cohort had at least one abnormal finding on SIJ MRI, including BME or structural damage; 36 of 103 patients had BME. We identified a significant positive correlation between SPARCC scores and severe erosion assessed by focal joint space widening (fJSW) (p = 0.001) in these 36 patients. Fifty-eight of the 103 enrolled patients fulfilled the ASAS criteria for nr-axSpA in the either absence or presence of BME. Of these 58 patients, 57 and 19 had erosions or fJSW, respectively, and the presence of BME was significantly correlated with fJSW (phi score of 0.319 and p = 0.015). We demonstrated a significant positive correlation between fJSW and either the presence or the severity of BME in patients with nr-axSpA who met the ASAS definition. There was a positive correlation between BME and fJSW across the whole study cohort (phi score of 0.389; p < 0.001). The area under the ROC curve (AUC) for fJSW on SIJ MRI was 0.736, p < 0.001. In both HLA-B27-positive and -negative groups, BME was more common in the presence of fJSW (phi scores of 0.370 and 0.377, p = 0.018 and 0.003, respectively) and SPARCC scores were higher in patients with fJSW (p < 0.001 and p = 0.005). We also identified a positive correlation between fJSW and BME in patients with nr-axSpA and normal serum levels of C-reactive protein (phi score of 0.362 and p = 0.001). CONCLUSION: Structural damage detected on SIJ MRI, sclerosis, erosions and fJSW may be present in patients without detectable inflammation on SIJ MRI. However, fJSW is significantly correlated with the severity of inflammation seen on SIJ MRI, which contributes to the accurate diagnosis of nr-axSpA, and it could be used as an alternative diagnostic test for nr-axSpA in the general population, especially for those who do not carry the HLA-B27 gene, Asian patients without BME, or patients with normal serum inflammatory biomarkers.
Assuntos
Antígeno HLA-B27 , Espondilartrite , Canadá , Diagnóstico Precoce , Antígeno HLA-B27/genética , Humanos , Imageamento por Ressonância Magnética , Estudos Prospectivos , Espondilartrite/diagnóstico por imagemRESUMO
A case of intractable IgG4-related orbital disease (IgG4-ROD) was successfully treated by debulking surgery combined with low-dose prednisolone and azathioprine as maintenance therapy. A 64-year-old man visited our clinic with progressive bilateral upper eyelid swelling and right eye fullness of a year's duration. He was previously treated with systemic corticosteroids for the IgG4-ROD and experienced a partial clinical response but relapsed upon prednisolone cessation. The patient underwent debulking surgery of the right lacrimal gland and right upper eyelid. His post-operative medication was oral prednisolone (5 mg) every other day and 50 mg azathioprine per day. The patient's right eye remained asymptomatic during the 18 months of follow-up. Debulking surgery combined with low-dose prednisolone and azathioprine, as a maintenance therapy, is an effective and alternative treatment for the long-term control of intractable IgG4-ROD.
Assuntos
Azatioprina , Doenças Orbitárias , Azatioprina/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Humanos , Imunoglobulina G , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêuticoRESUMO
Primary Sjögren's syndrome (PSS) is an autoimmune disease targeting exocrine glands. It ten times more dominantly affects women than men with an onset peak at menopause. The genetic factor predisposing women to PSS remains unclear. Therefore, we aimed to identify susceptibility loci for PSS in women. We performed genome-wide association study (GWAS) using 242 female PSS patients and 1444 female control in Han Chinese population residing in Taiwan. Replication was conducted in an independent cohort of 178 female PSS and 14,432 control subjects. We identified rs117026326 on GTF2I with GWAS significance (P = 1.10 × 10-15) and rs13079920 on RBMS3 with suggestive significance (P = 2.90 × 10-5) associating with PSS in women. The association of RBMS3 was further evidenced by imputation in which rs13072846 (P = 4.89 × 10-5) was identified and confirmed as female PSS associating SNP within the same LD with rs13079920. PSS pathogenesis involves both immune (effector) and exocrine (target) system. We suggested that while GTF2I is a previously reported associating gene which may function in immune system, RBMS3 is a novel susceptibility gene that predisposes women to PSS potentially through modulating acinar apoptosis and TGF-ß signaling in target exocrine system.
Assuntos
Predisposição Genética para Doença , Proteínas de Ligação a RNA/genética , Síndrome de Sjogren/genética , Transativadores/genética , Fatores de Transcrição TFII/genética , Células Acinares/metabolismo , Adulto , Apoptose/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Síndrome de Sjogren/patologia , Fator de Crescimento Transformador beta/genéticaRESUMO
It has long been recognized that patients with myositis and positive anti-Jo1 antibody tend to be associated with interstitial lung disease. Recent studies revealed that such patients may also have fever, Raynaud's phenomenon, mechanic's hand, polyarthralgia, or usually mild, self-limiting, non-erosive or erosive polyarthritis known as antisynthetase syndrome. The hallmark of this disorder is the presence of the autoantibodies that recognize the aminoacyl-tRNA synthetases, which play a critical role in protein synthesis. The most well recognized of the autoantibodies is anti-histidyl (Jo-1). Antisynthetase syndrome cases associated with other autoimmune diseases are rarely reported. We here present a case of antisynthetase syndrome presented with right ventricle thrombus and deep vein thrombosis in the lower limbs. Secondary antiphospholipid syndrome was then diagnosed after a series of examinations. The patient was successfully treated with anticoagulant alone without surgical thrombectomy. Our case revealed that clinical physicians should watch for thrombotic complications when facing patients with antisynthetase syndrome. Medical therapy with anticoagulants alone may be an alternative treatment option in patients with right ventricle thrombus who cannot tolerate surgical thrombectomy.
Assuntos
Anticorpos Antinucleares/sangue , Síndrome Antifosfolipídica/complicações , Cardiopatias/complicações , Miosite/complicações , Trombose/complicações , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Cardiopatias/sangue , Cardiopatias/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Miosite/imunologia , Trombose/sangue , Trombose/imunologiaRESUMO
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can lead to damage to several vital organs. Antiphospholipid syndrome (APS), manifesting as vascular thromboembolic events and morbidities of pregnancy in the presence of antiphospholipid antibodies (aPL), has been described in patients with SLE. Catastrophic antiphospholipid syndrome (CAPS), in contradistinction to APS, is defined as three or more organs affected by thrombotic microangiopathy in patients demonstrating aPL and can result in mortality up to 50%. We describe a unique SLE patient who was diagnosed with recurrent APS presented with axillary venous thrombosis and subsequent superficial edema and compartment syndrome. The CAPS followed and revealed thromboses over liver, spleen, and acute pancreatitis. The spontaneous hemorrhage of left fourth intercostal artery (ICA) and left axillary artery occured at the same time without vasculitis or severe trauma. Though emergency transcatheter arterial embolization (TAE) of the left fourth ICA was successfully accomplished by the radiologist. The repeated computed tomography angiogram of chest demonstrated remission of ruptured ICA. Nevertheless, the patient died of diffuse alveolar hemorrhage and respiratory failure and shock. Both disseminated intravascular coagulation (DIC) and CAPS share similar characteristics encompassing thrombotic microangiopathy, bleeding, thromboembolism, and multiple organ dysfunction. It is difficult to distinguish between them, especially in cases such as our uremic SLE patient with a calamitous disease progression. The emphasis of treatment for DIC is on platelet and fresh plasma transfusion, in contrast with anti-coagulant for CAPS. To the best of our knowledge, this is the first report describing ICA hemorrhage in an SLE patient without vasculitis or aneurysm. The lupus flare initiated a pathological immunological cascade and resulted in the CAPS and the vascular damage.
Assuntos
Síndrome Antifosfolipídica/diagnóstico , Hemorragia/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Síndrome Antifosfolipídica/complicações , Artéria Axilar/patologia , Doença Catastrófica , Evolução Fatal , Feminino , Hemorragia/complicações , Hemorragia/terapia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Pessoa de Meia-Idade , Artérias Torácicas/patologia , Trombose/complicações , Trombose/diagnóstico , Trombose/terapiaRESUMO
To investigate the association of blood pressure and hypertension with disease severity among the patients with ankyloing spondylitis (AS). There were 167 AS patients enrolled in the cross-sectional study. Blood pressure was measured and the presence of hypertension was recorded. Patient's disease severity, including disease activity, functional ability, patient's global assessments, physical mobility and radiographic damage were evaluated. ESR and CRP levels were tested. We recorded patient's medication use of NSAIDs, DMARDs and TNF-α blockers. Smoking, exercise habit, diabetes mellitus, hypercholesterolemia and obesity indices were assessed. Multivariate linear regression showed that systolic blood pressure was associated with TNF-α blocker [standard coefficient (ß)â =â 0.194, Pâ =â .007], DMARDs (ßâ =â 0.142, Pâ =â .046), age (ßâ =â 0.211, Pâ =â .003), male gender (ßâ =â 0.242, Pâ =â .001) and body mass index (BMI) (ßâ =â 0.245, Pâ =â .001). Diastolic blood pressure was associated with cervical rotation (ßâ =â -0.174, Pâ =â .037), lateral lumbar flexion (ßâ =â -0.178, Pâ =â .019), m-SASSS (ßâ =â 0.198, Pâ =â .038) and BMI (ßâ =â 0.248, Pâ =â .003). Notably, multivariate logistic regression showed that hypertension was associated with m-SASSS (ORâ =â 1.033, Pâ =â .033), age (ORâ =â 1.098, Pâ =â .0010) and BMI (ORâ =â 1.210, Pâ =â .003). Using ROC cure analyses, age, BASMI, BASRI-Total, m-SASSS, waist circumference, BMI and waist-to-height ratio were useful in predicting hypertension, and m-SASSS is the best (AUCâ =â 0.784, Pâ <â .001). Advanced radiographic damage is an independent risk factor of hypertension in AS, and m-SASSS is the most useful disease severity parameter in predicting the presence of hypertension. Advanced radiographic damage, poor cervical rotation, lateral lumbar flexion, older age, male gender, TNF-α blocker, DMARDs use and obesity are associated with increased blood pressure.
Assuntos
Antirreumáticos , Hipertensão , Espondilartrite , Espondilite , Anti-Inflamatórios não Esteroides , Antirreumáticos/uso terapêutico , Pressão Sanguínea , Índice de Massa Corporal , Estudos Transversais , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Masculino , Obesidade , Fatores de Risco , Fator de Necrose Tumoral alfa , Circunferência da CinturaRESUMO
BACKGROUND: Chronic urticaria (CU) is comprised of diverse phenotypes, and thus, a shift towards a precision medical approach is warranted in its management. METHODS: This study enrolled 78 patients with CU. Serum erythrocyte sedimentation rate, hemoglobin, hematocrit, eosinophil count, IgE, antinuclear antibody (ANA), and serum diamine oxidase (DAO) levels of the patients were measured and were compared according to the patient's response to second-generation antihistamines (sgAH), corticosteroids, leukotriene receptor antagonist (LTRA), H2 blockers, and low-histamine diet. RESULTS: Age- and sex-adjusted logistic regression analysis showed that patients with duration of CU > 3 years (adjusted odd ratio [aOR] = 4.39) and a DAO level < 10 U/mL (aOR = 3.90) were significantly associated with a good sgAH response. Age > 50 years (aOR = 0.02), duration of chronic urticaria > 3 years (aOR =0.06), and an ANA titer ≥ 1 : 80 (aOR = 0.03) were significantly and inversely associated with corticosteroid response. A low-histamine diet response was significantly associated with LTRA response (aOR = 67.29). In addition, a DAO level < 5.4 U/mL (aOR = 71.95) was significantly associated with H2 blocker response. Furthermore, concomitant angioedema (aOR = 10.56), multiple food triggers (aOR = 11.69), and a DAO level < 5.4 U/mL (aOR = 3.78) were significantly associated with a low-histamine diet response. Conversely, dermatographic urticaria and a hematocrit level < 36% were significantly and inversely associated with low-histamine diet response. CONCLUSIONS: Several promising biomarkers were identified in this study to predict the efficacy of chronic urticaria treatment. DAO could be a novel biomarker for predicting the efficacy not only of dietary intervention but also for antagonists of H1 and H2 receptors.
Assuntos
Urticária Crônica , Urticária , Doença Crônica , Urticária Crônica/tratamento farmacológico , Dieta , Histamina , Humanos , Urticária/diagnóstico , Urticária/tratamento farmacológicoRESUMO
ABSTRACT: To investigate the association of sleep disturbance with calcium regulatory hormones, disease severity and health index among the patients with ankylosing spondylitis (AS).There were 104 AS patients enrolled in the cross-sectional study, and their sleep quality was recorded. Serum levels of calcium, parathyroid hormone, vitamin D3 and calcitonin were measured. We evaluated patient's disease activity, functional ability, patient's global assessment, physical mobility, radiographic damage and health index. Blood ESR and CRP levels were tested.Sleep quality was positively correlated with serum calcitonin levels (râ=â0.260, Pâ=â.008). Bad sleep and advanced radiographic damage were found among the AS patients with detectable serum calcitonin levels (Pâ<â.05). Sleep quality was significantly correlated with disease duration, CRP, BASDAI, ASDAS-ESR, ASDAS-CRP, BASFI, BAS-G, BASMI and ASAS-HI among the AS patients (all Pâ<â.05). Female gender, longer disease duration, higher ASDAS-CRP and serum calcitonin levels (OR [95% CI]â=â3.210 [1.012-10.181], Pâ=â.048) were independent factors associated with bad sleep. Inflammation, disease activity, functional ability, patient's global assessment and cervical rotation were useful in predicting bad sleep among the AS patients, and ASDAS-CRP was the best predictor (AUCâ=â0.772, Pâ<â.001).Serum calcitonin levels was elevated in the AS patients with bad sleep, and may participate in the pathophysiology of sleep disturbance. Bad sleep was associated with female gender, longer disease duration, higher inflammation, disease activity, functional impairment, mobility restriction, poor patient's global assessment and health index in AS. ASDAS-CRP was best in predicting bad sleep.
Assuntos
Calcitonina/sangue , Nível de Saúde , Medição de Risco/métodos , Transtornos do Sono-Vigília/etiologia , Sono/fisiologia , Espondilite Anquilosante/fisiopatologia , Adulto , Biomarcadores/sangue , Estudos Transversais , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/fisiopatologia , Espondilite Anquilosante/sangue , Espondilite Anquilosante/complicações , TaiwanRESUMO
A term "bone-breaking fever" is used in Chinese medicine to describe the symptoms of patients infected with dengue virus (DV). We examined the significance of the COX-prostaglandin pathway in human DC infected by DV. We show that DV infection induced the expression of COX-2 and the production of prostaglandin E2 (PGE2) in DC, and stimulated the DNA binding of NF-kappaB and the kinase activity of both IkappaBalpha kinase (IKK) alpha and beta. DV infection also activated MAPK and AP-1 signaling. Both IkappaBalpha kinase-NF-kappaB and MAPK-AP-1 were upstream of COX-2 activation. Our investigation into the significance of COX-2-PGE2 pathway also revealed that DV infection enhances DC migration by inducing CC chemokine receptor 7 (CCR7) expression, and that blocking COX-2 or MAPK activity suppresses DV-induced DC migration. Our data also suggest that PGE2 can induce CCR7 expression on DC and that antagonists of the PGE2 receptors EP2 and EP4 suppress DV-induced DC migration. We further show that the increased CCR7 expression was observed in both DV-infected and bystander DC, suggesting the presence of secondary effects in inducing CCR7 expression. Collectively, this study reveals not only the pathways involved in COX-2 synthesis in DV-infected DC but also the autocrine action of PGE2 on the migration of DV-infected DC.
Assuntos
Movimento Celular , Ciclo-Oxigenase 2/metabolismo , Células Dendríticas/virologia , Vírus da Dengue/fisiologia , Transdução de Sinais , Western Blotting , Células Cultivadas , Ciclo-Oxigenase 2/genética , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Dinoprostona/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Interações Hospedeiro-Patógeno , Humanos , Inflamação/genética , Inflamação/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Receptores CCR7/metabolismo , Receptores de Prostaglandina E/metabolismo , Receptores de Prostaglandina E Subtipo EP2 , Receptores de Prostaglandina E Subtipo EP4 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição AP-1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
AIM: To investigate total and central obesity in ankylosing spondylitis (AS), and assess the association with inflammation, disease severity and cardiovascular risk factors. METHODS: There were 105 AS patients enrolled. Anthropometry was measured to determine total (body mass index [BMI]) and central obesity (waist circumference [WC], waist-to-height ratio [WHtR]). We evaluated patients' disease activity, functional ability, global assessment, physical mobility, radiographic damage and health index. Erythrocyte sedimentation rate, C-reactive protein (CRP) and blood biochemistry profile were tested. Retrospective radiographic change was assessed in 39 patients. Presence of diabetes and hypertension were examined. RESULTS: The obese AS patients had higher inflammation (CRP), disease activity (Ankylosing Spondylitis Disease Activity Score [ASDAS] - CRP), physical mobility (Bath Ankylosing Spondylitis Metrology Index [BASMI]), radiographic damage (modified Stoke Ankylosing Spondylitis Spinal Score [m-SASSS]), liver function and blood pressure (all P < .05). Obesity (BMI, WC, WHtR) positively correlated with inflammation (CRP), physical mobility (BASMI), radiographic damage (m-SASSS), health index (Assessment of SpondyloArthritis International Society Health Index), liver function and blood pressure (all P < .05). Moreover, presence of central obesity (WC, WHtR) had correlation with disease activity (ASDAS-CRP) (r = .218, P = .027; r = .221, P = .025), and predicted longitudinal radiographic change (m-SASSS) (standard coefficient = 0.300, P = .041; standard coefficient = 0.288, P = .045). Importantly, central obesity was better in predicting high inflammation, disease activity, physical mobility, radiographic damage and health index in AS, and WHtR was the best for predicting m-SASSS (area under the curve = 0.734, P < .001). Obesity was associated with increased risk of diabetes and hypertension in AS. CONCLUSION: Obesity was associated with higher inflammation, disease activity, physical mobility, radiographic damage, health index, liver function and cardiovascular risk factors in AS. Central obesity could predict a patient's longitudinal radiographic change. Central obesity is a useful predictor for high disease severity in AS.
Assuntos
Doenças Cardiovasculares/etiologia , Inflamação/complicações , Obesidade Abdominal/complicações , Espondilite Anquilosante/complicações , Adulto , Antropometria , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/análise , Doenças Cardiovasculares/diagnóstico , Progressão da Doença , Feminino , Estado Funcional , Nível de Saúde , Fatores de Risco de Doenças Cardíacas , Humanos , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Obesidade Abdominal/diagnóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/fisiopatologiaRESUMO
Although human leucocyte antigen (HLA)-B27 is strongly associated with ankylosing spondylitis (AS), the association of unfolded protein response (UPR) induced by HLA-B27 misfolding in AS remains controversial. Since dendritic cells (DCs) are crucial in induction of AS in HLA-B27-transgenic rats, and plasmacytoid DCs (pDCs) belong to one type of DCs, we here aim to study the relevance of pDCs and UPR in AS. Peripheral pDCs were isolated from 27 HLA-B27(+) AS patients and 37 controls. The bone marrow (BM) and synovium of inflamed hips from AS patients and controls were obtained. We found a significantly higher frequency of pDCs in the peripheral blood, BM, or inflamed synovium of hips, which is associated with the enhanced expression of pDC trafficking molecules, CCR6 and CCL20 in the synovium of AS patients. Functional analysis further revealed that several inflammatory cytokines, including TNFα, IL-6, and IL-23, secreted by pDCs were significantly increased in AS patients as compared with those in controls. Remarkably, protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway in UPR was up-regulated in pDCs of AS patients. Notably, PERK inhibitor treatment significantly inhibited the enhanced cytokine production by pDCs of AS patients. Further, the extent of PERK activation was significantly associated with the increased disease severity of AS patients. Our data uncover the aberrant distribution and function of pDCs in AS patients. The up-regulated PERK pathway in UPR of pDCs not only contributes to enhanced cytokine production of pDCs, but also is associated with increased disease activity of AS patients.
Assuntos
Células Dendríticas/imunologia , Antígeno HLA-B27/genética , Espondilite Anquilosante/imunologia , Resposta a Proteínas não Dobradas , eIF-2 Quinase/genética , Adenina/análogos & derivados , Adenina/farmacologia , Células da Medula Óssea/imunologia , Células da Medula Óssea/patologia , Estudos de Casos e Controles , Contagem de Células , Quimiocina CCL20/genética , Quimiocina CCL20/imunologia , Células Dendríticas/patologia , Antígeno HLA-B27/imunologia , Quadril , Humanos , Imunofenotipagem , Indóis/farmacologia , Interleucina-23/genética , Interleucina-23/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Inibidores de Proteínas Quinases/farmacologia , Receptores CCR6/genética , Receptores CCR6/imunologia , Índice de Gravidade de Doença , Transdução de Sinais , Espondilite Anquilosante/genética , Espondilite Anquilosante/patologia , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , eIF-2 Quinase/antagonistas & inibidores , eIF-2 Quinase/imunologiaRESUMO
OBJECTIVE: SLE is an autoimmune disorder characterized by abnormal complement activation. Numerous new biomarkers have recently been used to diagnose or monitor disease activity in patients with SLE. We checked the levels of erythrocyte-bound C4d (E-C4d), an activation-derived fragment of C4 that is deposited on the erythrocytes, under different conditions of SLE in order to correlate these levels with disease activity. METHODS: We conducted a cross-sectional investigation of three groups of patients: (i) 63 patients with SLE; (ii) 43 patients with other diseases; and (iii) 26 healthy controls. Erythrocytes were analysed by flow cytometry to determine the levels of E-C4d. RESULTS: We found a significant elevation in the mean levels of E-C4d in SLE patients compared with patients with other diseases or healthy controls. In SLE patients, the levels of E-C4d were correlated with the SLEDAI and inversely correlated with serum C3/C4 levels. In the subgroup of SLE patients with haemolytic anaemia (HA), a significantly higher level of E-C4d was observed than that in SLE patients without HA. However, in SLE patients with HA, there was no correlation between the levels of E-C4d and other markers of disease activity, including SLEDAI and levels of anti-dsDNA, C3 and C4. CONCLUSION: E-C4d levels are useful diagnostic markers for SLE and can serve as biomarkers of disease activity in patients with SLE. However, E-C4d is of limited value in monitoring disease activity in SLE patients with HA.
Assuntos
Complemento C4b/análise , Eritrócitos/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Fragmentos de Peptídeos/análise , Adolescente , Adulto , Idoso , Anemia Hemolítica Autoimune/etiologia , Anemia Hemolítica Autoimune/imunologia , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto JovemRESUMO
Compounds 4a-f, 5a-f and 6-9, showed significant growth inhibition activity against human tumor cell lines. Of these compounds, 1-(2-((Z)-6-(2-(trifluoromethyl)phenyl)hexa-3-en-1,5-diynyl)phenyl)piperidin-2-one (8) displayed the most potent growth inhibition activity. Compound 8 also arrested cancer cells in G2/M phase and induced apoptosis via activation of caspase-3 and -9. According to western-blotting analysis, compound 8 can up-regulate Bax, down-regulate Bcl-2 and XIAP, as well as promote cytochrome c release.
Assuntos
Antineoplásicos/química , Apoptose , Piperidonas/química , Moduladores de Tubulina/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Caspase 3/metabolismo , Divisão Celular , Linhagem Celular Tumoral , Citocromos c/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Fase G2 , Células HeLa , Humanos , Piperidonas/síntese química , Piperidonas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/farmacologia , Proteína X Associada a bcl-2/metabolismoRESUMO
The presence of antibodies to cyclic citrullinated peptide (CCP) has high specificity in the diagnosis of rheumatoid arthritis (RA). Hepatitis C virus (HCV) infection may induce extra-hepatic manifestations, such as polyarthritis that mimic RA. The aim of this study was to determine the prevalence of anti-CCP antibodies in HCV-infected patients with or without arthritis, rheumatoid factor (RF), or cryoglobulinemia and to investigate whether anti-CCP antibodies may be helpful in discriminating patients with RA from patients with HCV-associated arthropathy. A total of 44 patients with RA, 34 patients with HCV infections, and 42 control patients with non-RA rheumatic diseases were recruited for the study. Anti-CCP antibody levels were determined by enzyme-linked immunosorbent assay. We found that, consistent with other reports, patients with RA were more likely to have high titers of anti-CCP antibody than HCV-infected or control patients. A significant number of HCV-infected patients with neither RF nor cryoglobulinemia were also positive for anti-CCP antibodies (the three positive values were 36.10, 8.65, and 5.83 U/ml, P < 0.01 compared with the control patients). The presence of cryoglobulinemia and/or RF in HCV-infected patients did not affect the anti-CCP outcomes. Although anti-CCP antibodies remain to be a very useful tool in discriminating RA from non-RA, HCV-infected patients with neither RF nor cryoglobulinemia may have anti-CCP antibodies. Because of limited patient numbers, this tentative conclusion may need further confirmation with inclusion of more patient population.
Assuntos
Anticorpos Anti-Idiotípicos/sangue , Artrite Reumatoide/imunologia , Artrite/imunologia , Crioglobulinemia/imunologia , Hepatite C/imunologia , Peptídeos Cíclicos/imunologia , Fator Reumatoide/imunologia , Adulto , Idoso , Artrite/diagnóstico , Artrite/etiologia , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Hepacivirus , Hepatite C/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
Polymyositis may occur along with other manifestations of chronic graft vs host disease after allogeneic bone marrow transplantation (BMT). Donor lymphocyte infusion (DLI) could produce durable remissions in relapsed patients with chronic myelogenous leukemia (CML) but it may contribute to the development of polymyositis. We report in this study a 25-year-old man who suffered from a relapse of CML 4 years after a sibling human leukocyte antigen-matched allogenic BMT. The patient developed polymyositis 18 months after DLI. Mini-pulse therapy with methylprednisolone was effective for his proximal weakness and elevated creatine phosphokinase. There was no relapse of symptoms of polymyositis on tapering of the medication.
Assuntos
Doença Enxerto-Hospedeiro/etiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Transfusão de Linfócitos/efeitos adversos , Polimiosite/etiologia , Transplante de Células-Tronco/efeitos adversos , Adulto , Terapia Combinada , Glucocorticoides/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/imunologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Masculino , Metilprednisolona/uso terapêutico , Polimiosite/tratamento farmacológico , Polimiosite/imunologia , Pulsoterapia , RecidivaRESUMO
Adult-onset Still's disease is a multisystem inflammatory disorder of unknown etiology and is characterized by high, spiking fever, arthritis, evanescent maculopapular rash, myalgia, serositis, leukocytosis, and involvement of various organs including the eyes. The ocular manifestations have been described including orbital pseudotumor, ptosis, and diplopia with orbital pain but never Purtscher's-like retinopathy. We describe a 21-year-old male patient with adult-onset Still's disease who developed the Purtscher's-like retinopathy. To our knowledge, this is the first reported adult-onset Still's disease patient with Purtscher's-like retinopathy as the initial presentation.