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1.
Zhongguo Zhong Yao Za Zhi ; 45(2): 451-456, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237331

RESUMO

To investigate the efficacy of Huangqin Qingre Chubi Capsules(HQC) in patients with ankylosing spondylitis(AS) and its effect on oxidative stress, and to explore its possible mechanism. Fifty-eight cases of AS patients were randomly divided into HQC group and salazosulfapyridine(SASP) group. Another 30 healthy people were employed as a control group. Superoxide dismutase(SOD), total antioxidant capacity(TAOC), malondialdehyde(MDA), lipid peroxidatio(LPO), interleukin-1ß(IL-1ß), IL-10, IL-4, and tumor necrosis factor-α(TNF-α) were detected by ELISA. The mRNA expression levels of AMP-activated protein kinase(AMPK-α), forkhead box O3a(FOXO3a), manganese superoxide dismutase(MnSOD), and peroxisome proliferator-activated receptor gamma(PPARγ) were detected by Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). The protein expression levels of AMPK-α, FOXO3a, p-FOXO3a, MnSOD, and PPARγ were detected by Western blot. A questionnaire was used to evaluate the disease activity score and observe the clinical efficacy of HQC in AS patients. The levels of MDA, LPO, TNF-α, and IL-1ß were significantly increased in the peripheral blood of AS patients, and SOD, TAOC, IL-4, IL-10 levels were significantly decreased. After HQC treatment, scores of disease active indexes were all decreased, and its clinical efficacy was significantly higher than that in SASP group. After HQC treatment, TAOC, SOD, IL-4, IL-10 were increased and MDA, LPO, TNF-α, IL-1ß were decreased; mRNA levels of AMPK-α, FOXO3a, MnSOD, PPARγ and protein levels of AMPK-α, FOXO3a, p-FOXO3a, MnSOD, PPARγ were increased(P<0.01 or P<0.05). HQC can effectively improve the clinical symptoms and oxidative stress of AS patients, and its mechanism may be related to activating PPARγ and up-regulating AMPK/FOXO3a signal pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Proteína Forkhead Box O3/metabolismo , Estresse Oxidativo , PPAR gama/metabolismo , Espondilite Anquilosante/tratamento farmacológico , Cápsulas , Humanos , Scutellaria baicalensis/química , Transdução de Sinais , Sulfassalazina/uso terapêutico
2.
PLoS One ; 15(3): e0230560, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32231384

RESUMO

PURPOSE: To investigate the efficacy and tolerance of systemic treatments for the prevention of HLA-B27-associated acute uveitis (AU) recurrence. METHODS: Retrospective review of patients with HLA-B27-associated uveitis followed in our tertiary center over a 15-year period. Systemic treatments were prescribed to patients with frequent (more than 2 flares per year) or severe uveitis, according to a step-up strategy. RESULTS: 101 patients (51.5% of men, 88.1% of white Europeans) with a median age of 37 years. AU was mostly recurrent (68.3%) and associated with spondyloarthritis (60.4%). After a median follow-up duration of 22 months (3-73), 37.6% of the patients have received systemic treatment. 88.5% of the patients have been treated with sulfasalazine (SSZ) for ophthalmologic purposes (23/26). Methotrexate (MTX) and anti-TNFα agents have been initiated for a rheumatologic indication in 81.8% (9/11) and 100% of the patients (13/13), respectively. The annual uveitis relapse rate significantly decreased on SSZ (0.37 recurrences/year versus baseline 2.46 recurrences/year; p<0.001) and MTX (1.54 recurrences/year versus 4.17/year; p = 0.008). Patients under ADA for ophthalmologic purposes (n = 2) did not experience any recurrence. CONCLUSION: We report an open-label strategy to prevent the recurrences of HLA-B27-associated AU. First-line sulfasalazine reduced uveitis relapses. The use of anti-TNFα agents for ophthalmologic purposes was unnecessary with rare exceptions.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antígeno HLA-B27/imunologia , Sulfassalazina/uso terapêutico , Uveíte/tratamento farmacológico , Adalimumab/uso terapêutico , Adulto , Antirreumáticos/uso terapêutico , Feminino , Humanos , Infliximab/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Uveíte/imunologia
4.
Ann Afr Med ; 18(4): 206-209, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31823956

RESUMO

Juvenile idiopathic arthritis (JIA) and Crohn's disease (CD) are diseases that are rarely seen in the black African child. CD has been reported to occur following therapy with etanercept in JIA patients. We report the case of a Nigerian child with JIA who developed CD following treatment for JIA. A 9-year-old male with JIA was referred to the pediatric gastroenterology unit of the Lagos University Teaching Hospital on the account of chronic diarrhea with occasional passage of bloody stools. He had been on prednisolone and methotrexate which had controlled the joint flares. Colonoscopy revealed extensive colitis, ulcers, abscesses, and ileocecal disease. Histology confirmed the CD. In view of the unavailability of the recommended treatment, namely biologics in the country and financial constraints; steroids; and sulfasalazine were added to his treatment regimen, and subsequently, he has made significant clinical improvement.


Assuntos
Artrite Juvenil/diagnóstico , Doença de Crohn/diagnóstico , Anti-Inflamatórios não Esteroides/uso terapêutico , Criança , Colonoscopia , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Humanos , Masculino , Metotrexato/uso terapêutico , Nigéria , Prednisolona/uso terapêutico , Esteroides/uso terapêutico , Sulfassalazina/uso terapêutico , Resultado do Tratamento
5.
Pediatr Rheumatol Online J ; 17(1): 80, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842940

RESUMO

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) may cause significant impairment in health-related quality of life (HrQoL), despite effective therapies. The aim of this study was to assess HrQoL during first-year treatment in patients with new-onset polyarticular JIA, and to compare treatment strategies. METHODS: In ACUTE-JIA Study, 60 patients with new-onset JIA were randomized to receive either infliximab with methotrexate (IFX+MTX); a triple therapy of methotrexate, hydroxychloroquine, and sulfasalazine (Triple); or methotrexate monotherapy (MTX). Efficacy was measured with American College of Rheumatology pediatric (ACRp) score, and juvenile arthritis disease activity score (JADAS). HrQoL was evaluated with Child Health Questionnaire (CHQ), which includes physical and psychosocial summary scores (PhS and PsS). Linear mixed models were utilized to compare groups over time. RESULTS: In the whole group of 60 patients, mean physical summary score (PhS) improved from 26.2 (SD 8.7) at week 0 to 49.7 (SD 13.2) at week 54 (p=0.046). Mean improvement of PhS was 20.3 (95% CI -15.5 to 56.2); 22.6 (-19.5 to 64.7); and 26.6 (-12.1 to 65.3) in IFX+MTX, Triple, and MTX, respectively. Changes in psychosocial summary score (PsS) were smaller: from 51.0 (SD 8.5) to 54.7 (6.3) (p=0.019) in all patients. No differences between the three treatment groups were detected in either of the measures. In multivariate analyses, Child Health Assessment Questionnaire (CHAQ), pain VAS, and time spent in inactive disease contributed to improvement in PhS; gender and CHAQ to PsS. CONCLUSIONS: HrQol improved during the first year on therapy for JIA irrespective of the treatment strategy. The timing of change in the different dimensions of HrQoL varied; improvement occurred earlier in physical than psychosocial domains of HrQol. TRIAL REGISTRATION: This study was registered within the Hospital District of Helsinki and Uusimaa (http://www.hus.fi) clinical trials, number 211864 in October 2002, and later on with ClinicalTrials.gov, number NCT01015547.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Infliximab/uso terapêutico , Metotrexato/uso terapêutico , Qualidade de Vida , Sulfassalazina/uso terapêutico , Adolescente , Antirreumáticos/administração & dosagem , Criança , Quimioterapia Combinada , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Infliximab/administração & dosagem , Masculino , Metotrexato/administração & dosagem , Sulfassalazina/administração & dosagem , Inquéritos e Questionários , Resultado do Tratamento
6.
United European Gastroenterol J ; 7(9): 1164-1170, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31700629

RESUMO

Background: Budesonide-MMX has an established role in the management of relapsing mild-to-moderate ulcerative colitis. Data regarding effectiveness and tolerability in real-life clinical practice are limited. Aim: The aim of this study was to assess the use of budesonide-MMX in ulcerative colitis, as well as short-term effectiveness and tolerability in real-life practice. Methods: We conducted a retrospective study of adult patients with mild-to-moderate ulcerative colitis treated with budesonide-MMX at four tertiary inflammatory bowel disease centres in Italy from June 2016 to February 2018. Demographic and clinical features of patients, the use of budesonide-MMX, disease course and concomitant therapy were recorded. The primary outcome assessed was clinical remission at 2 months. Results: A total of 82 patients with active mild-to-moderate ulcerative colitis were included in the study with a mean age of 45.9 years and a median partial Mayo Score of 4 (interquartile range 3-5). A total of 41 patients were male. Overall, 36 had extensive colitis, 38 left-sided colitis and eight proctitis. Treatments at the time of inclusion included 10 patients receiving biologic therapy, seven azathioprine and 54 mesalazine or salazopyrin. The main reasons for the addition of budesonide-MMX were clinical relapse (47.5%) or inadequate response to current therapy (39.0%). In total, 50% of patients achieved clinical remission, whereas 9.8% had clinical improvement. No response was noted in 40.2% of subjects. Using multivariate binary logistic regression, a moderate degree of activity was the main independent predictor of non-response. Eight significant adverse effects were reported in six patients with three discontinuing treatment. Conclusion: In real-life clinical practice, budesonide-MMX is commonly used in combination with other therapies, both for acute disease flares and for partial response to therapy.


Assuntos
Budesonida/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Glucocorticoides/administração & dosagem , Adulto , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Azatioprina/uso terapêutico , Budesonida/uso terapêutico , Colite Ulcerativa/patologia , Formas de Dosagem , Quimioterapia Combinada , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Itália , Modelos Logísticos , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Índice de Gravidade de Doença , Sulfassalazina/uso terapêutico , Resultado do Tratamento
7.
Food Funct ; 10(11): 7275-7290, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31621721

RESUMO

Inflammatory bowel disease (IBD) is characterized by severe mucosal damage in the intestine and a deregulated immune response. Natural products derived from plants that are rich in bioactive compounds are used by many patients with IBD. Xique-xique (Pilosocereus gounellei) is a cactus of the Caatinga family that has been used by the local population for food and medicinal purposes. The intestinal anti-inflammatory effect of xique-xique cladode juice was evaluated in the present study. A dose of 5 mL kg-1 had a protective effect on intestinal inflammation, with an improvement in macroscopic damage, and a decrease in pro-inflammatory markers and oxidative stress, in addition to preserving the colonic tissue. Immunohistochemical analysis revealed the downregulation of IL-17, NF-κB, and iNOS, and upregulation of SOCs-1, ZO-1, and MUC-2. These protective effects could be attributed to the phenolic compounds as well as the fibers present in xique-xique juice. Further studies are needed before suggesting the use of xique-xique juice as a new alternative for treating IBD.


Assuntos
Cactaceae/química , Colite/induzido quimicamente , Extratos Vegetais/uso terapêutico , Ácido Acético , Animais , Anti-Inflamatórios , Colite/tratamento farmacológico , Citocinas/genética , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Mucina-2/genética , Mucina-2/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Distribuição Aleatória , Ratos , Ratos Wistar , Sulfassalazina/uso terapêutico , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
8.
Reumatol. clín. (Barc.) ; 15(5): e5-e9, sept.-oct. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-189409

RESUMO

OBJECTIVE: To identify synovitis and tenosynovitis active by using the Ultrasound 7 (US 7) scoring system in patients with rheumatoid arthritis (RA) in clinical remission induced by synthetic disease-modifying antirheumatic drugs (DMARDs). METHODS: This is a multicentric, cross-sectional, observational study including 94 RA patients >18 years old who were in remission as defined by the 28-joints disease activity score (DAS28) <2.6 induced by synthetic DMARD during at least 6 months. Patients with a previous or current history of biologic DMARD treatment were not included in the study. Demographic and clinical data were collected by the local rheumatologist; the US evaluation was performed by a calibrated rheumatologist, who intended to detect grayscale synovitis and power Doppler (PD) using the 7-joint scale. Intra and inter-reader exercises of images between 2 ultrasonographers were realized. RESULTS: Patients' mean age was 49.1+/-13.7 years; 83% were women. The mean disease duration was 8+/-7 years and remission lasted for 27.5+/-31.8 months. The mean DAS28 score was 1.9+/-0.66. Grayscale synovitis was present in 94% of cases; it was mild in 87.5% and moderate in 12.5%. Only 12.8% of the patients had PD. The metatarsophalangeal, metacarpophalangeal, and carpal joints of the dominant hand were the joints more frequently affected by synovitis. Tenosynovitis by grayscale was observed in 9 patients (9.6%). The intra and inter-reading kappa value were 0.77, p < 0.003 (CI 95%, 0.34-0.81) and 0.81, p < 0.0001 (CI 95%, 0.27-0.83) respectively. CONCLUSIONS: Low percentage of synovitis and tenosynovitis active were founded according to PD US by 7 score in RA patients under synthetic DMARDs during long remission. This score has benefit because evaluate tenosynovitis, another element of subclinical disease activity


OBJETIVO: Identificar la sinovitis y tenosinovitis activa mediante el uso de ultrasonido en un índice de 7 articulaciones (US7) en pacientes con artritis reumatoide (AR) en remisión clínica inducida por fármacos antirreumáticos modificadores de la enfermedad sintética (DMARD). MÉTODOS: Se trata de un estudio observacional multicéntrico, transversal, que incluyó a 94 pacientes con AR mayores de 18 años que estaban en «remisión de acuerdo a DAS-28<2,6 inducida por DMARD sintético durante al menos 6 meses». Los pacientes con antecedentes previos o actuales de tratamiento biológico no fueron incluidos en el estudio. Los datos demográficos y clínicos fueron recogidos por el reumatólogo tratante; la evaluación de US fue realizada por un reumatólogo experimentado, para detectar sinovitis en escala de grises y power Doppler (PD) utilizando la escala de 7 articulaciones. Se realizaron ejercicios intra e inter-lector de imágenes entre 2 ultrasonografistas. RESULTADOS: La edad media de los pacientes fue de 49,1+/-13,7 años; el 83% eran mujeres. La duración media de la enfermedad fue de 8+/-7 años y la remisión duró 27,5+/-31,8 meses. La media de DAS-28 fue de 1,9+/-0,66. La sinovitis en escala de grises estuvo presente en el 94% de los casos; fue leve en el 87,5% y moderada en el 12,5%. Solo el 12,8% de los pacientes tenían PD. Las articulaciones metatarsofalángicas, metacarpofalángicas y carpales de la mano dominante fueron las articulaciones más frecuentemente afectadas por la sinovitis. La tenosinovitis en escala de grises se observó en 9 pacientes (9,6%). El valor de kappa intra e inter-lector fue 0,77, p < 0,003 (CI 95%: 0,34-0,81) y 0,81, p < 0,0001 (CI 95%: 0,27-0,83), respectivamente. CONCLUSIONES: Se observó un bajo porcentaje de sinovitis y tenosinovitis activa de acuerdo a PD por US7 en pacientes con AR tratados con DMARD sintéticos. Esta escala tiene ventaja porque evalúa tenosinovitis, otro elemento de la actividad inflamatoria subclínica


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Sinovite/diagnóstico por imagem , Artrite Reumatoide/diagnóstico por imagem , Cloroquina/uso terapêutico , Estudos Transversais , Hidroxicloroquina/uso terapêutico , Quimioterapia de Indução , Leflunomida/uso terapêutico , Metotrexato/uso terapêutico , Estudos Prospectivos , Índice de Gravidade de Doença , Sulfassalazina/uso terapêutico , Sinovite/epidemiologia , Ultrassonografia Doppler
9.
Int J Mol Sci ; 20(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514274

RESUMO

BACKGROUND: HIV-1 induces an uncontrolled inflammatory response of several immune components, such as inflammasomes. These molecular complexes, associated with Toll-like receptor (TLR) activity, induce the maturation and release of IL-1ß and IL-18 and eventually induce pyroptosis. It has been previously demonstrated that HIV induces inflammasome activation, which is significantly lower in the gastrointestinal tissue and blood from people living with HIV-1 with spontaneous control of viral replication. Therefore, immunomodulatory agents could be useful in improving HIV prognosis. OBJECTIVE: To evaluate the potential inhibitory effect of sulfasalazine (SSZ) on inflammasomes and TLRs in peripheral blood mononuclear cells (PBMCs) from people living with HIV and healthy donors. METHODS: PBMCs were obtained from 15 people living with HIV and 15 healthy donors. Cells were stimulated with agonists of TLRs and inflammasomes and subsequently treated with SSZ. The concentration of IL-1ß and the relative expression of NLRP3, NLRC4, NLRP1, AIM2, ASC, Caspase-1, IL-1ß, and IL-18 were quantified. RESULTS: Cells treated with SSZ exhibited a decreased IL-1ß production after inflammasome and TLR stimulation, as well as regulation of inflammasome-related genes, in both people with HIV and healthy individuals. The concentration of IL-1ß was positively correlated with the CD4+ T-cell count and negatively with the viral load. CONCLUSION: Our results suggest that SSZ has an immunomodulatory effect on inflammasome and TLR activation that depends on the clinical HIV status.


Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/fisiologia , Fatores Imunológicos/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/imunologia , Sulfassalazina/uso terapêutico , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Proteínas Reguladoras de Apoptose/metabolismo , Linfócitos T CD4-Positivos/imunologia , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Fatores Imunológicos/farmacologia , Inflamassomos/antagonistas & inibidores , Inflamassomos/metabolismo , Inflamação/patologia , Interleucina-1beta/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sulfassalazina/farmacologia , Receptores Toll-Like/metabolismo , Carga Viral , Adulto Jovem
10.
Pak J Pharm Sci ; 32(3 Special): 1415-1418, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31551223

RESUMO

To evaluate the clinical efficacy of combined therapy of Zushima tablet and western medicine in treatment of rheumatoid arthritis and analyze the MRI test results. A total of 170 patients who had been treated for rheumatoid arthritis at our hospital from August 2016 and June 2018, were enrolled as research objects. They were randomly divided into control group and research group, with 85 patients in each group. The patients in the control group were treated with western medicine, while patients in the research group were treated with combined therapy of Zushima tablet and western medicine. The clinical efficacies of two groups were compared. results showed that the overall effective rate of the research group was higher than that of the control group (p<0.05). Various clinical symptoms including joint swelling, joint tenderness, duration of morning stiffness for both groups before and after treatment were recorded, and results showed that the improvement of the research group was significantly better than that of the control group (p<0.05). Application of combined therapy of Zushima tablet and western medicine in treatment of rheumatoid arthritis could lead to favorable effects and improvement of the patients' clinical symptoms.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Adulto , Artrite Reumatoide/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Naproxeno/uso terapêutico , Prednisolona/uso terapêutico , Sulfassalazina/uso terapêutico , Comprimidos , Resultado do Tratamento , Ocidente
11.
Dermatol Ther ; 32(5): e13007, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31237078

RESUMO

Vitiligo is an acquired idiopathic pigmentary skin disorder characterized by the development of white macules and patches due to the loss of functioning melanocytes. In this report, we describe a case of a patient with a longstanding history of dermatitis herpetiformis (DH) and celiac disease that developed rapidly progressing, biopsy-confirmed generalized vitiligo after 11 months of treatment with anti-inflammatory medication sulfasalazine, prescribed for the patient's DH. To the best of our knowledge, this is the first case report which has demonstrated the possible biochemical pathways, triggered by sulfasalazine, in the development of vitiligo.


Assuntos
Doença Celíaca/tratamento farmacológico , Dermatite Herpetiforme/tratamento farmacológico , Pele/patologia , Sulfassalazina/efeitos adversos , Vitiligo/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Biópsia , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Dermatite Herpetiforme/complicações , Dermatite Herpetiforme/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Sulfassalazina/uso terapêutico , Vitiligo/diagnóstico
12.
Cells ; 8(6)2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151306

RESUMO

IBD98-M is a delayed-release formulation of mesalamine (mesalazine) and SH with a potential therapeutic role in ulcerative colitis (UC). A total of 51 patients with a modified Ulcerative Colitis Disease Activity Index (UCDAI) score of ≥4 and ≤10, and a modified UCDAI endoscopy subscore ≥1 were randomized for 6 weeks of double-blind treatment with IBD98 0.8 g/day or IBD 1.2 g/day or placebo. The efficacy and safety of IBD98-M in mild to moderate active UC were primarily evaluated. At week 6, 1 (5.9%), 2 (12.5%), and 2 (11.1%) patients receiving IBD98-M 0.8 g, IBD98-M 1.2 g, and placebo, respectively, (p > 0.999) achieved clinical remission. Higher clinical response was seen in IBD98-M 1.2 g (31.3%) versus placebo (16.7%) and endoscopic improvement in IBD98-M 0.8 g (29.4%) versus placebo (22.2%) was seen. Fecal calprotectin levels were reduced in IBD98-M groups versus placebo (p > 0.05). IBD98-M patients achieved significant improvement in physical health summary score component of the SF-36 (p = 0.01 and p = 0.03 respectively) compared to placebo. IBD98-M did not meet the primary end point but had higher clinical response (1.2 g/day) and endoscopic improvement (0.8 g/day) compared to placebo. The safety result shown that IBD98-M treatment was safe and well tolerated in this patient population. No new safety signals or unexpected safety findings were observed during the study. Further trials with different stratification and longer follow-up may be needed to evaluate the efficacy.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Mesalamina/uso terapêutico , Sulfassalazina/uso terapêutico , Adulto , Cápsulas , Preparações de Ação Retardada/efeitos adversos , Preparações de Ação Retardada/uso terapêutico , Método Duplo-Cego , Endoscopia , Feminino , Humanos , Masculino , Mesalamina/efeitos adversos , Pessoa de Meia-Idade , Placebos , Indução de Remissão , Sulfassalazina/efeitos adversos , Resultado do Tratamento
13.
Epilepsia ; 60(7): 1365-1377, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31211419

RESUMO

OBJECTIVE: Currently prescribed antiepileptic drugs (AEDs) are ineffective in treating approximately 30% of epilepsy patients. Sulfasalazine (SAS) is an US Food and Drug Administration (FDA)-approved drug for the treatment of Crohn disease that has been shown to inhibit the cystine/glutamate antiporter system xc- (SXC) and decrease tumor-associated seizures. This study evaluates the effect of SAS on distinct pharmacologically induced network excitability and determines whether it can further decrease hyperexcitability when administered with currently prescribed AEDs. METHODS: Using in vitro cortical mouse brain slices, whole-cell patch-clamp recordings were made from layer 2/3 pyramidal neurons. Epileptiform activity was induced with bicuculline (bic), 4-aminopyridine (4-AP) and magnesium-free (Mg2+ -free) solution to determine the effect of SAS on epileptiform events. In addition, voltage-sensitive dye (VSD) recordings were performed to characterize the effect of SAS on the spatiotemporal spread of hyperexcitable network activity and compared to currently prescribed AEDs. RESULTS: SAS decreased evoked excitatory postsynaptic currents (eEPSCs) and increased the decay kinetics of evoked inhibitory postsynaptic currents (eIPSCs) in layer 2/3 pyramidal neurons. Although application of SAS to bic and Mg2+ -free-induced epileptiform activity caused a decrease in the duration of epileptiform events, SAS completely blocked 4-AP-induced epileptiform events. In VSD recordings, SAS decreased VSD optical signals induced by 4-AP. Co-application of SAS with the AED topiramate (TPM) caused a significantly further decrease in the spatiotemporal spread of VSD optical signals. SIGNIFICANCE: Taken together this study provides evidence that inhibition of SXC by SAS can decrease network hyperexcitability induced by three distinct pharmacologic agents in the superficial layers of the cortex. Furthermore, SAS provided additional suppression of 4-AP-induced network activity when administered with the currently prescribed AED TPM. These findings may serve as a foundation to assess the potential for SAS or other compounds that selectively target SXC as an adjuvant treatment for epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Sulfassalazina/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Epilepsia/fisiopatologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Patch-Clamp , Sulfassalazina/farmacologia
14.
Int J Biol Macromol ; 136: 83-96, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31195039

RESUMO

The aim of this study was to develop and characterize a pH sensitive, biodegradable, interpenetrating polymeric network (IPNs) for colon specific delivery of sulfasalazine in ulcerative colitis. It also entailed in-vitro and in-vivo evaluations to optimize colon targeting efficiency, improve drug accumulation at the target site, and ameliorate the off-target effects of chemotherapy. Pectin was grafted with polyethylene glycol (PEG) and methacrylic acid (MAA) by free radical polymerization. Fourier transformed infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), energy dispersion X-ray (EDX) and powder X-ray diffraction (XRD) results confirmed the development of stable pectin-g-(PEG-co-MAA) hydrogels. The swelling and release studies exhibited that the hydrogels were capable of releasing drug specifically at colonic pH (pH 7.4). The toxicological potential of polymers, monomers and hydrogel was investigated using the Balb/c animal model, that confirmed the safety of the hydrogels. In vitro degradation of the hydrogel was evaluated using pectinase enzyme in various simulated fluids and the results showed that the hydrogels were susceptible to biodegradation by the natural microflora of the colon. In-vivo study was performed using Dextran sulphate sodium (DSS) rat model proved the hydrogels to be effective in the management of UC.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Hidrogéis/química , Hidrogéis/metabolismo , Animais , Colite Ulcerativa/metabolismo , Colo/metabolismo , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Feminino , Concentração de Íons de Hidrogênio , Masculino , Metacrilatos/química , Camundongos , Camundongos Endogâmicos BALB C , Pectinas/química , Polietilenoglicóis/química , Sulfassalazina/química , Sulfassalazina/uso terapêutico
15.
Prensa méd. argent ; 105(5): 309-316, jun 2019. tab, fig
Artigo em Inglês | LILACS, BINACIS | ID: biblio-1024643

RESUMO

Ulcerative colitis is an idiopathic chronic inflammatory disease of the colon for which a lot of treatment modalities are present. However, significant side effects are associated with them, and there is a need for a search for other tretment options. This study was aimed to assess the contribution of niclosamide in experimentally established colitis in rats. Animals were categorized into 5 groups; the control group undergoes no induction of UC, colitis group in which UC was induced, and animals receive no treatment, the niclosamide group that received niclosamide and sulfasalazine group that received sulfasalazine. Each group was composed of 10 animals. After the completion of a one-month period of the experiment animals were sacrificed and the following meausres were done: the weight of the colon, determination of the area of mucosal damage by mm2, histological scoring after hematoxylin and eosin stain together with MAC score and immunohistochemistry of IL-6, TNF-alpha, MPO, MDA, CD62, and ICAM1. The results of the current study revealed that Nicosamide was able to reduce the area of mucosal damage, colon weight, histological and Mac scores and immunohistochemical scores of inflammatory and oxidative markers, significantly when contrasted to a group of colitis (P< 0.05). It has been concluded that Niclosamide was proved to have a significant effect as an adjuvant mode of therapy for colitis through its, anti-inflamatory and anti-oxidant effects (AU)


Assuntos
Ratos , Sulfassalazina/uso terapêutico , Colite Ulcerativa/terapia , Efeito Secundário , Avaliação de Resultado de Intervenções Terapêuticas , Epidemiologia Experimental , Tempo para o Tratamento , Abate de Animais , Niclosamida/uso terapêutico
16.
Clin J Gastroenterol ; 12(6): 578-582, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31037567

RESUMO

A 47-year-old Japanese man was diagnosed with pancolitis-type ulcerative colitis. He was treated with mesalamine in a pH-dependent release form. On day 16 of administration, he was admitted because of fever and abdominal pain. We diagnosed his symptoms to be the side effects of mesalamine. Hyposensitization using unmodified and a time-dependent release form mesalamine was performed. On day 7 of mesalamine hyposensitization, a colonoscopy was performed. The patient presented with the same allergic symptoms 9 h after the administration of an oral sodium phosphate solution. Eventually, he was orally administered a course of salazosulfapyridine (SASP) at an initial dose of 2.5 mg/day, which was increased to 2000 mg/day. It is generally recognized that SASP intolerance is an indication to switch from SASP to mesalamine. The need to switch treatment from mesalamine to SASP is, therefore, rare because allergic reactions to mesalamine do not occur frequently. We report a very rare case which was presented with abdominal pain and myalgia because of intolerance to mesalamine in whom hyposensitization with and introduction of SASP were successful.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Hipersensibilidade a Drogas/etiologia , Mesalamina/efeitos adversos , Sulfassalazina/uso terapêutico , Dor Abdominal/induzido quimicamente , Administração Oral , Anti-Inflamatórios não Esteroides/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Dessensibilização Imunológica/métodos , Esquema de Medicação , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Humanos , Masculino , Mesalamina/administração & dosagem , Pessoa de Meia-Idade , Mialgia/induzido quimicamente
17.
BMJ Case Rep ; 12(5)2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31129640

RESUMO

Axial spondyloarthropathies are characterised by bilateral sacroiliitis, asymmetric oligoarthritis, association with the human leucocyte antigen (HLA)-B27, enthesitis and dactylitis. Although IgA nephropathy has a well-documented association with seronegative spondyloarthropathies, the association with Henoch-Schonlein purpura (HSP) has been documented only in few case reports. The present case is that of a 26-year-old man who presented with fever, lower limb arthritis, abdominal pain, palpable purpura over the buttocks and lower limbs, and clinical features of sacroiliitis. His blood tests showed elevated inflammatory markers and rheumatoid factor was negative. CT scan of the sacroiliac joints confirmed sacroiliitis. Skin biopsy revealed neutrophilic small vessel vasculitis. HLA-B27 was positive in blood. A diagnosis of HSP with HLA-B27 positive axial spondyloarthritis was made. HSP can be associated with HLA-B27 positive axial spondyloarthritis and has to be considered while evaluating for causes of cutaneous small vessel vasculitis in such patients.


Assuntos
Púrpura de Schoenlein-Henoch/diagnóstico , Espondilartrite/diagnóstico , Dor Abdominal/tratamento farmacológico , Dor Abdominal/etiologia , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Antígeno HLA-B27/sangue , Humanos , Masculino , Metotrexato/uso terapêutico , Púrpura de Schoenlein-Henoch/complicações , Sacroileíte/diagnóstico por imagem , Sacroileíte/tratamento farmacológico , Sacroileíte/etiologia , Espondilartrite/sangue , Espondilartrite/complicações , Espondilartrite/tratamento farmacológico , Sulfassalazina/uso terapêutico , Tomografia Computadorizada por Raios X
18.
Cancer Sci ; 110(4): 1431-1441, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30719824

RESUMO

The prognostic role of CD44v9, a variant isoform of CD44 and a new cell surface marker of cancer stem cells, remains unclear in bladder cancer (BC) patients. Furthermore, limited information is available on the functional role of sulfasalazine (SSZ), which could modulate the CD44v9-xCT system in order to enhance cisplatin (CDDP)-induced cytotoxicity and inhibit the metastatic potential of BC. CD44v9 protein expression was examined immunohistochemically in 63 muscle invasive BC (MIBC) patients who underwent radical cystectomy. CD44v9 expression was independently associated with disease recurrence and cancer-specific death in MIBC. Cytotoxic effects, glutathione levels, and reactive oxygen species production by SSZ and CD44v9 and phospho-p38MAPK protein expression by SSZ with or without CDDP were assessed in MBT-2V cells with highly metastatic potential. Sulfasalazine exerted cytotoxic effects against MBT-2V cells by inhibiting glutathione levels and inducing the production of reactive oxygen species. Sulfasalazine in combination with CDDP appeared to exert strong cytotoxic effects against MBT-2V cells by inhibiting CD44v9 expression and upregulating phospho-p38MAPK expression. The inhibitory effects of SSZ with or without CDDP were also investigated using an MBT-2V lung metastatic model. In the murine lung metastatic BC model, SSZ significantly prolonged animal survival. Furthermore, the combination of SSZ with CDDP exerted stronger inhibitory effects on the establishment of lung tumor nodules than SSZ or CDDP alone. CD44v9 expression could be a clinical biomarker for predicting poor outcomes in MIBC patients. Sulfasalazine in combination with CDDP has potential as a novel therapy against metastatic BC.


Assuntos
Cisplatino/uso terapêutico , Receptores de Hialuronatos/metabolismo , Sulfassalazina/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Feminino , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Recidiva , Sulfassalazina/farmacologia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Rheumatol Int ; 39(4): 657-662, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30783800

RESUMO

INTRODUCTION: Early arthritis clinics (EACs) have been well established since 1980s. Most of the data for their effectiveness comes from rheumatoid arthritis (RA) management and is largely limited to process outcomes. There is little evidence that such clinics improve clinical outcomes particularly for psoriatic arthritis (PsA). We examined whether EACs provide better outcomes irrespective of final arthritis diagnosis. METHODS: A 52-week prospective observational study of all inflammatory arthritis patients presenting to early arthritis service at our secondary care hospital in 2016 was undertaken. A protocolised approach to the early initiation of therapy (within 3 weeks) and 6-weekly review of treatment outcomes was embedded irrespective of the arthritis diagnosis. Statistical analysis was undertaken using Mann-Whitney U test for disease activity scores to ascertain the significance of outcomes. RESULTS: Of 1884 patients referred, 482 (25.5%) were triaged into EACs based on set criteria. 159 (64.3%) had RA, 55 (22%) with PsA and 33 had other inflammatory arthritides. Mean DAS28 for RA at first visit was 4.65 (0.6-8.0). Treating to target achieved DAS28 remission for 84 (53.5%) and low disease activity (LDA) for a further 44 (34%). Median time to achieve remission or LDA was 20 weeks (0-52 weeks). Mean tender (TJ) and swollen joint (SJ) counts for PsA at first visit were 8.2 (1-35) and 3.5 (0-14), respectively [n = 55]. The patient (PtGA) and physician (PhGA) global assessments mean were 3.0 and 2.9 (1-5). Target [TJ and SJ ≤ 2] was achieved for 38 patients (69%) and good PsARC response for a further four (7%). Median time to achieve the target or good response was 22 weeks (0-48 weeks). Final TJ and SJ mean was significantly better at 1.2 (0-4) and 0.3 (0-2) [p < 0.0001] with similar improvement in PtGA [mean 1.8 (1-4)] and PhGA [mean 1.6 (1-3)]. CONCLUSION: Dedicated EACs help achieve good clinical outcomes in majority of patients with RA and PsA. Nearly 80% of our cohort attained the target or good disease response in less than 6 months. This was despite a significant delay in patients presenting to their GPs and moderately high disease activity.


Assuntos
Assistência Ambulatorial/organização & administração , Antirreumáticos/uso terapêutico , Artrite Psoriásica/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Intervenção Médica Precoce/organização & administração , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Produtos Biológicos/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Leflunomida/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Índice de Gravidade de Doença , Sulfassalazina/uso terapêutico , Tempo para o Tratamento , Resultado do Tratamento , Adulto Jovem
20.
J Eur Acad Dermatol Venereol ; 33(7): 1249-1260, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30735612

RESUMO

Twenty per cent of patients with plaque psoriasis also have psoriatic arthritis - a disease affecting joints and entheses. Different treatment options exist but currently no succinct systematic overview exists. A systematic review of approved systemic treatments for psoriatic arthritis was conducted. We systematically searched in three databases (last update September 2017). Data were extracted for ACR20/50, HAQ-DI, SF-36 and adverse/serious adverse events after 16-24 weeks. We assessed the quality of evidence using GRADE. Twenty trials were included. Three trials compared two active substances. Results for ACR20 were infliximab + methotrexate vs. methotrexate: RR 1.40 (95% CI 1.07-1.84) very low quality evidence; ixekizumab Q2W vs. adalimumab Q2W: RR 1.08 (95% CI 0.86-1.36) very low quality, leflunomide vs. methotrexate: RR 1.01, (95% CI 0.84-1.21) low quality. Eighteen drug vs. placebo comparisons were included. For ACR20/50, HAQ-DI and SF-36, the active treatment was efficacious and the quality of the evidence was mostly moderate to low (15 of 18 comparisons). The quality of evidence for (serious) adverse events was mostly low; differences were rare. In three placebo-controlled comparisons, leflunomide, MTX and sulfasalazine failed to show statistical superiority for ACR. Besides the established treatment of anti-TNF antibodies and ustekinumab for psoriatic arthritis, the newer treatment options of IL17 antibodies and apremilast are also effective for the treatment of psoriatic arthritis. Based on just one comparative trial and one drug each, the new class of anti-IL 17 antibodies appears to be equally effective as the group of anti-TNF antibodies; for apremilast, this is yet unclear.


Assuntos
Artrite Psoriásica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Adalimumab/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Quimioterapia Combinada , Humanos , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Leflunomida/uso terapêutico , Metotrexato/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfassalazina/uso terapêutico , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Ustekinumab/uso terapêutico
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