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1.
Acta Gastroenterol Belg ; 84(3): 423-428, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34599566

RESUMO

Background-Aim: Intravenously administered biologicals are associated with a huge pressure to Infusion Units and increased cost. We aimed to assess the impact of switching infliximab to golimumab in ulcerative colitis (UC) patients in deep remission. Patients and method: In a prospective, single-centre pilot study UC patients on infliximab mono-therapy for = 2 years, whowere in deep remission, consented to switch to golimumab and were followed for 1 year with clinical assessment, serum and faecal biomarkers, work productivity, satisfaction with treatment and quality of life parameters. Endoscopic remission was assessed by colonoscopy at 1 year. Patients fulfilling the same inclusion criteria, who did not consent to switch to golimumab and continued to receive infliximab mono-therapy, for the same period, served as controls. Patients and methods: In a prospective, single-centre pilot study UC patients on infliximab mono-therapy for ≥ 2 years, who were in deep remission, consented to switch to golimumab and were followed for 1 year with clinical assessment, serum and faecal biomarkers, work productivity, satisfaction with treatment and quality of life parameters. Endoscopic remission was assessed by colonoscopy at 1 year. Patients fulfilling the same inclusion criteria, who did not consent to switch to golimumab and continued to receive infliximab mono-therapy, for the same period, served as controls. Results: Between October 2015 and October 2017, 20 patients were recruited; however one patient stopped therapy because of pregnancy. All 19 patients who were switched to golimumab were still in clinical, biomarker and endoscopic remission at 1 year and maintained excellent quality of life without any complications. In the control group, 18 of 19 patients were also in deep remission, since only one patient had a flare which was managed with IFX dose intensification. During a median 3 years extension treatment with golimumab only 2 patients experienced a flare of colitis. Conclusions: This pilot study indicates that switching from in-fliximab to golimumab in UC patients in deep remission does not compromise treatment effectiveness or the course of disease; golimumab offers a valid alternative to intravenous infliximab infusions during the COVID-19 pandemic.


Assuntos
COVID-19 , Colite Ulcerativa , Adalimumab , Anticorpos Monoclonais , Colite Ulcerativa/tratamento farmacológico , Humanos , Infliximab , Pandemias , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , SARS-CoV-2
2.
Acta Gastroenterol Belg ; 84(3): 509-512, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34599578

RESUMO

Condyloma acuminatum (CA) is a manifestation of Human Papillomavirus (HPV) infection which usually occurs in genital and perianal regions. We report a 46-year-old man with an ulcerative proctitis diagnosed four years earlier, asymptomatic for a long time under azathioprine but without any follow-up for three years. A colonoscopy was performed prior to potential immunosuppressive treatment discontinuation and showed a circumferential "laterally spreading tumour" in the rectum. Surprisingly biopsies revealed a CA with a very focally high-grade intra-epithelial lesion. Azathioprine was stopped and a transanal surgical resection was performed. At guided anamnesis, patient confirmed to be a former active "men who have sex with men". No recurrence of proctitis occurred despite azathioprine discontinuation. A retrospective review of the histological sections suggests that it was, in fact, an intestinal spirochetosis misdiagnosed as inflammatory bowel disease. Involvement of the rectal mucosa by HPV is a rare condition and this may have been promoted by inappropriate immunosuppressive treatment.


Assuntos
Colite Ulcerativa , Condiloma Acuminado , Azatioprina , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos
3.
Acta Cir Bras ; 36(8): e360805, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34644773

RESUMO

PURPOSE: The present study aimed at testing a new formulation of mesalazine linked to chondroitin sulfate and its components alone in the treatment of actinic proctitis in rats. METHODS: Forty-seven female Wistar rats were submitted to pelvic radiation and divided into eight groups: control A, mesalazine A, chondroitin A, and conjugate A, gavage of the according substance two weeks after irradiation and sacrifice three weeks after oral treatment; control C, mesalazine C, chondroitin C, and conjugate C, sacrifice six weeks after oral treatment. The rectum was submitted to histological characterization for each of the findings: inflammatory infiltrate, epithelial degeneration, mucosal necrosis, and fibrosis. RESULTS: The inflammatory infiltrate was more intense in chondroitin A, mesalazine A, and conjugate C. The collagen deposition was less intense in chondroitin A, and mesalazine A, and more intense in control C. CONCLUSIONS: Mesalazine and chondroitin alone were efficacious in inducing a delayed inflammatory response, hence reducing the late fibrosis. The conjugate was able to induce an ever more delayed inflammatory response.


Assuntos
Colite Ulcerativa , Proctite , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Feminino , Mesalamina/uso terapêutico , Proctite/tratamento farmacológico , Ratos , Ratos Wistar , Reto
5.
Int J Oral Sci ; 13(1): 31, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593756

RESUMO

Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0-40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31-40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.


Assuntos
Colite Ulcerativa , Porphyromonas gingivalis , Desiminases de Arginina em Proteínas , Animais , Colite Ulcerativa/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Porphyromonas gingivalis/enzimologia , Porphyromonas gingivalis/patogenicidade , Fatores de Virulência
6.
Zhongguo Zhen Jiu ; 41(10): 1127-34, 2021 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-34628746

RESUMO

OBJECTIVE: To observe the effect of moxibustion at "Zusanli" (ST 36) on distal, middle and proximal colonic mucosal injury and expression of calcitonin gene-related peptide (CGRP) positive nerve fibers of distal colonic mucosa in ulcerative colitis (UC) mice at different time points. METHODS: A total of 51 C57BL/6N mice were randomized into a 7-day control group (n=8), a 7-day model group (n=7), a 7-day moxibustion group (n=7), a 14-day control group (n=6), a 14-day model group (n=14) and a 14-day moxibustion group (n=9). In the model groups and the moxibustion groups, 2% dextran sulfate sodium (DSS) was given for 7-day free drinking to establish the UC model. Three days into modeling, moxibustion was applied at "Zusanli" (ST 36) in the 7-day moxibustion group and the 14-day moxibustion group, once a day, 10 min a time for 5 days and 12 days respectively. HE staining was used to observe the morphology of colonic tissue, the percentages of distal, middle and proximal colonic mucosal injury were calculated. Immunofluorescence staining was used to detected the expressions of positive nerve fibers of distal, middle and proximal colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa. RESULTS: Mucosal injury can be observed in mice after modeling, displaying epithelial layer disappearance, abnormal crypt structure or crypt disappearance. Compared with the 7-day control group, colon length was shortened (P<0.001), percentages of overall, distal, middle colonic mucosal injury were increased (P<0.001), the expressions of positive nerve fibers of distal, middle and proximal colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa were increased (P<0.001, P<0.05, P<0.01) in the 7-day model group. Compared with the 7-day model group, the expressions of positive nerve fibers of middle and distal colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa were decreased in the 7-day moxibustion group (P<0.05). Compared with the 14-day control group, the colon length was shortened (P<0.01), percentage of overall colonic mucosal injury was increased (P<0.001) in the 14-day model group. Compared with the 14-day model group, colon length was lengthened (P<0.05), percentage of overall colonic mucosal injury was decreased (P<0.05) in the 14-day moxibustion group. CONCLUSION: Moxibustion at "Zusanli" (ST 36) can reduce the expressions of positive nerve fibers of colonic mucosa and CGRP positive nerve fibers of distal colonic mucosa, thus, improve the colonic mucosal injury.


Assuntos
Colite Ulcerativa , Moxibustão , Animais , Calcitonina , Peptídeo Relacionado com Gene de Calcitonina/genética , Colite Ulcerativa/genética , Colite Ulcerativa/terapia , Mucosa Intestinal , Camundongos , Camundongos Endogâmicos C57BL , Fibras Nervosas
7.
World J Gastroenterol ; 27(36): 6142-6153, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34629825

RESUMO

BACKGROUND: Patients with inflammatory bowel disease (IBD) are associated with increased cardiovascular risk and have increased overall cardiovascular burden. On the other hand, urotensin II (UII) is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well. Furthermore, patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls. Since the features of IBD includes chronic inflammation and endothelial dysfunction as well, it is plausible to assume that there is connection between increased cardiac risk in IBD and UII. AIM: To determine serum UII levels in patients with IBD and to compare them to control subjects, as well as investigate possible associations with relevant clinical and biochemical parameters. METHODS: This cross sectional study consecutively enrolled 50 adult IBD patients (26 with Crohn's disease and 24 with ulcerative colitis) and 50 age and gender matched controls. Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines. Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn's Disease were used for endoscopic evaluation. Serum levels of UII were determined using the enzyme immunoassay kit for human UII, according to the manufacturer's instructions. RESULTS: IBD patients have significantly higher concentrations of UII when compared to control subjects (7.57 ± 1.41 vs 1.98 ± 0.69 ng/mL, P < 0.001), while there were no significant differences between Crohn's disease and ulcerative colitis patients (7.49 ± 1.42 vs 7.65 ± 1.41 ng/mL, P = 0.689). There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels (r = 0.491, P < 0.001) and a significant negative correlation between serum UII levels and total proteins (r = -0.306, P = 0.032). Additionally, there was a significant positive correlation between serum UII levels with both systolic (r = 0.387, P = 0.005) and diastolic (r = 0.352, P = 0.012) blood pressure. Moreover, serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity (r = 0.425, P = 0.048) and Simple Endoscopic Score for Crohn's Disease (r = 0.466, P = 0.028) scores. Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide (ß ± standard error, 0.262 ± 0.076, P < 0.001) and systolic blood pressure (0.040 ± 0.017, P = 0.030). CONCLUSION: It is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients, and its purpose should be investigated in further studies.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Urotensinas , Adulto , Colite Ulcerativa/diagnóstico , Estudos Transversais , Humanos
8.
BMC Gastroenterol ; 21(1): 364, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620103

RESUMO

BACKGROUND: Undelayed diagnosis is thought to be a major determinant for good prognosis in pediatric inflammatory bowel disease (PIBD). However, factors predicting diagnostic delay and the consequences of this remain poorly defined. We investigated these issues in a well-defined cohort of PIBD patients. METHODS: Comprehensive electronic data were collected from 136 PIBD patients retrospectively. Diagnostic delay was further classified into < 6 and ≥ 6 months, and < 12 and ≥ 12 months. Logistic regression was used to calculate whether the delay was associated with clinical features and/or risk of complications and co-morbidities at diagnosis. RESULTS: The median age of patients was 12.4 years and 43.4% were females. Altogether 35.5% had Crohn´s disease (CD), 59.1% ulcerative colitis (UC) and 6.6% IBD undefined (IBD-U). The median delay before diagnosis was 5.0 months in all, 6.6 months in CD, 4.1 months in UC, and 9.8 months in IBD-U (UC vs. CD, p = 0.010). In all but IBD-U most of the delay occurred before tertiary center referral. Abdominal pain predicted a delay > 6 months in all PIBD (OR 2.07, 95% CI 1.00-4.31) and in UC patients (3.15, 1.14-8.7), while bloody stools predicted a shorter delay in all PIBD (0.28, 0.14-0.59) patients and in CD (0.10, 0.03-0.41) patients. A delay > 6 months was associated with a higher frequency of complications (2.28, 1.01-5.19). CONCLUSIONS: Delay occurred mostly before specialist consultation, was longer in children presenting with abdominal pain and in CD and was associated with risk of complications. These findings emphasize the roles of active case-finding and prompt diagnostic evaluations.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Criança , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Diagnóstico Tardio , Feminino , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Estudos Retrospectivos
9.
BMJ Case Rep ; 14(10)2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598959

RESUMO

Diversion colitis (DC) that was refractory to standard treatments was successfully treated with infliximab. A 24-year-old man with a transverse colostomy suffered from severe DC. Topical steroids, 5-aminosalicylic acid (5-ASA) enemas and synbiotics were initially effective, and the colostomy was successfully closed with a covering ileostomy to minimise the risk of anastomotic leakage owing to the damaged colon. DC subsequently relapsed in the entire colon and was refractory to the previous protocol and autologous faecal transplantation. Intravenous methylprednisolone and oral 5-ASA were discontinued owing to possible adverse effects. Infliximab with intravenous prednisolone was introduced, and the protocol was so effective in suppressing the acute colitis that total colectomy was avoided. The stoma was subsequently closed, and the patient is currently symptom-free. Infliximab is used for ulcerative colitis but could also be effective against severe DC.


Assuntos
Colite Ulcerativa , Colite , Adulto , Colectomia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Humanos , Infliximab/uso terapêutico , Masculino , Mesalamina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
10.
BMJ Case Rep ; 14(10)2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34667052

RESUMO

Ménétrier's disease (MD) is a rare disease of the stomach, characterised by hypertrophic gastric folds leading to protein loss. The association with ulcerative colitis (UC) is rare but has been reported in the literature. We report a case of a 29-year-old male affected by UC with an additional diagnosis of MD 3 years after UC diagnosis. UC was refractory to several treatment lines (thiopurines, infliximab, vedolizumab and ustekinumab), and the patient underwent colectomy. Octreotide was administered for MD normalising blood biochemistry, but it was not effective in inducing endoscopic remission of the stomach. Treatment options in patients with MD and UC are discussed.


Assuntos
Colite Ulcerativa , Gastrite Hipertrófica , Adulto , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Gastrite Hipertrófica/complicações , Gastrite Hipertrófica/diagnóstico , Gastrite Hipertrófica/tratamento farmacológico , Humanos , Infliximab/uso terapêutico , Masculino , Ustekinumab
11.
Cells ; 10(9)2021 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-34571891

RESUMO

Intercellular communication mediated by cytokines is critical to the development of immune responses, particularly in the context of infectious and inflammatory diseases. By releasing these small molecular weight peptides, the source cells can influence numerous intracellular processes in the target cells, including the secretion of other cytokines downstream. However, there are no readily available bioinformatic resources that can model cytokine-cytokine interactions. In this effort, we built a communication map between major tissues and blood cells that reveals how cytokine-mediated intercellular networks form during homeostatic conditions. We collated the most prevalent cytokines from the literature and assigned the proteins and their corresponding receptors to source tissue and blood cell types based on enriched consensus RNA-Seq data from the Human Protein Atlas database. To assign more confidence to the interactions, we integrated the literature information on cell-cytokine interactions from two systems of immunology databases, immuneXpresso and ImmunoGlobe. From the collated information, we defined two metanetworks: a cell-cell communication network connected by cytokines; and a cytokine-cytokine interaction network depicting the potential ways in which cytokines can affect the activity of each other. Using expression data from disease states, we then applied this resource to reveal perturbations in cytokine-mediated intercellular signalling in inflammatory and infectious diseases (ulcerative colitis and COVID-19, respectively). For ulcerative colitis, with CytokineLink, we demonstrated a significant rewiring of cytokine-mediated intercellular communication between non-inflamed and inflamed colonic tissues. For COVID-19, we were able to identify cell types and cytokine interactions following SARS-CoV-2 infection, highlighting important cytokine interactions that might contribute to severe illness in a subgroup of patients. Such findings have the potential to inform the development of novel, cytokine-targeted therapeutic strategies. CytokineLink is freely available for the scientific community through the NDEx platform and the project github repository.


Assuntos
COVID-19/imunologia , Citocinas/metabolismo , Imunidade , Doenças Inflamatórias Intestinais/imunologia , Comunicação Celular , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Bases de Dados Genéticas , Humanos , Doenças Inflamatórias Intestinais/patologia , Transdução de Sinais
12.
Tohoku J Exp Med ; 255(1): 33-39, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511579

RESUMO

The onset age of ulcerative colitis has been increasing in several countries. Furthermore, the number of elderly patients with ulcerative colitis has been increasing in an aging society. We investigated the incidence of ulcerative colitis patients in Japan using a large-scale health insurance claims database to survey the ulcerative colitis incidence ratio and the clinical characteristics in late-onset ulcerative colitis patients. Newly diagnosed 2,791 ulcerative colitis between 2015 and 2018 was investigated. Medical treatment within 12 months of diagnosis was analyzed among 0-19, 20-39, 40-59 and 60-75 age groups. The mean age at diagnosis was 40.3 years (SD: 12.9), and the incidence ratio peaked in the 40's. Most of patients received 5-aminocylitic acid (91.7%), a subset of patients received prednisolone (20.1%), and a small number of patients took immunomodulator (6.8%), cytapheresis (3.3%), anti-TNFα therapy (4.3%), and colectomy (1.0%) within 12 months after diagnosis. All treatments except colectomy were most frequent in the 0-19 age group; however, colectomy was most frequent in 60-75 age group. The clinical course of ulcerative colitis that developed in adults did not differ significantly in terms of medical treatment within 12 months from the onset; meanwhile, the surgery rate was high in elderly patients. It is necessary to pay close attention to future trends regarding the aging of the onset age and the treatment, especially for late-onset ulcerative colitis patients.


Assuntos
Colite Ulcerativa/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Criança , Pré-Escolar , Colite Ulcerativa/terapia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Japão/epidemiologia , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Estudos Retrospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto Jovem
14.
Food Res Int ; 148: 110568, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507723

RESUMO

Ulcerative colitis (UC), is a chronic relapsing inflammatory condition of the gastrointestinal track. The purpose of this study is to explore whether Vitamin A (VA) can treat UC and its mechanisms. A mouse model of UC was established using 3.0% (w/v) dextran sodium sulfate (DSS). VA was used to treat UC by intragastric administration of 5000 international unit (IU) retinyl acetate. Fecal microbiota transplantation (FMT) was also used to treat the UC model mice to verify the effect of influenced gut microbiota. The content of short-chain fatty acids (SCFAs) in cecal contents was quantitatively detected by gas chromatography and mass spectrometry. VA supplementation significantly ameliorated UC. 16S rRNA sequencing indicated that VA-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased production of SCFAs in VA-treated mice. Gut microbiota depletion and FMT results confirmed the gut microbiota-dependent mechanism as that VA relieved UC via regulating gut microbiota: increase in SCFA-producing genera and decrease in UC-related genera. The restore of intestinal barrier and the inhibition of inflammation were also found to contribute to the amelioration of UC by VA. It was concluded that a VA supplement was enough to cause a significant change in gut microbiota and amelioration of UC.


Assuntos
Colite Ulcerativa , Microbioma Gastrointestinal , Animais , Colite Ulcerativa/tratamento farmacológico , Sulfato de Dextrana , Suplementos Nutricionais , Cromatografia Gasosa-Espectrometria de Massas , Camundongos , RNA Ribossômico 16S/genética , Vitamina A
15.
Phytomedicine ; 92: 153709, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34560518

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic idiopathic disease that is characterized by inflammation of the gastrointestinal tract. Proper management of IBD requires both early diagnosis and novel therapies and management programs. Many reports have suggested that Chinese medicine has unique properties favorable to the treatment of IBD. However, there are no systematic analyses on this topic. PURPOSE: This review summarizes recent studies that assessed the effects and mechanisms of Chinese medicine in the treatment of IBD in order to fully understand the advantages of Chinese medicine in the management of IBD. METHODS: A literature search was conducted using peer-reviewed and clinical databases, including PubMed, Web of Science, ClinicalTrials.gov, MEDLINE, EMBASE, Springer LINK, Wan-fang database, the Chinese Biomedicine Database, and the China National Knowledge Infrastructure (CNKI). Keywords used were inflammatory bowel disease (including Ulcerative colitis or Crohn's disease) and Chinese medicine. All selected articles were from 1997 to 2021, and each were assessed critically for our exclusion criteria. Studies describing the pathogenesis of IBD, the effects and mechanisms of Chinese medicine in the treatment of IBD, in particular their roles in immune regulation, intestinal flora regulation, and improvement of intestinal barrier function, were included. CONCLUSION: This review highlights recent progress in the use of Chinese medicine in the treatment of IBD. It also provides a reference for further evaluation and exploration of the potential of classical multi-herbal Chinese medicine in the treatment of IBD.


Assuntos
Colite Ulcerativa , Colite , Doenças Inflamatórias Intestinais , Humanos , Inflamação , Doenças Inflamatórias Intestinais/tratamento farmacológico , Medicina Tradicional Chinesa
16.
Phytomedicine ; 92: 153743, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34583225

RESUMO

BACKGROUND: Shaoyao decoction (SYD), a traditional Chinese medicine prescription that originated in the Jin-Yuan Dynasty, has shown effects in treating ulcerative colitis. However, the underlying mechanism is unclear. We combined network pharmacology with molecular biology technology to detect the mechanism underlying the effect of SYD on ulcerative colitis. We combined network pharmacology with molecular biology technology to detected the further mechanism in SYD effect on ulcerative colitis. PURPOSE: In this study, we investigated the mechanism by which SYD exerts a protective effect against ulcerative colitis in vivo and in vitro. STUDY DESIGN AND METHODS: We focused on two aspects of the mechanism by which SYD relieves ulcerative colitis, regulation of the MAPK cascade and the NF-κB signaling pathway, through analysis of the "active ingredient-target-disease" network followed by GO enrichment and KEGG pathway analysis according to network pharmacology. Mice with ulcerative colitis underwent 5% dextran sulfate sodium (DSS), and the RAW 264.7 cell model was used to identify important targets. RESULTS: We found that after 5% DSS treatment, the inflammation indexes and the expression of NLRP3-related proteins were increased concomitant with the loss of mucins and occludin. Treatment with SYD (2.25 g/kg, BW) significantly improved the expression of mucins and occludin after DSS at the protein and transcriptional levels. Furthermore, SYD treatment significantly reduced NF-κB P65 and P38 expression, thus exerting a great antinecrotic effect, as revealed by TUNEL staining and Western blotting. The beneficial effects of SYD were almost canceled by NSC 95397 (an inhibitor of mitogen-activated protein kinase phosphatase-1 (MKP1)) after DSS treatment in vivo or LPS treatment in vitro. In addition, treatment with SYD reduced caspase-1 activity and rescued the release of ASC and GSDMD, thus inhibiting the assembly of NLRP3 and maintaining the integrity of the intestinal barrier. We also conducted in vitro experiments in the LPS-induced RAW 264.7 cell model and found that cells incubated with 1 mg/ml SYD for 24 h possessed the highest cell viability. Next, we incubated 1 mg/ml SYD for 24 h after treatment with 1 µg/ml LPS for 6 h. We showed that 1 mg/ml SYD displayed anti-inflammatory and anti-necrotic effects through the NLRP3, NF-κB P65 and P38 pathways, and the effects of SYD were also inhibited by 10 nM NSC 95397. CONCLUSION: These results demonstrate that SYD has protective effects against ulcerative colitis and alleviates pyroptosis by inhibiting the MKP1/NF-κB/NLRP3 pathway.


Assuntos
Colite Ulcerativa , Colite , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Sulfato de Dextrana , Inflamassomos , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR
17.
ACS Biomater Sci Eng ; 7(10): 4859-4869, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34547895

RESUMO

KPV (Lys-Pro-Val), which is a tripeptide derived from α-MSH (α-melanocyte-stimulating hormone), has an anti-inflammatory effect on colitis. However, KPV solution is very unstable when rectally administered, compromising its therapeutic efficacy. Herein, cysteamine-grafted γ-polyglutamic acid (SH-PGA) was synthesized by conjugating cysteamine with the carboxyl groups of γ-PGA. The synthesized SH-PGA has the thiol grafting amount of 4.5 ± 0.3 mmol/g. Without the use of the cross-linker, the SH-PGA hydrogel with 4% of the polymer was formed by self-cross-linking of thiol groups. Moreover, the formation of the SH-PGA hydrogel was not affected by KPV. The KPV/SH-PGA hydrogel presented higher elastic modulus (G') than the corresponding viscous modulus (G″) at 0.01-10 Hz, exhibiting good mechanical stability. The KPV/SH-PGA hydrogel presented a shear-thinning behavior, which was helpful for rectal administration. Only 30% of KPV was released from the KPV/SH-PGA hydrogel within 20 min, followed by a sustained-release behavior. Importantly, the stability of KPV in the SH-PGA hydrogel was obviously enhanced, which was presented by detecting its anti-inflammatory activity and promoting cell migration potential after 2 h of exposure to 37 °C. The enhanced therapeutic effect of the KPV/SH-PGA hydrogel on colitis was confirmed on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis rats. The colitis symptoms including body weight loss and the disease activity index score were obviously attenuated by rectally administering the KPV/SH-PGA hydrogel. Besides, the KPV/SH-PGA hydrogel treatment prevented the colon shortening of TNBS-infused rats and decreased the colonic myeloperoxidase level. The morphology of the colon including the epithelial barrier, crypt, and intact goblet cells was recovered after KPV/SH-PGA hydrogel treatment. Besides, the KPV/SH-PGA hydrogel decreased the expression of proinflammatory cytokines such as tumor necrosis factor α and interleukin 6. Collectively, the KPV/SH-PGA hydrogel may provide a promising strategy for the treatment of ulcerative colitis.


Assuntos
Colite Ulcerativa , Animais , Colite Ulcerativa/induzido quimicamente , Cisteamina , Hidrogéis , Ácido Poliglutâmico/análogos & derivados , Ratos , Ácido Trinitrobenzenossulfônico/toxicidade
18.
Medicine (Baltimore) ; 100(38): e27283, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559136

RESUMO

INTRODUCTION: Golimumab is a fully human antitumor necrosis monoclonal antibody that can be administered by either subcutaneous injection or intravenous infusion. Golimumab is approved for the treatment of the adults with rheumatic diseases, and ulcerative colitis, Whereas in children, golimumab is indicated only for the treatment of active polyarticular juvenile idiopathic arthritis. We have written on the off-label use of subcutaneous golimumab, which helped to induce and maintain remission on a low-weight biologically experienced child with steroid-refractory ulcerative colitis flare. PATIENT CONCERNS: A 13-year-old pancolitis Syrian boy presented with abdominal pain and six to seven times bloody diarrhea. The child had treated with mesalamine 80 mg/kg/day, azathioprine 2.5 mg/kg/day, infliximab with an induction dose of 5 mg/kg at weeks 0, 2, and 6 followed by 5 mg/kg every 8 weeks. Infliximab did not maintain remission as the patient suffered from two flares that required hospital admission, intravenous corticosteroids, and infliximab escalation. Initial tests disclosed leukocytosis, anemia, hypoalbuminemia, an elevation in C-reactive protein and fecal calprotectin. All Stool studies were negative including routine stool cultures, Clostridium difficile toxin, Escherichia coli O157:H7, Cryptosporidium, and microscopy for ova and parasites. A sigmoidoscopy revealed multiple large ulcerations and spontaneous bleeding, colon biopsies were negative for Clostridium difficile and Cytomegalovirus. Cyclosporine, tacrolimus, and adalimumab were unavailable in Syria. Child's parents opposed colectomy as a treatment option. DIAGNOSIS: Ulcerative colitis flare. INTERVENTIONS: A subcutaneous golimumab with a loading dose of 200 mg at week 0, followed by 100 mg at week 2, then 50 mg every 4 weeks. OUTCOMES: The patient achieved clinical remission by week sixth and maintained the remission for the next 90 weeks. At the time of last evaluation, tests, including C-reactive protein and fecal calprotectin, were within normal limits, complete colonoscopy revealed erythema, edema, mucosal friability, loss of vascular patterns, and pseudo-polyps. The Pediatric Ulcerative Colitis Activity Index and Mayo scores were 5 and 2 points, respectively. No adverse events were documented. CONCLUSION: Golimumab has shown potential efficacy and safety in the treatment of ulcerative colitis in children which may indicate a significant future role for subcutaneous golimumab in pediatrics ulcerative colitis.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Adolescente , Humanos , Masculino , Exacerbação dos Sintomas
19.
BMC Gastroenterol ; 21(1): 347, 2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34538236

RESUMO

BACKGROUND: Up to 30% of patients with ulcerative colitis will undergo surgery resulting in an ileal pouch-anal anastomosis (IPAA) or permanent end ileostomy (EI). We aimed to understand how patients decide between these two options. METHODS: We performed semi-structured interviews with ulcerative colitis patients who underwent surgery. Areas of questioning included the degree to which patients participated in decision-making, challenges experienced, and suggestions for improving the decision-making process. We analyzed the data using a directed content and thematic approach. RESULTS: We interviewed 16 patients ranging in age from 28 to 68 years. Nine were male, 10 underwent IPAA, and 6 underwent EI. When it came to participation in decision-making, 11 patients felt independently responsible for decision-making, 3 shared decision-making with the surgeon, and 2 experienced surgeon-led decision-making. Themes regarding challenges during decision-making included lack of support from family, lack of time to discuss options with the surgeon, and the overwhelming complexity of the decision. Themes for ways to improve decision-making included the need for additional information, the desire for peer education, and earlier consultation with a surgeon. Only 3 patients were content with the information used to decide about surgery. CONCLUSIONS: Patients with ulcerative colitis who need surgery largely experience independence when deciding between IPAA and EI, but struggle with inadequate educational information and social support. Patients may benefit from early access to surgeons and peer guidance to enhance independence in decision-making. Preoperative educational materials describing surgical complications and postoperative lifestyle could improve decision-making and facilitate discussions with loved ones.


Assuntos
Colite Ulcerativa , Bolsas Cólicas , Proctocolectomia Restauradora , Adulto , Idoso , Anastomose Cirúrgica , Colite Ulcerativa/cirurgia , Humanos , Ileostomia , Masculino , Pessoa de Meia-Idade , Participação do Paciente , Complicações Pós-Operatórias , Resultado do Tratamento
20.
Anticancer Res ; 41(9): 4401-4405, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475060

RESUMO

BACKGROUND/AIM: We previously found in Swedish patients with inflammatory bowel disease (IBD), crypts in symmetric fission (CSF) and in asymmetric fission (CAF). This study aimed to examine CSF and CAF in a cohort of German patients with IBD. PATIENTS AND METHODS: H&E-sections from 106 IBD-patients [59 ulcerative colitis (UC) and 47 Crohn colitis (CCs)] were analysed. RESULTS: A total of 588 crypts in fission (CF) were found; 342 (58.2%) in UC and 246 (41.8%) in CCs. Out of the 505 CAFs found, 304 (60.2%) were recorded in UC, and 201(39.8%) in CCs (p=0.15272). CONCLUSION: Despite that German and Swedish populations reside in disparate geographical regions with different ecological milieus, the proportions of CAF and CSF were similar, thereby suggesting that CAF and CSF develop in IBD independently of the local environmental conditions in the two regions.


Assuntos
Colite Ulcerativa/patologia , Colite/patologia , Doença de Crohn/patologia , Biópsia , Estudos de Coortes , Colite/epidemiologia , Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Alemanha/epidemiologia , Humanos , Fatores de Risco , Suécia/epidemiologia
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