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1.
Chem Biol Interact ; 333: 109315, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33171134

RESUMO

Neutrophil infiltration, pro-inflammatory cytokines, and reactive oxygen species (ROS) production have been implicated in development and progression of ulcerative colitis (UC), an inflammatory bowel disease (IBD) characterized by ulcerating inflammation of the mucosal layer generally restricted to the colon. The side effects, safety and human intolerance are limitations of the currently approved treatments for UC. Hesperidin methyl chalcone (HMC) is a flavonoid used to treat chronic venous disease, which shows anti-inflammatory, analgesic, and antioxidant properties in pre-clinical studies, however, its effects on colitis have never been described. Therefore, we aimed to evaluate the protective effects of HMC in a mouse model of acetic acid-induced colitis. Treatment with HMC significantly reduced neutrophil infiltration, edema, colon shortening, macro and microscopic damages induced by intracolonic administration of acetic acid. The improvement of colitis after HMC treatment is related to the increase in colon antioxidant status, and the inhibition of pro-inflammatory cytokines TNF-α, IL-6, IL-1ß, and IL-33 in the colon. We observed, moreover, that HMC inhibited NF-κB activation in the colon, which might explain the reduction of the cytokines we observed. Finally, these results demonstrate a novel applicability of HMC to increase antioxidant response and reduce inflammation during acetic acid-induced colitis suggesting it as a promising therapeutic approach for the treatment of ulcerative colitis.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Chalconas/farmacologia , Colite Ulcerativa/tratamento farmacológico , Hesperidina/análogos & derivados , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Chalconas/uso terapêutico , Colite Ulcerativa/complicações , Colite Ulcerativa/imunologia , Colite Ulcerativa/metabolismo , Colo/efeitos dos fármacos , Colo/patologia , Citocinas/biossíntese , Modelos Animais de Doenças , Edema/complicações , Hesperidina/farmacologia , Hesperidina/uso terapêutico , Masculino , Camundongos , NF-kappa B/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
2.
Phytomedicine ; 80: 153372, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33113505

RESUMO

BACKGROUND: Feiyangchangweiyan capsule (FYC) is a traditional Chinese medicine formulation used in the clinical treatment of acute and chronic gastroenteritis and bacterial dysentery. However, the effect of FYC on ulcerative colitis (UC) and the mechanism thereof remains unknown. PURPOSE: To investigate the protective effect of FYC on UC mice induced by dextran sulfate sodium and illustrate the potential mechanism of this effect. METHODS: Here, we established a model of UC mice by dextran sulfate sodium and administered with FYC. The disease activity index (DAI), colon length, myeloperoxidase (MPO) content in serum, pathological structure and ultrastructural changes, and inflammatory cell infiltration of colon tissue were evaluated. Transcriptome and 16S rDNA sequencing were employed to illuminate the mechanism of FYC in the protection of UC mice. RESULTS: FYC significantly alleviates the pathological damage and the infiltration of inflammatory cells in colon tissue of dextran sulfate sodium induced UC mice, rescues shortened colon length, reduces DAI score, MPO content in serum, and pro-inflammatory factors including IL-1ß, IL-6, CCL11, MCP-1 and MIP-2, and increases anti-inflammatory factors such as IL-10. Transcriptomics revealed that Oncostatin M (OSM) and its receptor (OSMR) are the critical pathway for UC treatment by FYC. OSM and OSMR increased in UC mice compared to control mice, and decreased with FYC, which was verified via measurement of OSM and OSMR mRNA and protein levels. Furthermore, we observed that FYC modulates intestinal microbiome composition (e.g., the proportion of Barnesiella/Proteobacteria) by affecting the inflammatory factors. CONCLUSION: FYC exerts an effect on UC by inhibiting the OSM/OSMR pathway and regulating inflammatory factors to improve the intestinal flora.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Subunidade beta de Receptor de Oncostatina M/metabolismo , Oncostatina M/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Cápsulas , Quimiocinas/sangue , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/microbiologia , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Colo/ultraestrutura , Citocinas/sangue , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Microbioma Gastrointestinal/genética , Masculino , Camundongos Endogâmicos C57BL , Oncostatina M/genética , Subunidade beta de Receptor de Oncostatina M/genética , Substâncias Protetoras/farmacologia
3.
Postepy Biochem ; 66(3): 256-262, 2020 09 30.
Artigo em Polonês | MEDLINE | ID: mdl-33315320

RESUMO

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic diseases. The exact etiology of IBD is not well elucidated, however it is defined as a multifactorial disease. In addition, IBD carries the risk of serious complications and increases the risk of colorectal cancer. Also, in recent years, an increased rate of IBD cases has been noted. So far, there is no effective and well-defined therapy for IBD, and currently available drugs mainly provide symptomatic treatment. Unfortunately, conventional treatment does not always bring the expected benefits, moreover, it is often associated with unpleasant side effects. Currently, some research have been focused on unconventional forms of IBD treatment, testing therapies based on natural products. Individual polyphenols, as well as polyphenol-rich preparations and extracts are also valuable in IBD treatment through antioxidant, anti-inflammatory and bactericidal activity. Moreover, described here results of clinical trials suggest that polyphenols can alleviate symptoms and prevent recurrence of IBD.


Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Polifenóis/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/microbiologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/microbiologia , Humanos , Doenças Inflamatórias Intestinais/microbiologia
4.
Zhongguo Zhong Yao Za Zhi ; 45(22): 5362-5372, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33350195

RESUMO

To explore the mechanism of Sijunzi Decoction in the treatment of ulcerative colitis(UC) based on network pharmacology. The active components and corresponding targets of Sijunzi Decoction were extracted with Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets were standardized with the help of Uniprot database. The related targets of UC were obtained through GeneCards database and Disgenet database, and the intersection targets of drugs and diseases were screened by R language. The visual regulation network of "active ingredient-disease target" of Sijunzi Decoction was constructed by Cytoscape software, and the protein-protein interaction network was constructed by STRING database. The functional enrichment analysis of gene ontology(GO) and the enrichment analysis of Kyoto encyclopedia of genes and genomes(KEGG) pathway were carried out on Bioconductor platform, and some of the targets were verified by animal experiments. Through database analysis, a total of 135 active components of Sijunzi Decoction, 114 predicted targets and 80 common targets with UC were obtained. The core target proteins included interleukin 6(IL-6), caspase-3(CASP3), vascular endothelial growth factor A(VEGFA), epidermal growth factor receptor(EGFR) and so on. GO functional enrichment analysis involved 102 items, which mainly affected transcription factor activity, enzyme activity, receptor activity and biochemical process regulation. KEGG pathway enrichment analysis showed that 120 items were involved in human cytomegalovirus infection, cancer, apoptosis, inflammation and other pathways. Mouse experiments showed that Sijunzi Decoction could down-regulate the expression of target proteins IL-6 and caspase-3 and inhibit intestinal epithelial cell apoptosis. The treatment of UC with Sijunzi Decoction is the result of the interaction among multi-components, multi-targets and multi-pathways. It is proved by experiments that Sijunzi Decoction may play an effective role by regulating the expression of IL-6 and caspase-3, and getting involved in apoptosis, inflammation and other pathways.


Assuntos
Colite Ulcerativa , Medicamentos de Ervas Chinesas , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Camundongos , Fator A de Crescimento do Endotélio Vascular
5.
BMC Infect Dis ; 20(1): 922, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33272197

RESUMO

BACKGROUND: Bordetella bronchiseptica is a gram-negative, obligate aerobic coccobacillus known to cause disease in domesticated animals and pets. In humans, B. bronchiseptica commonly leads to respiratory infections like pneumonia or bronchitis, and animal contact usually precedes the onset of symptoms. CASE PRESENTATION: We report a case of post-traumatic B. bronchiseptica meningitis without recent surgery in the setting of immunosuppression with a monoclonal antibody. Our case concerns a 77-year-old male with ulcerative colitis on infliximab who sustained a mechanical fall and developed a traumatic cerebrospinal fluid leak complicated by meningitis. He received meropenem then ceftazidime during his hospital course, and temporary neurosurgical drain placement was required. His clinical condition improved, and he was discharged at his baseline neurological status. CONCLUSIONS: B. bronchiseptica is an unusual cause of meningitis that may warrant consideration in immunocompromised hosts with known or suspected animal exposures. To better characterize this rare cause of meningitis, we performed a systematic literature review and summarized all previously reported cases.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Bordetella/tratamento farmacológico , Bordetella bronchiseptica/isolamento & purificação , Ceftazidima/uso terapêutico , Meningite/tratamento farmacológico , Meningite/cirurgia , Meropeném/uso terapêutico , Idoso , Animais , Infecções por Bordetella/microbiologia , Vazamento de Líquido Cefalorraquidiano/complicações , Colite Ulcerativa/tratamento farmacológico , Drenagem/métodos , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Masculino , Meningite/etiologia , Meningite/microbiologia , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento
6.
Nihon Shokakibyo Gakkai Zasshi ; 117(12): 1093-1099, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33298675

RESUMO

A 30-year-old man presented with constipation and abdominal pain. He was suspected of having ulcerative colitis, and administration of 2400mg/day of oral mesalazine was initiated. After 10 days of treatment, he experienced fever and chest pain. Blood examination, electrocardiography, and cardiac ultrasonography revealed elevated cardiac enzymes, ST-segment elevation, and diffuse hypokinesis, respectively. Mesalazine-induced acute myocarditis was diagnosed based on a positive drug-induced lymphocyte stimulation test and the absence of other myocarditis-causing conditions. Prompt cessation of mesalazine quickly improved his heart function and test results. Although rare, clinicians should consider the possibility of cardiac adverse events caused by mesalazine.


Assuntos
Colite Ulcerativa , Miocardite , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Febre , Humanos , Masculino , Mesalamina/efeitos adversos , Miocardite/diagnóstico , Miocardite/diagnóstico por imagem
7.
Postepy Biochem ; 66(1): 42-48, 2020 03 31.
Artigo em Polonês | MEDLINE | ID: mdl-33320478

RESUMO

Sphingosine-1-phosphate (S1P) belongs to the group of biologically active sphingolipids. Because of its ability to regulate the migration of lymphocytes, S1P constitutes an important element of pathophysiology of several diseases, such as: lupus erythematosus, multiple sclerosis or inflammatory bowel diseases. Inflammatory bowel diseases (IBD) are the group of chronic and recurrent diseases of the gastrointestinal tract. The most common among IBD are: Crohn's disease and ulcerative colitis. Drugs that are currently used in the therapy of IBD alleviate symptoms, improve patients' quality of life and induce remission but their efficacy is not satisfactory. Modulators of S1P receptors constitu­te an emerging option in the therapy of IBD. In this review we will discuss the role of S1P, its receptor and enzymes that participate in the metabolism of S1P under physiological conditions and in the course of IBD. Moreover, we will sum up the results of preclinical and clinical studies on S1P receptors modulators in IBD.


Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Lisofosfolipídeos/metabolismo , Esfingosina/análogos & derivados , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Humanos , Qualidade de Vida , Esfingosina/metabolismo
8.
Medicine (Baltimore) ; 99(49): e23482, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285751

RESUMO

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by a relapsing and remitting course, and the curative medical therapy of UC is not yet available with its precise etiology unknown. Berberine hydrochloride, one of the main alkaloids in rhizomes of Coptis chinensis, has been reported the efficacy in patients with UC. However, there is no systematic review related to berberine hydrochloride for UC published. In this work, we will systematically evaluate the effectiveness and safety of berberine hydrochloride for UC by a meta-analysis method to provide a substantial conclusion for clinical practice. METHODS AND ANALYSIS: In this study, we will search the Chinese and English databases by electronic and manual search to find the related literature of berberine hydrochloride in the treatment of UC published from the inception date of each predefined database up to October 2020. Databases include PubMed, Embase, MEDLINE, Cochrane Library Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI) database, Wanfang Data Knowledge Service Platform, the VIP information resource integration service platform (cqvip), China Biology Medicine Disc (Sino Med), the Chinese Clinical Trial Registry (ChiCTR), and ClinicalTrials.gov. The 2 professional trained authors will independently select the qualified studies for data extraction and assess the risk of bias in included studies. Then the synthesis and analyses of data will be carried out in RevMan 5.4. The heterogeneity of statistics will be assessed by a heterogeneity X test and I tests. Sensitivity analysis is used to evaluate whether the outcomes of systematic review or meta-analysis are robust and reliable. The funnel plot is the main method to evaluate the bias of reporting. Finally, we will use The Grading of Recommendations Assessment, Development and Evaluation to evaluate the quality of evidence. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: Whether berberine hydrochloride is an effectiveness and safety for patients with UC will be judged in the conclusion of this systematic review. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/X57U3.


Assuntos
Berberina/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Resultado do Tratamento
9.
PLoS One ; 15(11): e0242342, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33180848

RESUMO

Vedolizumab (VDZ) is a therapeutic monoclonal antibody approved for the treatment of inflammatory bowel diseases (IBD). VDZ selectively binds to the α4ß7 integrin and blocks trafficking of a specific subset of gastrointestinal-homing T-lymphocytes to inflamed tissue. Although VDZ has shown promising results in numerous clinical studies a subgroup of patients do not respond adequately. Mechanistic insights and prognostic biomarkers able to predict which patients might benefit from VDZ therapy are currently lacking. Circulating exosomes were isolated from serum of blood donors and VDZ-treated patients by polymer-based precipitation. The surface expression of α4ß7 integrin was evaluated by flow cytometry and the levels of exosome-bound VDZ were investigated by Promonitor-VDZ ELISA kit. The capacity of exosomes to interfere with the adhesion of VDZ-treated CD4+ T cells was assessed by adhesion assay. In this study, we showed that serum exosomes isolated from both blood donor and ulcerative colitis patients express on their surface the VDZ target α4ß7 integrin. We observed an increased exosomal sequestration of VDZ in anti-TNF exposed patients compared to anti- TNFα naïve patients, according to a greater expression of α4ß7 integrin on vesicles surface. Circulating exosomes could compete for VDZ binding with CD4+ T cells since we found that the amount of VDZ bound to T cells was impaired in the presence of exosomes. In addition, we demonstrated that exosomes bind VDZ, which consequently becomes unable to block MadCAM-1-mediated adhesion of lymphocytes. Circulating exosomes might contribute to drug sequestration, possibly affecting the therapeutic efficacy of VDZ in IBD patients. Our data suggest that previous biologic therapy may have altered the sequestration capacity of circulating exosomes, thus reducing the efficacy of VDZ in patients who failed anti-TNF agents.


Assuntos
Anticorpos Monoclonais Humanizados/metabolismo , Exossomos/genética , Integrinas/genética , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Biomarcadores Farmacológicos/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Colite Ulcerativa/tratamento farmacológico , Exossomos/metabolismo , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Integrinas/metabolismo , Masculino , Pessoa de Meia-Idade , Ligação Proteica/genética , Ligação Proteica/fisiologia , Estudos Retrospectivos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/uso terapêutico
10.
PLoS One ; 15(11): e0241337, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33151988

RESUMO

INTRODUCTION: Indigo naturalis (IN) is a blue pigment extracted from Assam indigo and other plants and has been confirmed to be highly effective for ulcerative colitis (UC) treatment in several clinical studies. OBJECTIVE: We conducted a multicenter double-blind study to confirm the efficacy and safety of short-term IN administration. METHODS: A multicenter, randomized controlled trial was conducted between December 2015 and October 2018 in our facilities. Forty-six patients with mild to moderate active UC (Lichtiger index: 5-10) were randomly assigned to the IN group or the placebo group and received 5 capsules (500 mg) twice a day for 2 weeks. We investigated the efficacy according to blood tests and the Lichtiger index before and after administration, and we also examined adverse events. RESULTS: The analysis included 42 patients (20 males, 22 females) with an average age of 45 years. Nineteen patients were assigned to the placebo group, and 23 were assigned to the IN group. After treatment administration, in the placebo group, no change in the Lichtiger index was observed (7.47 to 6.95, p = 0.359), and hemoglobin was significantly reduced (12.7 to 12.4, p = 0.031), while in the IN group, the Lichtiger index (9.04 to 4.48, p = 0.001) and albumin (4.0 to 4.12, p = 0.022) improved significantly. Mild headaches were observed in 5 patients and 1 patient in the IN and placebo groups, respectively. CONCLUSIONS: Short-term administration of IN is highly effective without serious adverse events such as pulmonary hypertension or intussusception and may prevent the occurrence of serious adverse events.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Índigo Carmim/efeitos adversos , Índigo Carmim/uso terapêutico , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
Am J Gastroenterol ; 115(11): 1768-1774, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33156094

RESUMO

INTRODUCTION: De-escalation of biologic therapy is a commonly encountered clinical scenario. Although biologic discontinuation has been associated with high rates of relapse, the effectiveness of dose de-escalation is unclear. This review was performed to determine the effectiveness of dose de-escalation of biologic therapy in inflammatory bowel disease. METHODS: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception to October 2019. Randomized controlled trials and observational studies involving dose de-escalation of biologic therapy in adults with inflammatory bowel disease in remission were included. Studies involving biologic discontinuation only and those lacking outcomes after dose de-escalation were excluded. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: We identified 1,537 unique citations with 20 eligible studies after full-text review. A total of 995 patients were included from 18 observational studies (4 prospective and 14 retrospective), 1 nonrandomized controlled trial, and 1 subgroup analysis of a randomized controlled trial. Seven studies included patients with Crohn's disease, 1 included patients with ulcerative colitis, and 12 included both. Overall, clinical relapse occurred in 0%-54% of patients who dose de-escalated biologic therapy (17 studies). The 1-year rate of clinical relapse ranged from 7% to 50% (6 studies). Eighteen studies were considered at high risk of bias, mostly because of the lack of a control group. DISCUSSION: Dose de-escalation seems to be associated with high rates of clinical relapse; however, the quality of the evidence was very low. Additional controlled prospective studies are needed to clarify the effectiveness of biologic de-escalation and identify predictors of success.


Assuntos
Produtos Biológicos/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Adalimumab/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Infliximab/administração & dosagem , Recidiva
13.
Nihon Shokakibyo Gakkai Zasshi ; 117(11): 992-1000, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33177262

RESUMO

A 20-year-old woman with ulcerative colitis flare was admitted to Fukui Red Cross Hospital. During treatment with granulocyte and monocyte apheresis (GMA), the patient complained of chest discomfort and was diagnosed with pulmonary thromboembolism with central intravenous catheter thrombosis. Apixaban, a direct oral anticoagulant (DOAC), was used as monotherapy for anticoagulation, and thromboembolism was resolved without complication. Among extraintestinal complications in patients with ulcerative colitis, pulmonary thromboembolism can be a life-threatening condition and requires prompt anticoagulant therapy. Although the effectiveness of conventional pharmacological anticoagulation using warfarin and heparin has been reported, the efficacy of DOAC monotherapy remains controversial. DOAC monotherapy may be considered and innovative therapeutic strategy for a thromboembolic condition in patients with ulcerative colitis.


Assuntos
Colite Ulcerativa , Embolia Pulmonar , Trombose , Anticoagulantes/uso terapêutico , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Feminino , Humanos , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/etiologia , Pirazóis , Piridonas , Adulto Jovem
14.
Probl Sotsialnoi Gig Zdravookhranenniiai Istor Med ; 28(Special Issue): 1137-1145, 2020 Oct.
Artigo em Russo | MEDLINE | ID: mdl-33219771

RESUMO

AIM: to estimate the quality and availability of medical care for patients with ulcerative colitis (UC) and Crohn's disease (CD), to assess the impact of the economic burden of these diseases on the healthcare budget of Russia and to systematize the main problems in the organization of medical care and drug supply for patients with inflammatory bowel diseases (IBD). Regional IBD databases (2016-2018), official statistical databases, costs of treatment and results of expert interviews with specialists in IBD were used in the study. The analyzed databases showed 104,668 patients with UC in Russia in 2018 (prevalence rate 71 per 100,000 people) and 66,647 patients with CD (prevalence rate of 45 per 100,000 people). The economic burden including agents for biologic therapy (ABT) for the UC was 39.54 billion rubles a year (495 rubles per capita), and CD - 32.98 billion rubles a year (378 rubles per capita). It requires an additional 9.87 billion rubles annually for UC and 9.20 billion rubles annually for CD patients to provide the complete supply with ABT. The annual burden of IBD is 72.52 billion rubles, which is comparable to the costs of other socially significant diseases, including malignant tumors. It shows the high social and economic value of IBD for the country. The main problems of medical care and drug supply for IBD patients are the mismatch of official statistical data and real IBD prevalence in Russia due to absence of comprehensive register and the insufficient supply with ABT due to limited funding. A federal center for IBD should be founded for better quality of registration, for the precise monitoring and for the active management of personal drug supply.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Efeitos Psicossociais da Doença , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Humanos , Federação Russa/epidemiologia
15.
Dtsch Arztebl Int ; 117(33-34): 564-574, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-33148393

RESUMO

BACKGROUND: Ulcerative colitis is a chronic inflammatory bowel disease with an estimated 150 000 patients in Germany alone. METHODS: This review is based on publications about current diagnostic and therapeutic strategies for ulcerative colitis that were retrieved by a selective search in PubMed, and on current guidelines. RESULTS: The primary goal of treatment is endoscopically confirmed healing of the mucosa. Mesalamine, in various forms of administration, remains the standard treatment for uncomplicated ulcerative colitis. Its superiority over placebo has been confirmed in meta-analyses of randomized, controlled trials. Glucocorticoids are highly effective in the acute treatment of ulcerative colitis, but they should only be used over the short term, because of their marked side effects. Further drugs are available to treat patients with a more complicated disease course of ulcerative colitis, including azathioprine, biological agents, JAK inhibitors (among them TNF antibodies, biosimilars, ustekinumab, vedolizumab, and tofacitinib), and calcineurin inhibitors. Proctocolectomy should be considered in refractory cases, or in the presence of high-grade epithelial dysplasia. Ulcerative colitis beginning in childhood or adolescence is often characterized by rapid progression and frequent comorbidities that make its treatment a special challenge. CONCLUSION: A wide variety of drugs are now available for the treatment of ulcerative colitis, enabling the individualized choice of the best treatment for each patient. Regular surveillance colonoscopies to rule out colon carcinoma should be scheduled at intervals that depend on risk stratification.


Assuntos
Medicamentos Biossimilares , Colite Ulcerativa , Adolescente , Algoritmos , Criança , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Alemanha , Humanos , Mesalamina
16.
Nihon Shokakibyo Gakkai Zasshi ; 117(11): 971-977, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33177259

RESUMO

A 67-year-old man was diagnosed with ulcerative colitis one year ago. Remission was induced via the oral administration of prednisolone and azathioprine;prednisolone was gradually reduced and discontinued. He maintained remission with azathioprine but developed fever and general malaise and visited the Kagawa Prefectural Central Hospital. Chest radiography and a urinary antigen test revealed Legionella pneumonia. His symptoms reduced immediately after the initiation of levofloxacin. Azathioprine suppresses cellular immunity and may increase the risk of Legionella pneumonia.


Assuntos
Colite Ulcerativa , Legionella , Pneumonia , Idoso , Azatioprina/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Humanos , Imunossupressores/efeitos adversos , Masculino
17.
Acta Cir Bras ; 35(10): e202001002, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33237174

RESUMO

PURPOSE: To investigate the mechanism of Periplaneta americana extract promoting intestinal mucosal repair of OXZ-induced colitis in rat. METHODS: All experiments used an equal number of male and female SD rats (n=48). We injected OXZ into the colon to induce UC rat model. To determine the optimal concentration of P. Americana's extract (PA-40), it was classified into low (L), medium (M), and high (H) doses. After OXZ treatment, each drug was administered by enema for 7 consecutive days. Rats were divided into the following 6 groups: (1) Saline treatment group (NC), (2) OXZ treatment UC model group (MC), (3) OXZ + budesonide group (BUN), (4) OXZ + PA-40 L group, (5) OXZ + PA-40 M group, (6) OXZ + PA-40 H group. Disease activity index (DAI) scores, colon length, histopathological score, serum cytokine level (IL-4, IL-10, iNOS, tNOS), and amount of MPO, EGF, IL-13 in colonic mucosa were measured. RESULTS: PA treatment had a significant healing effect on the OXZ-colitis model and significantly reduced the lesioned area, especially in the PA-40H groups. PA treatment did not alter the expression of IL-10 and MPO level, but increased EGF (epidermal growth factor) and decrease IL-13 in the colonic tissue. PA inhibited the rise of NOSs (nitric oxide synthase) and decreased the serum IL-4 level. CONCLUSIONS: The data suggest that Periplaneta americana extract may be a potential compound for the treatment of colonic lesions. The mechanism may be related to inhibiting the secretion of IL-13 and promoting the formation of EGF.


Assuntos
Colite Ulcerativa , Periplaneta , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo , Feminino , Mucosa Intestinal , Masculino , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley
18.
Medicine (Baltimore) ; 99(47): e23038, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217804

RESUMO

BACKGROUD: Ulcerative colitis (UC) is a chronic inflammatory disease that involves the rectum, colon and ileum. Gancao Xiexin decoction (GCXXD) is a classic herbal formula in Shanghanlun. More and more research evidence shows that GCXXD has a certain therapeutic effect on UC. Therefore, we designed this study protocol aim to evaluate the efficacy and safety of GCXXD combine with mesalazine for UC. METHODS: We will systematically search 6 databases, including PubMed, the Cochrane Library, EMBASE, CNKI, VIP, Wang-fang database up to July 2020 to obtain eligible studies. The primary outcomes will focus on the clinical effectiveness. Review Manager 5.3 software will be used for data analysis. RESULTS: This study will provide the systematic evidence of UC treated with GCXXD combine with mesalazine. CONCLUSION: The findings of this meta-analysis will provide evidence to judge whether GCXXD combine with mesalazine is a more effective intervention compare to mesalazine only for patient of UC. INPLASY REGISTRATION NUMBER: INPLASY202080008.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Mesalamina/uso terapêutico , Projetos de Pesquisa , Quimioterapia Combinada , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
19.
Medicine (Baltimore) ; 99(47): e23344, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217875

RESUMO

This study aimed to investigate the short-term effectiveness of adalimumab therapy in patients with ulcerative colitis (UC), especially its rapid response.This retrospective, multicenter, cohort study involved 7 institutes in Japan, compiling data from patients with UC who had received at least 1 induction dose of 160 mg of adalimumab between June 2013 and May 2017. Patients should have a Lichtiger clinical activity index score of ≥5 at the initial adalimumab administration. Remission was defined as clinical activity index score of ≤4, whereas response was defined as a reduction of ≥50% from the baseline value. Rapid responders are defined as patients who achieved response at 2 weeks.A total of 91 patients were included in this study: 37.4% and 45.1% achieved clinical response at 2 and 8 weeks, respectively, whereas clinical remission rates 12 weeks were 45.1%. Among the rapid responders, 82.4% achieved clinical remission at 12 weeks. Multivariate logistic regression analysis identified a higher platelet count as an independent prognostic factor for a higher rate of rapid response. Receiver operating characteristic curve showed that a platelet counts cutoff value of ≥312 × 10/L was associated with a rapid response.Approximately 40% of patients with UC showed a rapid response to adalimumab therapy after 2 weeks. Up to 80% of the rapid responders also achieved remission at 12 weeks. A higher platelet count was identified as an independent prognostic factor for a higher rapid response rate.


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/sangue , Colite Ulcerativa/tratamento farmacológico , Adulto , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Indução de Remissão , Estudos Retrospectivos
20.
Lancet Gastroenterol Hepatol ; 5(12): 1063-1075, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33031757

RESUMO

BACKGROUND: Cobitolimod is a topically administered, DNA-based oligonucleotide that activates Toll-like receptor 9 (TLR9), and previous research has shown clinical efficacy in patients with moderate-to-severe ulcerative colitis. Here we assessed the efficacy and safety of different dose regimens of cobitolimod for induction therapy in patients with moderate-to-severe, left-sided ulcerative colitis. METHODS: CONDUCT was a randomised, double-blind, five-arm, placebo-controlled, dose-ranging phase 2b study that recruited patients with moderate-to-severe, left-sided ulcerative colitis, with inadequate response to conventional or biological therapies, from 91 hospitals or outpatient clinics in 12 European countries. Eligible patients had a Mayo score of 6-12 with a centrally read endoscopic subscore (modified to exclude friability from grade 1) of 2 or higher and no individual subscore of less than 1, and confirmation of left-sided disease. Patients were randomised (1:1:1:1:1; block size of ten) via a computer-generated schedule and centralised interactive voice and web response system to receive rectal enemas of cobitolimod at 31 mg, 125 mg, or 250 mg at weeks 0 and 3 (2 × 31 mg, 2 × 125 mg, and 2 × 250 mg groups), cobitolimod at 125 mg at weeks 0, 1, 2, and 3 (4 × 125 mg group), or placebo. Randomisation was stratified by current glucocorticosteroid and previous tumour necrosis factor inhibitor treatment. Patients and all study personnel were masked to treatment allocation. The primary endpoint was the proportion of patients achieving clinical remission (Mayo subscores for rectal bleeding of 0, for stool frequency of 0 or 1 [with ≥1-point decrease from baseline], and for endoscopy of 0 or 1 [excluding friability]) at week 6. The primary analysis (based on intention to treat) and safety analysis were done in all randomly assigned patients who received at least one dose of active study drug or placebo. In this exploratory study, statistical tests were one-sided; p values of less than 0·10 were regarded as statistically significant, with no adjustment for multiplicity. This study is registered with ClinicalTrials.gov, NCT03178669, and is completed; the results here represent the final analysis. FINDINGS: 213 patients were randomly assigned between June 30, 2017, and June 26, 2019. Of these, 211 patients received study treatment: 40 in the cobitolimod 2 × 31 mg group, 43 in the 2 × 125 mg group, 42 in the 4 × 125 mg group, 42 in the 2 × 250 mg group, and 44 in the placebo group. A greater proportion of patients were in clinical remission at week 6 in the cobitolimod 2 × 250 mg group than in the placebo group (nine [21%] of 42 patients vs three [7%] of 44; odds ratio [OR] 3·8 [80% CI 1·5-9·5]; one-sided p=0·025). We identified no significant difference in the proportion of patients with clinical remission in the cobitolimod 2 × 31 mg group (five [13%] of 40 patients; OR 2·0 [80% CI 0·7-5·5], p=0·18), 2 × 125 mg group (two [5%] of 43; 0·7 [0·2-2·2], p=0·66), or 4 × 125 mg (four [10%] of 42; 1·4 [0·5-3·9], p=0·33) compared with the placebo group. Treatment-emergent adverse events occurred in 21 (48%) patients in the placebo group, ten (25%) patients in the cobitolimod 2 × 31 mg group, 17 (40%) patients in the 2 × 125 mg group, 15 (36%) patients in the 4 × 125 mg group, and 18 (43%) patients in the 2 × 250 mg group. Severe adverse events occurred in eight (4%) of 211 patients (worsening of ulcerative colitis [seven patients] and abdominal hernia and wound dehiscence [one patient]). Ten patients (two [5%] in the placebo group, two [5%] in the cobitolimod 2 × 31 mg group, two [5%] in the 4 × 125 mg, and four [10%] in the 2 × 250 mg group) had a total of 13 serious adverse events; these were worsening of ulcerative colitis (eight events) and pruritus, rash, abdominal hernia, fascia dehiscence, and deep vein thrombosis (one event each). One patient in the placebo group died from total organ failure after receiving a colectomy for a serious adverse event of disease worsening. INTERPRETATION: Two topical administrations of cobitolimod 250 mg were well tolerated and more effective than placebo in inducing clinical remission 6 weeks after the start of treatment. TLR9 activation is a promising novel therapeutic target in ulcerative colitis and warrants further testing, with phase 3 trials of cobitolimod planned. FUNDING: InDex Pharmaceuticals.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Índice de Gravidade de Doença , Resultado do Tratamento
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