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1.
J Ethnopharmacol ; 266: 113442, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33027643

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Qingchang Suppository (QCS) is a Traditional Chinese Medicine formula (TCM) for Ulcerative Colitis (UC), which has been used for the treatment of UC for more than 30 years with therapeutic effect. This formula is optimized from a classic formula called "Qingdai San". Although some experiments have shown QCS effective for UC, its mechanism on UC is still unclear and needs to be clarified. AIM OF THE STUDY: To investigate the usage of QCS in our hospital, clarify the main compounds in QCS and their anti-inflammation effect both in vivo and in vitro. MATERIALS AND METHODS: Prescription analysis was performed in the clinical department and pharmacology network prediction was predicted for relative signal pathways. 2,4,6-Trinitrobenzenesulfonic acid (TNBS)-induced colitis rats and Lipopolysaccharide (LPS)-induced Caco-2 cell as an inflammatory model were used to evaluate the effect of QCS. RESULTS: QCS and its herbs were associated with inflammatory and immunological diseases. QCS and its ingredients showed little toxicity on Caco-2 cell and could down-regulate the level of Interleukin-6 (IL-6) and expression of signal transducer and activator of transcription 3 (P-STAT3 Tyr705) in LPS-induced Caco-2 cell. In an animal experiment, QCS and its ingredients (indigo and gallic acid) could alleviate the symptoms of TNBS-induced colitis of rats, significantly decrease pro-inflammatory factors and anti-inflammatory factors as well as inhibit the expressions of P-STAT3 and Tyr705. CONCLUSION: QCS and its components could improve UC by anti-inflammation. JAK2/STAT3 pathway might be the possible signaling pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Adulto , Animais , Anti-Inflamatórios/isolamento & purificação , Células CACO-2 , Colite Ulcerativa/fisiopatologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Janus Quinase 2/metabolismo , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Supositórios , Ácido Trinitrobenzenossulfônico
2.
J Ethnopharmacol ; 265: 113251, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32810615

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Application of cyclosporine A (CsA) as a rescue treatment in acute severe ulcerative colitis (UC) is limited by its narrow therapeutic window and great interpatient variability. As a substrate of cytochrome P450 3A enzyme (CYP3A) and P-glycoprotein (P-gp), the oral pharmacokinetics of CsA is susceptible to disease status and concomitant medications. Combined treatment with ginseng, a famous medicinal herb frequently prescribed for ameliorating abnormal immune response in many diseases including UC, showed immunologic safety in CsA-based immunosuppression. AIM OF THE STUDY: Since the therapeutic levels of CsA can be achieved within 24 h, this study first assessed the impact of acute colitis and ginseng intervention on the single oral dose pharmacokinetics of CsA and explored the underlying mechanisms in dextran sulfate sodium (DSS)-induced colitis rats and Caco-2 cells. MATERIALS AND METHODS: Rats received drinking water (normal group), 5% DSS (UC group), or 5% DSS plus daily oral ginseng extract (GS+UC group). On day 7, GS+UC group only received an oral dose of CsA (5 mg/kg), while animals of normal or UC group received an oral, intravenous (1.25 mg/kg), or intraperitoneal dose of CsA (1.25 mg/kg), respectively. Blood, liver/intestine tissues and fecal samples were collected for determining CsA and main hydroxylated metabolite HO-CsA or measuring hepatic/intestinal CYP3A activity. Caco-2 cells were incubated with gut microbial culture supernatant (CS) of different groups or ginseng (decoction or polysaccharides), and then CYP3A, P-gp and tight junction (TJ) proteins were determined. RESULTS: Oral CsA exhibited enhanced absorption, systemic exposure and tissue accumulation, and lower fecal excretion, while intravenous or intraperitoneal CsA showed lower systemic exposure and enhanced distribution, in colitis rats. Diminished intestinal and hepatic P-gp expression well explained the changes with DSS-induced colitis. Moreover, blood exposures of HO-CsA in both normal and colitis after oral dosing were significantly higher than intravenous/intraperitoneal dosing, supporting the dominant role of intestinal first-pass metabolism. Interestingly, colitis reduced CYP3A expression in intestine and liver but only potentiated intestinal CYP3A activity, causing higher oral systemic exposure of HO-CsA. Oral ginseng mitigated colitis-induced down-regulation of CYP3A and P-gp expression, facilitated HO-CsA production, biliary excretion and colonic sequestration of CsA, while not affected CsA oral systemic exposure. In Caco-2 cells, gut microbial CS from both colitis and GS+UC group diminished P-gp function, while ginseng polysaccharides directly affected ZO-1 distribution and suppressed TJ proteins expression, explaining unaltered oral CsA systemic exposure. CONCLUSIONS: DSS-induced colitis significantly altered oral CsA disposition through regulating intestinal and hepatic P-gp and CYP3A. One-week ginseng treatment enhanced colonic accumulation while not altered the systemic exposure of CsA after single oral dosing, indicating pharmacokinetic compatibility between the two medications.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Ciclosporina/farmacocinética , Panax/química , Extratos Vegetais/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Administração Oral , Animais , Células CACO-2 , Colite Ulcerativa/fisiopatologia , Ciclosporina/administração & dosagem , Citocromo P-450 CYP3A/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Interações Ervas-Drogas , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
3.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(3): 211-215, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32981274

RESUMO

Objective: To investigate the effects of miR-31 on TLR4/NF-κB signaling pathway and apoptosis-related proteins in dextran sulfate sodium (DSS) induced mouse colon colitis. Methods: ① Mouse model of colon colitis: 1% DSS was used to induce mouse ulcerative colitis (UC). Fourteen FVB non-transgenic mice were randomly divided into control group (n= 6), DSS group (n= 8), and 16 FVB miR-31 transgenic mice were randomly divided into miR-31 overexpression group (n= 8), miR-31 overexpression +DSS group (n= 8). DSS was dissolved in water and administered to mice by drinking water. The DSS group and miR-31+DSS group drank 1% DSS water in the first week, normal sterilized water in the second week, and 1% DSS water in the third week, after 5 weeks, the modeling was completed, then the colon tissues of the mice were collected. Western blot and IHC were used to detect the expressions of NF-κB p65, TLR4, Bax and Bcl-2 proteins in mouse colon tissue, TUNEL was used to detect apoptosis of mouse colon tissues. ② Cell culture experiments: Transfection of miR-31mimic and inhibitor by lipofectamine resulted in overexpression or knockdown of miR-31 in human colon epithelial cell line HCT 116 cells, each group was repeated three times and cells were collected 48 h later, Western blot was used to detect the expressions of NF-κB p65 and TLR4 protein. Results: ① In animal experiments, compared with the control group, the expression levels of NF-κB p65, TLR4 protein and apoptotic cell index in the DSS group and miR-31 overexpression group in mouse colon tissue were significantly increased (P<0.05 or P<0.01), and the Bcl-2 / Bax ratio was significantly reduced (P<0.05 or P<0.01); and compared with the DSS group, the expression levels of NF-κB p65, TLR4 protein and apoptotic cell index in the miR-31+DSS group were significantly increased (P<0.01), while the Bcl-2/Bax ratio was significantly decreased (P<0.01). ② In cell experiments, compared with the control group, the expression levels of NF-κB p65 and TLR4 protein in the over-expressed miR-31 group of HCT 116 cells were significantly increased (P<0.05 or P<0.01), the expressions of NF-κB p65 and TLR4 protein in miR-31 knockdown group were decreased (P<0.05). Conclusion: miR-31 promotes the development of colitis by promoting TLR4/NF-κB signaling pathway and mediating apoptosis of intestinal epithelial cells.


Assuntos
Colite Ulcerativa , MicroRNAs , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Animais , Linhagem Celular , Colite Ulcerativa/fisiopatologia , Colo/fisiopatologia , Modelos Animais de Doenças , Expressão Gênica , Humanos , Camundongos , MicroRNAs/genética , NF-kappa B/genética , NF-kappa B/metabolismo , Distribuição Aleatória , Transdução de Sinais/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
4.
Medicine (Baltimore) ; 99(32): e21686, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769938

RESUMO

Inflammatory bowel disease is associated with an increased risk of colorectal cancer. The study aims to identify the risk factors for ulcerative colitis-colorectal cancer and to perform a survival curve analysis of the outcome.This retrospective cohort study included 254 patients from March 2016 to October 2017. Age, age at diagnosis, follow-up time, smoking status, and family history of colorectal cancer were analyzed as risk factors for colorectal cancer.The mean patient age was 46.6 ±â€Š16.9 years; 5.5% of the patients were smokers and 49.6% had pancolitis. Six patients (2.36%) had colorectal cancer, which was associated with age at diagnosis (odds/hazard ratio 1.059 [95% confidence interval: 1.001-1.121]; P = .04), family history of colorectal cancer (12.992 [1.611-104.7]; P = .02), and follow-up time (0.665 [0.513-0.864]; P = .002). Active smoking was the main identified risk factor, after both logistic (8.477 [1.350-53.232]; P = .02) and Cox proportional-hazards (32.484 [2.465-428.1]; P = .008) regression analysis. The risk of colorectal cancer was 3.17% at 10 years and 4.26% at 20 years of follow-up.Active smoking and family history were identified as risk factors for colorectal cancer. These findings should aid the early identification of patients who require vigorous surveillance, and prevent exposure to risk factors.


Assuntos
Colite Ulcerativa/etiologia , Neoplasias Colorretais/complicações , Fatores de Risco , Adulto , Idoso , Estudos de Coortes , Colite Ulcerativa/fisiopatologia , Neoplasias Colorretais/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida
5.
Khirurgiia (Mosk) ; (7): 18-24, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32736459

RESUMO

OBJECTIVE: To compare quality of life in patients undergoing proctocolectomy with ileal pouch procedure and ileostomy taking into account sexual function. MATERIAL AND METHODS: The comparative observational study included 138 patients with ulcerative colitis for the period 2013-2018. All patients underwent surgery with one- or two-stage formation of pelvic pouch (n=76) or ileostomy (n=62). Validated questionnaires SF-36, The International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI) were used in the study. RESULTS: Patients with pelvic pouch were significantly younger than patients with terminal ileostomy (33.7±10.9 and 44.6±14.9 years, respectively, p<0.0001). The majority of the parameters of SF-36 questionnaire were similar in both groups. Pain syndrome intensity was the only sign demonstrating the advantage of ileostomy over pelvic pouch. However, regression analysis did not confirm the effect of surgical technique on pain severity. Orgasmic function was significantly better in men with pelvic pouch compared to ileostomy. Other indicators of sexual function were similar. According to FSFI questionnaire, women with pelvic pouch also showed significantly better results than patients with permanent ileostomy. However, multivariate regression analysis revealed no significant effect of surgical technique on sexual function in men and women. At the same time, significant negative correlation between IIEF and FSFI scores and age was revealed. CONCLUSION: No significant influence of surgical technique on postoperative QOL was observed in patients with ulcerative colitis. Better sexual function in men and women with pelvic pouch are due to younger age rather type of surgery.


Assuntos
Colite Ulcerativa/cirurgia , Ileostomia/efeitos adversos , Proctocolectomia Restauradora/efeitos adversos , Qualidade de Vida , Disfunções Sexuais Fisiológicas/etiologia , Adulto , Fatores Etários , Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Fatores Sexuais , Disfunções Sexuais Psicogênicas/etiologia , Sexualidade/fisiologia , Adulto Jovem
7.
Aliment Pharmacol Ther ; 51(12): 1373-1383, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32383166

RESUMO

BACKGROUND: Transabdominal ultrasound is useful to assess inflammation in patients with ulcerative colitis (UC); however, the assessment of the rectum is challenging and a barrier for its widespread use. AIM: To evaluate if transperineal ultrasound is useful for predicting endoscopic and histological findings of the rectum in UC. METHODS: Fifty-three consecutive adults with UC who required colonoscopy were included and transperineal ultrasound was performed in combination with transabdominal ultrasound within a week before or after colonoscopy with rectal biopsy. Mayo endoscopic subscore (MES) ≤1 was defined as endoscopic healing and Geboes score <2.1, Robarts histopathology index ≤6, and Nancy index ≤1 were defined as histological healing. Limberg score and bowel wall thickness were recorded with transperineal ultrasound. Faecal calprotectin was also measured. RESULTS: Excellent correlation was confirmed between colonoscopy and transabdominal ultrasound in all segments except for the rectum. Rectal bowel wall thickness and Limberg score in transperineal ultrasound well correlated with rectal MES and histological indices. Bowel wall thickness ≤4 mm predicted endoscopic (Area under the curve [AUC] = 0.90) and histological (AUC = 0.87-0.89) healing. In multivariable logistic regression analysis, only bowel wall thickness in transperineal ultrasound was a significant independent predictor for rectal endoscopic and histologic healing (P < 0.05) and the predictability was better than faecal calprotectin. CONCLUSIONS: Transperineal ultrasound predicts endoscopic and histological healing of the rectum. The combination of transperineal ultrasound with transabdominal ultrasound visualises the entire colorectum and is an ideal modality for the treat-to-target strategy. Clinical Trials Registry number UMIN000033611 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000038323).


Assuntos
Colite Ulcerativa/diagnóstico , Endoscopia Gastrointestinal/métodos , Períneo/diagnóstico por imagem , Ultrassonografia/métodos , Cicatrização , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colite Ulcerativa/fisiopatologia , Colonoscopia/métodos , Feminino , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Mucosa Intestinal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Períneo/patologia , Períneo/fisiopatologia , Prognóstico , Reto/diagnóstico por imagem , Reto/patologia , Reto/fisiopatologia , Índice de Gravidade de Doença , Adulto Jovem
8.
Inflamm Bowel Dis ; 26(7): 971-973, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32393973

RESUMO

First detected in Wuhan, China, the novel 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus responsible for an unprecedented, worldwide pandemic caused by COVID-19. Optimal management of immunosuppression in inflammatory bowel disease (IBD) patients with COVID-19 infection currently is based on expert opinion, given the novelty of the infection and the corresponding lack of high-level evidence in patients with immune-mediated conditions. There are limited data regarding IBD patients with COVID-19 and no data regarding early pregnancy in the era of COVID-19. This article describes a patient with acute severe ulcerative colitis (UC) during her first trimester of pregnancy who also has COVID-19. The case presentation is followed by a review of the literature to date on COVID-19 in regard to inflammatory bowel disease and pregnancy, respectively.


Assuntos
Aborto Espontâneo , Colite Ulcerativa , Infecções por Coronavirus , Ciclosporina/administração & dosagem , Metilprednisolona/administração & dosagem , Pandemias , Pneumonia Viral , Complicações na Gravidez , Indução de Remissão/métodos , Adulto , Antivirais/administração & dosagem , Betacoronavirus/isolamento & purificação , Proteína C-Reativa/análise , Técnicas de Laboratório Clínico/métodos , Colite Ulcerativa/sangue , Colite Ulcerativa/complicações , Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/terapia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Feminino , Humanos , Imunossupressores/administração & dosagem , Gravidade do Paciente , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Gravidez , Complicações na Gravidez/fisiopatologia , Complicações na Gravidez/terapia , Sigmoidoscopia/métodos , Resultado do Tratamento
9.
F1000Res ; 92020.
Artigo em Inglês | MEDLINE | ID: mdl-32399194

RESUMO

Inflammatory bowel diseases are common, complex, immune-mediated conditions with a sharply rising global prevalence. While major advances since 2000 have provided strong mechanistic clues implicating a de-regulation in the normal interaction among host genetics, immunity, microbiome, and the environment, more recent progress has generated entirely new hypotheses and also further refined older disease concepts. In this review, we focus specifically on these novel developments in the pathogenesis of ulcerative colitis.


Assuntos
Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/genética , Feminino , Humanos , Imunidade , Masculino , Microbiota
11.
Am J Gastroenterol ; 115(6): 832-840, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32224703

RESUMO

Various lifestyle factors including physical activity and obesity, stress, sleep, and smoking may modify the risk of developing inflammatory bowel diseases (IBDs). In patients with established IBD, these lifestyle factors may significantly impact the natural history and clinical outcomes. Recreational exercise decreases the risk of flare and fatigue in patients with IBD. In contrast, obesity increases the risk of relapse and is associated with higher anxiety, depression, fatigue, and pain and higher health care utilization. Obesity also modifies pharmacokinetics of biologic agents unfavorably and is associated with a higher risk of treatment failure. Sleep disturbance is highly prevalent in patients with IBD, independent of disease activity, and increases the risk of relapse and chronic fatigue. Similarly, stress, particularly perceived stress rather than major life events, may trigger symptomatic flare in patients with IBD, although its impact on inflammation is unclear. Cigarette smoking is associated with unfavorable outcomes including the risk of corticosteroid dependence, surgery, and disease progression in patients with Crohn's disease; in contrast, smoking does not significantly impact outcomes in patients with ulcerative colitis, although some studies suggest that it may be associated with a lower risk of flare. The effect of alcohol and cannabis use in patients with IBD is inconsistent, with some studies suggesting that cannabis may decrease chronic pain in patients with IBD, without a significant effect of biological remission. Although these lifestyle factors are potentially modifiable, only a few interventional studies have been conducted. Trials of structured exercise and psychological therapy including mindfulness-based therapies such as meditation and yoga and gut-directed hypnotherapy have not consistently demonstrated benefit in clinical and/or endoscopic disease activity in IBD, although may improve overall quality of life.


Assuntos
Fumar Cigarros/epidemiologia , Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Exercício Físico , Fadiga/fisiopatologia , Obesidade/epidemiologia , Transtornos do Sono-Vigília/fisiopatologia , Consumo de Bebidas Alcoólicas/epidemiologia , Ansiedade/psicologia , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/psicologia , Colite Ulcerativa/terapia , Doença de Crohn/epidemiologia , Doença de Crohn/psicologia , Doença de Crohn/terapia , Depressão/psicologia , Progressão da Doença , Serviços de Saúde/estatística & dados numéricos , Humanos , Hipnose , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/psicologia , Doenças Inflamatórias Intestinais/terapia , Estilo de Vida , Uso da Maconha/epidemiologia , Meditação , Atenção Plena , Ioga
12.
Nutrients ; 12(2)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32023881

RESUMO

Crohn's disease (CD) and ulcerative colitis (UC) are chronic, relapsing, inflammatory disorders of the digestive tract that characteristically develop in adolescence and early adulthood. The reported prevalence of malnutrition in inflammatory bowel disease (IBD) patients ranges between 20% and 85%. Several factors, including reduced oral food intake, malabsorption, chronic blood and proteins loss, and intestinal bacterial overgrowth, contribute to malnutrition in IBD patients. Poor nutritional status, as well as selective malnutrition or sarcopenia, is associated with poor clinical outcomes, response to therapy and, therefore, quality of life. The nutritional assessment should include a dietetic evaluation with the assessment of daily caloric intake and energy expenditure, radiological assessment, and measurement of functional capacity.


Assuntos
Colite Ulcerativa/fisiopatologia , Doença de Crohn/fisiopatologia , Desnutrição/diagnóstico , Programas de Rastreamento/métodos , Avaliação Nutricional , Adolescente , Adulto , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Inquéritos sobre Dietas , Feminino , Humanos , Masculino , Desnutrição/etiologia , Estado Nutricional , Prevalência , Adulto Jovem
13.
Drug Dev Ind Pharm ; 46(3): 365-375, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32041433

RESUMO

Objectives: The objective of the present work to encapsulate the resveratrol (RES) inside the chitosan-based microsponges, employing the systematic optimization by 33 Box-Behnken design for the colonic targeting.Significance: Enhanced therapeutic efficacy of RES-loaded microsponges and matrix tablets, vis-a-vis pureRES for ulcerative colitis.Methods: RES-loaded microsponges were prepared employing the systematic optimization by 33 Box-Behnken design for the colonic targeting. The best-optimizedRES-loaded microsponge was compressed in the form of a tablet, employing pectin as a matrix-forming material. The encapsulation of RES inside microsponge was confirmed by XRD, DSC and FT-IR. Further, both RES-loaded microsponges and matrix tablets were evaluated for in vitro release kinetics and further evaluated for in vivo ulcerative colitis animal model.Results: Optimization experiments was obtained as the high value of r2 (particle size = 0.9999; %EE = 0.9652; %CDR = 0.9469) inferred excellent goodness of fit. SEM revealed nearly spherical and porous nature of RES-loaded microsponges. The in vitro release kinetic showed zero-order release for RES-loaded microsponges and Korsmeyer-Peppas model for matrix tablets. The pharmacodynamic studies, in ulcerative colitis rat model, indicated better therapeutic efficacy of drug-loaded microsponges and matrix tablets, vis-a-vis pure RES. Thus, the present study advocates the potential of RES based microsponges delivered by pectin based matrix tablet, in the treatment of various colonic disorders.Conclusion: The present study proved that RES-loaded microsponges and matrix tablets based on chitosan and pectin can be the ideal delivery system for colonic delivery of RES.


Assuntos
Antioxidantes/administração & dosagem , Colite Ulcerativa/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Resveratrol/administração & dosagem , Ácido Acético , Animais , Antioxidantes/farmacologia , Química Farmacêutica , Quitosana/química , Colite Ulcerativa/fisiopatologia , Colo/metabolismo , Colo/fisiopatologia , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Tamanho da Partícula , Pectinas/química , Ratos , Ratos Wistar , Resveratrol/farmacologia , Comprimidos
14.
Updates Surg ; 72(3): 827-833, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31953786

RESUMO

Advances in the pharmacological treatment of ulcerative colitis (UC) have enormously decreased the frequency of emergent surgeries. Ileal pouch-anal anastomosis (IPAA) is the procedure of choice in surgical treatment of refractive UC and J-pouch configuration is by far the most preferred pouch design by surgeons. Pouch configuration probably influences the outcomes of the surgery. In this study, we compared the impact of J-pouch size on the functional and quality of life (QoL) outcomes of patients. In this prospective cohort study, we recruited patients who underwent IPAA in two referral centers of our university with two different J-pouch sizes. Demographic data of patients were collected using the patients' medical files. To assess the QoL and bowel function status, SF-36 and Öresland scores were used to evaluate patients 6 and 12 months after the operation. Data analysis was performed with SPSS ver 21. 62 patients were evaluated in the study (31 subjects in each group). The mean age of patients was 40.85 ± 12.98. Thirty-nine patients (60.0%) were males and 23 (35.9%) were females. The mean of SF-36 and Öresland score was 84.30 ± 13.39 and 3.33 ± 2.45, respectively. The mean of SF-36 was significantly higher in patients with shorter J-pouch (P value 0.00). The mean of Öresland score was relatively lower in patients with shorter J-pouch but the difference was not statistically significant (P value 0.06). QoL was correlated with bowel functional outcomes and shorter length of the J-pouch. The only demographic parameter that was correlated with QoL was body mass index.


Assuntos
Colite Ulcerativa/cirurgia , Íleo/cirurgia , Proctocolectomia Restauradora/métodos , Qualidade de Vida , Recuperação de Função Fisiológica , Adulto , Estudos de Coortes , Colite Ulcerativa/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
15.
Biomed Pharmacother ; 124: 109847, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31981944

RESUMO

Ulcerative colitis (UC) is an inflammatory bowel disease accompanied by abdominal pain, diarrhea, and rectal bleeding. The aim of this study was to investigate whether puerarin, one of the main components of the root of Pueraria lobata, exerts anti-inflammatory and anti-oxidative effects against UC. To examine the anti-inflammatory and anti-oxidative effects of puerarin against colitis, we used a mouse model of dextran sulfate sodium (DSS)-induced colitis. Administration of puerarin alleviated colon shortening, pathological damage to the colon, and myeloperoxidase (MPO) activity. Puerarin significantly inhibited inflammation through the down-regulation of nuclear factor-κB (NF-κB) and the secretion of pro-inflammatory mediators. Moreover, puerarin showed anti-oxidative effects through the regulation of the expression of the NF-E2 p45-related factor 2 (Nrf2) pathway and antioxidant enzymes. Puerarin inhibited intestinal epithelial barrier dysfunction by increasing the expression of tight junction proteins. These results suggest that puerarin has anti-inflammatory and anti-oxidative effects in the mouse model of colitis.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Inflamação/tratamento farmacológico , Isoflavonas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Colite Ulcerativa/fisiopatologia , Colo/efeitos dos fármacos , Colo/fisiopatologia , Sulfato de Dextrana , Modelos Animais de Doenças , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Junções Íntimas/metabolismo
16.
Dig Dis Sci ; 65(1): 250-259, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31372911

RESUMO

BACKGROUND: With a lifelong perspective, 12% of ulcerative colitis patients will need a colectomy. Further reconstruction via ileo-rectal anastomosis or pouch can be affected by patients' perspective of their quality of life after surgery. AIM: To assess the function and quality of life after restorative procedures with either ileo-rectal anastomosis or ileal pouch-anal anastomosis in relation to the inflammatory activity on endoscopy and in biopsies. METHOD: A total of 143 UC patients operated with subtotal colectomy and ileo-rectal anastomosis or pouches between 1992 and 2006 at Linköping University Hospital were invited to participate. Those who completed the validated questionnaires (Öresland score, SF-36, Short Health Scale) were offered an endoscopic evaluation including multiple biopsies. Associations between anorectal function and quality of life with type of restorative procedure and severity of endoscopic and histopathologic grading of inflammation were evaluated. RESULTS: Some 77 (53.9%) eligible patients completed questionnaires, of these 68 (88.3%) underwent endoscopic evaluation after a median follow-up of 12.5 (range 3.5-19.4) years after restorative procedure. Patients with ileo-rectal anastomosis reported better overall Öresland score: median = 3 (IQR 2-5) for ileo-rectal anastomosis (n = 38) and 10 (IQR 5-15) for pouch patients (n = 39) (p < 0.001). Anorectal function (Öresland score) and endoscopic findings (Baron-Ginsberg score) were positively correlated in pouch patients (tau: 0.28, p = 0.006). CONCLUSION: Patients operated with ileo-rectal anastomosis reported better continence compared to pouches. Minor differences were noted regarding the quality of life. Ileo-rectal anastomosis is a valid option for properly selected ulcerative colitis patients if strict postoperative endoscopic surveillance is carried out.


Assuntos
Colite Ulcerativa/cirurgia , Bolsas Cólicas/efeitos adversos , Defecação , Incontinência Fecal/etiologia , Proctocolectomia Restauradora/efeitos adversos , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/psicologia , Incontinência Fecal/diagnóstico , Incontinência Fecal/fisiopatologia , Incontinência Fecal/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
17.
J Oncol Pharm Pract ; 26(3): 730-734, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31315551

RESUMO

INTRODUCTION: Immune checkpoint inhibitors have transformed the field of oncology moving immuno-oncology to the forefront of cancer treatment. However, immune checkpoint inhibitors can result in serious immune-related adverse events. Hematologic toxicities are rare with incidence of neutropenia from nivolumab less than 1%. CASE REPORT: We present a case of refractory neutropenia in a 75-year-old woman with ulcerative colitis on adjuvant nivolumab for stage III melanoma. MANAGEMENT AND OUTCOME: The patient's neutropenia did not improve with high-dose intravenous steroids, filgrastim, mycophenolate mofetil, or intravenous immunoglobulin. She also developed significant neurological symptoms from nivolumab. She was transitioned to comfort measures given her persistent symptoms and poor functional status. DISCUSSION: Though hematologic malignancies of immune checkpoint inhibitors are rare, they should be considered after other diagnoses are excluded. We discuss the serious immune-related adverse effects of immune checkpoint inhibitors in a patient with an underlying autoimmune disease and general treatment approaches.


Assuntos
Colite Ulcerativa/fisiopatologia , Imunoterapia/efeitos adversos , Melanoma/tratamento farmacológico , Neutropenia/induzido quimicamente , Idoso , Feminino , Humanos , Imunoterapia/métodos , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos
19.
Curr Vasc Pharmacol ; 18(1): 27-37, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30488796

RESUMO

Inflammatory bowel diseases (IBD), largely represented by Crohn's disease (CD) and ulcerative colitis (UC), alter gastrointestinal physiology and mucosal immunity through a complex inflammatory process. These diseases can lead to significant arterial endothelial dysfunction. There is also evidence linking IBD with a modification of cardiac structure and function. A growing body of research has associated IBD with an acceleration of arterial stiffness and atherosclerosis and an increased risk of cardiovascular (CV) morbidity and mortality. The focus of this review is two-fold. Firstly, the literature on IBD in relation to CV dysfunction was evaluated (mainly based on 25 relevant surveys carried out between 2005 and 2018). The vast majority of these studies support a significant association of IBD with a deterioration in CV function. Secondly, the literature available regarding the effect of IBD treatment on CV dysfunction was considered based on studies published between 2007 and 2018. This literature search suggests that IBD treatment may have the potential to ameliorate CV dysfunction resulting in CV benefits. This review will analyse the literature as well as consider emerging research perspectives regarding how IBD treatment could improve CV dysfunction.


Assuntos
Artérias/fisiopatologia , Doenças Cardiovasculares/etiologia , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Endotélio Vascular/fisiopatologia , Coração/fisiopatologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/terapia , Doença de Crohn/diagnóstico , Doença de Crohn/fisiopatologia , Doença de Crohn/terapia , Humanos , Prognóstico , Medição de Risco , Fatores de Risco
20.
Int J Vitam Nutr Res ; 90(1-2): 17-22, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30982443

RESUMO

Purpose: In inflammatory bowel disease increased asymmetric dimethylarginine (ADMA) levels could inhibit nitric oxide (NO) synthase. Vitamin D may increase activity and expression of endothelial NO synthase, which could be done through its possible mechanism of decreasing ADMA levels. The aim of this study is to investigate the possible effect of Vitamin D3 on serum ADMA levels in ulcerative colitis (UC) patients. Methods: Ninety mild to moderate UC patients were randomized. Each patient received one single muscular injection of 300,000 IU (7500 µg) Vitamin D3 (Vitamin D group) or 1 ml normal saline (Placebo group). At baseline and 90 days after the intervention measurements were done. Data were analyzed using independent t-test and analysis of covariance. Baseline correlations were assessed by Pearson and Spearman correlation coefficients. Results: Following data analysis of 86 participants (40 in placebo and 46 in vitamin D group), there was no correlation between baseline ADMA with baseline vitamin D, ESR and hs-CRP at baseline (p = 0.77) and at the end of study (p = 0.82). Serum ADMA levels were not statistically different between two groups. Adjustment for baseline ADMA levels and baseline body mass index (BMI) did not change the results. With subgroup analyses based on gender and vitamin D level no statistical differences in ADMA levels between two groups were found. Conclusions: In this study, we found no significant changes in serum ADMA levels 3 months following a high dose vitamin D administration in mild to moderate UC patients. Further studies in vitamin D deficient patients are needed.


Assuntos
Colite Ulcerativa , Vitamina D , Vitaminas/farmacologia , Arginina/análogos & derivados , Arginina/química , Arginina/farmacologia , Colite Ulcerativa/fisiopatologia , Humanos , Vitamina D/farmacologia
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