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1.
Korean J Gastroenterol ; 83(5): 197-199, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38783621

RESUMO

5-Aminosalicylic acid (5-ASA) is recommended for managing ulcerative colitis. Common adverse effects associated with 5-ASA include gastrointestinal disorders, headaches, and skin rashes. Perimyocarditis induced by 5-ASA is a rare adverse effect, with only a limited number of cases reported. This paper presents a case of 5-ASA-induced perimyocarditis in a 29-year-old female who had been taking 5-ASA for three weeks. The patient was admitted to the emergency department with dyspnea, chest discomfort, and fever. She subsequently underwent laboratory investigations, including electrocardiography, transthoracic echocardiography, chest computed tomographic angiography, cardiac magnetic resonance imaging, and heart biopsy. Intravenous steroid was administered, and 5-ASA was discontinued. The patient's signs and symptoms improved significantly within a few days of discontinuing 5-ASA, leading to her subsequent discharge. This case highlights the importance of considering perimyocarditis in patients exhibiting cardiac symptoms during 5-ASA therapy, despite it being a rare adverse effect. Drug withdrawal in such cases may lead to rapid clinical improvement.


Assuntos
Anti-Inflamatórios não Esteroides , Colite Ulcerativa , Ecocardiografia , Eletrocardiografia , Mesalamina , Miocardite , Humanos , Feminino , Mesalamina/uso terapêutico , Mesalamina/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/diagnóstico , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/efeitos adversos , Miocardite/diagnóstico , Miocardite/induzido quimicamente , Miocardite/tratamento farmacológico , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Angiografia por Tomografia Computadorizada
2.
J Ethnopharmacol ; 328: 118131, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38565408

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sarcandra glabra is officially named Zhong Jie Feng as a traditional medicine. In the nationality of Yao and Zhuang, it has been used to treat digestive diseases like stomachache and dysentery. Similarly, in Dai nationality, it has been used to treat intestinal diseases like gastric ulcers. However, the effect and mechanism of S. glabra on experimental ulcerative colitis (UC) are known. AIM OF STUDY: The main objective of this study was to investigate the effect and mechanism of S. glabra on experimental UC. MATERIALS AND METHODS: The chemical components in the water extract of S. glabra (ZJF) were analyzed by UPLC-MS/MS method. The HCoEpiC cell line was used to assess the promotive effect on intestinal proliferation and restitution. RAW264.7 cells were used to assess the in vitro anti-inflammatory effect of ZJF. The 3% DSS-induced colitis model was used to evaluate the in vivo effect of ZJF (4.5 g/kg and 9.0 g/kg). Mesalazine (0.5 g/kg) was used as the positive drug. ELISA, RT-qPCR, Western blot, and multiplex immunohistochemical experiments were used to test gene levels in the colon tissue. The H&E staining method was used to monitor the pathological changes of colon tissue. TUNEL assay kit was used to detect apoptosis of epithelial colonic cells. RESULTS: ZJF could alleviate the DSS-caused colitis in colon tissues, showing a comparative effect to that of the positive drug mesalazine. Mechanism study indicated that ZJF could promote normal colonic HCoEpiC cell proliferation and restitution, inhibit overexpression of pro-inflammatory cytokines, restore the M1/M2 ratio, decrease epithelial colonic cell apoptosis, rescue tight junction protein levels, and modulate IL-17/Notch1/FoxP3 pathway to treat experimental UC. CONCLUSION: Our results indicated that S. glabra can promote intestinal cell restitution, balance immune response, and modulate IL-17/Notch1/FoxP3 pathway to treat experimental UC.


Assuntos
Colite Ulcerativa , Colite , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Mesalamina/efeitos adversos , Cromatografia Líquida , Interleucina-17/metabolismo , Espectrometria de Massas em Tandem , Colo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Fatores de Transcrição/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
3.
PLoS One ; 19(2): e0296940, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38306390

RESUMO

Mesalazine is a well-established treatment for ulcerative colitis by oral or topical administration. However, the pharmacokinetic (PK) and safety profiles of mesalazine administered by an enema has not been clarified in Chinese population. We conducted an open-label study to assess the PK and safety profiles of mesalazine in 11 healthy Chinese subjects after receiving mesalazine enema (1 g/100 mL) once daily for 7 consecutive days. Blood and urine samples were collected for assay of mesalazine and N-acetyl mesalazine by liquid chromatography-tandem mass spectrometry. The PK and safety data were summarized using descriptive statistics. The mean (standard deviation) maximum plasma concentration (Cmax), area under plasma drug concentration-time curve from time 0 to the last measurable plasma concentration time point (AUC0-t) and elimination half-life (t1/2) of mesalazine were 1007.64 (369.00) ng/mL, 9608.59 (3533.08) h·ng/mL and 3.33 (1.99) h, respectively after the first dose administration. In multiple-dose study, the estimated accumulation factor of mesalazine was 1.09. The cumulative urinary excretion rate of parent and major metabolite of mesalazine was 27.77%. After the last doe administration, 2.21% of the administered dose was excreted as mesalazine and 24.47% as N-acetyl mesalazine in urine within 24 h. Overall, 9 adverse events (AEs) were reported in 4 of the 11 subjects (36.4%), including oral ulcer, toothache, upper respiratory tract infection (1 each) and laboratory abnormalities (6 cases). All AEs were mild and recovered spontaneously without treatment, and were not considered as related to mesalazine. Mesalazine enema (1 g/100 mL) was safe and well tolerated in healthy Chinese subjects. These findings support further clinical trials in Chinese patients. Trial registration: This trial was registered to Chinese Clinical Trial Registry (ChiCTR) at https://www.chictr.org.cn (registration number: ChiCTR2300073148).


Assuntos
Mesalamina , Espectrometria de Massas em Tandem , Humanos , Administração Oral , Área Sob a Curva , China , Cromatografia Líquida , Relação Dose-Resposta a Droga , Voluntários Saudáveis , Mesalamina/efeitos adversos , Espectrometria de Massas em Tandem/métodos
4.
BMC Gastroenterol ; 24(1): 22, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191328

RESUMO

BACKGROUND/AIMS: The prevalence of ulcerative colitis (UC) has been increasing, also in older adults. Here, we retrospectively compared the efficacy and safety of tacrolimus (TAC) in older and younger patients with UC. METHODS: We included younger (age < 65 years; n = 116) and older patients (age ≥ 65 years; n = 21) with UC who received TAC from April 2009 through December 2022(mean follow-up, 1230 ± 175 days) and achieved remission. Evaluations included age at onset, laboratory values, estimated glomerular filtration rate (eGFR), use of 5-aminosalicylic acid (5-ASA), biological experience, colonoscopy scores, remission at 1 month after treatment initiation, and adverse events. Treatment duration and renal function were assessed in patients with follow-up data (younger patients, n = 110; older patients, n = 19). RESULTS: Older patients had a higher age at onset and treatment initiation but less 5-ASA use and biological experience. Before treatment, hemoglobin, albumin, and eGFR were significantly lower in the older group and CRP was significantly higher. The remission rate was 80.1% in the younger group and 66.6% in the older group (P = 0.1862). Adverse events were similar in both groups. The older group had a shorter treatment duration and significantly less change in renal function at all time points. DISCUSSION: Rates of TAC-induced remission and adverse events were similar in older and younger adults with UC. CONCLUSION: TAC can be used safely in elderly patients with moderate to severe UC with careful monitoring.


Assuntos
Colite Ulcerativa , Idoso , Humanos , Colite Ulcerativa/tratamento farmacológico , Estudos Retrospectivos , Tacrolimo/efeitos adversos , Mesalamina/efeitos adversos , Albuminas
5.
Clin Gastroenterol Hepatol ; 22(2): 243-251.e5, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-36858143

RESUMO

BACKGROUND & AIMS: Some patients with irritable bowel syndrome (IBS) demonstrate low-grade inflammation in the intestine. Mesalamine, which has anti-inflammatory effects, may be an efficacious treatment for IBS, but studies are conflicting. We conducted a systematic review and meta-analysis to assess efficacy and safety of mesalamine in IBS. METHODS: We searched the medical literature up to September 14, 2022, to identify randomized controlled trials (RCTs) of mesalamine in IBS. We judged efficacy and safety using dichotomous assessments of effect on global IBS symptoms, abdominal pain, bowel habit or stool frequency, and occurrence of any adverse event. We pooled data using a random effects model, with efficacy and safety reported as pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: We identified 8 eligible RCTs (820 patients). Mesalamine was more efficacious than placebo for global IBS symptoms (RR of global symptoms not improving, 0.86; 95% CI, 0.79-0.95; number needed to treat = 10; 95% CI, 6-27), but not for abdominal pain or bowel habit or stool frequency. Subgroup analyses demonstrated efficacy of mesalamine in IBS with diarrhea for global IBS symptoms (RR, 0.88; 95% CI, 0.79-0.99), but not patients with other predominant bowel habits or those with post-infection IBS. Adverse event rates were no higher with mesalamine (RR, 1.20; 95% CI, 0.89-1.63) but were reported in only 5 trials. CONCLUSIONS: Mesalamine may be modestly efficacious for global symptoms in IBS, particularly IBS with diarrhea, but quality of evidence was low. Adequately powered high quality RCTs of mesalamine in IBS are needed.


Assuntos
Síndrome do Intestino Irritável , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/tratamento farmacológico , Mesalamina/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Dor Abdominal , Resultado do Tratamento
6.
Intern Med ; 63(8): 1081-1085, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37661446

RESUMO

This report describes the case of a 76-year-old man with ulcerative colitis who developed interstitial nephritis after starting 5-Aminosalicylic acid (5-ASA) therapy. The patient experienced an initial improvement in symptoms, but developed fatigue, anorexia, and severe renal dysfunction 2.5 months later. Renal biopsy confirmed drug-induced interstitial nephritis, and conservative treatment with fluid replacement and the discontinuation of 5-ASA improved the patient's condition. Clinicians should monitor patients receiving 5-ASA therapy for potential adverse effects, particularly renal injury, and promptly investigate symptoms of renal dysfunction. Early recognition and discontinuation of the offending agent may prevent further damage and improve patient outcomes.


Assuntos
Colite Ulcerativa , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Nefrite Intersticial , Insuficiência Renal , Masculino , Humanos , Idoso , Mesalamina/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/patologia , Rim/patologia , Insuficiência Renal/patologia , Anti-Inflamatórios não Esteroides/efeitos adversos
7.
Ther Umsch ; 80(9): 386-392, 2023 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-38095251

RESUMO

INTRODUCTION: Ulcerative colitis is characterized by a chronic intestinal inflammation limited to the mucosa of the colon, of variable proximal extent. Main symptoms are diarrhea, possibly bloody, and abdominal pain. It evolves with phases of relapse and remission. The diagnosis of ulcerative colitis is made based on clinical, endoscopic, and histologic findings. Currently, the various drug treatment options act by, among other things, reducing the activity of the immune system locally or systemically. In mild to moderate forms, 5-ASA remains the mainstay of both induction and maintenance treatment. In more severe flares, cortisone is the treatment of choice. To limit the prolonged/repeated intake of corticosteroids, there are several options of biologics with distinct ranges of action and safety profiles for inducing and/or maintaining remission. Therapeutic goals are evolving and go beyond achieving clinical remission. Endoscopic and histological remission are new targets to further improve quality of life and limit long-term complications, such as colorectal cancer.


Assuntos
Colite Ulcerativa , Humanos , Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/terapia , Inflamação/tratamento farmacológico , Mesalamina/efeitos adversos , Qualidade de Vida
8.
Medicina (Kaunas) ; 59(11)2023 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-38004039

RESUMO

Background and Objectives: Urtica dioica, a source of bioactive functional compounds, provides nutritional and gastrointestinal therapeutic benefits. This study attempted to investigate the prophylactic coloprotective action of an aqueous extract of Urtica dioica (AEUD) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). Materials and Methods: Phenolic compounds, total sugar, and mineral levels were determined in AEUD. Then, AEUD at different doses (50, 100, and 200 mg/kg, BW, p.o.) and mesalazine (MESA) as a standard treatment (100 mg/kg, BW, p.o.) were given orally for 21 days. Acute colitis was induced by administering drinking water with 5% (w/v) DSS for 7 days. Body weight variation, fecal occult blood, and stool consistency were determined daily. The severity of colitis was graded according to colon length, disease activity index (DAI), histological evaluations, and biochemical alterations. Rats orally administered DSS regularly developed clinical and macroscopic signs of colitis. Results: Due to its richness in phenolic and flavonoid compounds (247.65 ± 2.69 mg EAG/g MS and 34.08 ± 0.53 mg EQt/g MS, respectively), AEUD markedly ameliorated DAI, ulcer scores, colon length shortening, colonic histopathological changes, and hematological and biochemical modifications. Taken together, AEUD treatment notably (p < 0.01) suppressed DSS-induced UC by reducing oxidative stress via lowering MDA/H2O2 production and stimulating the effect of enzyme antioxidants as well as attenuating inflammation by decreasing CRP levels by 79.5% between the DSS and DSS + AEUD-50 groups compared to the MESA group (75.6%). Conclusions: AEUD was sufficient to exert a coloprotective effect that might be influenced by its bioactive compounds' anti-inflammatory and antioxidant capabilities.


Assuntos
Colite Ulcerativa , Colite , Urtica dioica , Ratos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/prevenção & controle , Sulfato de Dextrana/efeitos adversos , Peróxido de Hidrogênio/efeitos adversos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Mesalamina/efeitos adversos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Modelos Animais de Doenças
9.
Nihon Shokakibyo Gakkai Zasshi ; 120(9): 764-772, 2023.
Artigo em Japonês | MEDLINE | ID: mdl-37690832

RESUMO

A 73-year-old woman developed ulcerative colitis with mesalazine intolerance a year ago. She relapsed 10 months later. Although she was in clinical remission with salazosulfapyridine (SASP) and prednisolone administration, she developed agranulocytosis 53 days following SASP administration. She went into septic shock;however, she recovered with antibiotics, granulocyte colony-stimulating factor, and cardiotonic agents. Drug-induced lymphocyte stimulation test was positive for both mesalazine and SASP. Drug selection should be carefully determined in patients with 5-aminosalicylic acid intolerance.


Assuntos
Agranulocitose , Colite Ulcerativa , Choque Séptico , Feminino , Humanos , Idoso , Colite Ulcerativa/tratamento farmacológico , Mesalamina/efeitos adversos , Sulfassalazina/efeitos adversos , Agranulocitose/induzido quimicamente
10.
Pediatr Int ; 65(1): e15553, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37551649

RESUMO

BACKGROUND: No previous study of Japanese children with ulcerative colitis (UC) has reported the risk factors for intolerance of 5-aminosalicylic acid (5-ASA). We aimed to identify risk factors for intolerance of oral 5-ASA preparations in pediatric UC. METHODS: Patients with childhood-onset UC who were seen at our hospital between November 2003 and March 2020 were investigated. Intolerance of 5-ASA was defined as having clinical symptoms (pyrexia, abdominal pain, diarrhea, bloody stool) that worsened after starting oral administration of 5-ASA and improved after discontinuation of 5-ASA. Patient sex, age, body size, laboratory data, pediatric UC activity index scores, and colonoscopy-based determinations of the extent and severity of the affected lesion at initiation of 5-ASA of intolerant and tolerant groups were compared. RESULTS: Fifteen patients were in the intolerant group, and 37 were in the tolerant group. The leukocyte count, C-reactive protein level, and erythrocyte sedimentation rate were significantly higher in the intolerant group than the tolerant group; the albumin level in the intolerant group was significantly lower. All intolerant patients and 68% of tolerant patients had pancolitis (Paris classification E4). Patients with a large, affected area (Paris classifications E3 and E4) more frequently had intolerance to 5-ASA than patients with a small lesion. The cumulative Mayo endoscopic subscore (cMES), which is the sum of MES scores for six regions of the large intestine, was significantly higher in the intolerant group. CONCLUSIONS: Pediatric UC patients with more intense inflammation and a large lesion could have an increased risk of intolerance for 5-ASA.


Assuntos
Colite Ulcerativa , Mesalamina , Criança , Humanos , Mesalamina/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Fatores de Risco
11.
Sci Rep ; 13(1): 12241, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37507482

RESUMO

Although many therapeutic options are available for inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA) is still the key medication, particularly for ulcerative colitis (UC). However, the mechanism of action of 5-ASA remains unclear. The intestinal microbiota plays an important role in the pathophysiology of IBD, and we hypothesized that 5-ASA alters the intestinal microbiota, which promotes the anti-inflammatory effect of 5-ASA. Because intestinal inflammation affects the gut microbiota and 5-ASA can change the severity of inflammation, assessing the impact of inflammation and 5-ASA on the gut microbiota is not feasible in a clinical study of patients with UC. Therefore, we undertook a translational study to demonstrate a causal link between 5-ASA administration and alterations of the intestinal microbiota. Furthermore, by rigorously controlling environmental confounders and excluding the effect of 5-ASA itself with a vertical transmission model, we observed that the gut microbiota altered by 5-ASA affected host mucosal immunity and decreased susceptibility to dextran sulfate sodium-induce colitis. Although the potential intergenerational transmission of epigenetic changes needs to be considered in this study, these findings suggested that alterations in the intestinal microbiota induced by 5-ASA directed the host immune system towards an anti-inflammatory state, which underlies the mechanism of 5-ASA efficacy.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Animais , Camundongos , Mesalamina/efeitos adversos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Inflamação/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Colo , Camundongos Endogâmicos C57BL
13.
Pancreatology ; 23(6): 569-573, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37302896

RESUMO

BACKGROUND: Nearly all medications used for inflammatory bowel disease (IBD) have been reported as causes of acute pancreatitis (AP), with the thiopurines being among the most frequently described. However, with the development of newer medications, thiopurine monotherapy has largely been replaced by newer immunosuppressive drugs. There are few data on the association between AP and biologic/small molecule agents. METHODS: VigiBase, the World Health Organization's Global Individual Case Safety Report database, was used to assess the association between AP and common IBD medications. A case/non-case disproportionality analysis was performed and disproportionality signals were reported as a reporting odds ratio (ROR) with 95% confidence intervals (CIs). RESULTS: A total of 4,223 AP episodes were identified for common IBD medications. Azathioprine (ROR 19.18, 95% CI 18.21-20.20), 6-mercaptopurine (ROR 13.30, 95% CI 11.73-15.07), and 5-aminosalicylic acid (ROR 17.44, 95% CI 16.24-18.72) all had strong associations with AP, while the biologic/small molecule agents showed weaker or no disproportionality. The association with AP was much higher for thiopurines when used for Crohn's disease (ROR 34.61, 95% CI 30.95-38.70) compared to ulcerative colitis (ROR 8.94, 95% CI 7.47-10.71) or rheumatologic conditions (ROR 18.87, 95% CI 14.72-24.19). CONCLUSIONS: We report the largest real-world database study investigating the association between common IBD medications and AP. Among commonly used IBD medications including biologic/small molecule agents, only thiopurines and 5-aminosalicylic acid are strongly associated with AP. The association between thiopurines and AP is much stronger when the drug is used for Crohn's disease compared to ulcerative colitis and rheumatologic conditions.


Assuntos
Artrite Reumatoide , Produtos Biológicos , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Pancreatite , Humanos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Mesalamina/efeitos adversos , Farmacovigilância , Doença Aguda , Pancreatite/induzido quimicamente , Pancreatite/epidemiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Produtos Biológicos/efeitos adversos
14.
Appl Microbiol Biotechnol ; 107(7-8): 2597-2609, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36869880

RESUMO

Compound prebiotics (CP) have been explored in modulation of intestinal microbiota and remission of inflammatory responses in the acute colitis (AC). Yet, research on the roles of simultaneous prophylactic and therapeutic CP intervention in relation to AC remains lacking. Here, CP were pre-fed to examine preventive effects. CP, CP combined with mesalazine (5-aminosalicylic acid) (CPM), and mesalazine were used to evaluate therapeutic effects on the dextran sulfate sodium (DSS)-induced AC. Results showed that prophylactic CP and therapeutic CPM alleviated AC, evidenced by variations of body weight, colon length, spleen index, disease activity index score, histological score, and intestinal mucosa. Ruminococcus and Bifidobacterium were detected in significant abundance in the prophylactic CP and therapeutic CPM groups, respectively. Phylogenetic ecological network analysis revealed that therapeutic CPM probably had the strongest coupling between microbes in changing intestinal microbiota to influence treatment. However, changes in short-chain fatty acids (SCFAs) seemed to have no persuasive results, probably due to reduced SCFA level in feces and variability in transit, absorption, and utilization. Furthermore, therapeutic CP exerted higher value in terms of observed species and Shannon diversity, as well as a more concentrated distribution by principal coordinates analysis. Together, the favorable roles of CP in colitis provide directions for prebiotics in designing effective prophylactic functional diets and treatment strategies. KEY POINTS: • Prebiotics as prophylactic intervention effectively inhibited acute colitis. • Prebiotics as prophylactic and therapeutic interventions had distinct effects on gut microbiota. • Prebiotics combined with drug intervention had higher efficacy in treating acute colitis.


Assuntos
Colite , Prebióticos , Camundongos , Animais , Mesalamina/efeitos adversos , Filogenia , Colite/tratamento farmacológico , Colite/prevenção & controle , Colite/induzido quimicamente , Colo/microbiologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
15.
J Proteome Res ; 22(4): 1287-1297, 2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-36921116

RESUMO

Ulcerative colitis (UC) is a systematic chronic disease characterized by insufficient intestinal absorption, and mesalazine is a common medical treatment. In the present study, 20 normal healthy controls (NC group), 10 unmedicated UC patients (UC group), and 20 mesalazine-responsive and 20 mesalazine-nonresponsive UC patients were recruited. A total of 42 serum BA metabolites, including 8 primary bile acids and 34 secondary bile acids (SBAs), were quantitatively measured. Compared with the NC group, serum SBAs in the UC patients were significantly lower but increased after mesalazine therapy. Differences in the serum TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S metabolites were found between the UC and NC groups, with AUC values of 0.777, 0.800, 0.815, 0.775, and 0.740, respectively. Furthermore, we identified 12-keto LCA as a specific BA marker of UC and BA biomarkers of mesalazine responsiveness. It was concluded that serum SBAs were decreased in UC patients, and TDCA, DCA, GDCA-3S, 12-keto LCA, and GCDCA-3S might aid in the diagnosis of UC. The abundance of SBAs increased after the mesalazine therapy, and serum 12-keto LCA was identified as an alternative invasive biomarker associated with UC diagnosis and therapeutic response, thereby providing a new approach for the prediction of response to mesalazine therapy in UC patients.


Assuntos
Colite Ulcerativa , Mesalamina , Humanos , Mesalamina/uso terapêutico , Mesalamina/efeitos adversos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Ácidos e Sais Biliares , Biomarcadores , Anti-Inflamatórios não Esteroides/uso terapêutico
16.
Clin Med (Lond) ; 23(2): 173-174, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36958845

RESUMO

A 45-year-old woman presented to the hospital with bloody diarrhoea and significant weight loss over the past 1 month. On admission and evaluation, she was found to have acute ulcerative colitis. She was started on prednisolone and mesalamine therapy. Within 24 hours of initiation of this therapy, the patient complained of giddiness and chest discomfort and was found to have sinus bradycardia on ECG with no acute coronary event. After withdrawing mesalamine, her heart rate normalised within 24 hours and she remained symptom-free. This is a rare case report of severe symptomatic sinus bradycardia due to mesalamine therapy; to our knowledge, only four cases of mesalamine-induced bradycardia have been reported in the literature.


Assuntos
Colite Ulcerativa , Mesalamina , Feminino , Humanos , Pessoa de Meia-Idade , Mesalamina/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Bradicardia/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Prednisolona/uso terapêutico
17.
J Pediatr Gastroenterol Nutr ; 76(3): 331-337, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36729656

RESUMO

BACKGROUND AND OBJECTIVES: Renal and/or urinary manifestations (RUM) have been reported in pediatric patients with inflammatory bowel disease (IBD) but their incidence is unknown. The aims of this study were to assess the prevalence and causes of these manifestations in children with IBD and determine the causal link with 5-aminosalicylic acid (5-ASA) treatment. METHODS: A retrospective observational study was performed with children with diagnosis of IBD. All children with RUM during follow-up and/or impaired renal function [estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m 2 ] were identified. RESULTS: Of 228 included patients, 9 (3.9%) had a RUM during follow-up [follow-up: 5 years (1-12 years)] at a median age of 16 years (8-17 years). It concerned 7 of 171 patients with Crohn disease and 2 of 57 with ulcerative colitis. Seven patients were taking 5-ASA at the time of the RUM. Only 1 of them had an iatrogenic renal complication related to this treatment. Patients with RUM had a more severe disease with increased anti-tumor necrosis factor-α use ( P = 0.031), more abscesses ( P = 0.003), and a higher rate of digestive surgery ( P = 0.04). For the whole cohort, a significant decrease in eGFR was found during follow-up (121 vs 107 mL/min/1.73 m 2 , P < 0.001). At the end of follow-up, 38 of 202 (19%) patients had an eGFR < 90 mL/min/1.73 m 2 . CONCLUSION: In children with IBD, RUM can occur, independently of treatment with 5-ASA. During follow-up, a significant decrease in eGFR was observed. We suggest monitoring renal function in all patients with IBD.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Criança , Adolescente , Prevalência , Doenças Inflamatórias Intestinais/epidemiologia , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Mesalamina/efeitos adversos , Rim/fisiologia , Rim/patologia , Estudos Retrospectivos
18.
Int Immunopharmacol ; 115: 109621, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36574744

RESUMO

Ulcerative colitis (UC) is a global inflammatory bowel disease. This study aimed to assess the effects of icosapent ethyl on acetic acid-induced colitis in rats as well as the underlying mechanisms involved. 36 male Wister rats were equally divided into six groups: control, UC, mesalamine 100 mg/kg, icosapent 150mg/kg, icosapent 300 mg/kg, and EX527-icosapent 300 mg/kg groups. Except for control group, UC was induced by acetic acid instillation into colon. Drugs were administered once daily for one week then under thiopental anaesthesia, colons were excised. Colitis macroscopic and microscopic scores were assessed. A part of colon was homogenized for detection of malondialdehyde (MDA), inerleukin1 (IL-1ß), tumor necrosis factor (TNF-α), superoxide dismutase (SOD), phosphorylated Akt (pAkt) and caspase 3 levels. Silent information regulator 1 (SIRT1), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2 (Nrf2) mRNA expressions were detected. Mallory-stained colonic sections were examined for collagen fibres detection. Immunohistochemistry of NF-κB and p53 expressionsin colonic sections were assessed. Acetic acid induced colitis with increments in MDA, IL-1ß, TNF-α, and caspase 3 levels while decreased SOD, pAkt, SIRT1, HO-1, and Nrf2 with increased collagen fibres as well as NF-κB and p53. Icosapent decreased macro& microscopic colitis scores, MDA, IL-1ß, TNF-α, and caspase 3 levels while increased SOD, pAkt, SIRT1, HO-1, and Nrf2 with decreased collagen fibres as well as NF-κB and p53. The effects of icosapent 300 mg/kg were similar to mesalamine. Icosapent effects were antagonized by EX527. Icosapent alleviated acetic acid-induced colitis via its anti-inflammatory, antioxidant, and anti-apoptotic effects mediated in part by SIRT1 pathway activation.


Assuntos
Colite Ulcerativa , Colite , Ratos , Masculino , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Ácido Eicosapentaenoico/efeitos adversos , Ácido Eicosapentaenoico/metabolismo , Sirtuína 1/metabolismo , Caspase 3/metabolismo , NF-kappa B/metabolismo , Mesalamina/efeitos adversos , Mesalamina/metabolismo , Ácido Acético/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ratos Wistar , Colite/induzido quimicamente , Transdução de Sinais , Colo/patologia , Superóxido Dismutase/metabolismo , Colágeno/metabolismo
19.
J Pediatr Gastroenterol Nutr ; 76(4): 460-467, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36576855

RESUMO

BACKGROUND: Sulfasalazine (SZ) is commonly used to treat pediatric ulcerative colitis (UC). SZ can be compounded into a suspension form which is beneficial for children with difficulty swallowing a pill. Despite being utilized for over 40 years, there is a lack of published data on the efficacy and safety of SZ suspension in children with UC. Recently, third-party payors have begun refusing to pay for SZ suspension due to lack of data. METHODS: In this retrospective study, we reviewed the electronic medical records of patients ages <18 years diagnosed with UC from June 1999 to December 2019 at Boston Children's Hospital and treated with SZ suspension as a first-line agent. We obtained demographics, clinical, and endoscopic data to measure outcomes at 1 year and long term. RESULTS: Of 57 patients treated with SZ suspension, 52 (91%) had a follow-up and 26 of 52 (50%) remained in steroid-free remission at 1 year. Two patients were switched to SZ tablets due to nonmedical reasons and 11 (21%) required rescue treatment (2 infliximab, 1 tacrolimus, 8 6-mercaptopurine/azathioprine) within a year. Three required colectomy within a year and 5 in long term. Four (8%) developed nonserious adverse reactions and switched to 5-aminosalicylates (5-ASA) by 1 year. The median duration of long-term follow-up was 36 months (range, 2-205 months) with 28 requiring treatment escalation in long term. CONCLUSIONS: SZ suspension is a safe and effective treatment for UC in children with difficulty swallowing a pill. The 1-year remission rate on this treatment is comparable to 5-ASA utilized in children.


Assuntos
Colite Ulcerativa , Adolescente , Criança , Humanos , Azatioprina/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Imunossupressores/uso terapêutico , Infliximab/uso terapêutico , Mesalamina/efeitos adversos , Estudos Retrospectivos , Sulfassalazina/efeitos adversos , Resultado do Tratamento
20.
Intern Med ; 62(6): 929-933, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35945022

RESUMO

In drug-induced lupus (DIL), symptoms similar to those of systemic lupus erythematosus (SLE) usually resolve after discontinuation of the offending drug. A 41-year-old-woman with a history of ulcerative colitis presented with polyarthritis and myositis and was positive for anti-double stranded (ds) DNA IgG antibody. After discontinuation of mesalazine, the symptoms resolved, and the antibody titer decreased. The patient was diagnosed with DIL. Six months later, lupus myocarditis developed. After treatment with glucocorticoids, cyclophosphamide, intravenous immunoglobulin, and an intra-aortic balloon pump, she showed dramatic improvement. Patients with DIL and an immunological predisposition, such as anti-dsDNA antibodies, may have SLE and should be carefully monitored.


Assuntos
Lúpus Eritematoso Sistêmico , Miocardite , Feminino , Humanos , Adulto , Mesalamina/efeitos adversos , Miocardite/induzido quimicamente , Miocardite/diagnóstico , Miocardite/tratamento farmacológico , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Ciclofosfamida/uso terapêutico , Anticorpos Antinucleares/uso terapêutico
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