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1.
Dtsch Med Wochenschr ; 149(7): 369-373, 2024 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-38479421

RESUMO

Acute abdominal pain may relate to specific organ systems and needs an interdisciplinary approach with close collaboration between internal and surgical disciplines. Main objective is to shorten the diagnostic work-up between the beginning of the symptoms and their therapy. After clarifying of the five w-questions: when, how, how long, why, and where, abdominal ultrasound, ECG, laboratory diagnostics and early application of computed tomography should be performed.For the most part, chronic abdominal pain is caused by disorders of the gut-brain-axis such as the irritable bowel syndrome. Because of the synaptic plasticity, the processing of pain is dynamic and cannot be related to a single organ system. This problem is obvious in patients with irritable bowel syndrome and colonic diverticula, which may be interpreted as symptomatic uncomplicated diverticular disease (SUDD, type 3a). However, a reliable clinical differentiation between both groups is not possible. The establishment of SUDD (type 3a) considerable widened the application area of mesalazine.


Assuntos
Doenças Diverticulares , Diverticulose Cólica , Síndrome do Intestino Irritável , Humanos , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/terapia , Doenças Diverticulares/diagnóstico , Doenças Diverticulares/terapia , Doenças Diverticulares/complicações , Diverticulose Cólica/complicações , Diverticulose Cólica/diagnóstico , Diverticulose Cólica/terapia , Mesalamina/uso terapêutico , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia
2.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474043

RESUMO

Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medically resistant patients. Although oral steroids are effective, they are associated with significant morbidity, and disease recurrence is common when discontinued. The development of additional steroid sparing therapies is therefore needed. Mesalazine is a commonly used therapeutic in inflammatory bowel disease, which shares a similar disease profile with chronic rhinosinusitis. This exploratory in vitro study aims to investigate whether mesalazine could be repurposed to a nasal wash, which is safe on human nasoepithelial cells, and retains its anti-inflammatory effects. CRS patients' human nasal epithelial cells (HNECs) were collected. HNECs were grown at an air-liquid interface (ALIs) and in a monolayer and challenged with mesalazine or a non-medicated control. Transepithelial electrical resistance, paracellular permeability, and toxicity were measured to assess epithelial integrity and safety. The anti-inflammatory effects of mesalazine on the release of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) were analysed using human leukemia monocytic cell line (THP-1). mesalazine did not impact the barrier function of HNEC-ALIs and was not toxic when applied to HNECs or THP-1 cells at concentrations up to 20 mM. mesalazine at 0.5 and 1 mM concentrations significantly inhibited TNF-α release by THP-1 cells. mesalazine effectively decreases TNF-α secretion from THP-1 cells, indicating the possibility of its anti-inflammatory properties. The safety profile of mesalazine at doses up to 20 mM suggests that it is safe when applied topically on HNECs.


Assuntos
Mesalamina , Sinusite , Humanos , Mesalamina/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Células Cultivadas , Sinusite/metabolismo , Mucosa Nasal/metabolismo , Interleucina-6/metabolismo , Anti-Inflamatórios/farmacologia , Doença Crônica , Células Epiteliais/metabolismo
3.
Funct Integr Genomics ; 24(2): 55, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38467948

RESUMO

Huang Qin decoction (HQD) is a traditional Chinese medicine formula for treating colitis, but the effects and molecular mechanism of action of HQD in colitis-associated carcinogenesis (CAC) are still unclear. Therefore, we aimed to determine the beneficial effects of HQD on CAC in mice and to reveal the underlying mechanism involved. AOM/DSS was used to induce CAC in mice, and the effects of HQD on tumorigenesis in mice were examined (with mesalazine serving as a positive control). Mesalazine or HQD treatment alleviated body weight loss and decreased the disease activity index in mice induced by AOM/DSS. Mesalazine or HQD treatment also suppressed the shortening of colon tissue length, the number of tumors, and the infiltration of inflammatory cells. The genes targeted by HQD were predicted and verified, followed by knockout experiments. Elevated SLC6A4 and inhibited serotonin production and inflammation were observed in HQD-treated mice. HQD inhibited the NFκB and NLRP3/caspase1/GSDMD pathways. The therapeutic effect of HQD was diminished in SLC6A4-deficient AOM/DSS mice. Additionally, the downregulation of SLC6A4 mitigated the inhibitory effect of HQD-containing serum on MODE-K cell pyroptosis. Our findings suggest that SLC6A4 is a pivotal regulator of HQD-alleviated CAC via its modulation of the NLRP3/caspase1/GSDMD pathway.


Assuntos
Colite , Scutellaria baicalensis , Camundongos , Animais , Mesalamina , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Colite/induzido quimicamente , Colite/complicações , Colite/tratamento farmacológico , Carcinogênese/metabolismo , Camundongos Endogâmicos C57BL
4.
AAPS PharmSciTech ; 25(3): 61, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485901

RESUMO

Mesalamine is a first-line drug for the treatment of inflammatory bowel diseases. However, its premature release associated with marketed formulations leads to adverse effects like gastric trouble, vomiting, and diarrhoea. To minimize these side effects, colon-targeted drug delivery is essential. Besides conventional pharmacotherapy, bifidogenic probiotics with anti-inflammatory activity has been reported to elicit a significant impact on the remission of ulcerative colitis. Bifidogenic probiotics being acid-labile necessitate developing a gastro-resistant formulation for enhancing the delivery of viable cells to the colon. The present study was aimed at developing a fixed-dose unit dosage form of mucoadhesive hydrogel beads loaded with mesalamine and Bifidobacterium bifidum further encapsulated in Eudragit® capsules for the targeted drug delivery at colonic pH. The hydrogel beads were prepared by ionotropic gelation, with the effect of single and dual-crosslinking approaches on various formulation characteristics studied. Standard size 00 Eudragit® gastro-resistant capsules were prepared and the dried beads were filled inside the capsule shells. The formulation was then evaluated for various parameters, including physicochemical characterization, in vitro biocompatibility and anti-inflammatory activity. No interaction was observed between the drug and the polymers, as confirmed through FTIR, XRD, and DSC analysis. The mean particle size of the beads was ~ 457-485 µm. The optimized formulation showed a drug entrapment efficiency of 95.4 ± 2.58%. The Eudragit® capsule shells disintegrated in approximately 13 min at pH 7.4. The mucoadhesive hydrogel beads sustained the drug release above 18 h, with 50% of the drug released by the end of 12 h. The optimized formulation demonstrated significant (p < 0.05) gastro-resistance, biocompatibility, sustained drug release, cell viability, and anti-inflammatory activity.


Assuntos
Bifidobacterium bifidum , Mesalamina , Ácidos Polimetacrílicos , Hidrogéis/farmacologia , Colo , Anti-Inflamatórios/farmacologia
5.
Pharmazie ; 79(1): 2-5, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38509631

RESUMO

Nanoparticles are used in a variety of fields; for example, titanium oxide nanoparticles are used in paints, food additives, cosmetics, and sunscreen materials. Although the use of titanium oxide nanoparticles is regulated, their safety has not been established. Furthermore, the interaction between titanium oxide nanoparticles and various chemical substances and pharmaceuticals is unknown. We co-administered rutile-type titanium oxide nanoparticles (nTR) or anatase-type titanium oxide nanoparticles (nTA) to mice together with paraquat (PQ), cisplatin (CDDP), or anti-5-aminosalicylic acid (5-ASA), and investigated the extent, if any, of liver and kidney injury. As a result, when nTA and nTR were administered alone, no increases were observed in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which are indicators of liver damage, or urea nitrogen (BUN), which is an indicator of kidney damage. Next, nTA and nTR were co-administered with PQ, CDDP or 5-ASA. Although no increase in ALT or AST was observed, BUN levels increased significantly and acute kidney injury was induced. The findings suggested that titanium oxide nanoparticles induce acute kidney injury through their interaction with chemicals and drugs.


Assuntos
Injúria Renal Aguda , Nanopartículas , Titânio , Camundongos , Animais , Cisplatino/toxicidade , Paraquat , Mesalamina , Nanopartículas/química , Injúria Renal Aguda/induzido quimicamente
6.
Nat Commun ; 15(1): 1024, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310093

RESUMO

Osteoarthritis (OA) is a progressive and irreversible degenerative joint disease that is characterized by cartilage destruction, osteophyte formation, subchondral bone remodeling, and synovitis. Despite affecting millions of patients, effective and safe disease-modifying osteoarthritis drugs are lacking. Here we reveal an unexpected role for the small molecule 5-aminosalicylic acid (5-ASA), which is used as an anti-inflammatory drug in ulcerative colitis. We show that 5-ASA competes with extracellular-matrix collagen-II to bind to osteoclast-associated receptor (OSCAR) on chondrocytes. Intra-articular 5-ASA injections ameliorate OA generated by surgery-induced medial-meniscus destabilization in male mice. Significantly, this effect is also observed when 5-ASA was administered well after OA onset. Moreover, mice with DMM-induced OA that are treated with 5-ASA at weeks 8-11 and sacrificed at week 12 have thicker cartilage than untreated mice that were sacrificed at week 8. Mechanistically, 5-ASA reverses OSCAR-mediated transcriptional repression of PPARγ in articular chondrocytes, thereby suppressing COX-2-related inflammation. It also improves chondrogenesis, strongly downregulates ECM catabolism, and promotes ECM anabolism. Our results suggest that 5-ASA could serve as a DMOAD.


Assuntos
Cartilagem Articular , Osteoartrite , Humanos , Masculino , Animais , Camundongos , Mesalamina/farmacologia , Mesalamina/uso terapêutico , PPAR gama/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Modelos Animais de Doenças
7.
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
8.
Eur J Med Res ; 29(1): 102, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321559

RESUMO

OBJECTIVE: To explore the mechanism of huankuile (HKL) in colon injury repair in rats with ulcerative colitis (UC). METHODS: Fifty SPF Wistar male rats were divided randomly into a normal group, a negative control group, an HKL intervention group ('HKL group') and a 5-aminosalicylic acid intervention group ('5-ASA group'). After 14 days of intervention with corresponding drugs, pathological scores were obtained using the results of immunohistochemical staining; morphological changes were observed by hematoxylin-eosin staining, and the mRNA expression levels of tumour necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP9) and interleukin-13 (IL-13) were detected by real-time quantitative PCR. RESULTS: After the successful construction of the rat model, it was compared with the rats in the normal group. In the negative group, it was found that the expression of TNF-α and MMP9 was significantly increased in the colonic mucosal epithelia of the rats, the pathological score was significantly increased (P < 0.05), and the mRNA expression levels of TNF-α, MMP9 and IL-13 were increased (P < 0.05). After treatment with HKL, the colonic morphology of the rats returned to normal, the expression of TNF-α and MMP9 in the colonic mucosal epithelium of the rats returned to normal, the pathological score grade was significantly reduced (P < 0.05), and the mRNA expression levels of TNF-α, MMP9 and IL-13 were reduced; these results were largely consistent with those of the normal group, with no statistically significant difference. CONCLUSION: HKL effectively improved the general symptoms and tissue injury in UC rats, and the therapeutic effect was better than that of 5-ASA group. Ulcerative colitis in rats increased the expression of TNF-α, MMP9 and IL-13. HKL repaired UC-induced colonic injury in rats by decreasing the expression of TNF-α, MMP9 and IL-13.


Assuntos
Colite Ulcerativa , Traumatismos Torácicos , Animais , Masculino , Ratos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Colite Ulcerativa/metabolismo , Colo/metabolismo , Interleucina-13/metabolismo , Interleucina-13/uso terapêutico , Metaloproteinase 9 da Matriz/metabolismo , Mesalamina/metabolismo , Mesalamina/uso terapêutico , Ratos Wistar , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética
9.
Medicine (Baltimore) ; 103(6): e37195, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335414

RESUMO

RATIONALE: Amebic colitis has been less prevalent in recent times in China, and the similarity of its symptoms to those of inflammatory bowel disease (IBD) results in the difficulty of early identification and diagnosis. PATIENT CONCERNS: A 31-year-old male who exhibited intermittent diarrhea and hematochezia was highly suspected as IBD initially. Despite the partial relief of symptoms following the administration of mesalamine, the endoscopic ulcers remained largely unchanged. DIAGNOSES: Two years after the onset of mesalamine therapy, amebic cysts were detected in stool microscopy and trophozoites were found on the surface of cecal ulcers. The patient was then diagnosed with amebic colitis. INTERVENTIONS: After 2 rounds of standardized metronidazole treatment, amebic colitis remained refractory until diloxanide was administered. OUTCOMES: The patient remained asymptomatic, and the mucosa of colon was normal during the annual follow-up. LESSONS: Individuals newly diagnosed with IBD should undergo essential screening for amebiasis. And the use of steroids should be taken with caution, especially in cases where the effect of mesalamine is limited. For symptomatic intestinal amebiasis, even after the administration of tissue amebicides, the continued use of luminal amebicides is necessary to prevent recurrence.


Assuntos
Amebicidas , Disenteria Amebiana , Doenças Inflamatórias Intestinais , Masculino , Humanos , Adulto , Disenteria Amebiana/diagnóstico , Disenteria Amebiana/tratamento farmacológico , Amebicidas/uso terapêutico , Mesalamina/uso terapêutico , Úlcera/tratamento farmacológico , Diagnóstico Diferencial , Doenças Inflamatórias Intestinais/diagnóstico
10.
Free Radic Biol Med ; 214: 219-235, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367927

RESUMO

Ulcerative colitis (UC) is a chronic gastrointestinal disease that can be managed with 5-aminosalicylic acid (5-ASA), the standard treatment for UC. However, the effectiveness of 5-ASA is not always optimal. Our study revealed that despite 5-ASA treatment, cells continued to experience excessive ferroptosis, which may hinder mucosal healing in UC and limit the success of this treatment approach in achieving disease remission. We found that combining 5-ASA with the ferroptosis inhibitor Fer-1 led to a significant inhibition of ferroptosis in macrophages present in the colon tissue, along with an increase in the proportion of M2 macrophages, suggesting that targeting ferroptosis in M2 macrophages could be a potential therapeutic strategy for alleviating UC. Our study also demonstrated that M2 macrophages are more susceptible to ferroptosis compared to M1 macrophages, and this susceptibility is associated with the activated arachidonic acid (AA) metabolism pathway mediated by ERK-cPLA2-ACSL4. Additionally, we found that the expression of cPLA2 gene pla2g4a was increased in the colon of UC patients compared to healthy controls. Furthermore, targeted metabolomics analysis revealed that the combination treatment group, as opposed to the 5-ASA treatment group, exhibited the ability to modulate AA metabolism. Overall, our findings emphasize the importance of addressing macrophage ferroptosis in order to enhance macrophage anti-inflammation, improve mucosal healing, and achieve better therapeutic outcomes for patients with UC.


Assuntos
Colite Ulcerativa , Ferroptose , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Ferroptose/genética , Metabolismo dos Lipídeos , Macrófagos , Mesalamina
11.
Drug Metab Rev ; 56(1): 80-96, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38230664

RESUMO

Two aminosalicylate isomers have been found to possess useful pharmacological behavior: p-aminosalicylate (PAS, 4AS) is an anti-tubercular agent that targets M. tuberculosis, and 5-aminosalicylate (5AS, mesalamine, mesalazine) is used in the treatment of ulcerative colitis (UC) and other inflammatory bowel diseases (IBD). PAS, a structural analog of pABA, is biosynthetically incorporated by bacterial dihydropteroate synthase (DHPS), ultimately yielding a dihydrofolate (DHF) analog containing an additional hydroxyl group in the pABA ring: 2'-hydroxy-7,8-dihydrofolate. It has been reported to perturb folate metabolism in M. tuberculosis, and to selectively target M. tuberculosis dihydrofolate reductase (mtDHFR). Studies of PAS metabolism are reviewed, and possible mechanisms for its mtDHFR inhibition are considered. Although 5AS is a more distant structural relative of pABA, multiple lines of evidence suggest a related role as a pABA antagonist that inhibits bacterial folate biosynthesis. Structural data support the likelihood that 5AS is recognized by the DHPS pABA binding site, and its effects probably range from blocking pABA binding to formation of a dead-end dihydropterin-5AS adduct. These studies suggest that mesalamine acts as a gut bacteria-directed antifolate, that selectively targets faster growing, more folate-dependent species.


Assuntos
Ácido Aminossalicílico , Mycobacterium tuberculosis , Tuberculose , Humanos , Mesalamina/farmacologia , Ácido 4-Aminobenzoico/farmacologia , Ácido Aminossalicílico/farmacologia , Ácido Fólico/metabolismo , Ácido Fólico/farmacologia
12.
Yakugaku Zasshi ; 144(2): 239-242, 2024.
Artigo em Japonês | MEDLINE | ID: mdl-38296500

RESUMO

We experienced a case in which long-term use of nivolumab in a patient with a history of ulcerative colitis led to disease control of gastric cancer. The case is a 77-year-old man. The patient had a history of ulcerative colitis and remained in remission on mesalazine 1500 mg/d. With continuous monitoring, nivolumab could be continued up to 16 courses, but was withdrawn due to the appearance of diarrhea (grade 1) and bloody stools, which was relieved with prednisolone (PSL) 40 mg/d. After two more courses, diarrhea (grade 3) appeared again, which improved with PSL 60 mg/d and increased dose of mesalazine. It is difficult to distinguish whether colitis that occurs after nivolumab administration is due to relapse exacerbation or irAE. The onset of irAE colitis is often reported within 3 months, and the fact that this patient developed irAE colitis after 8 months, despite having ulcerative colitis, is considered novel. In the future, we hope to accumulate cases so that immune checkpoint inhibitors can be used safely in patients with ulcerative colitis, and to establish appropriate methods for their use.


Assuntos
Colite Ulcerativa , Colite , Neoplasias Gástricas , Masculino , Humanos , Idoso , Nivolumabe/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Mesalamina , Prednisolona , Diarreia
13.
Int J Pharm ; 652: 123838, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38266937

RESUMO

Ulcerative colitis (UC) is an idiopathic disease characterized by colonic mucosal tissue destruction secondary to an excessive immune response. We synthesized pH-sensitive cross-linked chitosan/Eudragit® S100 nanoparticles (EU S100/CS NPs) as carriers for 5-aminosalicylic acid (5-ASA) and hesperidin (HSP), then conducted in-vitro and in-vivo studies and evaluated the therapeutic effects. In-vitro analysis revealed that the 5-ASA-loaded EU S100/CS NPs and the HSP-loaded EU S100/CS NPs had smooth and curved surfaces and ranged in size between 250 and 300 nm, with a zeta potential of 32 to 34 mV. FTIR analysis demonstrated that the drugs were loaded on the nanoparticles without significant alterations. The loading capacity and encapsulation efficiency of loading 5-ASA onto EU S100/CS NPs were 25.13 % and 60.81 %, respectively. Regarding HSP, these values were 38.34 % and 77.84 %, respectively. Drug release did not occur in simulated gastric fluid (SGF), while a slow-release pattern was recorded for both drugs in simulated intestinal fluid (SIF). In-vivo macroscopic and histopathological examinations revealed that both NPs containing drugs significantly relieved the symptoms of acetic acid (AA)-induced UC in Wistar rats. We conclude that the synthesized pH-sensitive 5-ASA/EU S100/CS NPs and HSP/EU S100/CS NPs offer promise in treating UC.


Assuntos
Quitosana , Colite Ulcerativa , Hesperidina , Nanopartículas , Ácidos Polimetacrílicos , Ratos , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Portadores de Fármacos/uso terapêutico , Quitosana/uso terapêutico , Mesalamina , Ratos Wistar , Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio
14.
Dis Mon ; 70(1S): 101674, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38185603

RESUMO

Behçet's disease (BD) is a rare, inflammatory vascular disorder with recurrent oral and genital aphthous ulcers, along with ocular and cutaneous manifestations. Gastrointestinal (GI) BD may involve any portion of the GI tract. However, it is commonly described in the terminal ileum, followed by the ileocecal region. Diagnosis is challenging given lack of pathognomonic tests; therefore, it is based on clinical criteria. Management of intestinal BD includes different classes of medications including corticosteroids, 5-aminosalicylic acid, immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody agents. In this review, we aim to focus on intestinal BD and provide details of clinical manifestations, diagnosis and therapeutic options of intestinal BD from gastroenterology viewpoint.


Assuntos
Síndrome de Behçet , Gastroenteropatias , Humanos , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Gastroenteropatias/terapia , Anticorpos Monoclonais/uso terapêutico , Mesalamina/uso terapêutico
15.
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
16.
Immun Inflamm Dis ; 12(1): e1147, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38270298

RESUMO

BACKGROUND: Nexrutine is an herbal extract derived from Phellodendron amurense, known for its anti-inflammatory, antidiarrheal, and hemostatic properties. However, its effect on ulcerative colitis (UC) remains unclear. METHODS: A mouse model of UC was induced by 3% dextran sulfate sodium, while human colonic epithelial cells NCM-460 were exposed to lipopolysaccharide. Both models were treated with Nexrutine at 300 or 600 mg/kg, with Mesalazine applied as a positive control regimen. The disease activity index (DAI) of mice was calculated, and the pathological injury scores were assessed through hematoxylin and eosin staining. The viability of NCM-460 cells was determined using the CCK-8 method. Inflammatory cytokines were detected using ELISA kits. Expression of mucin 3 (MUC3), Claudin-1, and tight junction protein (ZO-1) was detected to analyze mucosal barrier integrity. Target genes of Nexrutine were predicted using bioinformatics tools. Expression of RELA proto-oncogene (RELA) was analyzed using qPCR and western blot assays. RESULTS: The Nexrutine treatments significantly alleviated DAI of mice, mitigated pathological changes in their colon tissues, decreased the production of pro-inflammatory cytokines, enhanced the barrier integrity-related proteins, and increased NCM-460 cell viability in vitro. RELA, identified as a target gene of Nexrutine, showed elevated levels in UC models but was substantially suppressed by Nexrutine treatment. Adenovirus-mediated RELA upregulation in mice or the overexpression plasmid of RELA in cells counteracted the effects of Nexrutine treatments, exacerbating UC-related symptoms. CONCLUSION: This study demonstrates that Nexrutine alleviates inflammatory mucosal barrier damage in UC by suppressing RELA transcription.


Assuntos
Colite Ulcerativa , Extratos Vegetais , Humanos , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Mesalamina , Citocinas , Inflamação/tratamento farmacológico , Fator de Transcrição RelA/genética
17.
Int J Mol Sci ; 25(2)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38255764

RESUMO

Inflammatory bowel disease (IBD) is a group of intestinal inflammatory diseases characterized by chronic, recurrent, remitting, or progressive inflammation, which causes the disturbance of the homeostasis between immune cells, such as macrophages, epithelial cells, and microorganisms. Intestinal macrophages (IMs) are the largest population of macrophages in the body, and the abnormal function of IMs is an important cause of IBD. Most IMs come from the replenishment of blood monocytes, while a small part come from embryos and can self-renew. Stimulated by the intestinal inflammatory microenvironment, monocyte-derived IMs can interact with intestinal epithelial cells, intestinal fibroblasts, and intestinal flora, resulting in the increased differentiation of proinflammatory phenotypes and the decreased differentiation of anti-inflammatory phenotypes, releasing a large number of proinflammatory factors and aggravating intestinal inflammation. Based on this mechanism, inhibiting the secretion of IMs' proinflammatory factors and enhancing the differentiation of anti-inflammatory phenotypes can help alleviate intestinal inflammation and promote tissue repair. At present, the clinical medication of IBD mainly includes 5-aminosalicylic acids (5-ASAs), glucocorticoid, immunosuppressants, and TNF-α inhibitors. The general principle of treatment is to control acute attacks, alleviate the condition, reduce recurrence, and prevent complications. Most classical IBD therapies affecting IMs function in a variety of ways, such as inhibiting the inflammatory signaling pathways and inducing IM2-type macrophage differentiation. This review explores the current understanding of the involvement of IMs in the pathogenesis of IBD and their prospects as therapeutic targets.


Assuntos
Doenças Inflamatórias Intestinais , Monócitos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/etiologia , Macrófagos , Mesalamina , Anti-Inflamatórios , Inflamação
18.
Rev Esp Enferm Dig ; 116(1): 49-51, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37073710

RESUMO

Rectal perforations due to topical treatments (enemas or foams) are unusual complications and they have been mostly reported in the use of barium enemas or in elderly patients with constipation. Very little has been reported about perforations secondary to topical treatment in patients with ulcerative colitis. We present the case of a patient with ulcerative colitis who suffered a rectal perforation complicated with a superinfected collection after the application of topical mesalazine foam.


Assuntos
Colite Ulcerativa , Perfuração Intestinal , Humanos , Idoso , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Mesalamina/uso terapêutico , Enema/efeitos adversos , Perfuração Intestinal/induzido quimicamente , Doença Iatrogênica , Anti-Inflamatórios não Esteroides/uso terapêutico
19.
Inflamm Bowel Dis ; 30(2): 213-221, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37084279

RESUMO

BACKGROUND: Data regarding patients with ulcerative colitis (UC) not receiving maintenance treatment are scarce. In this nationwide study, we aimed to explore the frequency and long-term outcomes of untreated patients with UC vs treated patients. METHODS: We retrieved data from Israel's Health Maintenance Organizations, covering 98% of the population. No maintenance treatment (NMT) was defined as lack of treatment during the period from 3 to 6 months from diagnosis, allowing at most 3 months for induction treatment. RESULTS: A total of 15 111 patients have been diagnosed with UC since 2005, of whom 4410 (29%) have had NMT, with 36 794 person-years of follow-up. NMT was more likely in adults (31%) and in elderly-onset UC (29%) than in pediatric-onset UC (20%; P < .001) and decreased from 38% in 2005 to 18% in 2019 (P < .001). The probability of remaining without treatment was 78%, 49%, and 37% after 1, 3, and 5 years from diagnosis, respectively. In propensity score-matched analysis of 1080 pairs of treated (93% with 5-aminosalicylic acid) and untreated patients, outcomes were comparable for time to biologics (P = .6), surgery (P = .8), steroid dependency (P = .09), and hospitalizations (P = .2). Multivariable modeling indicated that failing NMT was less likely in adults or elderly-onset patients who received at most rectal therapy or antibiotics as induction therapy. CONCLUSIONS: Nowadays, 18% of patients with UC do not receive maintenance therapy, of whom half remain without treatment after 3 years. Matched pairs of patients on NMT and 5-aminosalicylic acid, representing the mildest patients of the latter, had similar outcomes. Prospective studies are needed to further explore the role of NMT in UC.


The rate of no maintenance treatment (NMT) decreased in the last years, but in a propensity score­matched analysis, 5-aminosalicylic acid monotherapy did not demonstrate any therapeutic advantage over NMT. NMT seems to be a viable option in a subset of patients with mild ulcerative colitis.


Assuntos
Colite Ulcerativa , Mesalamina , Adulto , Criança , Humanos , Idoso , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/induzido quimicamente , Anti-Inflamatórios não Esteroides , Prevalência
20.
Expert Rev Clin Immunol ; 20(3): 277-290, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38059454

RESUMO

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a significant health-care burden worldwide. While medical therapy aims to induce and maintain remission, optimal management of mild to moderate UC remains challenging due to heterogeneity in severity classifications and non-standardized approaches. This comprehensive review summarizes current evidence and knowledge gaps to optimize clinical decision-making in patients with mild to moderate UC. AREAS COVERED: After an extensive literature search of PubMed, Medline, and Embase through August 2023, we provide an overview of definitions utilized to characterize mild to moderate UC severity and established therapeutic targets. Current medical treatments including mesalazine formulations, corticosteroids, and their combinations are surveyed. The role of emerging intestinal ultrasound, telemedicine, and home testing is explored. Individualized, patient-centered paradigms aiming to streamline care delivery through proactive identification of relapses are also examined. EXPERT OPINION: Addressing inconsistencies in disease activity stratification will better align tailored regimens with each patient's profile. Advancing noninvasive technologies like ultrasound criteria and home testing could improve UC management by enabling personalized models. Realizing individualized plans through informed shared-decision making between health-care providers and fully engaged patients holds promise to maximize quality of life outcomes. Continuous improvement relies on innovation bridging different domains to overcome current limitations and push the field toward more predictive and tailored care.


Assuntos
Colite Ulcerativa , Humanos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Anti-Inflamatórios/uso terapêutico , Budesonida/efeitos adversos , Qualidade de Vida , Mesalamina/uso terapêutico
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