Polymeric Systems for Colon-specific Mesalazine Delivery in the Intestinal Bowel Diseases Management.

The anti-inflammatory 5-aminosalicylic acid (5-ASA) is the main therapeutic option used to prevent and treat inflammatory bowel diseases. The upper intestinal tract performs rapid and almost complete absorption of this drug when administered orally, making local therapeutic levels of the molecule in the inflamed colonic mucosa difficult to achieve. Micro and nanoparticle systems are promising for 5-ASA incorporation because the reduced dimensions of these structures can improve the drug's pharmacodynamics and contribute to more efficient and localized therapy. Together, the association of these systems with polymers will allow the release of 5-ASA through specific targeting mechanisms to the colon, as demonstrated in the mesalazine modified-release dosage form. This review will summarize and discuss the challenges for the oral administration of 5-ASA and the different colon-specific delivery strategies using polymers.

C-reactive protein levels and prevalence of leukopenia in patients with inflammatory bowel disease treated with azathioprine and/or mesalazine: a real-life study.

OBJECTIVE: To examine serum C-reactive protein levels and the prevalence of leukopenia in patients with Crohn's disease or ulcerative colitis undergoing treatment with azathioprine and/or mesalazine. METHODS: Retrospective observational study based on clinical and laboratory data collected from medical records of 76 adult patients with inflammatory bowel disease treated with azathioprine, mesalazine or both. Sex, age, diagnosis, number of blood samples and elevated serum C-reactive protein levels during the follow-up period were recorded. The following variables were analyzed in terms of C-reactive protein levels and leukopenia episodes: sex, age, diagnosis of inflammatory bowel disease and type of drug. Statistical analyses included multiple logistic regression and the Fisher's exact test for qualitative variables. RESULTS: Leukopenia was observed in 18.4% of patients and was associated with older age and higher doses of medication. In 44% of patients, C-reactive protein levels were high. However, symptoms were not associated with abnormal levels of this marker. CONCLUSION: Regardless of symptoms, serum C-reactive protein levels were not a reliable indicator of controlled inflammatory bowel disease. Leukopenia was independently associated with older age and higher doses of medication and is a common side effect, which should be routinely monitored.

Therapeutics in radiation-induced proctopathy: a systematic review

Malignant neoplasms are increasingly prevalent in the daily clinical practice. Up to 61% of patients with pelvic malignancies undergo pelvic radiotherapy in different doses, which may cause intestinal damage, and the rectum is the segment most frequently affected due to its fixed position in the pelvis. Currently, there are several strategies to minimize the effects of radiation on the tissues surrounding the neoplastic site; despite those strategies, radiotherapy can still result in serious damage to organs and structures, and these injuries accompany patients throughout their lives. One of the most common damages resulting from pelvic radiotherapy is acute proctitis.The diagnosis is confirmed by visualizing the rectal mucosa through rigid or flexible rectosigmoidoscopy and colonoscopy. The objective of the present study was to review the forms of radiation-induced proctopathytherapy, and to evaluate the results of each method to propose a standardization for the treatment of this pathology. Despite the prevalence of radiation-induced proctopathy, there is no definitive standardized treatment strategy so far. The first approach can be tried with local agents, such as mesalazine and formalin. For refractory cases, control can usually be achieved with argon plasma coagulation, hyperbaric oxygen, and radiofrequency ablation therapies. Regarding the study of radiation-induced proctopathy, there is a lack of robust studies with large samples and standardized therapies to be compared. There is a lack of double-blinded, randomized controlled studies to determine a definitive standard treatment algorithm. (AU)

Characteristics, Properties and Analytical/Bioanalytical Methods of 5-Aminosalicylic Acid: A Review.

Five-aminosalicylic acid (5-ASA) is an anti-inflammatory drug indicated in the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. Among the analytical methods of quantification of 5-ASA described in the literature, the High Efficiency Liquid Chromatography stands out, a sensitive technique but with a high cost. In recent years, alternative methods have been developed, presenting efficiency and reduced cost, such as UV/visible spectrophotometric, spectrofluorescent, and electrochemical methods, techniques recommended for the application in quality control and quantification of 5-ASA in pharmaceutical forms and biological fluids. This article aims to review the physicochemical characteristics, pharmacokinetics, mechanisms of action, controlled release systems, and the different analytical and bioanalytical methods for the quantification of 5-ASA.

Real-world experience with MMX mesalazine use in Mexican patients with ulcerative colitis at two tertiary care centers.

INTRODUCTION AND AIMS: The 5-aminosalicylates, especially mesalazine, are the first option in the treatment of mild-to-moderate ulcerative colitis (UC). High rates of remission induction and maintenance have been observed with the new multimatrix (MMX) mesalazine formulation, mainly in patients with distal disease. Our aim was to describe the real-world experience with MMX mesalazine in patients with UC at two tertiary care centers. MATERIALS AND METHODS: A retrospective cohort study was conducted that included 142 patients with confirmed UC diagnosis, analyzed in three study groups: 1) oral MMX mesalazine as monotherapy for remission induction, 2) oral MMX mesalazine as monotherapy for remission maintenance, and 3) oral MMX mesalazine plus topical therapy for remission induction. RESULTS: The frequency of clinical remission induction in group 1 was 80.3%, with biochemical remission of 74.2%. Group 2 had 100% clinical and biochemical remission maintenance. The frequency of clinical remission induction in group 3 was 88.6%, biochemical remission was 85.7%, and topical therapy was suspended in 87.3% at the end of follow-up. No adverse events were documented. CONCLUSIONS: There were high percentages of clinical and biochemical remission in the two corresponding study groups and topical therapy was suspended in the majority of patients in ashort follow-up period.

Evaluation of mesalazine polymeric conjugate in the treatment of actinic proctitis in rats.

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

Evaluation of mesalazine polymeric conjugate in the treatment of actinic proctitis in rats

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

Xylan microparticles for controlled release of mesalamine: Production and physicochemical characterization.

Xylan extracted from corn cobs was used to produce mesalamine-loaded xylan microparticles (XMP5-ASA) by cross-linking polymerization using a non-hazardous cross-linking agent. The microparticles were characterized by thermal analysis (DSC/TG), X-ray diffraction (XRD), Infrared spectroscopy (FTIR-ATR) and scanning electron microscopy (SEM). A comparative study of the in vitro drug release from XMP5-ASA and from gastro-resistant capsules filled with XMP5-ASA (XMPCAP5-ASA) or 5-ASA was also performed. NMR, FTIR-ATR, XRD and DSC/TG studies indicated molecularly dispersed drug in the microparticles with increment on drug stability. The release studies showed that XMPCAP5-ASA allowed more efficient drug retention in the simulated gastric fluid and a prolonged drug release lasting up to 24 h. XMPCAP5-ASA retained approximately 48 % of its drug content after 6 h on the drug release assay. Thus, the encapsulation of 5-ASA into xylan microparticles together with gastro-resistant capsules allowed a better release control of the drug during different simulated gastrointestinal medium.

Colonoscopy-guided therapy for the prevention of post-operative recurrence of Crohn's disease.

BACKGROUND: About half of patients with Crohn's disease (CD) require surgery within 10 years of diagnosis. Resection of the affected segment is highly effective, however the majority of patients experience clinical recurrence after surgery. Most of these patients have asymptomatic endoscopic recurrence weeks or months before starting with symptoms. This inflammation can be detected by colonoscopy and is a good predictor of poor prognosis.Therapy guided by colonoscopy could tailor the management and improve the prognosis of postoperative CD. OBJECTIVES: To assess the effects of prophylactic therapy guided by colonoscopy in reducing the postoperative recurrence of CD in adults. SEARCH METHODS: The following electronic databases were searched up to 17 December 2019: MEDLINE, Embase, CENTRAL, Clinical Trials.gov, WHO Trial Registry and Cochrane IBD specialized register. Reference lists of included articles, as well as conference proceedings were handsearched. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs and cohort studies comparing colonoscopy-guided management versus management non-guided by colonoscopy. DATA COLLECTION AND ANALYSIS: Two review authors independently considered studies for eligibility, extracted the data and assessed study quality. Methodological quality was assessed using both the Cochrane 'Risk of bias' tool for RCTs and Newcastle-Ottawa scale (NOS) for cohort studies. The primary outcome was clinical recurrence. Secondary outcomes included: endoscopic, surgical recurrence and adverse events. We calculated the risk ratio (RR) for each dichotomous outcome and extracted the hazard ratio (HR) for time-to-event outcomes. All estimates were reported with their corresponding 95% confidence interval (CI). Data were analysed on an intention-to-treat (ITT) basis. The overall quality of the evidence was evaluated using GRADE criteria. MAIN RESULTS: Two RCTs (237 participants) and five cohort studies (794 participants) met the inclusion criteria. Meta-analysis was not conducted as the studies were highly heterogeneous. We included two comparisons. Intensification of prophylactic-therapy guided by colonoscopy versus intensification guided by clinical recurrence One unblinded RCT and four retrospective cohort studies addressed this comparison. All participants received the same prophylactic therapy immediately after surgery. In the colonoscopy-based management group the therapy was intensified in case of endoscopic recurrence; in the control group the therapy was intensified only in case of symptoms. In the RCT, clinical recurrence (defined as Crohn's Disease Activity Index (CDAI) > 150 points) in the colonoscopy-based management group was 37.7% (46/122) compared to 46.1% (21/52) in the control group at 18 months' follow up (RR 0.82, 95% CI: 0.56 to 1.18, 174 participants, low-certainty evidence). There may be a reduction in endoscopic recurrence at 18 months with colonoscopy-based management (RR 0.73, 95% CI 0.56 to 0.95, 1 RCT, 174 participants, low-certainty evidence). The certainty of the evidence for surgical recurrence was very low, due to only four cohort studies with inconsistent results reporting this outcome. Adverse events at 18 months were similar in both groups, with 82% in the intervention group (100/122) and 86.5% in the control group (45/52) (RR 0.95, 95% CI:0.83 to 1.08, 1 RCT, 174 participants, low-certainty of evidence).The most common adverse events reported were alopecia, wound infection, sensory symptoms, systemic lupus, vasculitis and severe injection site reaction. Perforations or haemorrhages secondary to colonoscopy were not reported. Initiation of prophylactic-therapy guided by colonoscopy versus initiation immediately after surgery An unblinded RCT and two retrospective cohort studies addressed this comparison. The control group received prophylactic therapy immediately after surgery, and in the colonoscopy-based management group the therapy was delayed up to detection of endoscopic recurrence. The effects on clinical and endoscopic recurrence are uncertain (clinical recurrence until week 102: RR 1.16, 95% CI 0.73 to 1.84; endoscopic recurrence at week 102: RR 1.16, 95% CI 0.73 to 1.84; 1 RCT, 63 participants, very low-certainty evidence). Results from one cohort study were similarly uncertain (median follow-up 32 months, 199 participants). The effects on surgical recurrence at a median follow-up of 50 to 55 months were also uncertain in one cohort study (RR 0.79, 95% CI 0.38 to 1.62, 133 participants, very low-certainty evidence). There were fewer adverse events with colonoscopy-based management (54.8% (17/31)) compared with the control group (93.8% (30/32)) but the evidence is very uncertain (RR 0.58, 95% CI 0.42 to 0.82; 1 RCT, 63 participants). Common adverse events were infections, gastrointestinal intolerance, leukopenia, pancreatitis and skin lesions. Perforations or haemorrhages secondary to colonoscopy were not reported. AUTHORS' CONCLUSIONS: Intensification of prophylactic-therapy guided by colonoscopy may reduce clinical and endoscopic postoperative recurrence of CD compared to intensification guided by symptoms, and there may be little or no difference in adverse effects. We are uncertain whether initiation of therapy guided by colonoscopy impacts postoperative recurrence and adverse events when compared to initiation immediately after surgery, as the certainty of the evidence is very low. Further studies are necessary to improve the certainty of the evidence of this review.

Ulcerative colitis: epidemiology, clinical features and associated factors with surgical treatment in a tertiary hospital in Mexico.

BACKGROUND: An increase incidence of ulcerative colitis (UC) has been reported in Mexico. It is important to know the clinical features of patients with UC, their clinical course, need for surgical treatment and outcomes. OBJECTIVE: To describe the demographic and clinical features of patients with UC, emphasizing the factors associated with the need for surgical treatment. METHOD: A retrospective, cross-sectional, analytical study was made which included 60 patients with diagnosis of UC confirmed by histopathology. The demographic, clinical and biochemical data of each patient will be collected. The severity was measured based on the Truelove and Witts scale, endoscopic Mayo score and Riley histological index. RESULTS: Of the patients included, the proportion was equal between men and women. The mean age of presentation was 40.6 ± 13.3 years. The extent of the disease at the time of diagnosis was proctitis in the majority of patients (61.7%). Nineteen patients (31.8%) presented extraintestinal manifestations. 55% of the patients had as sole treatment 5-aminosalicylates. Fourteen patients (23.3%) required surgical treatment mainly due to lack of response to medical treatment. CONCLUSIONS: The clinical features of UC are useful to identify patients who may present a torpid evolution of the disease and who may require surgical treatment.

ANTECEDENTES: Se tiene evidencia de un aumento en la incidencia de la colitis ulcerosa crónica idiopática (CUCI) en México, pero varía según el Estado e incluso entre hospitales de una misma región. Es importante conocer las características clínicas de los pacientes con CUCI, su curso clínico, necesidad de tratamiento quirúrgico y desenlaces. OBJETIVO: Describir las características demográficas y clínicas de los pacientes con CUCI, enfatizando en los factores asociados a la necesidad de tratamiento quirúrgico. MÉTODO: Estudio retrospectivo que incluyó 60 pacientes con diagnóstico de CUCI confirmado por histopatología. Se colectaron los datos demográficos, clínicos y bioquímicos de cada paciente. La gravedad se midió con la escala de Truelove y Witts, la escala endoscópica de Mayo y el índice histológico de Riley. RESULTADOS: Se incluyeron 30 hombres y 30 mujeres. La media de edad fue de 40.6 ± 13.3 años. La extensión de la enfermedad fue proctitis en el 61.7%. Diecinueve pacientes (31.8%) presentaron manifestaciones extraintestinales. El 55% tenían como tratamiento único ácido 5-aminosalicílico. Catorce pacientes (23.3%) requirieron tratamiento quirúrgico, principalmente por falta de respuesta al tratamiento médico. CONCLUSIONES: Las características clínicas de la CUCI son útiles para identificar a los pacientes que pudieran presentar una evolución tórpida de la enfermedad y requerir tratamiento quirúrgico.

Enemas with mesalazine increase the tissue contents of mucins in the colonic mucosa devoid of fecal stream.

PURPOSE: To evaluate the inflammatory reaction and measure the content of mucins, in the colonic mucosa without fecal stream submit to intervention with mesalazine. METHODS: Twenty-four rats were submitted to a left colostomy and a distal mucous fistula and divided into two groups according to euthanasia to be performed two or four weeks. Each group was divided into two subgroups according daily application of enemas containing saline or mesalazine at 1.0 g/kg/day. Colitis was diagnosed by histological analysis and the inflammatory reaction by validated score. Acidic mucins and neutral mucins were determined with the alcian-blue and periodic acid of Schiff techniques, respectively. Sulfomucin and sialomucin were identified by high iron diamine-alcian blue technique. The tissue contents of mucins were quantified by computer-assisted image analysis. Mann-Whitney test was used to analyze the results establishing the level of significance of 5%. RESULTS: Enemas with mesalazine in colonic segments without fecal stream decreased the inflammation score and increased the tissue content of all subtypes of mucins. The increase of tissue content of neutral, acid and sulfomucin was related to the time of intervention. CONCLUSION: Mesalazine enemas reduce the inflammatory process and preserve the content of mucins in colonic mucosa devoid of fecal stream.

Enemas with mesalazine increase the tissue contents of mucins in the colonic mucosa devoid of fecal stream

Purpose: To evaluate the inflammatory reaction and measure the content of mucins, in the colonic mucosa without fecal stream submit to intervention with mesalazine. Methods: Twenty-four rats were submitted to a left colostomy and a distal mucous fistula and divided into two groups according to euthanasia to be performed two or four weeks. Each group was divided into two subgroups according daily application of enemas containing saline or mesalazine at 1.0 g/kg/day. Colitis was diagnosed by histological analysis and the inflammatory reaction by validated score. Acidic mucins and neutral mucins were determined with the alcian-blue and periodic acid of Schiff techniques, respectively. Sulfomucin and sialomucin were identified by high iron diamine-alcian blue technique. The tissue contents of mucins were quantified by computer-assisted image analysis. Mann-Whitney test was used to analyze the results establishing the level of significance of 5%. Results: Enemas with mesalazine in colonic segments without fecal stream decreased the inflammation score and increased the tissue content of all subtypes of mucins. The increase of tissue content of neutral, acid and sulfomucin was related to the time of intervention. Conclusion: Mesalazine enemas reduce the inflammatory process and preserve the content of mucins in colonic mucosa devoid of fecal stream.(AU)

Aminosalicylates, thiopurines and methotrexate in inflammatory bowel disease: Is it possible to discontinue the treatment? / Aminosalicilatos, tiopurínicos y metotrexato en la enfermedad inflamatoria intestinal, ¿es posible suspender el tratamiento?

The current goals of treatment in inflammatory bowel disease, both Crohn's disease and ulcerative colitis, are to achieve clinical, endoscopic and ideally histological remission and improve the quality of life of these patients. Current therapies are effective in achieving remission in most cases, but there is a lack of clear guidelines on their optimal duration. This review aims to evaluate the current evidence on the withdrawal of therapy with 5-aminosalicylates, thiopurines and methotrexate. We also aim to identify which specific group of patients, while in remission and in the absence of risk factors, may be able to discontinue therapy without a significant risk of relapse.

Diagnóstico y manejo de la colitis microscópica / Diagnosis and management of microscopic colitis

Microscopic colitis (MC) is a clinical condition characterized by chronic watery diarrhea, normal colonic mucosa and characteristic histological findings. It is composed of two main entities: collagenous colitis (CC) and lymphocytic colitis (LC). Its incidence has been increasing, currently accounting for between 8 to 16% of studies for chronic diarrhea. It is more frequent in elderly women and is strongly associated with other autoimmune disorders. Its pathogenesis is not very well understood, but it supposes the immune activation secondary to the exposure of the colonic mucosa to different luminal antigens, mainly drugs. Management includes suspension of the potential causative agent and the use of anti-diarrheal medications. Oral budesonide has proven to be effective in induction and maintenance of remission, but with a high rate of recurrence upon discontinuation. Immune-modulators drugs such as azatioprine and metrotrexate have been tested in patients dependent to corticoids with variable results. Antibodies against tumor necrosis factors (TNF) are under studies, with promising results.

La colitis microscópica (CM) es una condición clínica caracterizada por diarrea crónica acuosa con mucosa colónica normal y hallazgos histológicos característicos. Está compuesta por dos entidades principales: la colitis colágena (CC) y la colitis linfocítica (CL). Su incidencia ha ido en aumento, siendo en la actualidad la responsable del 8 a 16% de los casos por diarrea crónica. Es más frecuente en mujeres de edad avanzada con una fuerte asociación a otras enfermedades autoinmunes. Su etiopatogenia no es del todo conocida, pero se cree juega un rol la activación inmune secundaria a la exposición de la mucosa colónica a diferentes antígenos luminales, principalmente fármacos. Dentro del manejo se incluye la suspensión del potencial agente causal y el uso de fármacos antidiarreicos. La budesonida oral ha demostrado alta efectividad en la inducción y mantención de la remisión, pero con una alta tasa de recurrencia al suspenderla. Fármacos inmunomoduladores como azatioprina y metrotrexato se han probado en pacientes corticodependendientes con resultados variables. El uso de anticuerpos monoclonales anti factor de necrosis tumoral (TNF) se encuentra en estudio, con resultados prometedores.

Enemas with mesalazine increase the tissue contents of mucins in the colonic mucosa devoid of fecal stream

Abstract Purpose: To evaluate the inflammatory reaction and measure the content of mucins, in the colonic mucosa without fecal stream submit to intervention with mesalazine. Methods: Twenty-four rats were submitted to a left colostomy and a distal mucous fistula and divided into two groups according to euthanasia to be performed two or four weeks. Each group was divided into two subgroups according daily application of enemas containing saline or mesalazine at 1.0 g/kg/day. Colitis was diagnosed by histological analysis and the inflammatory reaction by validated score. Acidic mucins and neutral mucins were determined with the alcian-blue and periodic acid of Schiff techniques, respectively. Sulfomucin and sialomucin were identified by high iron diamine-alcian blue technique. The tissue contents of mucins were quantified by computer-assisted image analysis. Mann-Whitney test was used to analyze the results establishing the level of significance of 5%. Results: Enemas with mesalazine in colonic segments without fecal stream decreased the inflammation score and increased the tissue content of all subtypes of mucins. The increase of tissue content of neutral, acid and sulfomucin was related to the time of intervention. Conclusion: Mesalazine enemas reduce the inflammatory process and preserve the content of mucins in colonic mucosa devoid of fecal stream.

Synergistic effects of hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) administration in ameliorating animal model of ulcerative colitis / Efeitos sinérgicos do extrato aquoso da fruta da jujuba em combinação com administração de Mesalazina (via oral) e Asacol (intracolônico) na melhora de colite ulcerativa em modelo animal

ABSTRACT This study was done to investigate the synergistic impacts hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) administration in ameliorating animal model of ulcerative colitis (UC). After the induction of UC and with the development of signs, the treatment groups daily received the hydro extract of jujube fruit (200 mg/kg, orally, enema), Mesalazine (30 mg/kg, orally) and Asacol (10 mg/kg, enema). After 10 days, rats were euthanized and were studied. Findings indicated a significant increase in Myeloperoxidase (161.66 ± 10.40), Nitric oxide (216.01 ± 17.55), IL-6 (138.54 ± 7.02), and TNF-α (123.87 ± 9.80) colon tissue levels and pathological damage of positive control group compared with the negative control group. Hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) group represented a higher capability in significantly decreasing Myeloperoxidase (73.33 ± 9.07), Nitric oxide (81.66 ± 10.50), IL-6 (51.69 ± 5.19), TNF-α (30.59 ± 5.50) levels and pathological damage in compared with the other treatment groups. Considering accessibility and affordability of jujube fruit and the side effects of routine drugs, taking a combination of jujube fruit with low doses of routine pharmaceutical drugs can improve and cure ulcerative colitis disease.

RESUMO Este estudo foi realizado para investigar os impactos sinérgicos do extrato aquoso do fruto da jujuba em combinação com a administração de Mesalazina (por via oral) e Asacol (intracolônico) na melhora do modelo animal de colite ulcerativa. Após a indução da colite ulcerativa e com o desenvolvimento de sinais, os grupos de tratamento receberam diariamente o extrato aquoso do fruto da jujuba (200 mg/kg, via oral, enema), Mesalazina (30 mg/kg, via oral) e Asacol (10 mg/kg, enema). Após 10 dias, os ratos foram eutanasiados e estudados. Os achados indicaram um aumento significativo dos níveis de mieloperoxidase (161,66 ± 10,40), óxido nítrico (216,01 ± 17,55), IL-6 (138,54 ± 7,02) e TNF-α (123,87 ± 9,80) no tecido do cólon e dano patológico do grupo controle positivo comparado com o grupo controle negativo. O extrato aquoso da fruta de jujuba em combinação com Mesalazina (oral) e Asacol (intracolônico) representou maior capacidade de redução significativa dos níveis de mieloperoxidase (73,33 ± 9,07), óxido nítrico (81,66 ± 10,50), IL-6 (51,69 ± 5,19), TNF-α (30,59 ± 5,50) e dano patológico em comparação com os outros grupos de tratamento. Considerando a acessibilidade e disponibilidade do fruto da jujuba e dos efeitos colaterais dos medicamentos de rotina, tomar uma combinação de jujuba com baixas doses de medicamentos farmacêuticos de rotina pode melhorar e curar a colite ulcerativa.

Antioxidant and anti-inflammatory effect of plumieride in dextran sulfate sodium-induced colitis in mice.

This study aimed to investigate the potential effect of plumieride, an iridoid glycoside isolated from Alamanda cathartica L. flowers, against dextran sulfate sodium (DSS)-induced colitis in mice. Colitis was induced in female swiss mice by adding DSS 3% to the drinking water. The animals were treated with vehicle (water), 5-aminosalicylic acid (100?mg/kg) or plumieride (10, 30 and 100?mg/kg) once a day, during 7 days. The body weight progression and the disease activity index was evaluated daily. On the eighth day, colons were collected for the measurement of the size, histological, histochemical, biochemical and inflammatory analysis. The cytotoxicity of plumieride on intestinal epithelial cell (IEC-6 cell line) was also evaluated. Plumieride, at dose of 100?mg/kg, significantly attenuated the mice weight loss, showed lower score in the disease activity index, diminished the colon shortening, improved the histological damage and avoided mucosa intestinal mucus depletion when compared with vehicle-treated only group. Moreover, plumieride was able to reduce the amount of colonic lipid hydroperoxides, while augmented reduced glutathione levels and superoxide dismutase activity. Although DSS intake stimulated an increase in myeloperoxidase activity and in tumor necrosis factor content on the colon tissue of the vehicle-treated group, the colons obtained from mice treated with plumieride did not present any of these changes. Taking together, the results of the present study disclose that plumieride exhibited a significant efficacy in attenuating the parameters of experimental ulcerative colitis, which may be mediated by an antioxidant and anti-inflammatory effect.

New mesalamine polymeric conjugate for controlled release: Preparation, characterization and biodistribution study.

Mesalamine (5-ASA) consists of the first-line therapy for the treatment of ulcerative colitis; however, it has low bioavailability, can cause several systemic adverse events, and has low treatment adherence due to the inconvenient dosing scheme. In this work, a new drug delivery system consisting of chondroitin sulfate linked to 5-ASA was synthesized using a carbodiimide as conjugating agent. The system was characterized by spectroscopic techniques (UV, ATR-FTIR, XRD, and NMR 1H) and thermal analysis (TG/DTG and DSC), suggesting the conjugation between the drug and the polymer. The in vitro release and the corresponding kinetics were also evaluated, revealing that approximately 40% of the drug linked was released at pH9 for up to 50h, following Higuchi's model. The conjugate did not show cytotoxicity for the human monocytic cell line at the doses tested, and an in vivo biodistribution study showed that the conjugate remained in the lower GIT for up to 8h with no uptake in the upper GIT. These data corroborate with the radiation found per segment of GIT and in blood. For this last test the conjugate was radiolabeled with Technetium-99m to allow the scintigraphy evaluation and radiation quantification. In conclusion, the polymeric conjugate was successfully synthesized and demonstrated a mucoadhesiveness on the colon as desired, thus supporting its potential use in the treatment of ulcerative colitis.