Sporadic gastrinoma with refractory benign esophageal stricture: A case report.

BACKGROUND: Gastrinoma is characterized by an excessive release of gastrin, leading to hypersecretion of gastric acid, subsequently resulting in recurrent peptic ulcers, chronic diarrhea, and even esophageal strictures. This case report aims to improve awareness and facilitate early diagnosis and treatment of gastrinoma by presenting a rare case of gastrinoma with refractory benign esophageal stricture (RBES). Additionally, it highlights the persistent challenges that gastroenterologists encounter in managing RBES. CASE SUMMARY: This case demonstrates a patient with gastrinoma who developed RBES and complete esophageal obstruction despite management with maximal acid suppressive therapy, multiple endoscopic bougie dilations and endoscopic incisional therapy (EIT). CONCLUSION: It is essential to diagnose gastrinoma as early as possible, as inadequately controlled acid secretion over an extended period increases the risk of developing severe esophageal strictures. In patients with esophageal strictures causing complete luminal obstruction, blind reopening EIT presents challenges and carries a high risk of perforation.

Association Between Long-Term Exposure to Ambient Air Pollution and the Risk of Mild Cognitive Impairment in a Chinese Urban Area: A Case-Control Study.

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

Painterly Style Transfer With Learned Brush Strokes.

Real-world paintings are made, by artists, using brush strokes as the rendering primitive to depict semantic content. The bulk of the Neural Style Transfer (NST) is known transferring style using texture patches, not strokes. The output looks like the content image, but some are traced over using the style texture: it does not look painterly. We adopt a very different approach that uses strokes. Our contribution is to analyse paintings to learn stroke families-that is, distributions of strokes based on their shape (a dot, straight lines, curved arcs, etc.). When synthesising a new output, these distributions are sampled to ensure the output is painted with the correct style of stroke. Consequently, our output looks more "painterly" than NST output based on texture. Furthermore, where strokes are placed is an important contributing factor in determining output quality, and we have also addressed this aspect. Humans place strokes to emphasize salient semantically meaningful image content. Conventional NST uses a content loss premised on filter responses that is agnostic to salience. We show that replacing that loss with one based on the language-image model benefits the output through greater emphasis of salient content.

Inhibitory Mechanism of Prenylated Flavonoids Isolated from Mulberry Leaves on α-Glucosidase by Multi-Spectroscopy and Molecular Dynamics Simulation.

Flavonoids have always been considered as the chemical basis for the hypoglycemic effect of mulberry leaves. In the course of our search for hypoglycemic effect agents from natural sources, a systematic study was launched to explore prenylated flavonoids from mulberry leaves. Herein, chemical investigation led to the isolation of 10 characteristic prenylated flavonoids, including two new compounds (1 and 3). Their structures were elucidated based on spectroscopic data. All compounds exhibited good α-glucosidase inhibitory activity in vitro, among which compound 2 had the best activity (IC50 = 2.6 µM), better than acarbose (IC50 = 19.6 µM). Additional in vivo tests have further demonstrated compound that compound 2 has a good ability to reduce postprandial blood glucose. Then, multi-spectroscopic methods and molecular simulation studies were used to study the inhibition mechanism. The results showed that compound 2 was a mixed inhibition of α-glucosidase and the binding process was spontaneous, with van der Waals forces as the main driving force, followed by hydrogen bonding and electrostatic forces. The above studies enriched the chemical basis of mulberry leaves, and the application of computational chemistry also provided a reference for future research on such structures.

Tissue Reactions and Mechanism in Cardiovascular Diseases Induced by Radiation.

The long-term survival rate of cancer patients has been increasing as a result of advances in treatments and precise medical management. The evidence has accumulated that the incidence and mortality of non-cancer diseases have increased along with the increase in survival time and long-term survival rate of cancer patients after radiotherapy. The risk of cardiovascular disease as a radiation late effect of tissue damage reactions is becoming a critical challenge and attracts great concern. Epidemiological research and clinical trials have clearly shown the close association between the development of cardiovascular disease in long-term cancer survivors and radiation exposure. Experimental biological data also strongly supports the above statement. Cardiovascular diseases can occur decades post-irradiation, and from initiation and development to illness, there is a complicated process, including direct and indirect damage of endothelial cells by radiation, acute vasculitis with neutrophil invasion, endothelial dysfunction, altered permeability, tissue reactions, capillary-like network loss, and activation of coagulator mechanisms, fibrosis, and atherosclerosis. We summarize the most recent literature on the tissue reactions and mechanisms that contribute to the development of radiation-induced cardiovascular diseases (RICVD) and provide biological knowledge for building preventative strategies.

Identification of Crucial Genes and Related Transcription Factors in Ulcerative Colitis.

OBJECTIVE: Ulcerative colitis (UC) is a chronic, relapsing, and non-specific inflammatory bowel disease. To date, the pathogenesis of UC has not been fully understood. This study aimed to identify crucial genes and related transcription factors in UC by bioinformatic methods. METHODS: Datasets GSE75214 and GSE48958 were used to identify the common differentially expressed genes (DEGs). GO and KEGG pathway enrichment analyses were performed using the STRING database. The protein-protein interaction (PPI) network was constructed to screen hub genes using the STRING database and Cytoscape software. The expressions of the identified hub genes were verified using dataset GSE73661, and their correlations with Mayo scores were analyzed using dataset GSE92415. The transcriptional factor (TF) regulatory network of the hubgenes was constructed by Network Analyst. RESULTS: A total of 147 common DEGs, including 114 up-regulated and 33 down-regulated genes, were screened out, among which CXCL9, TIMP1, PTGS2, ICAM1, CXCL1, MMP9, IL1B, CXCL8, and IL6 were identified as hub genes with high degrees in the PPI network. Correlation analysis showed that the expressions of these hub genes were significantly correlated with Mayo scores in UC patients. Finally, RELA, FLI1, and BACH1 were predicted to be the key TFs regulating these nine hub genes. CONCLUSIONS: This study systematically analyzed the differential gene expression pattern and associated key TFs in UC, which may provide new insights into the pathogenesis and offer opportunities for discovering novel biomarkers and therapeutic targets for UC.

Structure-Preserving Neural Style Transfer.

State-of-the-art neural style transfer methods have demonstrated amazing results by training feed-forward convolutional neural networks or using an iterative optimization strategy. The image representation used in these methods, which contains two components: style representation and content representation, is typically based on high-level features extracted from pretrained classification networks. Because the classification networks are originally designed for object recognition, the extracted features often focus on the central object and neglect other details. As a result, the style textures tend to scatter over the stylized outputs and disrupt the content structures. To address this issue, we present a novel image stylization method that involves an additional structure representation. Our structure representation, which considers two factors: i) the global structure represented by the depth map and ii) the local structure details represented by the image edges, effectively reflects the spatial distribution of all the components in an image as well as the structure of dominant objects respectively. Experimental results demonstrate that our method achieves an impressive visual effectiveness, which is particularly significant when processing images sensitive to structure distortion, e.g. images containing multiple objects potentially at different depths, or dominant objects with clear structures.

TMEM9 mediates IL-6 and IL-1ß secretion and is modulated by the Wnt pathway.

Novel studies have shown that the Transmembrane protein 9 (TMEM9) gene is localized at 1q41 and encodes a protein consisting of 183 amino acids with an N-terminus containing many important domains. As a novel human transmembrane protein, TMEM9 is highly conserved in species from Caenorhabditis elegans to humans and is widely expressed in many tissues and cells. Moreover, TMEM9 may play an important role in intracellular transport and the growth of hepatoma cells. However, evidence for the function of TMEM9 in inflammation is still limited. We studied the expression of TMEM9 and its effect on cytokine secretion in tumor necrosis factor-alpha (TNF-α)-induced LX-2 cells. We proved that overexpression of TMEM9 by transfection with pEGFP-C2-TMEM9 may increase the expression of IL-6 and IL-1ß in LX-2 cells. At the same time, knockdown of TMEM9 expression by transfection with a TMEM9-siRNA decreased IL-6 and IL-1ß secretion in LX-2 cells. Additionally, our results proved that overexpression of TMEM9 enhanced the protein expression levels of the canonical Wnt/ß-catenin accompanied by an upregulation of wnt2b, wnt3a and ß-catenin protein levels in LX-2 cells treated with TNF-α. These results indicate that TMEM9 plays a significant role in TNF-α-enhanced cytokines (IL-6 and IL-1ß) secretion in LX-2 cells and that the canonical Wnt/ß-catenin signaling pathway is involved in the induction of these cytokine expressions.

Suspected drug-induced liver injury associated with iguratimod: a case report and review of the literature.

BACKGROUND: Iguratimod is a novel anti-rheumatic drug with the capability of anti-cytokines as report goes. It has been reported that iguratimod is effective and safe for rheumatoid arthritis and other rheumatisms. As side effects, iguratimod can cause gastrointestinal reactions, dizziness, headache and itchy. CASE PRESENTATION: In this case report, a 60-year-old female patient was admitted with suspected drug-induced liver injury (DILI) caused by iguratimod. The causality assessment was done by the updated RUCAM, and the possibility of the case in our paper diagnosed as highly probable for the score was 9 points. Iguratimod was discontinued immediately, and methylprednisolone was used for acute liver injury and Sjogren's syndrome. The data showed the patient has improved gradually, and she was discharged on day 27. The true incidence of iguratimod-related hepatotoxicity and its pathogenic mechanism are largely unknown. It is difficult to recognize and diagnose DILI, and there is no standard for diagnosis of DILI. At the same time, the DILI is still lack of specific treatment. CONCLUSIONS: Based on this rare case of severe liver injury, we recommend careful monitoring of liver function throughout iguratimod treatment for diseases.

Relationship of distraction rate with inferior alveolar nerve degeneration-regeneration shift.

Distraction osteogenesis is an important technique for the treatment of maxillofacial abnormities and defects. However, distraction osteogenesis may cause the injury of the inferior alveolar nerve. The relationship between distraction rate and nerve degeneration-regeneration shift remains poorly understood. In this study, 24 rabbits were randomly divided into four groups. To establish the rabbit mandibular distraction osteogenesis model, the mandibles of rabbits in distraction osteogenesis groups were subjected to continuous osteogenesis distraction at a rate of 1.0, 1.5 and 2.0 mm/d, respectively, by controlling rounds of screwing each day in the distractors. In the sham group, mandible osteotomy was performed without distraction. Pin-prick test with a 10 g blunt pin on the labium, histological and histomorphometric analyses with methylene blue staining, Bodian's silver staining, transmission electron microscopy and myelinated fiber density of inferior alveolar nerve cross-sections were performed to assess inferior alveolar nerve conditions. At 28 days after model establishment, in the pin-prick test, the inferior alveolar nerve showed no response in the labium to a pin pricks in the 2 mm/d group, indicating a severe dysfunction. Histological and histomorphometric analyses indicated that the inferior alveolar nerve suffered more degeneration and injuries at a high distraction rate (2 mm/d). Importantly, the nerve regeneration, indicated by newborn Schwann cells and axons, was more abundant in 1.0 and 1.5 mm/d groups than in 2.0 mm/d group. We concluded that the distraction rate was strongly associated with the inferior alveolar nerve function, and the distraction rates of 1.0 and 1.5 mm/d had regenerative effects on the inferior alveolar nerve. This study provides an experimental basis for the relationship between distraction rate and nerve degeneration-regeneration shift during distraction osteogenesis, and may facilitate reducing nerve complications during distraction osteogenesis.

Reduction of Aß Generation by Schisandrin B through Restraining Beta-Secretase 1 Transcription and Translation.

BACKGROUND Beta-secretase 1 (BACE1) is a rate-limiting enzyme in the generation of amyloid beta peptides, which are associated with Alzheimer's disease (AD). It has been reported that Schisandrin B could improve cognitive functions in animal models of AD, but the underlying mechanisms are not completely understood. MATERIAL AND METHODS In this research, in order to investigate the effects of Schisandrin B on amyloid-ß (Aß) metabolism and its mechanisms, amyloid precursor protein (APP) and its proteolytic products were determined by enzyme-linked immunosorbent assay (ELISA), western blotting, and RT-PCR after incubation of N2a/Swe cells with Schisandrin B. RESULTS The results indicated that Schisandrin B can significantly reduce the level of secretion of Aß40 and Aß42 secreted in N2a/Swe cells. Additionally, there was nonsignificant change in APP level after Schisandrin B treatment. Treatment of Schisandrin B dramatically reduced the mRNA and protein expression levels of BACE1. Moreover, Schisandrin B treatment resulted in a reduction of protein level of sAPPß, an APP fragment cleavage by BACE1. CONCLUSIONS These results suggest that Schisandrin B inhibits the transcription and translation of BACE1, suppresses the activity of BACE1, and ultimately attenuates Aß generation, which provides a novel mechanism for the regulation of Aß metabolism by Schisandrin B.

Effect of diclofenac on the levels of lipoxin A4 and Resolvin D1 and E1 in the post-ERCP pancreatitis.

OBJECTIVES: Acute pancreatitis is one of the most common complications of endoscopic retrograde cholangiopancreatography (ERCP). Numerous studies have shown that administered nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the incidence of acute pancreatitis after ERCP. Little is known, however, about the mechanism of NSAIDs in preventing pancreatitis (PEP). METHODS: In this study, we assigned patients to receive a single dose of intramuscular diclofenac 75 mg immediately after ERCP (diclofenac group) or without (control group). The primary outcome measure was the occurrence of PEP. The serum amylase levels were measured before ERCP and at 3 and 24 h post-procedure in all patients. The Lipoxin A4 (LXA4), Resolvin D1 (Rvd1), and Resolvin E1 (RvE1) levels were measured before ERCP, and 3 and 24 h after the procedure in 30 patients from the diclofenac group and 30 patients from the control group. RESULTS: A total of 120 patients were enrolled and completed the follow-up. The overall incidence of PEP was 13.3% (16/120). It occurred in four of 60 patients (6.67%) in the diclofenac group and in 12 of 60 patients (20.00%) in the control group (p = 0.032). The LxA4, RvD1, and RvE1 levels in the diclofenac group at 3 h after ERCP were significantly increased compared with before ERCP (p < 0.05). Compared with the control group, the LxA4, RvD1, and RvE1 levels in the diclofenac group at 3 and 24 h after ERCP were significantly increased (p < 0.05). CONCLUSIONS: Intramuscular diclofenac after ERCP can reduce the incidence of PEP. This may be related to the fact that diclofenac can increase the levels of LxA4, RvD1, and RvE1.

Association of MYO9B gene polymorphisms with inflammatory bowel disease in Chinese Han population.

AIM: To explore the association of MYO9B gene polymorphisms with clinical phenotypes and intestinal permeability of individuals with inflammatory bowel disease (IBD) in China. METHODS: A total of 442 IBD patients and 402 healthy volunteers were genotyped for two single nucleotides (rs962917 and rs1545620) using the ligase detection reaction and polymerase chain reaction. Allelic and genotype frequency analyses were performed for the two groups. Intestinal permeability was evaluated using lactulose (L) and mannitol (M) excretion. The association of MYO9B gene polymorphisms with intestinal permeability between the normal and high intestinal permeability groups was analyzed. RESULTS: Overall, there was no significant difference in the genotypic and allelic frequencies of MYO9B between IBD patients and controls. Although no association was found with ulcerative colitis in the comparison between the subgroups, the frequencies of rs962917 and rs1545620 were different in the Crohn's disease (CD) subgroup with ileocolitis (CC vs CT and TT, P = 0.014; and AA vs AC and CC, P = 0.022, respectively). rs1545620 variants appear to be the genetic susceptibility factor for perianal disease in CD patients (AA vs AC CC, P = 0.029). In addition, the L/M ratio was significantly higher in IBD patients than in controls (0.065 ± 0.013 vs 0.020 ± 0.002, P = 0.02), but no association was found between the MYO9B gene and the L/M ratio in IBD patients. CONCLUSION: MYO9B gene polymorphisms may influence the sub-phenotypic expression of CD in China. No association between these MYO9B polymorphisms and intestinal permeability in IBD patients was found.

Effect of homocysteine on intestinal permeability in rats with experimental colitis, and its mechanism.

OBJECTIVE: To investigate the effect of homocysteine (Hcy) on intestinal permeability in rats with TNBS/ethanol-induced colitis and elucidate its mechanism. METHODS: Sprague-Dawley rats were divided into four groups: normal, normal + Hcy injection, TNBS model, and TNBS model + Hcy injection. Experimental colitis was induced by trinitrobenzene sulfonic acid (TNBS) in 50% ethanol; rats were injected subcutaneously with Hcy from the first day after the induction of experimental colitis on 30 consecutive days. To determine the severity of colitis, the disease activity index (DAI) was evaluated; colon tissues were collected for the detection of the activity of myeloperoxidase (MPO) and the contents of MDA, IL-1ß, IL-6, TNF-α, MMP-2, and MMP-9. Intestinal epithelial permeability was assessed with Evans blue (EB) dye. The levels of Hcy in plasma and colon mucosa were measured by high-performance liquid chromatography-fluorescence detection (HPLC-FD). RESULTS: Compared with the normal group, the DAI scoring and MPO activity, contents of MDA, IL-1ß, IL-6, TNF-α, MMP-2, MMP-9 in the colon and EB in the small intestine were significantly increased in the TNBS group (P < 0.01). Compared with the TNBS model group, the DAI scoring, plasma and colonic mucosa Hcy levels, MPO activity and contents of MDA, IL-1ß, IL-6, TNF-α, MMP-2, MMP-9 in colon and EB in small intestine were significantly increased in the TNBS-induced colitis rats with simultaneous Hcy injection (P < 0.01). CONCLUSION: Hcy can increase intestinal permeability and aggravate inflammatory damage in rats with TNBS-induced colitis, the underlying mechanisms of which may be attributed to its effects of promoting the expression of MMP-2 and MMP-9, leading to injury of the intestinal barrier.

Ulcerative colitis flair induced by mesalamine suppositories hypersensitivity.

Mesalamine suppositories have been used widely for the treatment of distal ulcerative colitis and considered to be safer than systemic administration for its limited systemic absorption. However, previous studies have shown that mesalamine suppository occasionally causes severe hypersensitivity reactions including fever, rashes, colitis exacerbation and acute eosinophilic pneumonia. Here we present a 25-year-old woman with ulcerative colitis with bloody diarrhea accompanied by abdominal pain and fever which were aggravated after introduction of mesalamine suppositories. In light of symptom exacerbation of ulcerative colitis, increased inflammatory injury of colon mucosa shown by colonoscopy and elevated peripheral eosinophil count after mesalamine suppositories administration, and the Naranjo algorithm score of 10, the possibility of hypersensitivity reaction to mesalamine suppositories should be considered, warning us to be aware of this potential reaction after administration of mesalamine formulations even if it is the suppositories.

Translocation of protein kinase C δ contributes to the moderately high glucose-, but not hypoxia-induced proliferation in primary cultured human retinal endothelial cells.

Diabetic retinopathy is one of the most common complications in patients with diabetes and affects ~75% of them within 15 years of the onset of the disease. Activation of protein kinase C (PKC) is a key feature of diabetes mellitus and may be involved in the pathogenesis of diabetic retinopathy. The present study aimed to examine the translocation of protein kinase C (PKC) isoforms, which are triggered by high an moderately high glucose levels as well as hypoxic conditions. The underlying cell mechanisms of PKC translocation in primary cultured human retinal endothelial cells (HRECs) were also investigated. The expression levels of PKC isoforms were assessed using western blot analysis. Cell proliferation was determined using the MTT assay and DNA synthesis was assessed by bromodeoxyuridine incorporation. Translocation of PKC isoforms was examined by western blot analysis and immunofluorescence. The expression of PKC α, ßI, ßII, δ and ε was detected, while PKC ζ was not detected in HRECs. The results of the present study were consistent with the findings of a previous study by our group, reporting that moderately high glucose levels and hypoxia, but not high glucose levels, significantly increased cell proliferation. It was demonstrated that the PKC δ isoform was translocated from the cytosol to the membrane only under moderately high glucose conditions, while PKC α and ε isoforms were translocated from the cytosol to the membrane at high glucose conditions. In addition, PKC ßI was translocated under all three conditions. Translocation of PKC ßII was comparable among all groups. Furthermore, rottlerin, an inhibitor of PKC δ, blocked cell proliferation, which was induced by moderately high glucose levels, but not by hypoxia. Ro32-0432, an inhibitor of PKC α, ßI and ε, did not significantly affect proliferation of HRECs in all treatment groups. In conclusion, the present study suggested that PKC α, ßI, ßII, δ and ε were expressed in primary cultured HRECs, whereas PKC ζ was not. Cell proliferation induced by moderately high glucose concentrations was associated with translocation of the PKC δ isoform; however, hypoxic conditions did not induce translocation.

Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice.

AIM: To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. METHODS: Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. RESULTS: Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. CONCLUSION: Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.

A protective effect of melatonin on intestinal permeability is induced by diclofenac via regulation of mitochondrial function in mice.

AIM: This study investigated the effect of intragastrically administered melatonin on intestinal mucosal permeability induced by diclofenac in mice. METHODS: Intestinal mucosal permeability was induced in mice by intragastric administration of diclofenac (2.5 mg/kg). Melatonin was given intragastrically (10 mg/kg) once per day for 3 d after diclofenac administration. The small intestine was examined macroscopically and microscopically for pathologic injury to the intestinal mucosa. Intestinal mucosal permeability was evaluated by Evans blue and FITC-dextran methods. Mitochondrial functional parameters, including mitochondrial membrane potential, mitochondrial ATPase and succinate dehydrogenase (SDH) activity, were assessed. The malondialdehyde (MDA) and myeloperoxidase (MPO) levels were determined from small intestinal mucosal homogenates. RESULTS: As compared with control mice, the permeability, pathologic score, MDA and MPO levels and ulceration of the intestinal mucosa were increased significantly by diclofenac treatment, and a broadened junctional complex and enlarged intercellular space were observed by transmission electron microscopy (TEM). Melatonin treatment significantly reduced the intestinal mucosal permeability, pathologic score, MDA, and MPO levels and ulceration of the intestinal mucosa. By TEM, the small intestine villus morphology and intercellular spaces were nearly normal in melatonin-treated mice. At the level of the mitochondria, melatonin treatment significantly restored the activities of ATPase and SDH. CONCLUSION: The intestinal damage and increased intestinal permeability induced by diclofenac in mice was limited by melatonin; moreover, melatonin preserved several aspects of mitochondrial function.

Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice.

AIM: To investigate the effect of balsalazine treatment on intestinal mucosal permeability in dextran sulfate sodium (DSS)-induced colitis and to determine the mechanism of the balsalazine-induced changes. METHODS: Experimental colitis was induced in C57BL/6J mice by the administration of 5% DSS. Balsalazine was administered intragastrically at doses of 42, 141, and 423 mg/kg. The disease activity index (DAI) score was evaluated and colon tissue was collected for the assessment of histological changes. The amount of malondialdehyde (MDA) in the colon was determined, along with the activity of myeloperoxidase (MPO), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Mucosa from the small intestine was collected to determine the levels of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. The mucosa was ultrastructurally examined with transmission electron microscopy and intestinal permeability was assayed using Evans blue. RESULTS: Balsalazine was found to reduce the DAI score and the histological index (HI) score, decrease the MDA content and the activity of MPO, and increase the activity of SOD and GSH-Px in colitis mice. At the same time, balsalazine ameliorated microvillus and tight junction structure, resulting in a decrease in the amount of Evans blue permeating into the intestinal wall and the levels of TNF-alpha and IFN-gamma in colitis mice. CONCLUSION: In colitis mice, the anti-colitis effect of balsalazine results in a decrease in intestinal mucosal permeability. The mechanism of this effect is partly associated with balsalazine's antioxidative and anti-inflammatory effects.Acta Pharmacologica Sinica (2009) 30: 987-993; doi: 10.1038/aps.2009.77.