Vascular endothelial growth factor, endostatin levels and clinical features among patients with ulcerative colitis and irritable bowel syndrome and among healthy controls: a cross-sectional analytical study

ABSTRACT BACKGROUND: Increased angiogenetic activity in inflammatory bowel disease (IBD) has been shown in previous studies. The aim of this study was to evaluate the relationship of serum vascular endothelial growth factor (VEGF) and endostatin levels with clinical features and mucosal expression in patients with ulcerative colitis (UC). DESIGN AND SETTING: Cross-sectional analytical study conducted in a tertiary-level public hospital. METHODS: Serum VEGF and endostatin levels were determined in 82 individuals: 39 with UC, 28 with irritable bowel syndrome (IBS) and 15 healthy controls (HCs), using enzyme-linked immunosorbent assays (ELISA). VEGF and endostatin expressions were studied using immunohistochemistry (IHC). RESULTS: Mean serum VEGF and endostatin levels were significantly higher in patients with UC than in patients with IBS and in HCs (511.9 ± 377.5 pg/ml, 305.0 ± 121.42 pg/ml and 36.1 ± 40.6 pg/ml; P = 0.001 for VEGF; and 155.50 ± 59.8 ng/ml, 116.9 ± 23.8 ng/ml and 102.2 ± 22.4 ng/ml; P < 0.001 for endostatin, respectively). There was a positive correlation between serum VEGF and endostatin levels (r = 0.422; P < 0.01). Mean H-scores for VEGF expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma, endothelium and epithelium. Mean H-scores for endostatin expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma and endothelium. There was no endostatin expression in the epithelium. CONCLUSION: Increased endostatin appears to be a defensive reaction to increased VEGF in patients with UC.

Antioxidant supplements and gastrointestinal diseases: a critical appraisal

The gastrointestinal tract digests and absorbs dietary nutrients, protects the body against physical and chemical damage from contents in its lumen, provides immunity against external antigens, and keeps an optimum environment for the gut microbiota. These functions cannot be performed normally in several diseases of which the following are discussed here: irritable bowel syndrome and inflammatory bowel disease, which includes Crohn's disease and ulcer-ative colitis

Because these diseases are associated with oxi-dative stress, a host of antioxidant supplements are used for maintenance and recovery of the gut functions. However, the benefits of these supplements have not been established

The available 80 human trials were rated for levels of confidence and for benefits of the antioxidant supplements. For Crohn's disease, the supplements for which clear benefits occurred in at least 2 studies were allopurinol, Boswellia serrata [frankincense or shallaki], Artemesia species [worm-Wood], Tripterygium wilfordii [lei gong teng], and omega-3 fatty acids. Similar beneficial supplements for ulcerative colitis were allopurinol, Motricorio chamomillo [chamomile], Curcuma longa [curcumin in turmeric], and omega-3 fatty acids. There was also a clear benefit for ulcerative colitis in 2 studies where a multiherbal Chinese medicine preparation and an Ayurvedic medicine preparation were used. For irritable bowel syndrome, there was only a marginal benefit of some of the antioxidant supplements. Thus, some antioxidant supplements may be beneficial at certain stages of specific diseases. This is consistent with the current concept that antioxidants act by inhibiting oxidative stress pathways in a tissue- and environment-specific manner and not by simply acting asscavengers

Changes in mast cell infiltration: a possible mechanism in detrusor overactivity induced by visceral hypersensitivity

ABSTRACT Objective: To establish the detrusor overactivity (DO) model induced by visceral hypersensitivity (VH) and investigate the relationship between mast cell (MC) infiltration and DO. Materials and Methods: Sixty rats are divided into 4 groups randomly: Group 1:Baseline group; Group 2: DO group; Group 3: CON group; Group 4: VH group. The colorectal distension (CRD) and abdominal withdral reflex (AWR) scores are performed to evaluate VH. The cystometric investigation and histological test of MC infiltration are assessed. Results: The threshold pressure of CRD in the VH group is significantly lower than that in the CON group (P<0.001). At the distension pressure ≥20 mmHg, the AWR scores of the VH group are significantly higher than those of the CON group (10 mmHg: P=0.33; 20 mmHg: P=0.028; 40 mmHg: P<0.001; 60 mmHg: P<0.001; 80 mmHg: P<0.001). DO model is successfully established in the VH group (DO rate=100%). Compared with the CON group, the numbers of MC infiltration are significantly increased in the VH group, including submucosa of bladder (P<0.001), mucosa lamina propria/mesentery of small intestine (P<0.001), and mucosa lamina propria/mesentery of large intestine (P<0.001). Furthermore, more MC activation as well as degranulation are observed in the VH group. Conclusions: It is indicated that DO model can be established in the VH rats. The MC infiltration may play an important role in DO induced by VH, and may be helpful to understand the mechanisms of DO in VH patients.

Role of psychiatric disorders and irritable bowel syndrome in asthma patients

OBJECTIVES: The goals of the study were the following: 1) to determine the frequency of psychiatric disorders and irritable bowel syndrome in patients with asthma and 2) to compare the frequency of these disorders in patients with asthma to their frequency in healthy controls. INTRODUCTION: Patients with asthma have a higher frequency of irritable bowel syndrome and psychiatric disorders. METHODS: We evaluated 101 patients with bronchial asthma and 67 healthy subjects. All subjects completed the brief version of the Bowel Symptoms Questionnaire and a structured clinical interview for DSM-IV axis disorders (SCID-I/CV). RESULTS: There were 37 cases of irritable bowel syndrome in the group of 101 stable asthma patients (36.6 percent) and 12 cases in the group of 67 healthy subjects (17.9 percent) (p = 0.009). Irritable bowel syndrome comorbidity was not related to the severity of asthma (p = 0.15). Regardless of the presence of irritable bowel syndrome, psychiatric disorders in asthma patients (52/97; 53.6 percent) were more common than in the control group (22/63, 34.9 percent) (p = 0.02). Although psychiatric disorders were more common in asthma patients with irritable bowel syndrome (21/35, 60 percent) than in those without irritable bowel syndrome (31/62, 50 percent), the difference was not significant (p = 0.34). In asthma patients with irritable bowel syndrome and psychiatric disorders, the percentage of forced expiratory volume in 1 s (FEV1) was lower than it was in those with no comorbidities (p = 0.02). CONCLUSIONS: Both irritable bowel syndrome and psychiatric disorders were more common in asthma patients than in healthy controls. Psychiatric disorders were more common in asthma patients with irritable bowel syndrome than in those without irritable bowel syndrome, although the differences failed to reach statistical significance. In asthma patients with IBS and psychiatric disorders, FEV1s were significantly lower than in other asthma patients. It is important for clinicians to accurately recognize that these comorbid conditions are associated with additive functional impairment.

A acupuntura como terapêutica da síndrome do intestino irritável / Acupuncture as treatment for irritable bowel syndrome

Introdução: A Síndrome do Intestino Irritável (SII) é uma das mais comuns desordens gastrointestinais dasociedade ocidental, afetando cerca de 15% da população, especialmente adultos jovens. Tratamentos efetivostêm permanecidos indefinidos, já que muitos pacientes não conseguem o alívio adequado para os seus sintomascom o uso das terapias convencionais.Discussão: Tratamentos alternativos, como a acupuntura, estão tornando-se cada vez mais populares. Dentre as doenças do trato gastrointestinal, o uso mais comum dessas terapias é na SII. A resposta-placebo nos casos de SII pode chegar a 80% em ensaios simples,com uma resposta média de aproximadamente 40%, sendo que os preditores de uma resposta-placebo nãosão conhecidos e requerem análise de dados individuais tanto quanto a metanálise de ensaios publicados. Schneider et al. (Gut 2006;55:649-4), no maior estudo controlado e randomizado sobre o assunto, não achou diferença entre acupuntura e falsa acupuntura em relação aos principais desfechos pesquisados. Conclusão: Os efeitos da acupuntura na SII parecemser devidos ao efeito placebo. A razão para essa alta resposta pode ser atribuída às intensas particularidadespessoais durante o tratamento com acupuntura, combinada com a capacidade do paciente de relaxar emdeterminados ambientes calmos.

Introduction: Irritable bowel syndrome (IBS) is one of the most common disorders of western society; hence15% of its population is affected, especially young adults. Effective treatment has been remaining undefined,since many patients fail to reach adequate relief to their symptoms through conventional therapies.Discussion: Complementary therapies like acupuncture are growing in popularity. The most common use ofthese therapies in gastrointestinal diseases is the IBS. Placebo-effect efficacy in IBS can reach 80% in simplestudies, with an average response of nearly 40%. The predictors for placebo-effect efficacy are unknown and need analysis of individual data as much as of methanalysis of published studies. Schneider et al. (Gut 2006;55:649-4), at the largest controlled randomized study on the subject, found no difference between real and false acupuncture on the researched outcomes. Conclusion: Effects of acupuncture in IBS seem tobe due to placebo-effect. The reason for such high response can be given to the personal particularities of acupuncturetherapy, combined with the patient’s capacity of relaxation on calm environments.

The Pathophysiology of Irritable Bowel Syndrome: Inflammation and Motor Disorder / 대한소화기학회지

Irritable bowel sydrome (IBS) is one of the most common disorders and a heterogeneous condition in view of symptoms and underlying mechanisms. Though underlying causes of pathophysiologic changes remain unclear, low grade mucosal inflammation and abnormal intestinal motility are accepted mechanisms which alter gut function and generate symptoms of IBS. First, before 1980s, abnormal colonic and rectal motor functions were regarded as the main pathophysiology of IBS, but only 25-75% of IBS patients have apparent motor abnormalities which differ from the motor functions in normal controls. So, various gastrointestinal motility tests were not indicated for the diagnosis of IBS. The high-amplitude propagating contractions of colon in IBS patients may be related to the visceral pain perception. Second, the low grade mucosal inflammation may be involved in the pathophysiology of visceral hypersensitivity. Post infectious IBS (PI-IBS) occupied 6-17% of the total IBS and some previous prospective studies reported that 7-33% of acute bacterial enteritis patients developed IBS after 6-12 months of infection. The relative risk of IBS in the gastroenteritis cohort was 11.9 and the strongest risk factor is the duration of diarrhea. After enteritis event, the increased number of immunocytes, mast cells and large amount of lymphocytes infiltration were revealed in mucosa and enteric nervous system of the gut. Beside the inflammatory cells, enterochromaffin cells, cytokines and inducible nitric oxide may be related to the pathophysiologic mechanism of PI-IBS. Lastly, the abnormalities in the gastrointestinal autonomic nervous system can induce constipation or motor disorders, but further research should elucidate it.

Role of mucosal mast cells in visceral hypersensitivity in a rat model of irritable bowel syndrome

The involvement of mucosal mast cells (MMC) in the pathophysiology of irritable bowel syndrome (IBS) is still controversial. We aimed to re-evaluate the role of MMC in visceral hypersensitivity associated with IBS using a rat IBS model that develops the IBS symptom after a subsidence of acetic acid-induced colitis. No significant difference in the number of MMC was observed between normal rat colon and IBS rat colon. (61.7 +/-2.9/mm 2 in normal vs. 88.7 +/-13.3/mm 2 in IBS, p >0.29). However, the degranulation rate of MMC was significantly higher in IBS rat colon (49.5 +/-2.4% in normal vs. 68.8 +/-3.4% in IBS, p >0.05). Pretreatment of a mast cell stabilizer, doxantrazole (5 mg/kg, i.p.), reduced the degranulation rate of MMC and significantly attenuated visceral hypersensitivity to rectal distension in IBS rat, whereas it had no effect on the visceral sensory responses in normal rat. These results suggest that, although the number of MMC is not significantly changed in IBS rat colon, the higher degranulation rate of MMC is responsible for visceral hypersensitivity in this model IBS.

Activated Mast Cells Infiltrate in Close Proximity to Enteric Nerves in Diarrhea-predominant Irritable Bowel Syndrome

Mast cells (MC) may be one factor influencing the response of visceral afferent nerves to mechanical and chemical stimuli. The aim of this study was to evaluate the degree of infiltration and activity of colonic MC in irritable bowel syndrome (IBS). Biopsy specimens were obtained from the cecum and rectum of 14 diarrhea predominant IBS and 14 normal controls. Electron microscopy was used to determine the number of intact and degranulated colonic MC and to quantify these separately according to the distance between MC and enteric nerves. An increased number of MC in both cecum and rectum in the IBS group in comparison with the control group was demonstrated (p<0.05). Activated MC in close proximity to enteric nerves were significantly increased in both cecum and rectum of the IBS group compared to control group (p<0.005). In addition, activated MC were significantly increased in close proximity to the nerves compared to those in the remote area in both cecum and rectum of the IBS group (p<0.0001). MC were significantly increased and activated in both cecum and rectum of the IBS group compared to controls. MC may play a role in the gut sensory hypersensitivity of IBS.