Role of antispasmodics in the treatment of irritable bowel syndrome

Irritable bowel syndrome(IBS)is a long-lasting,relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits.Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis,both of which require effective treatment.Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission.Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades.Alverine citrate,a spasmolytic,decreases the sensitivity of smooth muscle contractile proteins to calcium,and it is a selective 5-HT1A receptor antagonist.Alverine,in combination with simethicone,has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial.Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis.Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control;nevertheless,in recent placebo-controlled studies,mebeverine did not exhibit superiority over placebo.Otilonium bromide is poorly absorbed from the GI tract,where it acts locally as an L-type calcium channel blocker,an antimuscarinic and a tachykinin NK2receptor antagonist.Otilonium has effectively reduced pain and improved defecation alterations in placebocontrolled trials in IBS patients.Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract.Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients.Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial.Antispasmodics have excellent safety profiles.T-type calcium channel blockers can abolish visceral hypersensitivity in animal models,which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS.

Association between autoimmune pancreatitis and systemic autoimmune diseases

AIM: To investigate the association between autoimmune pancreatitis (AIP) and systemic autoimmune diseases (SAIDs) by measurement of serum immunoglobulin G4 (IgG4). METHODS: The serum level of IgG4 was measured in 61 patients with SAIDs of different types who had not yet participated in glucocorticosteroid treatment. Patients with an elevated IgG4 level were examined by abdominal ultrasonography (US) and, in some cases, by computer tomography (CT). RESULTS: Elevated serum IgG4 levels (919 ± 996 mg/L) were detected in 17 (28%) of the 61 SAID patients. 10 patients had Sj gren's syndrome (SS) (IgG4: 590 ± 232 mg/L), 2 of them in association with Hashimoto's thyroiditis, and 7 patients (IgG4: 1388 ± 985.5 mg/L) had systemic lupus erythematosus (SLE). The IgG4 level in the SLE patients and that in patients with SS were not significantly different from that in AIP patients (783 ± 522 mg/L). Abdominal US and CT did not reveal any characteristic features of AIP among the SAID patients with an elevated IgG4 level. CONCLUSION: The serum IgG4 level may be elevated in SAIDs without the presence of AIP. The determination of serum IgG4 does not seem to be suitable for the differentiation between IgG4-related diseases and SAIDs.

Frequency and prognostic role of mucosal healing in patients with Crohn's disease and ulcerative colitis after one-year of biological therapy

AIM:To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease(CD)and ulcerative colitis(UC).METHODS:The data from 41 patients with CD and 22 patients with UC were assessed.Twenty-four CD patients received infliximab,and 17 received adalimumab.The endoscopic severity of CD was quantified with the simplified endoscopic activity score for Crohn’s disease in CD and with the Mayo endoscopic subscore in UC.RESULTS:Mucosal healing was achieved in 23 CD and7 UC patients.Biological therapy had to be restarted in78%of patients achieving complete mucosal healing with CD and in 100%of patients with UC.Neither clinical remission nor mucosal healing was associated with the time to restarting the biological therapy in either CD or UC.CONCLUSION:Mucosal healing did not predict sustained clinical remission in patients in whom the biological therapies had been stopped.

Elevated miR-33a and miR-224 in steatotic chronic hepatitis Cliver biopsies

AIM:To assess the expression of selected microRNAs(miRNA) in hepatitis C,steatotic hepatitis C,noninfected steatotic and normal liver tissues.METHODS:The relative expression levels of miR-21,miR-33 a,miR-96,miR-122,miR-125 b,miR-221 and miR-224 were determined in 76 RNA samples isolated from 18 non-steatotic and 28 steatotic chronic hepatitis C(CHC and CHC-Steatosis,respectively) cases,18 non-infected,steatotic liver biopsies of metabolic origin(Steatosis) and 12 normal formalin-fixed paraffin-embedded liver tissues using TaqMan MicroRNA Assays.All CHC biopsy samples were obtained prior to initiating therapy.Patients' serum biochemical values,which included glucose,triglyceride,cholesterol,alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl-transferase(GGT),alkaline phosphatase(AP),were obtained and correlated with relative miRNA expression.RESULTS:When compared with control non-infected liver samples,miR-122 and miR-221 levels were reduced in CHC-Steatosis(P < 0.03) and in CHC,CHCSteatosis and Steatosis(P < 0.01).Alternatively,the expression of miR-33 a and miR-224 were elevated in CHC-Steatosis and Steatosis in comparison to control tissue(P < 0.01).The levels of miR-33 a and miR-224 in CHC-Steatosis(P < 0.02) and miR-224 in Steatosis(P < 0.001) were increased in comparison to CHC samples.By contrast,the expression of miR-21 did not differ statistically between diseased and normal liver samples.Levels of miR-33 a correlated negatively with serum AST and AP levels in Steatosis as well as with necroinflammatory grade in CHC,whereas miR-21 correlated positively with AST in Steatosis and displayed negative correlation with triglyceride level in CHC-Steatosis.In contrast,miRNA levels were not correlated with ALT,GGT,cholesterol levels or fibrosis stage.CONCLUSION:Differences in miRNA expression were observed between CHC and steatotic CHC,CHC and steatotic liver,but not between steatotic CHC and steatotic liver of metabolic origin.

Synchronous electrogastrographic and manometric study of the stomach as an esophageal substitute

AIM: To investigate the electric and contractile mechanisms involved in the deranged function of the transposed stomach in relation to the course of the symptoms and the changes in contractile and electrical parameters over time.METHODS: Twenty-one patients after subtotal esophagectomy and 18 healthy volunteers were studied.Complaints were compiled by using a questionnaire, and a symptom score was formed. Synchronous electrogastrography and gastric manometry were performed in the fasting state and postprandially.RESULTS: Eight of the operated patients were symptomfree and 13 had symptoms. The durations of the postoperative periods for the symptomatic (9.1±6.5 mo)and the asymptomatic (28.3±8.8 mo) patients were significantly different. The symptom score correlated negatively with the time that had elapsed since the operation. The percentages of the dominant frequency in the normogastric, bradygastric and tachygastric ranges differed significantly between the controls and the patients.A significant difference was detected between the power ratio of the controls and that of the patients. The occurrence of tachygastria in the symptomatic and the symptom-free patients correlated negatively both with the time that had elapsed and with the symptom score. There was a significant increase in motility index after feeding in the controls, but not in the patients. The contractile activity of the stomach increased both in the controls and in the symptom-free patients. In contrast, in the group of symptomatic patients, the contractile activity decreased postprandially as compared with the fasting state.CONCLUSION: The patients' post-operative complaints and symptoms change during the post-operative period and correlate with the parameters of the myoelectric and contractile activities of the stomach. Tachygastria seems to be the major pathogenetic factor involved in the contractile dysfunction.

Utility of serum TNF-a,infliximab trough level,and antibody titers in inflammatory bowel disease

AIM:To assess tumor necrosis factor-a(TNF-a),infliximab(IFX)concentrations,and antibodies against IFX molecules in patients with inflammatory bowel disease(IBD)who develop loss of response,side effects,or allergic reaction during anti TNF-a therapy.METHODS:Blood samples of 36 patients with response loss,side effects,or hypersensitivity to IFX therapy(Group?Ⅰ)and 31 patients in complete clinical remission(GroupⅡ)selected as a control group were collected to measure trough serum TNF-a level,IFX,and anti-IFX antibody(ATI)concentration.We examined the correlation between loss of response,the development of side effects or hypersensitivity,and serum TNF-a,IFX trough levels,and ATI concentrations.RESULTS:The serum TNF-a level was shown to be correlated with the presence of ATI;ATI positivity was significantly correlated with low trough levels of IFX.ATIs were detected in 25%of IBD patients with loss of response,side effects,or hypersensitivity,however no association was revealed between these patients and antibody positivity or lower serum IFX levels.Previous use of IFX correlated with the development of ATI,although concomitant immunosuppression did not have any impact on them.CONCLUSION:On the basis of the present study,we suggest that the simultaneous measurement of serum TNF-a level,serum anti TNF-a concentration,and antibodies against anti TNF-a may further help to optimize the therapy in critical situations.