New paradigm of oral rehydration in patients affected by irritable bowel syndrome with chronic diarrhea

Irritable bowel syndrome with diarrhea is a very frequent clinical condition characterized by disabling intestinal symptoms.This disease presents with daily abdominal pain for at least 3 months related to defecation and associated with a change in the frequency of bowel movements and the shape of the stool.International surveys about this disease report a global prevalence of about 1.5%.A new amino acid based electrolyte solution has recently been commercialized for oral rehydration in diarrhea.It is composed of water,electrolytes,and five selected amino acids that function as sodium co-transporters without containing glucose.In recent years,some studies explored the effectiveness of the amino acid based electrolyte beverage in oncologic patients with gastrointestinal mucositis,reporting good results.Recently,a prospective study to evaluate the clinical impact of the amino acid based medical beverage was conducted in patients with diarrhea predominant irritable bowel syndrome.The research was based on a real-life methodology minimizing the disruption of the routine care.One hundred patients suffering from irritable bowel syndrome with diarrhea drank a solution based on selected amino acids twice a day for 2 wk.Each enrolled patient completed the study and showed a significant response rate with regard to stool consistency and pain reduction.Based on this data,we can hypothesize that the amino acid based oral rehydration solution could be a valid tool in the treatment of patients affected by irritable bowel syndrome with diarrhea.It is certainly necessary to plan highquality clinical trials comparing glucose based oral solutions and amino acid based solutions in patients with persisting diarrhea.Probably in the near future all oral rehydration solutions will contain amino acids.

Current Research Status of Traditional Chinese Medicine External Treatment for Diarrhea Type Irritable Bowel Syndrome

Irritable bowel syndrome(IBS-D)with diarrhea is a common gastrointestinal functional disease in clinical practice,which seriously affects the quality of life of patients.Cur‐rently,Western medicine has poor therapeutic effects,while traditional Chinese medi‐cine has unique advantages in relieving IBS-D symptoms and preventing recurrence.In recent years,especially with external treatment of traditional Chinese medicine,it has become a new treatment direction in clinical practice and has achieved good therapeutic effects.This article will provide a review of recent research on the treatment of IBS-D using traditional Chinese medicine external treatment methods.

Increased expression of brain-derived neurotrophic factor is correlated with visceral hypersensitivity in patients with diarrheapredominant irritable bowel syndrome

BACKGROUND Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome(IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor(BDNF) was found to mediate visceral hypersensitivity via facilitating sensory nerve growth in pre-clinical studies. We hypothesized that BDNF might play a role in the pathogenesis of diarrhea-predominant IBS(IBS-D).AIM To investigate BDNF levels in IBS-D patients and its role in IBS-D pathophysiology.METHODS Thirty-one IBS-D patients meeting the Rome IV diagnostic criteria and 20 ageand sex-matched healthy controls were recruited. Clinical and psychological assessments were first conducted using standardized questionnaires. Visceral sensitivity to rectal distension was tested using a high-resolution manometry system. Colonoscopic examination was performed and four mucosal pinch biopsies were taken from the rectosigmoid junction. Mucosal BDNF expression and nerve fiber density were analyzed using immunohistochemistry. Mucosal BDNF mRNA levels were quantified by quantitative real-time polymerase chain reaction. Correlations between these parameters were examined.RESULTS The patients had a higher anxiety score [median(interquartile range), 6.0(2.0-10.0) vs 3.0(1.0-4.0), P = 0.003] and visceral sensitivity index score [54.0(44.0-61.0)vs 21.0(17.3-30.0), P < 0.001] than controls. The defecating sensation threshold[60.0(44.0-80.0) vs 80.0(61.0-100.0), P = 0.009], maximum tolerable threshold[103.0(90.0-128.0) vs 182.0(142.5-209.3), P < 0.001] and rectoanal inhibitory reflex threshold [30.0(20.0-30.0) vs 30.0(30.0-47.5), P = 0.032] were significantly lower in IBS-D patients. Intestinal mucosal BDNF protein [3.46 E-2(3.06 E-2-4.44 E-2) vs3.07 E-2(2.91 E-2-3.48 E-2), P = 0.031] and mRNA [1.57(1.31-2.61) vs 1.09(0.74-1.42), P = 0.001] expression and nerve fiber density [4.12 E-2(3.07 E-2-7.46 E-2) vs1.98 E-2(1.21 E-2-4.25 E-2), P = 0.002] were significantly elevated in the patients.Increased BDNF expression was positively correlated with abdominal pain and disease severity and negatively correlated with visceral sensitivity parameters.CONCLUSION Elevated mucosal BDNF may participate in the pathogenesis of IBS-D via facilitating mucosal nerve growth and increasing visceral sensitivity.

Comparison of 5-hydroxytryptophan signaling pathway characteristics in diarrhea-predominant irritable bowel syndrome and ulcerative colitis

AIM: To study differences in the visceral sensitivity of the colonic mucosa between patients with diarrheapredominant irritable bowel syndrome(IBS-D) and those with ulcerative colitis(UC) in remission and to relate these differences with changes in the 5-hydroxytryptophan(5-HT) signaling pathway. METHODS: Gastrointestinal symptoms were used to determine the clinical symptom scores and rectal visceral sensitivity of patients with IBS-D and patients with UC in remission. Blood levels of 5-HT and5-hydroxyindoleacetic acid(5-HIAA) were measured using an HPLC-electrochemical detection system. The levels of 5-HT 3 receptor(3R), 4R, and 7R m RNAs in colonic biopsy samples were detected using reverse transcription-polymerase chain reaction. The protein expression of TPH1 was analyzed by Western blot and immunohistochemistry.RESULTS: Abdominal pain or discomfort, stool frequency, and the scores of these symptoms in combination with gastrointestinal symptoms were higher in the IBS-D and UC groups than in the control groups. However, no significant differences were observed between the IBS-D and UC remission groups. With respect to rectal visceral sensitivity, the UC remission and IBS-D groups showed a decrease in the initial perception threshold, defecating threshold and pain threshold. However, these groups exhibited significantly increased anorectal relaxation pressure. Tests examining the main indicators of the 5-HT signaling pathway showed that the plasma 5-HT levels, 5-HIAA concentrations, TPH1 expression in the colonic mucosa, and 5-HT3 R and 5-HT5 R expression were increased in both the IBS-D and the UC remission groups; no increases were observed with respect to 5-HT7 R expression.CONCLUSION: The IBS-D and UC groups showed similar clinical symptom scores, visceral sensitivity, and levels of serotonin signaling pathway indicators in the plasma and colonic mucosa. However, the pain threshold and 5-HT7 R expression in the colonic mucosa were significantly different between these groups. The results reveal that(1) IBS-D and UC are related to visceral sensitivity pathogenesis and the clinical manifestations of these conditions and(2) the observed differences in visceral hypersensitivity are possibly due to differences in levels of the 5-HT7 receptor, a component of the 5-HT signaling pathway.

Refractory diarrhea: A paraneoplastic syndrome of neuroblastoma

Neuroblastoma(NB) is the most common extracranial solid tumor in children. Diarrheal NB is quite rare and is not easy to diagnose in the early stage. Six cases of diarrheal NB in our hospital treated from 1996 to 2006 were retrospectively analyzed, including characteristics such as electrolyte imbalance, pathologic features, vasoactive intestinal peptide(VIP) immunohistochemical staining results, treatment, and prognosis. All patients were boys with 3-8 loose or watery stools each day and routine fecal tests were normal. Abdominal tumors were identified by B-ultrasound. Drugs were ineffective. Three patients underwent surgery, and the remaining three patients received surgery and chemotherapy. Diarrhea stopped after treatment in five patients. Two patients died due to intractable hypokalemia. The tumor was located in the adrenal gland in four patients, in the upper retroperitoneum in one patient, and in the presacral area in one patient. Pathologic findings were NB and ganglioneuroblastoma. Five patients were at clinical stage Ⅰ-Ⅱ, and one was at stage Ⅲ. Four patients survived(followed-up for 6 mo to 4 years). Immunohistochemical staining for VIP was positive. Refractory diarrhea is a paraneoplastic syndrome of NB and is rare. Patients aged 1-3 years who present with chronic intractable diarrhea should be followed closely. Intractable diarrhea, hypokalemia, and dysplasia are the initial clinical manifestations. Increased VIP is characteristic of this disease. Potassium supplementation plays a vital role in the treatment procedure, especially preoperatively. The prognosis of diarrheal NB is good following appropriate treatment.

Increased intestinal mucosal leptin levels in patients with diarrhea-predominant irritable bowel syndrome

AIM To measure the leptin levels in patients with diarrheapredominant irritable bowel syndrome(IBS-D) and analyze the relationship of leptin with clinical features, visceral sensitivity, mast cells, and nerve fibers. METHODS Forty-two patients with IBS-D fulfilling the Rome Ⅲ criteria and 20 age-and sex-matched healthy controls underwent clinical and psychological evaluations using validated questionnaires(including IBS Symptom Severity Scale, IBS-specific Quality of Life, Hamilton Anxiety Scale, and Hamilton Depression Scale), along with colonoscopy, colonic mucosal biopsy, and visceral sensitivity testing. Serum leptin levels were assayed using enzyme-linked immunosorbent assay. Mucosal leptin expression and localization were evaluated using immunohistochemistry and immunofluorescence.Mucosal leptin m RNA levels were quantified using quantitative real-time reverse transcription polymerase chain reaction. Mast cell counts and activation rates were investigated by toluidine blue staining. Correlation analyses between these parameters were performed.RESULTS There were no statistically significant differences in age, gender, or body mass index between the IBS-D group and the control group. The median IBS Symptom Severity Scale score in the IBS-D group was 225.0(range, 100-475). IBS-D patients had significantly increased anxiety [IBS-D: median, 6.5; interquartile range(IQR), 3.3; control: median, 2.0; IQR, 2.0; P < 0.001] and depression(IBS-D: median, 7.0; IQR, 3.0; control: median, 3.0; IQR, 2.0; P < 0.001) scores. IBS-D patients had significantly lower first sensation threshold(IBS-D: median, 50.6; IQR, 25.9; control: median, 80.5; IQR, 18.6; P < 0.001), defecation sensation threshold(IBS-D: median, 91.5; IQR, 29.3; control: median, 155.0; IQR, 21.1; P < 0.001) and maximum tolerable threshold(IBS-D: median, 163.2; IQR, 71.2; control: median, 226.2; IQR, 39.3; P < 0.001). Mucosal leptin expression, as reflected by integrated optical density(IBS-D: median, 4424.71; IQR, 4533.63; control: median, 933.65; IQR, 888.10; P < 0.001), leptin mR NA expression(IBS-D: median, 1.1226; IQR, 1.6351; control: median, 0.8947; IQR, 0.4595; P = 0.009), and mast cell activation rate(IBS-D: median, 71.2%; IQR, 12.9%; control group: median, 59.4%; IQR, 18.88%; P < 0.001) were significantly increased in IBS-D patients. The colocalization of leptin and leptin receptors was observed on mast cells and PGP9.5-positive nerve fibers in the intestinal mucosa. Also, leptin expression was positively correlated with anxiety, depression, and the mast cell activation rate, but negatively correlated with the defecation sensation threshold and the maximum tolerance threshold during visceral sensitivity testing(adjusted P < 0.0038).CONCLUSION Increased levels of mucosal leptin may interact with mast cells and the nervous system to contribute to the pathogenesis of IBS-D.

Patients with irritable bowel syndrome-diarrhea have lower disease-specific quality of life than irritable bowel syndrome-constipation

AIM: To determine effect of irritable bowel syndrome(IBS) subtype on IBS-specific quality of life(QOL) questionnaire and its subscales.METHODS: We studied IBS patients visiting our functional gastroenterology disorder clinic at a tertiary care center of Unites States.IBS and IBS subtype were diagnosed using Rome-Ⅲ questionnaire.QOL was assessed using IBS-QOL questionnaire.IBSQOL assesses quality of life along eight subscales: dysphoria,interference with activities,body image,health worry,food avoidance,social reactions,sexual health,and effect on relationships.IBS-QOL and its subscales were both scored on a range of 0-100 with higher scores suggestive of better QOL.Results of overall IBS-QOL scores and subscale scores are expressed as means with 95%CI.We compared mean IBS-QOL score and its subscales among various IBSsubtypes.Analysis of variance(ANOVA) was used to compare the mean difference between more than two groups after controlling for age and gender.A posthoc analysis using Bonferroni correction was used only when P value for ANOVA was less than 0.05.RESULTS: Of 542 patients screened,243 had IBS as per Rome-Ⅲ criteria.IBS-mixed(IBS-M) was the most common IBS subtype(121 patients,49.8%) followed by IBS- diarrhea(IBS-D)(56 patients,23.1%),IBSconstipation(IBS-C)(54 patients,22.2%) and IBSunspecified(IBS-U)(12 patients,4.9%).Overall IBSQOL scores were significantly different among various IBS-subtypes(P = 0.01).IBS-QOL of patients with IBS-D(61.6,95%CI: 54.0-69.1) and IBS-M(63.0,95%CI: 58.1-68.0) was significantly lower than patients with IBS-C(74.5,95%CI: 66.9-82.1)(P = 0.03 and 0.02 respectively).IBS-D patients scored significantly lower than IBS-C on food avoidance(45.0,95%CI: 34.8-55.2 vs 61.1,95%CI: 50.8-71.3,P = 0.04) and interference with activity(59.6,95%CI: 51.4-67.7 vs 82.3,95%CI: 74.1-90.6,P < 0.001).IBS-M patients had more interference in their activities(61.6,95%CI: 56.3-66.9 vs 82.3,95%CI: 74.1-90.6,P = 0.001) and greater impact on their relationships(73.3,95%CI: 68.4-78.2 vs 84.7,95%CI: 77.2-92.2,P = 0.02) than IBS-C patients.Patients with IBS-M also scored significantly lower than IBS-C on food avoidance(47.2,95%CI: 40.7-53.7 vs 61.1,95%CI: 50.8-71.3,P = 0.04) and social reaction(66.1,95%CI: 61.1-71.1 vs 80.0,95%CI: 72.1-87.7,P = 0.005).CONCLUSION: IBS-D and IBS-M patients have lower IBS-QOL than IBS-C patients.Clinicians should recognize food avoidance,effects on daily activities and relationship problems in these patients.

Mitochondrial ATP 6 and 8 polymorphisms in irritable bowel syndrome with diarrhea

AIM: To investigate mitochondrial ATP 6 and 8 poly-morphisms in the colon and ileum of patients with ir-ritable bowel syndrome with diarrhea (IBS-D). METHODS: Twenty-eight patients fulfilling the Rome Ⅲ criteria for IBS-D and 28 healthy subjects were in-vestigated. All study participants underwent screening colonoscopy and mucosal biopsies were obtained from the colon and/or terminal ileum. Genomic DNA was ex-tracted from specimens based on standard protocols. Mitochondrial ATP (MT-ATP) 6 and 8 genes in speci-mens were polymerase chain reaction amplified and sequenced. Sequencing data were analyzed via Variant Reporter Software and compared with the reference sequence from Genbank (accession No. NC_012920) to indicate possible polymorphisms. The protocol was registered at www.clinicaltrials.gov as NCT01028898. RESULTS: Twenty-five polymorphic sites of MT-ATP 6 and 8 genes were detected and 12 of them were missense mutations. A median of two polymorphic sites in MT-ATP genes was found in colon specimens of controls while a median of three polymorphic sites was noted in patients with IBS-D (Mann-Whitney test, P=0.012). The variants of the colon and ileum speci-mens from the same subjects were identical in all but one case. Symptom duration in IBS was not found to be a significant factor associated with the mtDNA polymorphism (Spearman correlation, P=0.592). The mitochondrial DNA change at 8860 was present in all cases of both groups. The frequency of the 8701 poly-morphism was found to be the second most frequent; however, no statistical difference was noted between the groups (χ2 test, P=0.584). CONCLUSION: Patients with IBS-D have a higher inci-dence of MT-ATP 6 and 8 polymorphisms than healthy subjects, implying that the mtDNA polymorphism may play a role in IBS-D.

Altered metabolism of bile acids correlates with clinical parameters and the gut microbiota in patients with diarrhea-predominant irritable bowel syndrome

BACKGROUND Bile acids(BAs)have attracted attention in the research of irritable bowel syndrome with predominant diarrhea(IBS-D)due to their ability to modulate bowel function and their tight connection with the gut microbiota.The composition of the fecal BA pool in IBS-D patients is reportedly different from that in healthy populations.We hypothesized that BAs may participate in the pathogenesis of IBS-D and the altered BA profile may be correlated with the gut microbiome.AIM To investigate the role of BAs in the pathogenesis of IBS-D and the correlation between fecal BAs and gut microbiota.METHODS Fifty-five IBS-D patients diagnosed according to the Rome Ⅳ criteria and twentyeight age-,sex-,and body mass index-matched healthy controls(HCs)were enrolled in this study at the gastroenterology department of China-Japan Friendship Hospital.First,clinical manifestations were assessed with standardized questionnaires,and visceral sensitivity was evaluated via the rectal distension test using a high-resolution manometry system.Fecal primary BAs including cholic acid(CA)and chenodeoxycholic acid(CDCA),secondary BAs including deoxycholic acid(DCA),lithocholic acid(LCA),and ursodeoxycholic acid(UDCA)as well as the corresponding tauro-and glyco-BAs were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry.The gut microbiota was analyzed using 16S rRNA gene sequencing.Correlations between fecal BAs with clinical features and gut microbiota were explored.RESULTS Fecal CA(IBS-D:3037.66[282.82,6917.47]nmol/g,HC:20.19[5.03,1304.28]nmol/g;P<0.001)and CDCA(IBS-D:1721.86[352.80,2613.83]nmol/g,HC:57.16[13.76,1639.92]nmol/g;P<0.001)were significantly increased,while LCA(IBSD:1621.65[58.99,2396.49]nmol/g,HC:2339.24[1737.09,2782.40];P=0.002)and UDCA(IBS-D:8.92[2.33,23.93]nmol/g,HC:17.21[8.76,33.48]nmol/g;P=0.025)were significantly decreased in IBS-D patients compared to HCs.Defecation frequency was positively associated with CA(r=0.294,P=0.030)and CDCA(r=0.290,P=0.032)and negatively associated with DCA(r=−0.332,P=0.013)and LCA(r=−0.326,P=0.015)in IBS-D patients.In total,23 of 55 IBS-D patients and 15 of 28 HCs participated in the visceral sensitivity test.The first sensation threshold was negatively correlated with CDCA(r=−0.459,P=0.028)in IBS-D patients.Furthermore,the relative abundance of the family Ruminococcaceae was significantly decreased in IBS-D patients(P<0.001),and 12 genera were significantly lower in IBS-D patients than in HCs(P<0.05),with 6 belonging to Ruminococcaceae.Eleven of these genera were negatively correlated with primary BAs and positively correlated with secondary BAs in all subjects.CONCLUSION The altered metabolism of BAs in the gut of IBS-D patients was associated with diarrhea and visceral hypersensitivity and might be ascribed to dysbiosis,especially the reduction of genera in Ruminococcaceae.

Factorial study of moxibustion in treatment of diarrhea-predominant irritable bowel syndrome

AIM: To identify an appropriate therapeutic regimen for using aconite cake-separated moxibustion to treat diarrhea-predominant irritable bowel syndrome (D-IBS).

Watery diarrhea,hypokalemia and achlorhydria syndrome due to an adrenal pheochromocytoma

Watery diarrhea, hypokalemia and achlorhydria (WDHA) syndrome caused by vasoactive intestinal polypeptide (VIP) -producing tumor only rarely occurs in patients with nonpancreatic disease. A 49-year-old woman was referred for evaluation of a right adrenal tumor incidentally diagnosed by abdominal ultrasound during the investigation of chronic watery diarrhea. Laboratory findings showed hypokalemia and excessive production of VIP and catecholamines. After surgical resection of the tumor, diarrhea subsided and both electrolytes and affected hormone levels normalized. Immunohistochemical examination confirmed a diagnosis of pheochromocytoma, which contained VIP-positive ganglion-like cells. We herein present the clinical and histogenetic implications of this rare clinical entity, with literature review.

Genetic analysis of reproductive performance in sows during porcine reproductive and respiratory syndrome(PRRS)and porcine epidemic diarrhea(PED)outbreaks

Background: Porcine reproductive and respiratory syndrome(PRRS) is one of the most infectious swine diseases in the world, resulting in over 600 million dollars of economic loss in the USA alone. More recently, the USA swine industry has been having additional major economic losses due to the spread of porcine epidemic diarrhea(PED).However, information regarding the amount of genetic variation for response to diseases in reproductive sows is still very limited. The objectives of this study were to identify periods of infection with of PRRS virus(PRRSV) and/or PED virus(PEDV), and to estimate the impact their impact on the phenotypic and genetic reproductive performance of commercial sows.Results: Disease(PRRS or PED) was significant(P < 0.05) for all traits analyzed except for total piglets born.Heritability estimates for traits during Clean(without any disease), PRRS, and PED ranged from 0.01(number of mummies;Clean and PED) to 0.41(abortion;PED). Genetic correlations between traits within disease statuses ranged from-0.99(proportion born dead with number weaned;PRRS) to 0.99(number born dead with born alive;Clean). Within trait, between disease statuses, estimates ranged from-0.17(number weaned between PRRS and PED) to 0.99(abortion between Clean and PRRS).Conclusion: Results indicate that selection for improved performance during PRRS and PED in commercial sows is possible and would not negatively impact performance in Clean environments.

Effects of Zhenren Yangzang Decoction Combined with Modified Shenling Baizhu Powder on Immune Function and Intestinal Microecology of Diarrhea Patients with Deficiency and Cold Syndrome

OBJECTIVE: To observe the effects of Zhenren Yangzang Decoction combined with modified Shenling Baizhu Powder on the immune function and intestinal microecology of diarrhea patients with deficiency and cold syndrome. METHODS: A total of 60 diarrhea patients with deficiency and cold syndrome were randomly divided into observation group and control group, with 30 cases in each group. The control group was treated with conventional western medicine. The observation group was given the treatment of Zhenren Yangzang Decoction combined with modified Shenling Baizhu Powder on the basis of the same treatment for 4 weeks. The clinical symptoms, fecal flora and immunoglobulin content of the 2 groups were observed and the clinical efficacy was evaluated. RESULTS: After treatment, the symptoms scores of fecal diarrhea, aversion to cold, cold limbs, loss of appetite, cold and painful waist and knee, abdominal fullness, abdominal distension and abdominal pain, and intestinal bacilli contents were significantly decreased(P < 0.05). The contents of lactobacillus, bifidus bacilli, IgG, IgM and IgA were significantly increased(P < 0.05), and the improvement of the above indexes in the observation group was significantly better than that in the control group(P < 0.05). The total effective rate after treatment in the observation group was 93.3%, which was significantly higher than 73.3% of the control group(P < 0.05). CONCLUSION: The treatment of diarrhea patients with deficiency and cold syndrome with Zhenren Yangzang Decoction and modified Shenling Baizhu Powder can effectively improve the intestinal micro-ecological environment, improve the immune function of patients and promote the rapid recovery of patients.

Inhibitory effects of patchouli alcohol on stress-induced diarrhea-predominant irritable bowel syndrome

AIM To elucidate the mechanism of patchouli alcohol(PA) in treatment of rat models of diarrhea-predominant irritable bowel syndrome(IBS-D).METHODS We studied the effects of PA on colonic spontaneous motility using its cumulative log concentration(3 × 10^(-7) mol/L to 1 × 10^(-4)mol/L). We then determined the responses of the proximal and distal colon segments of rats to the folowing stimuli:(1) carbachol(1 × 10^(-9) mol/L to 1 × 10^(-5) mol/L);(2) neurotransmitter antagonists including N~ω-nitro-l-arginine methyl ester hydrochloride(10μmol/L) and(1 R~*, 2 S~*)-4-[2-Iodo-6-(methylamino)-9 Hpurin-9-yl]-2-(phosphonooxy)bicyclo[3.1.0]hexane-1-methanol dihydrogen phosphate ester tetraammonium salt(1 μmol/L);(3) agonist α,β-methyleneadenosine 5′-triphosphate trisodium salt(100 μmol/L); and(4) single KCl doses(120 mmol/L). The effects of blockers against antagonist responses were also assessed by pretreatment with PA(100 μmol/L) for 1 min. Electrical-field stimulation(40 V, 2-30 Hz, 0.5 ms pulse duration, and 10 s) was performed to observe nonadrenergic, noncholinergic neurotransmitter release in IBS-D rat colon. The ATP level of Kreb's solution was also determined.RESULTS PA exerted a concentration-dependent inhibitory effect on the spontaneous contraction of the colonic longitudinal smooth muscle, and the half maximal effective concentration(EC_(50)) was 41.9 μmol/L. In comparison with the KCl-treated IBS-D group, the contractile response(mg contractions) in the PA + KCl-treated IBS-D group(11.87 ± 3.34) was significantly decreased in the peak tension(P < 0.01). Compared with CCh-treated IBS-D rat colon, the cholinergic contractile response of IBS-D rat colonic smooth muscle(EC_(50) = 0.94 μmol/L) was significantly decreased by PA(EC_(50) = 37.43 μmol/L)(P < 0.05). Lack of nitrergic neurotransmitter release in stress-induced IBS-D rats showed contraction effects on colonic smooth muscle. Pretreatment with PA resulted in inhibitory effect on l-NAME-induced(10 μmol/L) contraction(P < 0.05). ATP might not be the main neurotransmitter involved in inhibitory effects of PA in the colonic relaxation of stressinduced IBS-D rats.CONCLUSION PA application may serve as a new therapeutic approach for IBS-D.

Direct costs of carcinoid syndrome diarrhea among adults in the United States

BACKGROUND The burden of carcinoid syndrome(CS)among patients with neuroendocrine tumors is substantial and has been shown to result in increased healthcare resource use and costs.The incremental burden of CS diarrhea(CSD)is less well understood,particularly among working age adults who make up a large proportion of the population of patients with CS.AIM To estimate the direct medical costs of CSD to a self-insured employer in the United States.METHODS CS patients with and without CSD were identified in the IBM®MarketScan®Database,including the Medicare Supplemental Coordination of Benefits database.Eligible patients had≥1 medical claim for CS with continuous health plan enrollment for≥12 mo prior to their first CS diagnosis and for≥30 d after,no claims for acromegaly,and no clinical trial participation during the study period(2014-2016).Baseline demographic and clinical characteristics,including comorbidities and treatment,were analyzed using descriptive statistics.Measures of healthcare resource use and costs were compared between patients with and without CSD,including Emergency Department(ED)visits,hospital admissions and length of stay,physician office visits,outpatient services,and prescription claims,using univariate and multivariate analyses to evaluate associations of CSD with healthcare resource use and costs,controlling for baseline characteristics.RESULTS Overall,6855 patients with CS were identified of which 4,043 were eligible for the analysis(1352 with CSD,2691 with CS only).Baseline demographic and clinical characteristics were similar between groups with the exception of age,underlying tumor type,and health insurance plan.Patients with CSD were older,had more comorbidities,and received more somatostatin analog therapy at baseline.Patients with CSD required greater use of healthcare resources and incurred higher costs than their peers without CSD,including hospitalizations(44%vs 25%)and ED visits(55%vs 31%).The total adjusted annual healthcare costs per patient were 50%higher(+$23865)among those with CSD,driven by outpatient services(+56%),prescriptions(+48%),ED visits(+26%),physician office visits(+21%),and hospital admissions(+11%).CONCLUSION The economic burden of CSD is greater than that of CS alone among insured working age adults in the United States,which may benefit from timely diagnosis and management.

Atypical Presentation of Classical Bartter Syndrome as a Case of Chronic Diarrhea and Failure to Thrive

The classical Bartter syndrome is an uncommon tubular disorder of autosomal recessive inheritance, characterized by early childhood onset of polyuria, polydipsia, vomiting, dehydration, constipation and salt craving habit. The long-term outlook for patients with Bartter syndrome is not certain. If not properly treated, it may lead to failure to thrive and growth retardation. We herein report a case of 18-month-old girl child who presented chronic diarrhea and failure to thrive and then was diagnosed as a case of classical Bartter syndrome. She was successfully treated with potassium supplementation and ibuprofen therapy.

Safety and efficacy of purified clinoptilolite-tuff treatment in patients with irritable bowel syndrome with diarrhea:Randomized controlled trial

BACKGROUND Irritable bowel syndrome(IBS)is a highly prevalent gastrointestinal disorder with poor response to treatment.IBS with predominant diarrhea(IBS-D)is accompanied by abdominal pain as well as high stool frequency and urgency.Purified clinoptilolite-tuff(PCT),which is approved by the Food and Drug Administration for use as a dietary supplement with the brand name G-PUR®,has previously shown therapeutic potential in other indications based on its physical adsorption capacity.AIM To assess whether symptoms of IBS-D can be ameliorated by oral treatment with PCT.METHODS In this randomized,placebo-controlled,double-blind pilot study,30 patients with IBS-D diagnosis based on Rome IV criteria were enrolled.Following a 4-wk run-in phase,14 patients were randomized to receive a 12-wk treatment with G-PUR®(2 g three times daily),and 16 patients received placebo.The relief from IBS-D symptoms as measured by the proportion of responders according to the Subject’s Global Assessment(SGA)of Relief was assessed as the primary outcome.For the secondary outcomes,validated IBS-D associated symptom questionnaires,exploratory biomarkers and microbiome data were collected.RESULTS The proportions of SGA of Relief responders after 12 wk were comparable in both groups,namely 21%in the G-PUR®group and 25%in the placebo group.After 4 wk of treatment,36%of patients in the G-PUR®group vs 0%in the placebo group reported complete or considerable relief.An improvement in daily abdominal pain was noted in 94%vs 83%(P=0.0353),and the median number of days with diarrhea per week decreased by 2.4 d vs 0.3 d in the G-PUR®and placebo groups,respectively.Positive trends were observed for 50%of responders in the Bristol Stool Form Scale.Positive trends were also noted for combined abdominal pain and stool consistency response and the Perceived Stress Questionnaire score.Only 64%in the G-PUR®group compared to 86%in the placebo group required rescue medication intake during the study.Stool microbiome studies showed a minor increase in diversity in the G-PUR®group but not in the placebo group.No PCT-related serious adverse events were reported.CONCLUSION In this randomized,double-blind,placebo-controlled study,the PCT product,G-PUR®,demonstrated safety and clinical benefit towards some symptoms of IBS-D,representing a promising novel treatment option for these patients.

Early-onset refractory diarrhea due to immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome associated with a novel mutation in the FOXP3 gene: A case report

BACKGROUND Immune dysregulation,polyendocrinopthy,enteropathy,X-linked(IPEX)syndrome is a rare X-linked recessive disease caused by mutations in the forkhead box protein 3(FOXP3)gene,which is a master transcriptional regulator for the development and function of CD4+CD25+regulatory T(Treg)cells.The dysfunction of these cells leads to multiple system autoimmune diseases.We present a case of IPEX due to a mutation not reported in the literature before.CASE SUMMARY We report a male patient with IPEX syndrome who presented with refractory diarrhea and malabsorption leading to failure to thrive,as well as with hypothyroidism and nephrotic syndrome.Laboratory investigation showed increased total IgE and Treg cells,decreased free triiodothyronine(FT3)and free thyroxine(FT4),and proteinuria.Multiple dietary and supportive treatments were introduced but did not improve the diarrhea during his hospital stay.Ultimately,whole exome sequencing revealed that the patient was hemizygous for the exon 5,c.542G>A(p.Ser181Asn)mutation of the FOXP3 gene,which has not been previously reported.The patient remains on prednisone and euthyrox while awaiting hematopoietic stem cell transplantation at the time of the compilation of this case report.CONCLUSION We report a novel FOXP3 gene mutation involved in IPEX.A high level of suspicion should be maintained in an early-onset refractory diarrhea patient.

Therapeutic Analysis of Fuzi Lizhong Wan with Trimebutine in the Treatment of Diarrhea Type lrritable Bowel Syndrome

Objective:To evaluate the clinical efficacy ofFuzi Lizhong Wan and trimebutine in the treatment of diarrhea irritab1e bowel syndrome.Methods:A tota1 of 90 patients with diarrhea irritable Dow1 syndrome were divided intocontro1 group(n=45)and treatment group(n=45)using the random.number table method.Patients in the control group were po administered withtrimebutine 0.2 g.three time daily for 4 weeks.Patients in the treatment group were po administered with Fuzi Lizhong Wan 9 g,three time daily for 4 weeks on the basis of the control group.The clinical efficacy and the TCM symptom scores were evaluated after treatment.The serological indicators in two groups were compared before and after treatment.Results:After treatment,the clinica1 efficacy and the TCM symptom scores in treatment group were significantly 1ower than that in contro1 group(P<0.05).The 1evels of serological indicators in both groups improved significant1y,and those in the treatment group were better than the control group(P<0.05).Conclusion:Combined therapy of Fuzi Lizhong Wan and trimebutine in the treatment of diarrhea type irritable bowe1 syndrome has a significant effect,which canrelieve clinical symptom;and reduce visceral sensitivity,and improve leve1s of inflammatory and quality of life.So it is suggested to be applied.

Post-infectious irritable bowel syndrome:Mechanistic insights into chronic disturbances following enteric infection

Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery.The appearance of new IBS symptoms following an infectious event is defined as post-infectiousIBS.Indeed,with the World Health Organization estimating between 2 and 4 billion cases annually,infectious diarrheal disease represents an incredible international healthcare burden.Additionally,compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features.A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota,epithelial barrier integrity,effector cell functions,and innate and adaptive immune features,all proposed physiological manifestations that can underlie GI abnormalities in IBS.Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms,and illicit successful infections.Consequently,the impact of infectious events on host physiology can be multidimensional in terms of anatomical location,functional scope,and duration.This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease,but may also lead to the establishment of chronic GI dysfunction compatible with IBS.