Gastroenterology

ABSTRAK
Sekolah Tinggi Ilmu Kesehatan Mandala Waluya Kendari
Program Studi Farmasi
Skripsi Penelitian,  September 2020
BORIS YASIN (F201601082)
“UJI EFEKTIVITAS GASTROPROTEKTIF EKSTRAK DAUN LABU KUNING (Cucurbita moschata) PADA TIKUS (Rattus norvegicus) YANG DIINDUKSI ASPIRIN”
Pembimbing I : apt. Jastria Pusmarani, S.Farm. M.Sc.
Pembimbing II : apt. Citra Dewi, S.Farm. M.Farm.
(xii + 86 Halaman + 5 Gambar + 6 Tabel + 9 Lampiran)

Di Indonesia Angka kejadian gastritis menurut World Health Organization (WHO) tahun 2017 cukup tinggi yaitu 274.396 kasus dari 283.452.952 jiwa penduduk. Efek samping dari penggunaan obat antiinflamasi non steroid (OAINS) menjadi 20% penyebab dari ulkus peptikum dan akan meningkat seiring bertambahnya usia. Pengobatan ulkus peptikum hingga saat ini menggunakan obat sintetik yang memiliki beberapa efek samping sehingga diperlukan pengobatan alternatif seperti pengobatan herbal. Daun labu kuning (Cucurbita moschata) mengandung senyawa flavonoid, saponin, tanin, alkaloid yang mampu melindungi mukosa lambung. Tujuan dilakukan penelitian ini adalah untuk mengetahui efektifitas gastroprotektif ekstrak daun labu kuning (Cucurbita moschata) pada tikus (Rattus norvegicus) yang  diinduksi aspirin.
Penelitian ini merupakan penelitian analitik laboratorium. Sampel diekstraksi menggunakan metode maserasi. Pengujian efek gastroprotektif menggunakan 18 ekor tikus yang dibagi menjadi 6 kelompok yaitu kelompok kontrol normal (Na.CMC 0,5%), kelompok kontrol positif (Omeprazole 20 mg/kgBB), kelompok kontrol induksi (Aspirin 300 mg/kgBB), kelompok (Dosis ekstrak 100 mg/kgBB), kelompok (Dosis ekstrak 200 mg/kgBB), dan kelompok (Dosis ekstrak 300 mg/kgBB). Analisis data menggunakan uji Kruskall Wallis dan Mann Whitney untuk mengetahui perbedaan tiap kelompok.
Hasil penelitian menunjukan adanya efek gastroprotektif ekstrak daun labu kuning (Cucurbita moschata) pada Dosis ekstrak 300 mg/kgBB dengan nilai P signifikan 0,037  <  0,05 yang sebanding dengan kelompok kontrol positif.

Kata Kunci : Gastroprotektif, Aspirin, Daun labu kuning (Cucurbita moschata).
Daftar Pustaka : 33 (2001-2018)

Removal of colorectal adenomas during colonoscopy reduces the incidence of colorectal carcinoma (CRC) and CRC-related mortality [1 -4]. Despite surveillance of patients after resection of adenomas [5] the risk of developing CRC remains higher than in the general population [6]. Moreover, it is known that CRC can be detected in the interval between scheduled surveillance colonoscopies [7]. One of the important causes for interval carcinomas is incomplete removal of the original adenoma [8 -10]. As residual adenomatous tissue has been shown to be capable of rapid regeneration , incomplete resection may result in local recurrence . Several studies have indicated that incomplete removal contributes to a higher subsequent incidence of CRC [5, 9, 14 -16].

Textbook in Internal medicine consists of 37 chapters. This textbook is made up of text material and enough illustrations, including clinical findings and schematic figures. The textbook is intended for English-speaking students of medical and pharmaceutical faculties of higher educational establishments of Ukraine.

Підручник з внутрішньої медицини складається з 37 розділів. Містить текстові матеріали та достатньо ілюстрацій, у тому числі клінічні матеріали та схематичні рисунки. Підручник призначений для англомовних студентів медичних та фармацевтичних факультетів вищих навчальних закладів України.

Background The use of non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with upper gastrointestinal symptoms such as heartburn and acid regurgitation. Aim To assess the efficacy of esomeprazole 20 and 40 mg for resolution of heartburn and acid regurgitation in continuous NSAIDs. Methods A post hoc analysis of five clinical trials was performed. Two identically designed, placebo-controlled, 4-week studies (NASA1, SPACE1) enrolled non-ulcer, NSAIDs-treated patients with upper abdominal pain, discomfort or burning. PLUTO and VENUS were identically designed, placebo-controlled, 6-month studies that enrolled patients at risk of NSAIDs-induced ulcers. Study 285 was an 8-week comparative study with ranitidine (300 mg/day) in patients with NSAIDs-induced gastric ulcers. Resolution of investigator-assessed heartburn and acid regurgitation was defined as symptom severity of 'none' in the last 7 days. Results In NASA1/SPACE1, heartburn resolved in 61% and 62% of patients taking esomeprazole 20 and 40 mg, respectively (vs. 36% on placebo, P < 0.001), and acid regurgitation resolved in 65% and 67% (vs. 48%, P < 0.001). Resolution of both symptoms was greater with esomeprazole than with placebo in PLUTO/VENUS (P £ 0.001), and than with ranitidine in study 285 (P < 0.05 for esomeprazole 20 mg). Conclusion Heartburn and regurgitation are common in patients taking NSAIDs and esomeprazole is efficacious for resolution of these symptoms.

Diabetes mellitus(DM) or impaired glucose tolerance occurs in up to 80% of patients with pancreatic cancer at the time of cancer diagnosis. It has been reported that plasma amylin (islet amyloid polypeptide) levels are elevated in all patients with pancreatic cancer who were diabetic and even moderately elevated in pancreatic cancer patients with normal glucose tolerance. The purpose of the present study was to determine the specificity of elevated amylin levels for pancreatic cancer. Methods: Plasma samples were obtained from patients with the medical conditions listed in the table below. Amylin was measured by specific radioimmunoassay after Sep-Pak cartridge extraction. One hundred and thirty-one patients (69 males, 62 females) with a median age of 59.5 years (range: 23-94) were evaluated. Mean amylin levels for the conditions are shown below. Summary: Elevated levels of plasma amylin were detected in several disorders besides pancreatic cancer, in particular, chronic pancreatitis, other GI malignancies and biliary obstruction from benign causes. Conclusion: These results suggest that elevated plasma amylin is not specific for pancreatic cancer, thereby, limiting its role as a tumor marker. Further studies are needed to see if amylin, used in conjunction with other biological markers, may be useful as a marker for the diagnosis of pancreatic cancer. 1483 DUAL·HEAD COINCIDENCE GAMMA CAMERA FDG PET IN PATIENTS WITH COLORECTAL AND ANAL CANCER. Eywin Bruun, Inge-Lis K. Hansen, Herlev Univ Hosp, Herlev, Denmark.

Colorectal cancer in African Americans has an increased incidence and mortality relative to Whites. The mean age of CRC development in African Americans is younger than that of Whites. There is also evidence for a more proximal colonic distribution of cancers and adenomas in African Americans.

Purpose: To retrospectively assess the performance of MR imaging in the evaluation and triage of pregnant patients presenting with acute abdominal or pelvic pain. Method and materials: MRI studies of pregnant patients who were referred for acute abdominal pain between 2001 and 2007 were included. MR images were retrospectively reviewed and compared with surgical and pathologic findings and clinical follow-up data. Analysis of imaging findings included evaluation of the visceral organs, bowel and mesentery, appendix (for presence of appendicitis), ovaries (detection and adnexal masses were evaluated), focal inflammation, presence of abscesses, and any other abnormal findings. Results: A total of 118 pregnant patients were included. MR findings were inconclusive in 2 patients and were positive for acute appendicitis in 11 patients (n = 9 confirmed by surgery, n = 2 improved without surgery). One patient with inconclusive MR had surgically confirmed appendicitis; the other patient with inconclusive MR had surgically confirmed adnexal torsion. Other surgical/interventional diagnoses suggested by MR imaging were adnexal torsion (n = 4), abscess (n = 4), acute cholecystitis (n = 1), and gastric volvulus (n = 1). Two patients with MR diagnosis of torsion improved without surgery. One patient with MR diagnosis of abscess had biliary cystadenoma at surgery. The rest of the MR diagnoses above were confirmed surgically or interventionally. MR imaging was normal in 67 patients and demonstrated medically treatable etiology in 28 patients: adnexal lesions (n = 9), urinary pathology (n = 6), cholelithiasis (n = 4), degenerating fibroid (n = 3), DVT (n = 2), hernia (n = 1), colitis (n = 1), thick terminal ileum (n = 1), rectus hematoma (n = 1). Three of these patients had negative surgical exploration and one had adnexal mass excision during pregnancy. Other patients were discharged with medical treatment. The sensitivity, specificity, accuracy, positive predictive values (ppv), and negative predictive values (npv) of MR imaging for acute appendicitis, and surgical/ interventional diagnoses were 90.0% vs. 88.9%, 98.1% vs. 95.0%, 97.5% vs. 94.1%, 81.8% vs. 76.2%, 99.1% vs. 97.9%, respectively. Conclusion: MR imaging is an excellent modality for diagnosis of acute appendicitis and exclusion of diseases requiring surgical/interventional treatment. Therefore MR imaging is useful for triage of pregnant patients with acute abdominal and pelvic pain.

A surrogate outcome measure is a laboratory measurement, a physical sign, or another intermediate substitute that is able to predict an intervention's effect on a clinically meaningful outcome. A clinical outcome detects how a patient feels, functions, or survives. Surrogate outcome measures occur faster or more often, are cheaper, and/or are less invasively achieved than the clinical outcome. In practice, validation is surprisingly often overlooked, especially if a biologic plausible rationale is proposed. Surrogate outcomes must be validated before use. The first step in validation is to demonstrate a correlation between the putative surrogate and the clinical outcome, e.g., the higher the surrogate the shorter time to death. However, a correlation is not sufficient to validate the surrogate. The second step is to establish if the intervention's effect on the surrogate outcome accurately predicts the intervention's effect on the clinical outcome. In hepatology a number of putative surrogate outcomes are used both in clinical research and in clinical practice without having been properly validated. Sustained virological response to interferons and ribavirin in patients with chronic hepatitis C, serum bilirubin concentration following ursodeoxycholic acid or immunosuppressants for patients with primary biliary cirrhosis, and nutritional outcomes following artificial nutrition for liver patients may not be valid surrogates for morbidity or mortality. The challenge is to develop reliable surrogates, both to facilitate the development of new interventions and to ensure our patients and us that these interventions are effective clinically. Ó

Hirschsprung's disease (HD) is a congenital disorder characterized by aganglionosis in the distal intestine. The zebrafish mutant, lessen (lsn), has HD phenotypic characteristics. We use the lsn mutant as an experimental model to unravel underlying developmental mechanisms for HD. This study aims to compare the neurochemical content of enteric neurons and gastrointestinal (GI)-motility patterns between wild-type zebrafish and lsn mutants to further validate this mutant as a suitable model for HD research. Immunofluorescence staining was used to detect specific neurochemical markers from 3 to 6 days post-fertilization (dpf) in the proximal (PI), mid (MI) and distal intestine (DI) of both wild-type and mutant embryos. Contractile activity of the GI-tract was filmed and the frequency and direction of contractions in each intestinal region were analyzed. Both mutant and wild-type embryos showed an increase in enteric neuron numbers over time. In mutants, the number of enteric neurons at each embryonic stage was significantly reduced in DI (absent at 3dpf) and MI, but less in PI. The proportion of nitrergic neurons was significantly reduced in all regions at 3dpf, but nearly unaffected in PI and MI at 4 and 5dpf. In mutants, serotonin, calretinin and calbindin showed a delayed expression and a decrease in both number and proportion at all points of time and in each intestinal region. In both mutant and wild-type embryos, galanin, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) were only detected in nerve fibers. In wild-type, VIP/PACAP-positive and galaninpositive fibers were present at all time points and in each region. Mutants only showed a few immunoreactive fibers at 3dpf in PI, while at 4dpf immunostained fibers appeared in MI and at 5dpf in DI, showing a delayed expression of these neuropeptides. GI-contractility analyses revealed that wild-type animals have defined motility patterns by 4dpf. When comparing motility patterns, the PI showed little change in when comparing wild-type to mutants. In contrast, we observed a decreased contractility in the MI and DI of mutants. The present study reveals abnormalities in the number and proportions of neurons expressing various neurochemical markers in the lsn mutant. These results are similar to previously reported data in the intestine proximal to the aganglionic segment and in the aganglionic segment of the lethal spotted mutant mice, an experimental HD model. Furthermore, in lessen GI-contractility is significantly perturbed in MI and DI. So, this study supports previous studies indicating that the zebrafish mutant lessen is a suitable model for HD research.

Pancreatic cancer is the fourth leading cause of cancer deaths in the USA in both sexes. Early diagnosis is difficult and the overall mortality rate is high. Individuals at high risk for pancreatic cancer include smokers, and persons with all forms of chronic alcoholic, metabolic, tropical or hereditary pancreatitis. The duration of exposure to inflammation seems to be the major factor involved in the transition from benign to malignant condition. Smoking, which appears to further accelerate the carcinogenic transformation, remains the strongest risk factor amenable to preventive intervention.

Among early colorectal carcinoma, endoscopic treatment is generally indicative for cases with intramucosal to submucosal (SM) superficial invasion, because cases with SM deep invasion should be treated surgically due to the risk of lymph node metastasis. It is important, therefore, to distinguish between superficial and deep SM invasion in early colorectal carcinoma prior to treatment. In this review we assessed the clinical usefulness and knack of pit pattern and narrow band imaging (NBI) diagnosis using magnifying observation. VN type pit pattern, type C3 in NBI Hiroshima classification and NBI type 3 in NBI international colorectal endoscopic (NICE) classification are useful predictors of SM deep invasion. In NBI magnifying observation evaluation of both the vascular pattern and surface pattern are important. We have to use pit pattern diagnosis and NBI magnifying diagnosis as the situation demands with the knowledge of both advantage and disadvantage in each diagnostic method.

Binge consumption of alcohol is an alarming global health problem. Binge (acute) ethanol (EtOH) is implicated in the pathophysiology of alcoholic liver disease (ALD). New studies from experimental animals and from humans indicate that binge EtOH has profound effects on immunological, signaling, and epigenetic parameters of the liver. This is in addition to the known metabolic effects of acute EtOH. Binge EtOH alters the levels of several cellular components and dramatically amplifies liver injury in chronically EtOH exposed liver. These studies highlight the importance of molecular investigations into binge effects of EtOH for a better understanding of ALD and also to develop therapeutic strategies to control it. This review summarizes these recent developments.

Background Patients with liver cirrhosis experience a large variety of metabolic disorders associated with more hepatic decompensation. Hepatic encephalopathy (HE) is a significant complication in liver cirrhosis patients, presenting a wide spectrum of neuropsychological symptoms. A deficiency of 25-hydroxy vitamin D (25-OHD) in the general population is associated with a loss of cognitive function, dementia, and Alzheimer&#39;s disease. Aim of the Study. Our study aims to check the relationship between low serum 25-OHD and HE in patients with HCV-related liver cirrhosis and assess its link with patient mortality. Patients and Methods. This study was observationally carried out on 100 patients with HCV-related liver cirrhosis. The patients were divided into 2 groups: Group A—included 50 HCV-related cirrhotic patients with HE, and Group B—included 50 HCV-related cirrhotic patients without HE. Assessment of disease severity using the end-stage liver disease (MELD) model and Child Turc...

Treatment of chronic hepatitis B virus (HBV) infection is aimed at suppressing viral replication to the lowest possible level, and thereby to halt the progression of liver disease and prevent the onset of complications. Two categories of drugs are used in HBV therapy: the interferons, including standard interferon alfa or pegylated interferon alfa, and specific nucleoside or nucleotide HBV inhibitors that target the reverse-transcriptase function of HBV-DNA polymerase. The reported results of clinical trials have used varying definitions of efficacy, failure, and resistance based on different measures of virologic responses. This article discusses HBV virologic markers and tests, and their optimal use both for planning and reporting clinical trials and in clinical practice.

Probiotics are characterized by their ability to interact with commensal microflora in the gastrointestinal tract to produce beneficial health effects. In vitro studies suggest that Lactobacillus species have the potential to suppress the growth of Helicobacter pylori. The goal of this study was to determine if pretreatment of mice with a commercial mixture of live probiotics (L. rhamnosus, strain R0011, and L. acidophilus, strain R0052) would suppress colonization of H. pylori, strain SS1. Thirty C57BL/6 female mice were divided into four groups: Group A was fed sterile water, group B received probiotics in sterile drinking water, group C was challenged orogastrically with H. pylori, and group D was pretreated with probiotics in drinking water prior to and following challenge with H. pylori. Rectal swabs, stomach homogenates, and luminal contents from ileum and colon were plated onto colistin nalidixic acid plates. Serial dilutions of stomach homogenates were plated onto H. pylori-sensitive agar plates and incubated under microaerophilic conditions. Tissue samples from the stomach were analyzed histologically to determine the degree of H. pylori colonization, mucosal inflammation, and epithelial cell apoptosis. Probiotics in drinking water did not affect the overall well-being of mice. Lactobacillus species were excreted in stools over the entire duration of treatment. Pretreatment with probiotics reduced the number of mice with H. pylori growth from stomach homgenates (100 to 50%; P = 0.02). The percentage of mice with moderate-severe H. pylori-induced inflammation in the gastric antrum was reduced with probiotic pretreatment (71 to 29%; P = 0.14). However, pretreatment with probiotics did not prevent H. pylori-induced apoptosis in the gastric mucosa. This preparation of probiotics provided a safe and novel approach for reducing H. pylori colonization and bacterial-induced inflammation of mice.

Patients and Methods Cirrhotic patients with acute esophageal variceal bleeding that was initially controlled with emergency sclerotherapy and in whom a hemodynamic evaluation could be performed within the first 24 hours of admission, were considered for inclusion in this study. All patients were admitted to our hospital with hematemesis and/or melena. Diagnostic endoscopy was performed between 1 and 5 hours later, as soon as safely possible after initial resuscitation. Variceal hemorrhage was defined when endoscopy showed active hemorrhage

The use of nurse endoscopists to perform flexible sigmoidoscopy is expanding, increasing the availability of colorectal cancer screening. However, the effectiveness of this practice has not been studied in randomized trials. The aim of this trial was to examine the miss rate of polyps, the depth of sigmoidoscope insertion, and the incidence of complications during flexible sigmoidoscopy performed by nurse endoscopists and by gastroenterologists. Methods: Three hundred twenty-eight patients were randomized to undergo screening flexible sigmoidoscopy performed by a nurse endoscopist or by a gastroenterologist. Frequency of missed polyps was determined by repeat sigmoidoscopy, performed by a gastroenterologist blinded to the identity of the first endoscopist. Multiple logistic regression analysis identified characteristics associated with missed polyps. Results: Gastroenterologists and nurse endoscopists had equivalent miss rates for adenomatous polyps (20% vs. 21%, respectively; P ‫؍‬ 0.91). No complications occurred in any patient. Gastroenterologists inserted the sigmoidoscope further than nurse endoscopists (61 vs. 55 cm, respectively; P F 0.00001). Polyp location in the descending colon (odds ratio, 4.1; 95% confidence interval, 1.7-10.3) was highly associated with missed polyps. Conclusions: No differences in detection of adenomatous polyps or frequency of complications were found. These data suggest that experienced nurse endoscopists may perform screening flexible sigmoidoscopy as safely and as effectively as gastroenterologists.

Gastrointestinal motility disorders are often present in diabetic patients. Even if this problem has been attributed to autonomic neuropathy, the pathophysiological mechanisms responsible are not completely defined. Aim of our study was to evaluate the effect of eradication of small-intestine bacterial overgrowth on oro-cecal transit time in diabetic patients in order to identify a possible role of bacterial overgrowth on dysmotility. We selected among 74 diabetic patients who underwent H2-lactulose breath test, 21 subjects (13M, 8F, mean age 43.7 years, 11 with type 1 and 10 with type 2 diabetes) affected by bacterial overgrowth and delayed oro-cecal transit time and with normal cardiovascular autonomic test. Patients were treated with rifaximin and underwent a control breath test. Data were analyzed using paired-data t-test. Three patients still showed bacterial overgrowth, 5 persistent delayed transit time without bacterial overgrowth; 13 patients (62%) showed a significant (P &l...

The new england journal of medicine 2674 * The most common adverse events are those that occurred in 10 percent or more of the patients in any treatment group. † Fisher's exact test was used for the comparison with the placebo-adefovir group (P<0.05). ‡ Fisher's exact test was used for the comparison with the adefovir-placebo group (P<0.05).

Health Improvement Network primary care database was used to identify 2 cohorts of patients aged 1-17 years between 2000 and 2005; patients with a recorded diagnosis of gastroesophageal reflux disease (GERD) during the study period (n = 1809) and a cohort of patients without GERD (n = 5000). Non-GERD patients were frequency matched to GERD patients by age, sex and calendar year. Among GERD patients, 2 sub-cohorts of patients were identified according to whether they had been prescribed a PPI within 1 year of GERD diagnosis; there were 487 GERD PPI users and 1322 GERD PPI non-users. All patients (GERD and non-GERD) were followed-up for up to 1 year from the start date (date of first prescription for GERD PPI users, date of GERD diagnosis for GERD PPI non-users and a random date for non-GERD patients). A total of 118 patients with a recorded diagnosis of fracture were identified; their medical records were reviewed manually to ascertain incident cases. There were a total of 45 fracture cases among GERD patients; 11 among PPI users and 34 among PPI non-users. Adjusted incidence rate ratios (IRRs) for fracture risk associated with exposure to PPIs were calculated. We also conducted a nested case-control analysis, using all 118 cases of fracture identified in both GERD and non-GERD cohorts. All remaining patients without fracture at the end of follow-up in both cohorts served as controls (n = 6656). The index date was the date of diagnosis for fracture cases and a random date for controls. Data on PPI use were obtained and odds ratios (ORs) for fracture risk associated with PPI use were calculated by multivariate adjusted logistic regression models. Results. Among GERD patients, there was no association between fracture risk and current (IRR: 0.68; 95% CI: 0.24-1.94) or recent/past use (IRR: 0.90; 95% CI: 0.40-2.05) of PPIs compared with non-use of PPIs. Similarly, among all patients (with or without GERD), neither current (OR: 0.71; 95% CI: 0.25-2.04) nor recent/past use (OR: 0.95; 95% CI: 0.41-2.18) of PPIs was associated with an increased risk of fracture compared with non-use of PPIs. However, these estimates were based on only four currently exposed cases and seven recently/past exposed cases. Conclusion. The results of our study do not support an association between PPI use and risk of fracture in children and adolescents with or without a diagnosis of GERD. However, it should be noted that only a small number of cases were exposed to a PPI.

Background and Aims: IBS is a complex disease with recurring clusters of symptoms. Genetic mutations and single nucleotide polymorphisms do not fit these traits. We reported previously that neonatal inflammatory insult enhances smooth muscle reactivity to ACh in adulthood, which enhances colonic motor function to induce diarrhea-like conditions. In this study, we tested the hypothesis that adverse early life events reprogram the expression of genes encoding vasoactive intestinal polypeptide (VIP) and pore-forming α 1C -subunit of the Ca v 1.2b channels (Canca1c) by epigenetic mechanisms in colonic muscularis externa to induce colonic motility dysfunction in adulthood. Methods: Ten-day old rat neonates received intraluminal 130 mg/kg TNBS in the colon; control pups received saline. Colonic muscularis externae (ME) were obtained 6 to 8-week later. Results: qRT-PCR and western blotting showed significant increases in the mRNA and protein expressions of VIP and α 1C -subunit in the ME of about 50% of adult rats that received neonatal inflammatory insult (IBS-rats). Chromatin immunoprecipitation assays showed marked increase in acetylation of histone H3 lysine 9 (H3K9Ac, a marker of transcriptional activation) (0.8±0.1 vs. 0.45±0.06 Ctr., p<0.05) and attenuation in trimethylation of histone H3 lysine 9 (H3K9me3, a marker of transcriptional repression) (0.8±0.07 vs.1.2±0.03 Ctr., p<0.05) in the core promoter region of Cacna1c in IBS-rats. As a result, the RNA polymerase II (RNAP II) association with the Cacna1c promoter significantly increased, indicating enhanced Cacna1c gene transcription. We investigated the role of VIP in the epigenetic modification of Cacna1c by incubating ME from naïve rats with 100 ng/ml VIP for 24 hours. VIP-treatment markedly increased H3K9Ac and decreased H3K9me3 at the upstream CREB-binding site (-2062/-2055) and around the transcription start site (+21~+168), and hence enhanced RNAP II interaction with this promoter region suggesting that VIP modulates epigenetic components at the Cacna1c promoter to stimulate Cacna1c gene transcription. VIP antagonist, (p-Chloro-D-Phe6,Leu17)-VIP, abrogated VIP-mediated RNAP II binding, H3K9 acetylation and trimethylation at the Cacna1c promoter. Intraperitoneal administration of 100 mM sodium butyrate, a histone deacetylase inhibitor, significantly elevated Cacna1c mRNA in ME of naïve adult rats (1.5±0.06 vs. 1±.01 Ctr., p<0.05), indicating that histone hyperacetylation is necessary for α 1C gene transcription. Conclusions: Our findings reveal the epigenetic mechanisms by which adverse early life events alter the gene expression of specific cell signaling proteins to cause colonic motor dysfunction in adulthood. The intensities of epigenetic modifications are modifiable by environmental influences, such as stress, which explains relapses and remissions of symptoms in IBS patients.

Rapid clinical dissemination of CT colonography (CTC) is occurring in parallel with continued research into technique optimisation and diagnostic performance. A need exists therefore for current guidance as to basic prerequisites for effective clinical implementation. A questionnaire detailing CTC technique, analysis, training and clinical implementation was developed by the

The role of oral supplementation with branched-chain amino acids (BCAA) in advanced cirrhosis is far from settled. A nutritional approach might prevent progressive liver failure and improve nutritional parameters and quality of life. Methods: A multicenter, randomized study comparing 1-year nutritional supplementation with BCAA against lactoalbumin or maltodextrins was performed in 174 patients with advanced cirrhosis. Primary outcomes were the prevention of a combined end point (death and deterioration to exclusion criteria), the need for hospital admission, and the duration of hospital stay. Secondary outcomes were nutritional parameters, laboratory data and Child-Pugh score, anorexia, health-related quality of life, and need for therapy. Results: Treatment with BCAA significantly reduced the combined event rates compared with lactoalbumin (odds ratio, 0.43; 95% confidence interval, 0.19 -0.96; P ‫؍‬ 0.039) and nonsignificantly compared with maltodextrins (odds ratio, 0.51; 95% confidence interval, 0.23-1.17; P ‫؍‬ 0.108). The average hospital admission rate was lower in the BCAA arm compared with control treatments (P ‫؍‬ 0.006 and P ‫؍‬ 0.003, respectively). In patients who remained in the study, nutritional parameters and liver function tests were, on average, stable or improved during treatment with BCAA and the Child-Pugh score decreased (P ‫؍‬ 0.013). Also, anorexia and health-related quality of life (SF-36 questionnaire) improved. Long-term compliance with BCAA was poor. Conclusions: In advanced cirrhosis, longterm nutritional supplementation with oral BCAA is useful to prevent progressive hepatic failure and to improve surrogate markers and perceived health status. New formulas are needed to increase compliance.

Abbreviations used in this paper: ANCA, antineutrophil cytoplasmic antibody; 95% CI, 95% confidence interval; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; IBD, inflammatory bowel disease; IL, interleukin; OC, oral contraceptive; pANCA; perinuclear ANCA; UC, ulcerative colitis.

Background & Aims: In healthy subjects, exercise pro-During exercise, an increase in cardiac output and a motes marked hemodynamic and humoral changes redistribution of blood flow from other territories (especharacterized by an increase in cardiac output, a rediscially the splanchnic area) through an adrenergic-meditribution of blood flow to muscular territories under acated vasoconstriction 6 are the main physiological changes tivity, and an increase in sympathoadrenergic activity.