Common variants in the HLA-DQ region confer susceptibility to idiopathic achalasia

Idiopathic achalasia is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus(1,2). This ultimately leads to massive dilatation and an irreversibly impaired megaesophagus. We performed a genetic association study in 1,068 achalasia cases and 4,242 controls and fine-mapped a strong MHC association signal by imputing classical HLA haplotypes and amino acid polymorphisms. An eight-residue insertion at position 227-234 in the cytoplasmic tail of HLA-DQ beta 1 (encoded by HLA-DQB1*05:03 and HLA-DQB1*06:01) confers the strongest risk for achalasia (P = 1.73 x 10(-19)). In addition, two amino acid substitutions in the. extracellular …

Effect of liraglutide on intragastric pressure (IGP) and satiation during intragastric nutrient drink infusion in healthy volunteers

Chemosensory signalling pathways involved in sensing of amino acids by the ghrelin cell

AbstractTaste receptors on enteroendocrine cells sense nutrients and transmit signals that control gut hormone release. This study aimed to investigate the amino acid (AA) sensing mechanisms of the ghrelin cell in a gastric ghrelinoma cell line, tissue segments and mice. Peptone and specific classes of amino acids stimulate ghrelin secretion in the ghrelinoma cell line. Sensing of L-Phe occurs via the CaSR, monosodium glutamate via the TAS1R1-TAS1R3 while L-Ala and peptone act via 2 different amino acid taste receptors: CaSR & TAS1R1-TAS1R3 and CaSR & GPRC6A, respectively. The stimulatory effect of peptone on ghrelin release was mimicked ex vivo in gastric but not in jejunal tissue …

Review article: a comparison of glucagon-like peptides 1 and 2.

Summary Background Recent advancements in understanding the roles and functions of glucagon-like peptide 1 (GLP-1) and 2 (GLP-2) have provided a basis for targeting these peptides in therapeutic strategies. Aim To summarise the preclinical and clinical research supporting the discovery of new therapeutic molecules targeting GLP-1 and GLP-2. Methods This review is based on a comprehensive PubMed search, representing literature published during the past 30 years related to GLP-1 and GLP-2. Results Although produced and secreted together primarily from L cells of the intestine in response to ingestion of nutrients, GLP-1 and GLP-2 exhibit distinctive biological functions that are governed by t…

The latent structure of the functional dyspepsia symptom complex: A taxometric analysis

OBJECTIVES: Rome III introduced a subdivision of functional dyspepsia (FD) into postprandial distress syndrome and epigastric pain syndrome, characterized by early satiation/postprandial fullness, and epigastric pain/burning, respectively. However, evidence on their degree of overlap is mixed. We aimed to investigate the latent structure of FD to test whether distinguishable symptom-based subgroups exist. METHODS: Consecutive tertiary care Rome II FD patients completed the dyspepsia symptom severity scale. Confirmatory factor analysis (CFA) was used to compare the fit of a single factor model, a correlated three-factor model based on Rome III subgroups and a bifactor model consisting of a g…

Unraveling the behavior of oral drug products inside the human gastrointestinal tract using the aspiration technique: History, methodology and applications

Fluid sampling from the gastrointestinal (GI) tract has been applied as a valuable tool to gain more insight into the fluids present in the human GI tract and to explore the dynamic interplay of drug release, dissolution, precipitation and absorption after drug product administration to healthy subjects. In the last twenty years, collaborative initiatives have led to a plethora of clinical aspiration studies that aimed to unravel the luminal drug behavior of an orally administered drug product. The obtained drug concentration-time profiles from different segments in the GI tract were a valuable source of information to optimize and/or validate predictive in vitro and in silico tools, freque…

Effect of the GLP-1 analog liraglutide on satiation and gastric sensorimotor function during nutrient-drink ingestion

Background/Aim:Liraglutide, a glucagon-like peptide-1 analog, induces weight loss. We investigated whether liraglutide affects gastric accommodation and satiation by measuring the intragastric pressure (IGP) during nutrient-drink consumption and using the barostat technique.Methods:Ten healthy volunteers (HVs) were tested after placebo, 0.3, 0.6 or 1.2 mg liraglutide administration. IGP was studied during intragastric nutrient-drink (1.5 kcal ml(-1)) infusion (60 ml min(-1)), while the HVs scored their satiation on a graded scale until maximal satiation. In a separate session, isobaric distentions were performed using the barostat with stepwise increments of 2 mm Hg starting from minimal di…