Liver X Receptor β regulates bile volume and the expression of Aquaporins and Cystic Fibrosis Transmembrane Conductance Regulator in the gallbladder

The gallbladder is considered an important organ in maintaining digestive and metabolic homeostasis. Given that therapeutic options for gallbladder diseases are often limited to cholecystectomy, understanding gallbladder pathophysiology is essential in developing novel therapeutic strategies.Since Liver X Receptor β (LXRβ), an oxysterol-activated transcription factor, is strongly expressed in gallbladder cholangiocytes, the aim was to investigate LXRβ physiological function in the gallbladder. Thus, we studied the gallbladders of WT and LXRβ-/- male mice using immunohistochemistry, electron-microscopy, qRT-PCR, bile duct cannulation, bile and blood biochemistry and duodenal pH measurements.LXRβ-/- mice presented a large gallbladder bile volume with high duodenal mRNA levels of the Vasoactive Intestinal Polypeptide (Vip), a strong mediator of gallbladder relaxation. LXRβ-/- gallbladders, showed lower mRNA and protein expression of Aquaporin-1, Aquaporin-8 and Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). A cystic fibrosis-resembling phenotype was evident in the liver showing higher serum cholestatic markers and the presence of reactive cholangiocytes. For LXRβ being a transcription factor, we identified 8 putative binding sites of LXR on the promoter and enhancer of the Cftr gene, suggesting Cftr as a novel LXRβ regulated gene. In conclusion LXRβ was recognized as a regulator of gallbladder bile volume through multiple mechanisms involving CFTR and Aquaporins.

Pengaruh Ekstrak Anggur Laut terhadap pH Lambung dan duodenum pada Rattus norvegicus Jantan yang Diinduksi Indometasin

Indomethacin is a nonsteroidal anti-inflammatory drugs (NSAIDs) that act to inhibit COX-1. The inhibition of COX-1 leads to inhibition of prostaglandin production. Prostaglandin is a regulator of gastric acid buffer secretion. Inhibition of prostaglandin decrease gastric and duodenum pH and damage the gastric and duodenum. Sea grapes (Caulerpa racemose var. cylindracea) are marcoalgae that contain flavonoids as antioxidants and anti-inflammatory. The aim of this study was to determine the effect of sea grapes on gastric and duodenum pH in rattus norvegicus induced by indomethacin. 32 male Rattus norvegicus were divided into 4 groups. Group K (-) without treatment. Group K (+) was induced by 30 mg/Kg BW indomethacin for 7 days. Group P1 was induced by 30mg/Kg BW indomethacin for 7 days followed by administration of 1g/100g BW sea grape extract for 14 days. Group P2 was induced by 30mg/Kg BW indomethacin for 7 days followed by administration of 2g/100g BW sea grape extract for 14 days. On the 29th day, rats were terminated, gastric and duodenal were isolated then the fluid pH was measured. One-way Anova test obtained p = 0,023. Post hoc test pH Gaster significantly different between group K (-) and K (+) (p= 0,005) and between group K (-) with P2 (p= 0,020). While in group K (+) with P1 and P2 there was no significant difference in pH. Post hoc test of pH duodenum showed no differences in all group. The administration of sea grape extract did not show a differences of the gastric and duodenal pH significantly between rats induced by indomethacin.

Characteristics of the course of gastric and duodenal ulcer disease concurrent with duodenal insufficiency

Aim. To comprehensively study the course of gastric ulcer disease (GUD) and duodenal ulcer disease (DUD) concurrent with chronic duodenal insufficiency (CDI). Materials and methods. Ulcer disease (UD) was verified on the basis of the results of clinical and fibrogastroduodenoscopic examinations. The data of contrast duodenography and cavitary manometry were used to identify CDI. Gastroduodenal motor activity was investigated using the peripheral electrogastrograph EGG-4M. The results of pH measurements were employed to assess the state of gastric acid secretion and duodenal pH values. Results. A comprehensive examination was made in 106 patients with UD concurrent with CDI (a study group) and 30 UD patients without CDI (a comparison group). Epigastric pain was noted in the patients with GUD in the study and comparison groups (91.5 and 84.6%, respectively), but the pain was mainly aching in the patients with concomitant CDI and more intense (77.8%) in those without this condition. In the study group, heartburn was more common in patients with GUD and DUD (75.3 and 71.4%, respectively) than in those with UD in the comparison group (28.5 and 37.5%, respectively). Helicobacter pylori tests were positive in 23.8% of the patients in the study group and in 57.2% in the comparison group. Electrogastrography indicated that the patients with GUD and CDI had bradygastria and hypokinesis on an empty stomach; the electrical activity was reduced after eating. In the comparison group, tachygastria and hyperkinesis were detected on an empty stomach; these postprandial indicators were elevated. H. pylori tests were positive in 34.7% of the patients with DUD and CDI and in 63.6% of those with DUD without CDI. The postprandial electrical activity increased in patients with DUD and decreased in the comparison group. The specific features of changes in gastric and duodenal pH values in GUD and DUD concurrent with CDI in comparison with the isolated course of UD. Conclusion. The immediate and long-term follow-ups show that GUD and DUD concurrent with CDI run a more persistent course; the time of ulcer healing increases and the periods of remission decrease.

Chito-oligosaccharide as growth promoter replacement for weaned piglets: performance, morphometry, and immune system

The objective of this study was to evaluate the chito-oligosaccharide (COS) against two growth promoter antibiotics, colistin and lincomycin, with respect to growth performance, incidence of diarrhea, visceral characteristics, morphometry, and serum immunoglobulin levels (IgA, IgG, and IgM). A total of 96 Pen Ar Lan® piglets (48 barrows and 48 females), weaned at 17 days and with body weight (BW) 5.33 ± 0.37 kg, were subjected to the evaluation of growth performance and serum. Twenty-four animals, females, 35-day-old and with BW 6.86 ± 0.64 kg, were used for the assessment of histology and visceral organ weight. The three treatments were a basic diet formulation supplemented with COS (100 mg kg-1), colistin (40 mg kg-1), or lincomycin (4.4 mg kg-1). The antibiotic treatments showed higher average daily gain (ADG) than COS treatment during the period of 49 to 63 days; whereas the feed conversion ratio (FCR) was higher and incidence of diarrhea was lower for the colistin treatment than for other treatments. The spleen weight and the small intestinal length were higher and duodenal pH was lower for COS than for antibiotics. Morphometry indicated greater villus height and higher ratio of villus height to crypt depth with colistin than with COS and a lower lesion score compared with other treatments. The serum IgA concentration was higher for COS in 35-day-old piglets. According to the results, COS was not efficient to replace colistin as a growth promoter for piglets weaned at 17 days; however, the results related to the immune system suggested that COS is a potentially promising product during weaning.

Acidic duodenal pH alters gene expression in the cystic fibrosis mouse pancreas

The duodenum is abnormally acidic in cystic fibrosis (CF) due to decreased bicarbonate ion secretion that is dependent on the CF gene product CFTR. In the CFTR null mouse, the acidic duodenum results in increased signaling from the intestine to the exocrine pancreas in an attempt to stimulate pancreatic bicarbonate ion secretion. Excess stimulation is proposed to add to the stress/inflammation of the pancreas in CF. DNA microarray analysis of the CF mouse revealed altered pancreatic gene expression characteristic of stress/inflammation. When the duodenal pH was corrected genetically (crossing CFTR null with gastrin null mice) or pharmacologically (use of the proton pump inhibitor omeprazole), expression levels of genes measured by quantitative RT-PCR were significantly normalized. It is concluded that the acidic duodenal pH in CF contributes to the stress on the exocrine pancreas and that normalizing duodenal pH reduces this stress.

Duodenal pH governs interdigestive motility in humans

In this study, we examined the potential influence of duodenal pH in regulating the occurrence of the interdigestive migrating myoelectric complex (IMMC). Fasting gastroduodenal motility, duodenal pH, and plasma motilin were studied in 15 healthy subjects. During phase I, duodenal pH remained stable at 7 +/- 0.2. Phase II was accompanied by a lowering of duodenal pH, which fluctuated between 2.0 and 7.5. During late phase II, the duodenal pH increased to 6.9 +/- 0.3 and remained in the alkaline range during phase III. In six of 46 episodes of the IMMC, the occurrence of gastric phase III was delayed. This was associated with a persistently low duodenal pH (< 4) during late phase II. Despite a normal cyclic increase of plasma motilin, no gastric phase III activity was observed until the duodenal pH exceeded 7.0. Further studies showed that lowering of duodenal pH by intraduodenal perfusion of HCl prevented the occurrence of gastric phase III. We concluded that regularity of IMMC is governed by duodenal pH. An alkaline pH is essential for the initiation of gastric phase III; lowering of duodenal pH prevents its occurrence despite normal cyclic increase of plasma motilin.