scholarly journals Bile Acid Malabsorption in Chronic Diarrhea: Pathophysiology and Treatment

2013 ◽  
Vol 27 (11) ◽  
pp. 653-659 ◽  
Author(s):  
Alan Barkun ◽  
Jonathan Love ◽  
Michael Gould ◽  
Henryk Pluta ◽  
A Hillary Steinhart
Keyword(s):  
Bile Acid ◽  
High Performance ◽  
Chronic Diarrhea ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Bile Acid Malabsorption ◽  
Ileal Dysfunction ◽  
Type 3

BACKGROUND: Bile acid malabsorption (BAM) is a common but frequently under-recognized cause of chronic diarrhea, with an estimated prevalence of 4% to 5%.METHODS: The published literature for the period 1965 to 2012 was examined for articles regarding the pathophysiology and treatment of BAM to provide an overview of the management of BAM in gastroenterology practice.RESULTS: BAM is classified as type 1 (secondary to ileal dysfunction), type 2 (idiopathic) or type 3 (secondary to gastrointestinal disorders not associated with ileal dysfunction). The estimated prevalence of BAM is >90% in patients with resected Crohn disease (CD) and 11% to 52% of unresected CD patients (type 1); 33% in diarrhea-predominant irritable bowel syndrome (type 2); and is a frequent finding postcholecystectomy or postvagotomy (type 3). Investigations include BAM fecal bile acid assay, 23-seleno-25-homo-tauro-cholic acid (SeHCAT) testing and high-performance liquid chromatography of serum 7-α-OH-4-cholesten-3-one (C4), to determine the level of bile acid synthesis. A less time-consuming and expensive alternative in practice is an empirical trial of the bile acid sequestering agent cholestyramine. An estimated 70% to 96% of chronic diarrhea patients with BAM respond to short-course cholestyramine. Adverse effects include constipation, nausea, borborygmi, flatulence, bloating and abdominal pain. Other bile acid sequestering agents, such as colestipol and colesevelam, are currently being investigated for the treatment of BAM-associated diarrhea.CONCLUSIONS: BAM is a common cause of chronic diarrhea presenting in gastroenterology practice. In accordance with current guidelines, an empirical trial of a bile acid sequestering agent is warranted as part of the clinical workup to rule out BAM.

scholarly journals Curtailing FGF19’s mitogenicity by suppressing its receptor dimerization ability

2020 ◽  
Vol 117 (46) ◽  
pp. 29025-29034
Author(s):  
Jianlou Niu ◽  
Jing Zhao ◽  
Jiamin Wu ◽  
Guanting Qiao ◽  
Junlian Gu ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Cholestatic Liver Disease ◽  
Insulin Sensitizer ◽  
Diet Induced Obesity ◽  
Major Interest ◽  
Clinical Potential

As a physiological regulator of bile acid homeostasis, FGF19 is also a potent insulin sensitizer capable of normalizing plasma glucose concentration, improving lipid profile, ameliorating fatty liver disease, and causing weight loss in both diabetic and diet-induced obesity mice. There is therefore a major interest in developing FGF19 as a therapeutic agent for treating type 2 diabetes and cholestatic liver disease. However, the known tumorigenic risk associated with prolonged FGF19 administration is a major hurdle in realizing its clinical potential. Here, we show that nonmitogenic FGF19 variants that retain the full beneficial glucose-lowering and bile acid regulatory activities of WT FGF19 (FGF19WT) can be engineered by diminishing FGF19’s ability to induce dimerization of its cognate FGF receptors (FGFR). As proof of principle, we generated three such variants, each with a partial defect in binding affinity to FGFR (FGF19ΔFGFR) and its coreceptors, i.e., βklotho (FGF19ΔKLB) or heparan sulfate (FGF19ΔHBS). Pharmacological assays in WT anddb/dbmice confirmed that these variants incur a dramatic loss in mitogenic activity, yet are indistinguishable from FGF19WTin eliciting glycemic control and regulating bile acid synthesis. This approach provides a robust framework for the development of safer and more efficacious FGF19 analogs.

scholarly journals Experimental huts trial of the efficacy of pyrethroids/piperonyl butoxide (PBO) net treatments for controlling multi-resistant populations of Anopheles funestus s.s. in Kpomè, Southern Benin

2018 ◽  
Vol 3 ◽  
pp. 71 ◽  
Author(s):  
Romaric Akoton ◽  
Genevieve M. Tchigossou ◽  
Innocent Djègbè ◽  
Akadiri Yessoufou ◽  
Michael Seun Atoyebi ◽  
...  
Keyword(s):  
High Performance ◽  
Anopheles Funestus ◽  
Piperonyl Butoxide ◽  
World Health ◽  
Experimental Huts ◽  
New Generation ◽  
Type 3 ◽  
Southern Benin

Background: Insecticides resistance in Anopheles mosquitoes limits Long-Lasting Insecticidal Nets (LLIN) used for malaria control in Africa, especially Benin. This study aimed to evaluate the bio-efficacy of current LLINs in an area where An. funestus s.l. and An. gambiae have developed multi-resistance to insecticides, and to assess in experimental huts the performance of a mixed combination of pyrethroids and piperonyl butoxide (PBO) treated nets on these resistant mosquitoes. Methods: The study was conducted at Kpomè, Southern Benin. The bio-efficacy of LLINs against An. funestus and An. gambiae was assessed using the World Health Organization (WHO) cone and tunnel tests. A released/recapture experiment following WHO procedures was conducted to compare the efficacy of conventional LLINs treated with pyrethroids only and LLINs with combinations of pyrethroids and PBO. Prior to huts trials, we confirmed the level of insecticide and PBO residues in tested nets using high performance liquid chromatography (HPLC). Results: Conventional LLINs (Type 2 and Type 4) have the lowest effect against local multi-resistant An. funestus s.s. and An. coluzzii populations from Kpomè. Conversely, when LLINs containing mixtures of pyrethroids and PBO (Type 1 and Type 3) were introduced in trial huts, we recorded a greater effect against the two mosquito populations (P < 0.0001). Tunnel test with An. funestus s.s. revealed mortalities of over 80% with this new generation of LLINs (Type 1 and Type 3),while conventional LLINs produced 65.53 ± 8.33% mortalities for Type 2 and 71.25 ±7.92% mortalities for Type 4. Similarly, mortalities ranging from 77 to 87% were recorded with the local populations of An. coluzzii. Conclusion: This study suggests the reduced efficacy of conventional LLINs (Pyrethroids alone) currently distributed in Benin communities where Anopheles populations have developed multi-insecticide resistance. The new generation nets (pyrethroids+PBO) proved to be more effective on multi-resistant populations of mosquitoes.

scholarly journals The role of bile acids in the pathogenesis of bowel diseases

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Magdalena Panek-Jeziorna ◽  
Agata Mulak
Keyword(s):  
Colorectal Cancer ◽  
Bile Acid ◽  
Bile Acids ◽  
Molecular Mechanisms ◽  
Intestinal Barrier ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Bile Acid Malabsorption ◽  
Bowel Diseases

Bile acids not only play a cardinal role in the digestion and absorption of fat and fat-soluble vitamins, but also significantly affect gastrointestinal motor, sensory and secretory functions, intestinal barrier permeability and the regulation of the inflammatory response. The results of recent studies have revealed complex interactions between bile acids and the gut microbiota. In addition, bile acids also play a role of signaling molecules regulating the activity of lipid and glucose metabolic pathways, as well as a role of ligands for transcription factors. Genetic factors associated with the regulation of bile acid synthesis, transport and action may significantly influence gastrointestinal function and predispose to diarrhea resulting from bile acid malabsorption. Methods used in the diagnosis of bile acid malabsorption include 75selenium-homotaurocholic acid test, serum C4 and fibroblast growth factor 19 (FGF19), as well as fecal bile acid levels. The paper presents the latest data on the role of bile acid in the pathogenesis of irritable bowel syndrome, inflammatory bowel diseases and colorectal cancer. Advances in the treatment of disturbances in bile acids absorption and synthesis are also presented. A better understanding of molecular mechanisms regulating bile acid action may have implication for colorectal cancer prevention.

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