In recent years there have been tremendous advances in the understanding of the mechanisms behind the toxicity and bioactivity of different bile acids and these are covered at length in Bile Acids.
Prior to the publication of this book there was no single source of information on the toxicology and bioactivity properties of bile acids.
Bile Acids also uniquely collects all the relevant information together regarding the role of bile acids in human disease and the mechanisms underlying bile acid induced pathology.
Additionally, as bile acids are synthesised from cholesterol, there is wide recognition of the role for bile acids in obesity linked diseases and this is also covered in Bile Acids.
Contents
1. An Overview of Bile-Acid Synthesis, Chemistry and Function
- The Bile Acids
- Conjugated Bile-Acid Biosynthesis
- Bile-Acid Regulation
- Chemistry of Bile Acids and Their Effects on Digestion
- Micelles
- Biochemical Properties of Bile Acids and Their Effects on the GI Tract
- The Effect of pH on Bile-Acid Solubility
- Potential Therapies for the Deleterious Effects of Bile Acids
2. Bile-Acid Physiology and Measurement
- Bile-Acid Physiology: The Enterohepatic Circulation
- Transport in Blood
- The Hepatocyte
- Sodium Taurocholate Co-transporting Protein (NTCP)
- Organic-Anion-Transporting Peptide (OATP)
- Specificity of OATP and NTCP Transporters
- Regulation of Expression
- Transport across the Hepatocyte
- Bile-Acid Export from the Hepatocyte
- Bile Secretion
- Water Secretion
- Cholangiocytes
- Cholangiocyte Secretion
- Gallbladder
- Small Bowel
- Intestinal Fat Absorption
- Bile-Acid Absorption
- Transport across the Enterocyte
- Export into Portal Blood
- Colon
- Measurement of Bile Acids
3. Bile-Acid Induction of Apoptosis in Relation to Gastrointestinal Cancer
- Bile Acids Induce Oxidative/Nitrosative Stress in Cells of the GI Tract
- Bile Acids Induce DNA Damage in Cells of the GI Tract
- Bile Acids Activate NF-kB as a Stress Response and Survival Pathway Throughout the GI Tract
- Bile Acids Increase Mutant Cells in the GI Tract
- Repeated Exposure to High Concentrations of Bile Acids Probably Selects for Apoptosis Resistance in Cells of the GI Tract
- Apoptosis Resistance and Increased Mutation
- Modes of Cell Death: Apoptosis, Autophagy and Necrosis
4. The Genotoxicity of Bile Acids
- Definitions
- Bile Acids as Carcinogens
- DNA Adducts
- Bile Acids cause DNA Damage
- The Role of Reactive Oxygen and Nitrogen Species
- Mutagenic Effects of Bile Acids
- Bile Acids and Chromosomal Damage
- Chemoprevention Strategies
5. Bile Acids and Colorectal Cancer
- Multi-stage Colorectal Carcinogenesis
- Evidence that Bile Acids Play a Role in Colorectal Carcinogenesis
- Mechanisms of the Carcinogenic Activity of Secondary Bile Acids
- Colorectal Cancer Chemoprevention Strategies
- Targeting Bile Acids
6. Bile Acids and Oesophageal Adenocarcinoma (OA)
- Oesophageal Adenocarcinoma
- Oesophageal Bile Acid Exposure
- Bile Acids and Diet
- Duodeno-Gastro-Oesophageal Reflux (DGOR); Animal Models
- Duodeno-Gastro-Oesophageal Reflux (DGOR); Clinical Data
- Measurement of Bile in the Oesophagus
- Mechanisms behind the Carcinogenicity of Bile Acids
- The Interplay between Acid and Bile in GORD
- Deconjugation of Bile Acids in Nonacidic Stomach
- Effect of Acidity on Bile Acid Solubility
- Acid-Suppression Therapy and Risks of OA
- Bile Acid Therapy
7. Bile Acids and Obesity
- Obesity
- Adipose Tissue
- Common Complications of Obesity
- Effect of Bile Acids on Obesity
- Bile-Acid Sequestrants
8. The Role of Bile Acids in Cholesterol-Rich Gallstone Formation
- The Triple Defect of Cholesterol GBS Formation
- Vesicles versus Micelles
- Nucleation of Cholesterol Crystals
- Promoters and Inhibitors of Nucleation
- Stasis
- Indirect Evidence that Gallbladder Motor Dysfunction/Stasis is Important in the Pathogenesis of GBS
- The Octreotide Story
- Biliary Phospholipid Fatty-Acid Composition
- Biliary Bile-Acid Composition
- The Adverse Effects of Increased Proportions of DCA in Bile on Cholesterol Gallstone Formation
- Mechanism for the Increase in the % Biliary DCA Conjugates in Bile during Octreotide Treatment
- The Relationship between Colonic Transit and DCA Metabolism
- The Role of Prolonged Intestinal Transit in the Pathogenesis of Conventional Cholesterol Gallstones
- The Inter-Relationship between LBTT, Colonic Anaerobic Bacteriology, Bile-Acid-Metabolising
Enzymes, Intraluminal pH and DCA Metabolism
Index
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