Changes In Bile Composition Research Articles

Quality Assessment by Bile Composition in Normothermic Machine Perfusion of Rat Livers.

Background: The persistent challenge of organ scarcity in liver transplantation leads to an escalating dependence on organs obtained from extended criteria donors (ECD). Normothermic machine perfusion (NMP) is used for improved preservation. Due to the mimicked invivo conditions during normothermic machine perfusion, the liver is metabolically active, which allows quality assessment during perfusion. Bile seems to be of rising interest in clinical studies, as it is easily collectible for analysis. As there are currently no data on biliary bile acids during NMP, the primary objective of this study was to use our experimental rodent NMP model to assess changes in bile composition through organ damage during perfusion to inform clinical evaluation of donor organs during NMP. Methods: Thirty livers from male Sprague-Dawley rats in five groups underwent 6 h of NMP using either erythrocyte-supplemented DMEM or Steen solution, with or without 30 min of warm ischemia time (WIT). We conducted regular measurements of AST, ALT, LDH, and urea levels in the perfusate at 3-hour intervals. Bile samples were analyzed for biliary pH, LDH, and gamma glutamyltransferase, as well as biliary bile acids via mass spectrometry and UHPLC. Results: Compared with regular livers, liver injury parameters were significantly higher in our donation after circulatory death (DCD) model. Bile production was significantly reduced in livers exposed to WIT, and the bile showed a significantly more alkaline pH. This correlated with the concentration of total bile acids, which was significantly higher in livers experiencing WIT. However, regular livers produced a higher total amount of biliary bile acids during perfusion. Taurocholic acid and its metabolites were most prominent. Secondary bile acids were significantly reduced during perfusion due to the missing enterohepatic circulation. Conclusions: WIT-induced liver injury affects bile composition within our small-animal NMP model. We hypothesize this phenomenon to be attributed to the energy-driven nature of bile secretion, potentially explaining why DCD livers produce less, yet more concentrated, bile. Our results may inform clinical studies, in which biliary bile acids might have a potential as a quantifiable viability marker in human NMP liver transplantation studies.

Identification of changes in bile composition in pancreaticobiliary reflux based on liquid chromatography/mass spectrometry metabolomics.

Pancreaticobiliary reflux (PBR) can induce gallstone formation; however, its pathogenic mechanism remains unclear. In this study, we explored the mechanism of PBR by the non-targeted metabolomic analysis of bile in patients with PBR. The aim of this study was to investigate the pathogenic mechanism in PBR by the non-targeted metabolomic analysis of bile collected during surgery. Sixty patients who underwent gallstone surgery at our center from December 2020 to May 2021 were enrolled in the study. According to the level of bile amylase, 30 patients with increased bile amylase ( > 110 U/L) were classified into the PBR group, and the remaining 30 patients were classified into the control group (≤ 110 U/L). The metabolomic analysis of bile was performed. The orthogonal projections to latent structure-discriminant analysis of liquid chromatography mass spectrometry showed significant differences in bile components between the PBR and control groups, and 40 metabolites were screened by variable importance for the projection value (VIP > 1). The levels of phosphatidylcholine (PC) and PC (20:3(8Z,11Z,14Z)/14:0) decreased significantly, whereas the levels of lysoPC (16:1(9z)/0:0), lysoPC (15:0), lysoPC (16:0), palmitic acid, arachidonic acid, leucine, methionine, L-tyrosine, and phenylalanine increased. Significant differences in bile metabolites were observed between the PBR and control groups. Changes in amino acids and lipid metabolites may be related to stone formation and mucosal inflammation.

ACE Question

Article| December 2022 ACE Question ASA Monitor December 2022, Vol. 86, 11. https://doi.org/10.1097/01.ASM.0000904212.79262.98 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Search Site Citation ACE Question. ASA Monitor 2022; 86:11 doi: https://doi.org/10.1097/01.ASM.0000904212.79262.98 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll PublicationsASA Monitor Search Advanced Search Topics: anesthesiology continuing education (ace) Which of the following physiological factors related to hepatobiliary function is MOST likely to increase during pregnancy? Physiological changes during pregnancy significantly impact the well-being of both mother and baby and are important to recognize for optimal anesthetic management. There are several relevant changes in hepatobiliary function that occur during pregnancy. Although cardiac output and blood flow to several organs (e.g., uterus, kidneys) increase significantly during pregnancy, hepatic blood flow does not change significantly. Most of the liver enzymes, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT), remain within normal range. However, serum alkaline phosphatase more than doubles due to placental secretion of this enzyme. Pregnancy is associated with an increased frequency of gallstone disease. Acute appendicitis and acute cholecystitis are the most common diseases requiring surgery during pregnancy. Several factors, including biliary stasis and changes in bile composition, are implicated in creating a lithogenic environment for this higher frequency... You do not currently have access to this content.

Bile Composition as a Diagnostic and Prognostic Tool in Liver Transplantation.

Bile secretion and composition reflects the functional status of hepatocytes and cholangiocytes. Bile composition can have a role in the assessment of donor grafts before implantation in the recipient. In addition, changes in bile composition after liver transplantation can serve as a diagnostic and prognostic tool to predict posttransplant complications, such as primary nonfunction, acute cellular rejection, or nonanastomotic biliary strictures. With the popularization of liver machine perfusion preservation in the clinical setting, there is a revisited interest in biliary biomarkers to assess graft viability before implantation. This review discusses current literature on biliary biomarkers that could predict or assess liver graft and bile duct viability. Bile composition offers an exciting and novel perspective in the search for reliable hepatocyte and cholangiocyte viability biomarkers.

Prevalence of gallstones and biliary sludge formation during pregnancy detected by ultrasonography

The risk of gallstones is thought to increase with number of pregnancies. Cholesterol gallstones are more prevalent in women than men and primarily related to sex steroids, particularly progesterone. During pregnancy there are changes in bile composition and gallbladder motility that promote gallstone formation. This study was conducted to determine incidence and outcome of pregnancy related biliary sludge and gallstone formation. Two hundred and nine consecutive expectant women were evaluated by ultrasonography at 1st trimester, 3rd trimester and at 4-6 weeks after delivery. Socio-demographic, medical and obstetrical history were taken and recorded. Incidence of gallstone and sludge formation were found 5.7% and 2.9%, respectively. The results suggest that pregnancy may be a risk factor for gallstone and biliary sludge formation.Mediscope Vol. 4, No. 2: Jul 2017, Page 21-24

Cholic acid induces a Cftr dependent biliary secretion and liver growth response in mice.

The cause of Cystic fibrosis liver disease (CFLD), is unknown. It is well recognized that hepatic exposure to hydrophobic bile salts is associated with the development of liver disease. For this reason, we hypothesize that, CFTR dependent variations, in the hepatic handling of hydrophobic bile salts, are related to the development CFLD. To test our hypothesis we studied, in Cftr-/- and control mice, bile production, bile composition and liver pathology, in normal feeding condition and during cholate exposure, either acute (intravenous) or chronic (three weeks via the diet). In Cftr-/- and control mice the basal bile production was comparable. Intravenous taurocholate increased bile production to the same extent in Cftr-/- and control mice. However, chronic cholate exposure increased the bile flow significantly less in Cftr-/- mice than in controls, together with significantly higher biliary bile salt concentration in Cftr-/- mice. Prolonged cholate exposure, however, did not induce CFLD like pathology in Cftr-/- mice. Chronic cholate exposure did induce a significant increase in liver mass in controls that was absent in Cftr-/- mice. Chronic cholate administration induces a cystic fibrosis-specific hepatobiliary phenotype, including changes in bile composition. These changes could not be associated with CFLD like pathological changes in CF mouse livers. However, chronic cholate administration induces liver growth in controls that is absent in Cftr-/- mice. Our findings point to an impaired adaptive homeotrophic liver response to prolonged hydrophobic bile salt exposure in CF conditions.

Changes of bile composition in patients with chronic pancreatitis

Changes of bile composition in patients with chronic pancreatitis

Bile Acids as Modulators of Gut Microbiota Linking Dietary Habits and Inflammatory Bowel Disease: A Potentially Dangerous Liaison

Bile Acids as Modulators of Gut Microbiota Linking Dietary Habits and Inflammatory Bowel Disease: A Potentially Dangerous Liaison

Disruption of gallbladder smooth muscle function is an early feature in the development of cholesterol gallstone disease.

BACKGROUND; Decreased gallbladder smooth muscle (GBSM) contractility is a hallmark of cholesterol gallstone disease, but the interrelationship between lithogenicity, biliary stasis, and inflammation are poorly understood. We studied a mouse model of gallstone disease to evaluate the development of GBSM dysfunction relative to changes in bile composition and the onset of sterile cholecystitis. BALB/cJ mice were fed a lithogenic diet for up to 8 weeks, and tension generated by gallbladder muscle strips was measured. Smooth muscle Ca(2+) transients were imaged in intact gallbladder. Lipid composition of bile was altered lithogenically as early as 1 week, with increased hydrophobicity and cholesterol saturation indexes; however, inflammation was not detectable until the fourth week. Agonist-induced contractility was reduced from weeks 2 through 8. GBSM normally exhibits rhythmic synchronized Ca(2+) flashes, and their frequency is increased by carbachol (3 μm). After 1 week, lithogenic diet-fed mice exhibited disrupted Ca(2+) flash activity, manifesting as clustered flashes, asynchronous flashes, or prolonged quiescent periods. These changes could lead to a depletion of intracellular Ca(2+) stores, which are required for agonist-induced contraction, and diminished basal tone of the organ. Responsiveness of Ca(2+) transients to carbachol was reduced in mice on the lithogenic diet, particularly after 4-8 weeks, concomitant with appearance of mucosal inflammatory changes. These observations demonstrate that GBSM dysfunction is an early event in the progression of cholesterol gallstone disease and that it precedes mucosal inflammation.

Dietary fat‐induced taurocholic acid production promotes pathobiont and colitis in IL‐10−/− mice

The composite human microbiome of Western populations has changed over the past century, brought on by new environmental triggers that often have a negative impact on human health. Here we show that consumption of a diet high in saturated (milk derived)‐fat (MF) but not polyunsaturated (safflower oil)‐fat (PUFA) changes the conditions for microbial assemblage and promotes expansion of a rare, immunogenic, sulfite‐reducing pathobiont, Bilophila wadsworthia. This was associated with a proinflammatory TH1 immune response and the development of colitis in genetically susceptible IL‐10−/− mice. Because MF promotes the formation of taurine‐conjugated hepatic bile acids (a sulfur source for B. wadsworthia), we examined the possibility that the MF effects are mediated by changes in bile composition. Only bile obtained from MF‐fed mice promoted B. wadsworthia growth in vitro. In addition, a bloom of B. wadsworthia and development of colitis was seen when mice were fed a low‐fat (LF) diet supplemented with taurocholic, but not with glycocholic acid. Furthermore, when germ‐free IL‐10−/− mice were monoassociated with B. wadsworthia, the bacteria survived only when provided with the MF diet or taurocholic acid, and resulted in colitis, which was not observed when MF or taurocholic acid were fed alone. Together these data show that dietary fats differ in their effects on the host microbiota and immune system. The data also provide a plausible mechanistic basis by which Western type diets high in saturated fats may increase the prevalence of complex immune‐mediated diseases like inflammatory bowel diseases in genetically susceptible hosts.

Changes in bile composition and liver ultrastructure after TPN alone and TPN with ultra-short bowel syndrome

Summary Background & aims Two of the factors that can influence bile acid (BA) metabolism and biliary poles are long intestinal resections leading to short bowel syndrome (SBS) and prolonged starvation in total parenteral nutrition (TPN). These can act directly (by altering absorption) and/or indirectly (bacterial translocation, alterations of the hepato-intestinal hormonal complex,…). Our aim was to study the effects on bile metabolism and hepatic structure of the conditions of TPN with and without SBS in an animal model. Methods We used 3 experimental groups of Dunkin-Hartley guinea pigs: group A (GA: 10 animals), subjected to anaesthesia and a sham laparotomy, and fed for 10 days by TPN; group B (GB: 10 animals), subjected to a jejuno-ileal resection, and fed for 10 days by TPN; and a control group (6 animals) subjected to a sham laparotomy, and fed orally. At the end of the experimental period, bile samples were taken from the hepatic duct to study the bile composition, and blood samples from the vena cava for blood biochemistry. Following liver perfusion, samples of hepatic tissue were taken for electron microscopy. Results In GA and GB, there were significant losses in weight and increases in glycaemia and serum triglycerides, but a decrease in plasma cholesterol only in GB. For the bile composition, the concentrations of cholic acid (ChA), ketolithocholic acid (KLChA), and total conjugated BA were lowered in both GA and GB, while bile phospholipids (BPh) and bile cholesterol (BCh) were raised in GB only. The electron microscopy showed microsteatosis and a major loss of microvilli in the biliary poles or canaliculi in GA and even more so in GB, with the latter group also showing signs of fibrogenesis. Conclusions TPN and SBS affect the BPh, BCh, and BA composition, potentially increasing the risk of biliary lithogenicity. This was especially so in the association of SBS and TPN, with affection of the biliary duct anatomy, and induction of fibrogenesis and cholangitis.

Особливості жовчоутворення у щурів різної статі за дії естрону

The influence of estron (8 microg/100g of animal's body weight) on the exocrine function of liver and the changes in bile acid composition of bile on different sex rats was studied. It was shown, that hormone at the applied dose, effected choleresis of female rats more effectively. Estron also caused different changes in bile composition. So, estron stimulated bile acid conjugation with taurine and glycin in female rat liver. Increasing of free and conjugated bile acid biosynthesis in male rats was observed.

Impact of experimental colitis on hepatobiliary transporter expression and bile duct injury in mice

The pathogenetic link between ulcerative colitis and sclerosing cholangitis (SC) is unclear. We hypothesized that colitis induces changes in bile composition via inflammation-induced reduction of hepatobiliary transporter gene expression, ultimately resulting in cholestasis and bile duct injury. Alterations in transporter expression and bile secretion in acute dextran sulphate sodium (DSS)-induced colitis were compared with lipopolysaccharide (LPS)-treated mice serving as positive control. Whether chronic DSS-colitis elicits cholangitis in genetically predisposed animals was studied in heterozygous multidrug resistance gene 2 knockout mice (Mdr2(+/-)). LPS but not DSS-colitis changed major hepatobiliary transporters (Ntcp, Bsep, Mrp2-4, Ostalpha/beta, Abcg5/8, Oatp1-4, Mdr1b and Mdr2), enzymes (Cyp3a11 and Cyp7a1), nuclear receptors (RXRalpha, FXR, CAR and PXR) and proinflammatory mediators (tumour necrosis factor alpha and inducible nitric oxide synthase). Formation of toxic bile reflected by an increased bile acid/phospholipid ratio was observed neither in acute nor in chronic colitis, although heterozygous Mdr2(+/-) mice developed mild portal inflammation after chronic colitis. In contrast to LPS, DSS-colitis has a minor impact on hepatobiliary gene expression and bile secretion. Therefore, intestinal inflammation-associated changes of hepatobiliary transporter expression do not play a pathogenetic role in SC.

Flavouring Group Evaluation 5, Revision 1 (FGE.05Rev1):Esters of branched‐ and straight‐chain aliphatic saturated primary alcohols and of one secondary alcohol, and branched‐ and straight‐chain unsaturated carboxylic acids from chemical groups 1, 2, and 5 (Commission Regulation (EC) No 1565/2000 of 18 July 2000) ‐ Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in contact with

Flavouring Group Evaluation 5, Revision 1 (FGE.05Rev1):Esters of branched‐ and straight‐chain aliphatic saturated primary alcohols and of one secondary alcohol, and branched‐ and straight‐chain unsaturated carboxylic acids from chemical groups 1, 2, and 5 (Commission Regulation (EC) No 1565/2000 of 18 July 2000) ‐ Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in contact with

Effect of tamoxifen and raloxifene on cholesterol transformation to bile acids in ovariectomized rats

Tamoxifen is used as adjuvant therapy for prevention and treatment of metastatic breast cancer, whereas raloxoifene is approved for osteoporosis and is being investigated for breast cancer prevention. The most important aspects of these therapies are focused on their influence on bone and lipid metabolism. Several studies have reported the effect of tamoxifen and raloxifene on plasma lipids. Approximately 40% of total cholesterol removal occurs by conversion to bile acids, a process that takes place in the liver. The aim of the present study was to evaluate the influence of tamoxifen and raloxifene on the conversion of cholesterol to bile acids in estrogen-deficient in rats. The study included 40 female Wistar rats, divided into four groups: sham-operated controls, ovariectomized controls, ovariectomized rats treated with tamoxifen and ovariectomized rats treated with raloxifene. After 42 days of drug administration, bile was collected under anesthesia following administration of radioactive [4-14C]cholesterol and assayed for total 14C radioactivity; 14C-labeled bile acids were determined by the use of isotopic techniques after initial separation by thin-layer chromatography. Ovariectomy caused decreased excretion of bile and bile acids. Administration of tamoxifen and raloxifene significantly reduced the excretion of 14C-labeled bile and bile acids compared with ovariectomized controls. Tamoxifen therapy significantly reduced the excretion of taurocholic acid and glycochenodeoxycholic plus glycodeoxycholic acids, and excretion of cholic, litocholic and chenodeoxycholic plus deoxycholic acids was increased. Raloxifene significantly reduced the excretion of taurocholic, glycocholic and litocholic acids, taurochenodeoxycholic plus taurodeoxycholic acids, as well as chenodeoxycholic plus deoxycholic acids. The results of the present study suggest that tamoxifen and raloxifene did not reverse the changes in bile composition induced by estrogen deficiency. The decreased concentration of trihydroxy bile acids during therapy with raloxifene might decrease the risk of gallstone formation, although this hypothesis requires further investigation.

Ultrasonic Gallbladder Function in Chronic Kidney Disease: Does Predialysis, Hemodialysis, or CAPD Affect it?

Background. There are contradictory reports about the prevalence of cholelithiasis in chronic kidney disease (CKD). The pathogenesis of gallstones is associated with the lithogenic changes of bile composition, increased tendency to nucleation, and decreased gallbladder motility. The studies related to these factors can predict the development of cholelithiasis. The aim of this study was to evaluate the ultrasonic gallbladder function in CKD and to compare it in predialysis (PreD), hemodialysis (HD), and continuous ambulatory peritoneal dialysis (CAPD) patients. Methods. Age, gender, and body mass index matched 49 CKD patients (14 PreD, 19 HD, 16 CAPD), and 17 control individuals were included in the study. Diabetic and cirrhotic patients were not included. Ultrasonic gallbladder volume was evaluated in pre- and postprandial period, and ejection fraction was calculated. We also measured several biochemical parameters (cholesterol, triglyceride, blood urea nitrogen (BUN), creatinine, calcium, Phosphorus, parathormone, albumin, total protein) in blood. Results. Preprandial gallbladder volume in PreD, HD, CAPD, and control groups were 26.7 ± 13.6, 20.8 ± 10.4, 23.2 ± 14.7, and 26.4 ± 14.8 mL, respectively (p > 0.05). Ejection fractions were 54.1 ± 22.9%, 54.9 ± 23.9%, 48.6 ± 15.9%, and 51.8 ± 19.2% in PreD, HD, CAPD, and control groups, respectively (p > 0.05). Serum triglyceride was higher in PreD patients than control group (207 ± 144 vs. 110 ± 48 mg/dL) (p < 0.05). Serum BUN, Cre, P, and PTH levels were higher in CKD groups than the control group, whereas serum total protein and albumin levels were higher in the control group (p < 0.05). Serum Ca was lower in PreD and HD patients than in the controls (p < 0.05). Conclusions. In conclusion, CKD and renal replacement therapy (HD and CAPD) do not affect gallbladder functions, but more studies are needed to evaluate prevalence of gallstones, gallbladder motility, and the composition of bile in CKD.

Is bile flow reduced in patients with hypothyroidism?

Background. Disturbances in the sphincter of Oddi (SO) function may prevent normal bile flow and thus enhance the probability of common bile duct stone (CBDS) formation. We have previously shown increased prevalence of diagnosed hypothyroidism in CBDS patients, thyroxine (T4) -induced inhibition of the SO contractility both in animal and in human experiments ex vivo, and reduced bile flow to duodenum in hypothyroid rats. The aim of the present study was to investigate human biliary dynamics in relation to altered thyroid gland function. Methods. Eight female patients, 1 with diagnosed untreated hypothyroidism and 7 with total thyroidectomy performed due to thyroid cancer, were studied in hypothyroid stage and again after thyroxine replacement therapy in euthyroid stage, with quantitative 99mTc HIDA cholescintigraphy (QC), biliary ultrasonography, and serum determinations. Each patient served as her own control in the 2 stages of the study. Results. In QC, maximal uptake of 99mTc HIDA was not changed in hypothyroidism compared to euthyroidism. The first appearance of radioactivity to large bile ducts at the hepatic hilum remained unchanged in the 2 stages of the study. Hepatic clearance of 99mTc HIDA was decreased at 45 minutes (28% [11-38] vs 50% [33-54]; P =.028; median and range) and at 60 minutes (55% [28-80] vs 69% [61-79]; P =.028; median and range) and hilum-duodenal transit time increased by 31% compared to euthyroid stage. In US no changes were seen in gall bladder or bile ducts in the 2 stages of the study. Serum hypercholesterolemia was observed in the hypothyroid stage. Conclusions. We conclude that hypothyroidism may result in delayed emptying of the biliary tract, as studied with QC. In addition to the changes in bile composition and excretion rate suggested before to take place in hypothyroidism, according to the present study changes in biliary emptying also may be included in the probable causes for the increased prevalence of CBDS in hypothyroidism. This may be due to the absence of the prorelaxing effect of thyroxine on SO, which we have shown before to exist ex vivo. (Surgery 2003;133:288-93)

Biliary manometry, bacterial characteristics, bile composition, and histologic changes fifteen to seventeen years after endoscopic sphincterotomy

Aim: To evaluate the function of the biliary sphincter 15 to 17 years after endoscopic sphincterotomy and to investigate if loss of sphincter function is associated with bacterial colonization, changes in bile composition, or inflammation of the biliary system. Methods: Eight patients who had undergone endoscopic sphincterotomy for bile duct stones 15 to 17 years previously underwent ERCP with biliary manometry, bile sampling, and biopsy. Manometry was performed using a perfused triple-lumen manometry catheter and a station pull-through technique. Bile samples were cultured and analyzed for biliary lipids, bile salts, bacterial β-glucuronidase, and phospholipase A 2. Biopsy specimens were taken from the proximal common hepatic duct for histologic examination. Results: Manometry demonstrated absent basal sphincter pressure and no choledochoduodenal pressure gradient in all patients. Phasic contractions were observed in two patients. Cholangiography showed stones in one patient. Positive cultures were obtained in three patients, including the patient with stones. All bile samples showed a high content of biliary lipids and cholesterol. Some samples contained considerable amounts of hydrophobic bile salts. Five samples contained very high levels of phospholipase A 2 activity. Significant bacterial β-glucuronidase activity was found in one patient, the patient with stones. Biopsy specimens of the proximal common hepatic duct in three patients showed chronic inflammation with fibrosis and reactive epithelial changes. Conclusions: After endoscopic sphincterotomy for bile duct stones, the function of the biliary sphincter is permanently lost. This is associated with bacterial colonization, presence of cytotoxic components in the bile, and chronic inflammation of the biliary system. (Gastronintest Endosc 1997;45:400-5.)

Chronokinetics of Liposomal Encapsulated Ampicillin in Fasting and Nonfasting Rats

The chronobiological effect on the pharmacokinetics of liposomal encapsulated ampicillin (LEA) was compared at noon (1200) and midnight (2400) after intravenous injection of 50 mg/kg of LEA in rats. The effects of fasting on the circadian rhythms of LEA were also investigated. Serial blood samples were collected for 2h. Bile and urine were collected during the entire study. Plasma data was analyzed by noncompartmental methods. Dosing of LEA at 2400, when the animals were active, resulted in a 50% decrease in mean residence time (MRT) and a 20% increase in systemic clearance (Cltotal). The increase in Cltotal was reflected by increases in biliary (Clbile) and renal (Clrenal) clearance at 2400. In addition, the steady-state volume of distribution (Vss) at 2400 was also decreased by about 50% as compared to dosing at 1200. Interestingly, no difference in the pharmacokinetic parameters were observed in fasting animals at 1200 and 2400. Since rats consume very little food during their sleep cycle, restriction of food intake did not have any affect on the pharmacokinetics of LEA at 1200. However, fasting rats had an approximately 36% decrease in Cltotal as compared to nonfasting rats at 2400. This decrease in systemic clearance was paralleled by a 60% and 24% decrease in Clbile and Clrenal, respectively. These variations could be attributed to changes in bile composition and/ or lipoprotein concentrations in the plasma as a result of “forced” fasting at 2400 when the animals are generally more active and food intake is high.

A new way to obtain contrast-free bile during ERCP

Experiments with human bile have relied on samples obtained from the gallbladder during cholecystectomy or from various biliary drainage tubes such as nasobiliary drains, T-tubes, or percutaneous biliary catheters. 1 McAllister EW Carey LC Brady PG Heller R Kovacs SG The role of polymeric surface smoothness of biliary stents in bacterial adherence, biofilm deposition, and stent occlusion. Gastrointest Endosc. 1993; 39: 422-425 Abstract Full Text PDF PubMed Scopus (89) Google Scholar , 2 Leung JWC Ling TKW Kung JLS Vallance-Owen J The role of bacteria in the blockage of biliary stents. Gastrointest Endosc. 1988; 34: 19-22 Abstract Full Text PDF PubMed Scopus (160) Google Scholar Although these approaches provide large quantities of bile, they have limitations. Bile obtained from the gallbladder of patients undergoing cholecystectomy cannot be considered normal, since most gallbladders removed surgically are diseased, and gallbladder bile is quite different qualitatively from fresh “hepatic bile” obtained from the bile ducts. 3 Nathanson MH Boyer JL Mechanisms and regulation of bile secretion. Hepatology. 1991; 14: 551-566 Crossref PubMed Scopus (372) Google Scholar In addition, subjects with external drainage devices usually have obstructed biliary systems, which can lead to important changes in bile composition.