Soluble Syndecan-1: A Novel Biomarker of Small Bowel Mucosal Damage in Children with Celiac Disease.

BACKGROUND: Syndecan-1 (SDC1) is essential for maintaining normal epithelial barrier. Shedding of SDC1 ectodomain, reflected by serum soluble syndecan-1 (SSDC1) levels, is regulated by inflammation. Increased intestinal permeability plays a central role in celiac disease (CD). The association between SSDC1 levels and mucosal damage in CD has not been evaluated. AIMS: To evaluate serum SSDC1 levels in children with CD and to determine its relationship with histological grading classified by modified Marsh criteria. METHODS: This is a cross-sectional, pilot study, in which serum SSDC1 was analyzed by ELISA in a cohort of 49 untreated children with CD and 15 children with nonspecific abdominal pain (AP). CD was diagnosed based on positive celiac serology and small intestinal biopsy. SSDC1 levels at the time of biopsy were correlated with Marsh grading. Controls were defined by AP, negative celiac serology, normal upper endoscopy, and small intestinal biopsies. RESULTS: SSDC1 levels were significantly higher in CD patients compared to AP controls (116.2 ± 161 vs. 41.3 ± 17.5 ng/ml, respectively, p < 0.01). SSDC1 levels were significantly higher in patients with Marsh 3c lesion compared to AP controls (170.6 ± 201 vs. 41.3 ± 17.5 ng/ml, respectively, p < 0.05). SSDC1 concentrations displayed a significant correlation with mucosal damage defined by Marsh (r = 0.39, p < 0.05). CONCLUSION: This is the first study demonstrating elevated levels of serum SSDC1 in children with CD. Our results suggest that SSDC1 is a potentially novel marker of intestinal mucosal damage in patients with CD. Its applicability as a surrogate biomarker in CD remains to be determined.

Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial.

Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62(+) expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects.

Dietary enrichment with alpha-linolenic acid during pregnancy attenuates insulin resistance in adult offspring in mice.

OBJECTIVE: Our objective was to test the contribution of dietary enrichment in essential or saturated fatty acids, in normocaloric diets, on the lipid accumulation and insulin resistance in the adult offspring in a C57Bl6/J mice model. METHODS: Pregnant mothers were fed normocaloric diets containing 6% fat enriched in essential fatty acids (EFA): alpha-linolenic (ALA-18:3, n-3), linoleic (LA-18:2, n-6), or saturated fatty acids (SFA). After a washing-out period with regular diet, the offspring received a high-fat diet before euthanization. RESULTS: Adult mice fed maternal ALA showed lower body weight gain and lower liver fat accumulation, lower HOMA index and lower stearoyl-CoA desaturase (SCD1) activity than those fed maternal SFA. CONCLUSION: The results observed using this novel model suggest that ALA in maternal diet may have the potential to inhibit insulin resistance in adult offspring.

Characterization of novel CD55 isoforms expression in normal and neoplastic tissues.

CD55 (decay-accelerating factor, DAF) is overexpressed in several types of cancer, including colorectal cancer. Because of its inhibitory effect on the complement system, it has been suggested as a possible target for cancer immunotherapy. However, CD55 is also expressed in normal tissues, body fluids and stroma, limiting the use of anti-CD55 therapeutic antibodies. Two novel CD55 splice variants or isoforms have recently been identified. These have been shown to contain part or all of intron 7 (CD55(int7+)), in contrast to the previously identified splice variants (CD55(wt)), which do not contain intron 7. Our aim was to determine the pattern of expression of the CD55(int7+) isoforms in normal and cancer tissues and to compare it to CD55(wt). We found that while CD55's isoforms levels vary directly, CD55(wt) is much more abundant (on average 48 times more) than CD55(int7+). Moreover, colon cancers that express high CD55(wt) mRNA levels tend to upregulate CD55(int7+) to a further extent. Finally, we compared the protein levels of CD55(int7+) to CD55(wt) by immunohistochemistry in various colorectal pathological conditions including neoplasia, and found that the levels of both isoforms were elevated in all types of colonic pathology. These results show that the levels of CD55(int7+) in normal tissue are much lower than CD55(wt), while in tumors it is restricted to the epithelial structures unlike CD55(wt). Thus, CD55(int7+) may be a more suitable target for cancer immunotherapy.

Phase 1/2a, dose-escalation, safety, pharmacokinetic and preliminary efficacy study of intratumoral administration of BC-819 in patients with unresectable pancreatic cancer.

BC-819 is a DNA plasmid that was developed to target the expression of diphtheria-toxin gene under the control of H19 regulatory sequences. BC-819 has the potential to treat pancreatic cancer that overexpresses the H19 gene. The objectives were to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of BC-819 administered intratumorally in subjects with unresectable, locally advanced, non-metastatic pancreatic cancer. Nine patients with unresectable pancreatic adenocarcinoma were enrolled in an open-label, dose-escalation trial. Subjects were entered into one out of two cohorts with escalating doses of BC-819. Each cohort received 2 weeks of twice weekly intratumoral injection of BC-819 under computerized tomography (CT) (n = 3) or endoscopic ultrasound (EUS) (n = 6) guidance. Patients were assessed by CT or positron emission tomography (PET)/CT during week 4 for tumor response. The maximum tolerated dose of BC-819 was not reached in this study at the highest dose. Asymptomatic elevation of lipase, which was considered as an adverse event with dose-limiting toxicity, occurred in only one subject in the high-dose group and was resolved spontaneously. The tumors did not increase in size 4 weeks after initiating treatment. Two weeks after completing the treatment, the two subjects who went on to receive subsequent chemotherapy or chemoradiation therapy, pancreatic tumors were downstaged and considered surgically resectable. Remarkably, three of the six subjects in cohort no. 2 evaluated at month 3 had a partial response. BC-819 can be safely administered intratumorally via EUS- or CT-guided injection at a dose of at least 8 mg per injection weekly twice. BC-819 given locally in combination with systemic chemotherapy may provide an additional therapeutic benefit for the treatment of pancreatic cancer.

Prospective multicenter performance evaluation of the second-generation colon capsule compared with colonoscopy.

BACKGROUND AND STUDY AIMS: A second-generation capsule endoscopy system, using the PillCam Colon 2, was developed to increase sensitivity for colorectal polyp detection compared with the first-generation system. The performance of this new system is reported. PATIENTS AND METHODS: In a five-center feasibility study, second-generation capsule endoscopy was prospectively compared with conventional colonoscopy as gold standard for the detection of colorectal polyps and other colonic disease, in a cohort of patients scheduled for colonoscopy and having known or suspected colonic disease. Colonoscopy was independently performed within 10 hours after capsule ingestion. Capsule-positive but colonoscopy-negative cases were counted as false-positive. RESULTS: 104 patients (mean age 49.8 years) were enrolled; data from 98 were analyzed. Patient rate for polyps of any size was 44 %, 53 % of these patients having adenomas. No adverse events related to either procedure were reported. The capsule sensitivity for the detection of patients with polyps >or= 6 mm was 89 % (95 % confidence interval [CI] 70 - 97) and for those with polyps >or= 10 mm it was 88 % (95 %CI 56 - 98), with specificities of 76 % (95 %CI 72 - 78) and 89 % (95 %CI 86 - 90), respectively. Both polyps missed by colonoscopy and mismatch in polyp size by study definition lowered specificity. Overall colon cleanliness for capsule endoscopy was adequate in 78 % of patients (95 %CI 68 - 86). CONCLUSIONS: The new second-generation colon capsule endoscopy is a safe and effective method for visualizing the colon and detecting colonic lesions. Sensitivity and specificity for detecting colorectal polyps appear to be very good, suggesting a potential for improved accuracy compared with the first-generation system. Further prospective and comparative studies are needed.

Nonspecific esophageal motility disorders may be an early stage of a specific disorder, particularly achalasia.

The clinical significance of nonspecific esophageal motility disorder (NEMD) is unclear. Our aim was to investigate the natural history of NEMD. All manometries performed at Meir Hospital from 1997 to 2004 and diagnosed as NEMD were reviewed. Manometric criteria for NEMD included either low-amplitude peristalsis, nonprogression of peristalsis, prolonged retrograde or triple-peaked waves, or incomplete relaxation of the lower sphincter. Patients determined to have NEMD were contacted and asked to complete a questionnaire and undergo a second manometry. NEMD had been diagnosed in 137 patients. Upon review of manometry results, 65 patients were eligible for the study (36 men and 29 women). The other 72 patients did not have NEMD when we reviewed their manometry tracing, applying strict criteria as specified in Table 1. The average age was 64 +/- 16 years (range 24-83 years). The average follow-up period was 7 +/- 2 years. All 65 patients were symptomatic at their initial prestudy visit. By the second visit, symptoms had resolved in 33 (51%) patients and improved in 13 (19%). Dysphagia, chest pain, and food regurgitation had improved, whereas heartburn and respiratory symptoms had not. Of 37 patients with triple-peaked waves, only 11 (30%) had improved clinically. Of the 65 study patients, 17 (26%) had a second manometry during the study, which was normal in 2 (12%), unchanged in 11 (69%), and revealed achalasia in 4 (23%), representing 6% of all study patients. NEMD is generally a benign disorder that improves clinically in most cases. Nevertheless, in about 6% of patients, NEMD may evolve into achalasia.

Toilet reading habits in Israeli adults.

Although toilet reading (TR) is a common habit, the effect of TR on bowel movements is neglected in the medical literature. Our hypothesis was that TR provides a distraction and acts as an unconscious relaxation technique and allows an easier defecation process. The aim of this study was to assess how common is TR and to map the reading/playing toilet habits in the Israeli adult population. In addition, we aimed to explore a possible connection between TR and the nature of bowel habits in general and constipation and haemorrhoids in particular. Five hundred adults who represent the diverse demographic backgrounds have been asked to fill an anonymous short questionnaire. The subjects were questioned regarding their demographic details, their TR and playing habits, their bowel habits, whether they suffer from haemorrhoids and whether they use some sort of faecal softener. We found that TR is common and involves 52.7% of the population. Males, younger age, secular population, higher education level and white collar workers compose the TR profile. Although toilet readers spent significantly more time in the toilets, no differences were noted for the type or frequency of stools. Nevertheless, the TR group considered themselves to be less constipated (8.0%vs 13.7%) and had more haemorrhoids (23.6%vs 18.2%). These differences, however, were not significant. Toilet reading is a common and benign habit. It is involved with a longer time spent in the toilet. It seems to be more for fun and not necessarily to solve or due to medical problems.

Low-dose heparin for the prevention of post-ERCP pancreatitis: a randomized placebo-controlled trial.

BACKGROUND: As suggested by observational and animal studies, heparin has antiinflammatory effects that could prevent acute post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Low-molecular-weight heparin did not reduce the incidence of post-ERCP pancreatitis in a controlled study. The current study aimed to determine whether prophylactic administration of low-dose unfractionated heparin, which has potentially more antiinflammatory capability, can prevent acute post-ERCP pancreatitis. METHODS: Patients scheduled for ERCP in the authors' department were randomized to receive unfractionated heparin (5,000 IU) or placebo (saline solution 0.5 ml) administered subcutaneously 20 to 30 min before the ERCP. Patients who had undergone endoscopic sphincterotomy in the past were excluded from the study. Post-ERCP pancreatitis was defined according to criteria established by Cotton: abdominal pain combined with a threefold elevation of blood amylase 24 h after the ERCP. RESULTS: The study enrolled 106 patients. One patient was excluded from the analysis due to inaccessible papilla of Vater, leaving 51 patients in the heparin group and 54 in the placebo group, for a total of 105 patients (62 women and 43 men) with a mean age of 64.6 years. The rate of post-ERCP pancreatitis was not different between the groups (heparin, 4 patients, 7.8%; placebo, 4 patients, 7.4%). Two patients in each group experienced mild bleeding. CONCLUSIONS: The study did not demonstrate a significant effect of low-dose unfractionated heparin in the prevention of post-ERCP pancreatitis. A multicenter trial with a larger number of patients is needed to demonstrate a benefit from this drug.

The clinical significance of bile duct sludge: is it different from bile duct stones?

BACKGROUND: Some patients with suspected common bile duct (CBD) stones are found to have sludge and no stones. Although sludge in the gallbladder is a precursor of gallbladder stones, the significance of bile duct sludge (BDS) is poorly defined. This study aimed to compare BDS with bile duct stones in terms of frequency, associated risk factors, and clinical outcome after endoscopic therapy. METHODS: The study enrolled 228 patients who underwent therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for suspected choledocholithiasis. The patients were divided into two groups: patients with BDS but no stones on ERCP and patients with CBD stones. The presence of risk factors for bile duct stones (age, periampullary diverticulum, ductal dilation or angulation, previous open cholecystectomy) were assessed at ERCP. Follow-up data (36 +/- 19 months) were obtained from medical records and by patient questioning. RESULTS: Bile duct sludge occurred in 14% (31/228) of patients and was more common in females. After endoscopic clearance, CBD stones recurred in 17% (33/197) of the patients with CBD stones, and in 16% (5/31) of the patients with BDS (p = 0.99). Common bile duct dilation was less common in the sludge group. The other known risk factors for recurrent CBD stones (age, previous open cholecystectomy, bile duct angulation, and the presence of a peripampullary diverticulum) were not statistically different between the two groups. CONCLUSIONS: The findings indicate that the clinical significance of symptomatic BDS is similar to that of CBD stones. Bile duct sludge seems to be an early stage of choledocholithiasis.

Risk factors for severity and relapse of pseudomembranous colitis in an elderly population.

OBJECTIVE: Pseudomembranous colitis (PMC) is well recognized as an important cause of diarrhoea in patients receiving antibiotics, with significant consequences of morbidity and mortality. Mortality among elderly patients is high, and even with successful treatment, a significant number of patients relapse. To evaluate the outcome of elderly patients with PMC, and to try to identify risk factors that might influence mortality or relapse. METHOD: We studied 72 consecutive hospitalized patients with endoscopically proven PMC. The medical records of all patients with their clinical history and laboratory data were reviewed in detail. These data included: pre-hospitalization residence and physical status, background medical history, presenting symptoms, antibiotic history, haematological and biochemical parameters, treatment, duration of hospitalization, complications, mortality within 30 days of hospitalization and relapse. RESULTS: Of the 72 patients (M/F=34/38, mean age=77 years), 47% were nursing home residents. Prior to hospitalization, 91.6% of patients had received antibiotic treatment (cephalosporins - 64%, penicillins - 42% and quinolones - 28%), 26% of patients received antacid therapy and 36% had been fed with a nasogastric tube (NGT). Thirty-seven (51%) patients recovered without complications, 21 (29%) patients died within 30 days of hospitalization and 14 (19%) patients were re-hospitalized because of relapse of PMC. Multivariate analysis revealed that white blood cell count above 20 x 10(3)/mm3 (P=0.009), serum albumin level of less than 2.5 g/dl (P=0.02), and pre-hospitalization NGT feeding (P=0.01) were associated with high mortality. Treatment with acid-reducing drugs (P=0.01) and living at a nursing home (P=0.06) were associated with high relapse rates. CONCLUSION: Pseudomembranous colitis is an important complication of antibiotic therapy and is associated with high mortality and recurrence rate, especially in old and debilitated persons. Pre-admission NGT feeding, severe leucocytosis and hypoalbuminaemia on admission are associated with increased mortality. Pre-hospitalization acid reducing treatment and nursing home residency are associated with increased risk of recurrence.

An angulated common bile duct predisposes to recurrent symptomatic bile duct stones after endoscopic stone extraction.

BACKGROUND: Endoscopic sphincterotomy and stone extraction are standard procedures for the removal of bile duct stones. Stone recurrence can, however, occur in up to 25% of cases. Risk factors have been poorly defined, but are believed to be related to bile stasis. This study investigated whether an angulated common bile duct (CBD) that may predispose to bile stasis influences symptomatic stone recurrence after successful endoscopic therapy. METHODS: This study included 232 consecutive patients (mean age, 64.1 years; 86 men) who had undergone therapeutic endoscopic retrograde cholangiopancreatography for bile duct stones. Data from the follow-up period (36 +/- 17 months) were obtained from medical records and patient questioning. Common bile duct angulation and diameter were measured from the cholangiogram after stone removal. RESULTS: Symptomatic bile duct stones recurred in 16% of the patients (36/232). Three independent risk factors were identified by multivariate analysis: an angulated CBD (angle, < or = 145 degrees; relative risk [RR], 5.2; 95% confidence interval [CI], 2.2-12.5; p = 0.0002), a dilated CBD (diameter, > or = 13 mm; RR, 2.6; 95% CI, 1.2-5.7; p = 0.017), and a previous open cholecystectomy (RR, 2.7; 95% CI, 1.3-5.9; p = 0.0117). Gender, age, urgency of procedure, or a periampullary diverticulum did not influence the recurrence rate. CONCLUSIONS: Angulation of the CBD (< or = 145 degrees) on endoscopic cholangiography, a dilated CBD, and a previous open cholecystectomy are independent risk factors for symptomatic recurrence of bile duct stones. The findings support the role of bile stasis in stone recurrence. Further studies using these data prospectively to identify high-risk patients are warranted.

CT findings of latrogenic complications following gastrointestinal endoluminal procedures.

Abdominal CT, a simple and safe imaging modality, plays an important role in evaluating patients suspected of having abdominal complications following nonsurgical gastrointestinal procedures, to accurately determine the presence or absence of such insults. This pictorial article reviews and demonstrates the CT findings of various complications following upper endoscopy, percutaneous endoscopic gastrostomy, endoscopic retrograde cholangiopancreatography, endoscopic US, colonoscopy, and enemas (barium as well as cleansing).

Consecutive instances of gallstone ileus due to obstruction first at the ileum and then at the duodenum complicating a gallbladder carcinoma: a case report.

Ectopic gallstone obstruction, gallstone ileus, due to cholecystoenteric fistula is an infrequent condition. Its occurrence as a complication of a gallbladder (GB) carcinoma is even more rare. We describe an unusual case of a GB carcinoma complicated by a cholecystoduodenal fistula leading to first gallstone obstruction in the ileum and then, later, in the duodenum, in which an accurate preoperative diagnosis was based on pathognomonic computerized tomography (CT) features. A correct diagnosis of this may be crucial and requires prompt surgical intervention; radiologists should be familiar with their classic CT appearance.

Endoscopic sphincterotomy and temporary internal stenting for bile leaks following complex hepatic trauma.

BACKGROUND: Biliary leak secondary to blunt or penetrating hepatic trauma and damage to the intrahepatic biliary tree remains a challenging problem. The role and safety of endoscopic retrograde cholangiopancreatography (ERCP) and stenting in this setting were studied. METHODS: All trauma victims who developed a bile leak secondary to hepatic trauma were included. Bile leak was defined as the appearance of bile in a surgical wound or intra-abdominal drain after surgery, following percutaneous drainage of a perihepatic bile collection, or evidence of a leak on hepatobiliary scintigraphy. ERCP was performed within 24 h of diagnosis and included biliary sphincterotomy and internal stenting. Recovery was defined as cessation of leakage. RESULTS: Between 1996 and 2004, six patients with penetrating injuries and five with blunt abdominal injuries were treated according to the study protocol. Eight underwent surgery to control bleeding or for additional intra-abdominal injuries. All bile leaks resolved completely within 10 days of ERCP. One patient died from pulmonary sepsis; ten recovered without hepatobiliary sequelae. CONCLUSION: ERCP, biliary sphincterotomy and temporary internal stenting, together with percutaneous drainage of intra-abdominal or intrahepatic bile collections, represent a safe and effective strategy for the management of bile leaks following both blunt and penetrating hepatic trauma.

Faecal sterol output is increased by arachidyl amido cholanoic acid (Aramchol) in rats.

Fatty acid-bile acid conjugates (FABACs) were shown recently to have important and multiple effects on cholesterol metabolism. In human fibroblasts, they were found to markedly enhance cholesterol efflux by an ATP-binding cassette transporter A1-dependent pathway. In C57L/J mice, they increased CYP7A1 activity and RNA expression, while decreasing moderately 3-hydroxy-3-methylglutaryl-CoA reductase activity. In C57L/J mice and in hamsters, they also decreased serum cholesterol levels, whereas in other animals, this effect was not seen in short-term experiments. In the present study, we investigated potential mechanisms of action of arachidyl amido cholanoic acid (Aramchol), with particular reference to biliary and faecal sterol outputs in rats. Supplementation with Aramchol at a dose of 150 mg x kg(-1) x day(-1) increased neutral sterol output by approx. 50%, while the faecal outputs of bile salts and total sterols increased by almost 2-fold. Biliary lipid outputs were not significantly different between the control and FABAC-supplemented animals. These findings indicate an overall catabolic effect of FABACs on body cholesterol.

Cytokine network in nonresponding chronic hepatitis C patients with genotype 1: role of triple therapy with interferon alpha, ribavirin, and ursodeoxycholate.

OBJECTIVE: (i) to characterize the profile of tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6), IL 10, Fas-ligand and transforming growth factor beta (TGF beta), chronic hepatitis C (HCV) patients with genotype 1; (ii) to determine the influence of triple therapy (TT) with interferon alpha (IFN alpha) + ribavirin + ursodeoxycholic acid on these cytokines and (iii) to establish the relationship between the pro-inflammatory cytokines and the outcome of treatment. DESIGN AND METHODS: 22 patients infected with HCV-genotype 1 a/b and non responsive to IFN-alpha monotherapy were enrolled in the TT. The controls were 49 HCV naïve patients with genotype 1 a/b. Cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The baseline TNF alpha values (pg/mL) in the sustained responders (SRs) (63+/-3) were significantly lower than non-responders (NRs) (140+/-16) (p < 0.001). Baseline Fas (ng/mL) levels were also lower in SRs (4.3+/-0.2) than NRs (5.4+/-0.4) (p < 0.05). CONCLUSIONS: Fas and TNF alpha may be used as serological markers of inflammation and effectiveness of therapy.

Fatty acid bile acid conjugates (FABACs)--new molecules for the prevention of cholesterol crystallisation in bile.

BACKGROUND: Cholesterol gall stones are a frequent disease for which at present surgery is the usual therapy. Despite the importance of bile acids it has become evident that phospholipids are the main cholesterol solubilisers in bile. Even phospholipid components, such as fatty acids, have anticrystallising activity. AIM: To synthesise fatty acid bile acid conjugates (FABACs) and study their effects on cholesterol crystallisation in bile in vitro and in vivo. METHODS: FABACs were prepared by conjugation of cholic acid at position 3 with saturated fatty acids of variable chain length using an amide bond. Cholesterol crystallisation and its kinetics (crystal observation time, crystal mass) were studied in model bile, pooled enriched human bile, and fresh human bile using FABACs with saturated fatty acids of varying chain length (C-6 to C-22). Absorption of FABACs into blood and bile was tested in hamsters. Prevention of biliary cholesterol crystallisation in vivo was tested in hamsters and inbred mice. RESULTS: FABACs strongly inhibited cholesterol crystallisation in model as well as native bile. The FABACs with longer acyl chains (C-16 to C-22) were more effective. At a concentration of 5 mM, FABACs almost completely inhibited cholesterol crystallisation in fresh human bile for 21 days. FABACs were absorbed and found in both portal and heart blood of hamsters. Levels in bile were 2-3 times higher than in blood, indicating active secretion. Appreciable levels were found in the systemic circulation 24-48 hours after a single administration. Ingested FABACs completely prevented the formation of cholesterol crystals in the gall bladders of hamsters and mice fed a lithogenic diet. CONCLUSIONS: FABACs are potent inhibitors of cholesterol crystallisation in bile. They are absorbed and secreted into bile and prevent the earliest step of cholesterol gall stone formation in animals. These compounds may be of potential use in cholesterol gall stone disease in humans.