鲤醇的合成研究

鲤醇(cyprinol)最初是Haslewood(1955)从鲤鱼胆汁的水解液中分离得到的一种甾体化合物,其化学名称为3α,7α,12α,26,27-五羟基胆甾烷,它有两种构型(图1 Ⅰ、Ⅱ)

胰胆液反流的研讨

观察１５０例胆囊摘除、胆总管探查、Ｔ管引流者，将胆汁淀粉酶高于正常人血淀粉酶最大值作为胰胆液反流的依据、胆石症的胰胆液反流率明显高于非胆石组，泥沙石反流率高于胆固醇石反流，结石并发胰胆液反流与结石不并发胰胆液反流相比，前者胆总管扩张率明显增高；十二指肠反流是一种明显的胰胆液反流形式，并非无害。分析结石、阻道扩张与反流相关；胆囊摘除术前、后均可能发生反流，

High level of deoxycholic acid in human bile does not promote cholesterol gallstone formation

AIM:To study whether patients with excess deoxycholic acid (DCA) differ from those with normal percentage of DCA with respect to biliary lipid composition and cholesterol saturation of gallbladder bile. METHODS:Bile was collected during operation through puncturing into the gallbladder from 122 cholesterol gallstone patients and 46 gallstone-free subjects undergoing cholecystectomy.Clinical data,biliary lipids,bile add composition, presence of crystals and nucleation time were analyzed. RESULTS:A subgroup of gallstone patients displayed a higher proportion of DCA in bile than gallstone free subjects. By choosing a cut-off level of the 90th percentile,a group of 13 gallstone patients with high DCA levels (mean 50 percent of total bile acids) and a large group of 109 patients with normal DCA levels (mean 21 percent of total bile acids) were obtained.The mean age of the patients with high DCA levels was higher than that of the group with normal levels (mean age:62 years vs45 years) and so was the mean BMI (28.3 vs.24.7).Plasma levels of cholesterol and triglycerides were slightly higher in the DCA excess groups compared with those in the normal DCA group.There was no difference in biliary lipid composition,cholesterol saturation,nucleation time or occurrence of cholesterol crystals in bile between patients with high and normal levels of DCA. CONCLUSION:Gallstone patients with excess DCA were of older age and had higher BMI than patients with normal DCA.The two groups of patients did not differ with respect to biliary lipid composition,cholesterol saturation,nucleation time or occurrence of cholesterol crystals.It is concluded that DCA in bile does not seem to contribute to gallstone formation in cholesterol gallstone patients.

Postoperative bile leakage managed successfully by intrahepatic biliary ablation with ethanol

We report a case of postoperative refractory bile leakage managed successfully by intrahepatic biliary ablation with ethanol. A 75-year-old man diagnosed with hepatocellular carcinoma underwent extended posterior segmentectomy including the caudate lobe and a part of the anterior segment. The hepatic tumor attached to the anterior branch of the bile duct was detached carefully and resected. Fluid drained from the liver surface postoperatively contained high concentrations of total bilirubin, at a constant volume of 150 mL per day. On d 32 after surgery, a fistulogram of the drainage tube demonstrated an enhancement of the anterior bile duct. Endoscopic retrograde cholangiography demonstrated complete obstruction of the proximal anterior bile duct and no enhancement of the peripheral anterior bile duct. On d 46 after surgery, a retrograde transhepatic biliary drainage （RTBD） tube was inserted into the anterior bile duct under open surgery. However, a contrast study of RTBD taken 7 mo post-surgery revealed that the fistula remained patent despite prolonged conservative man- agement, so we decided to perform ethanol ablation of the isolated bile duct. Four mL pure ethanol was injected into the isolated anterior bile duct for ten minutes, the procedure being repeated five times a week. Following 23 attempts, the volume of bile juice reached less than 10 mL per day. The RTBD was clamped and removed two days later. After RTBD removal, the patient had no complaints or symptoms. Follow-up magnetic resonance imaging demonstrated atrophy of the ethanol-injected anterior segment without liver abscess formation.

Severe hypercholesterolemia associated with primary biliary cirrhosis in a 44-year-old Japanese woman

A 44-year-old woman developed jaundice and was diagnosed as stage Ⅱ of primary biliary cirrhosis(PBC).She showed a severely high total cholesterol level.This article focuses on atypical presentations of PBC and the need to test the total cholesterol level of PBC patients.

liver and the defects of cholesterol and bile acids biosynthesis: rare disorders many diagnostic pitfalls

In recent decades, biotechnology produced a growth of knowledge on the causes and mechanisms of metabolic diseases that have formed the basis for their study, diagnosis and treatment. Unfortunately, it is well known that the clinical features of metabolic diseases can manifest themselves with very different characteristics and escape early detection. Also, it is well known that the prognosis of many metabolic diseases is excellent if diagnosed and treated early. In this editorial we briefly summarized two groups of inherited metabolic diseases, the defects of cholesterol biosynthesis and those of bile acids. Both groups show variable clinical manifestations but some clinical signs and symptoms are common in both the defects of cholesterol and bile acids. The differential diagnosis can be made analyzing sterol profiles in blood and/or bile acids in blood and urine by chromatographic techniques(GC-MS and LC-MS/MS). Several defects of both biosynthetic pathways are treatable so early diagnosis is crucial. Unfortunately their diagnosis is made too late, due either to the clinical heterogeneity of the syndromes(severe, mild and very mild) that to the scarcity of scientific dissemination of these rare diseases. Therefore, the delay in diagnosis leads the patient to the medical observation when the disease has produced irreversible damages to the body. Here, we highlighted simple clinical and laboratory descriptions that can potentially make you to suspect a defect in cholesterol biosynthesis and/or bile acids, as well, we suggest appropriate request of the laboratory tests that along with common clinical features can help to diagnose these defects.

Effects of long term hydrophilic bile acid therapy on in vitro contraction of gallbladder muscle strips in patients with cholesterol gallstones

AIM:To evaluate ursodeoxycholic acid (UDCA) therapy on the in vitro contraction of gallbladder smooth muscle strips from cholesterol gallstone patients. METHODS:The contraction forces of gallbladder smooth muscle strips from 28 patients with cholesterol gallstones treated with UDCA were compared with contraction forces from 14 untreated patients. The strips were stimulated with increasing concentrations of cholecystokinin-8 (CCK-8). RESULTS:Although the contraction forces that developed in response to CCK-8 were higher in strips from specimens of UDCA treated patients compared to untreated patients,longer treatment periods (6-wk) caused more contraction responses than the short treatment period of 3-wk (F = 19.297,1.85 ± 0.22 g vs 1.70 ± 0.10 g,P < 0.01). Contraction forces developed with maximal stimulation with KCl in the 6-wk treatment group were also higher than contraction forces in the untreated group (F = 4.274,3.77 ± 0.45 g vs 3.30 ± 0.30 g,P < 0.05). CONCLUSION:Six-week UDCA treatment caused an increase in contractions of muscle strips from patients with cholesterol gallstones when compared to shorter treatment administration or controls. We suggest that extending UDCA treatment periods may cause more effective contractions in the gallbladder,and thereby increase the rate of response to treatment.

Prolonged cholestasis following successful removal of common bile duct stones:Beware patients on estrogen therapy

There are various well described forms of chronic cholestatic jaundice in adults, such as autoimmune cholangitis, drug-induced cholangitis and intrahepatic cholestasis of pregnancy. We present two cases of prolonged cholestasis following removal of gallstones at endoscopic retrograde cholangiopancreatography （ERCP） and subsequent clear cholangiography. Both patients were taking oral estrogens at the time of presentation, which were subsequently withdrawn. The first case responded rapidly to corticosteroid treatment, and the second case had a much slower resolution with ursodeoxycholic acid. Both cases highlighted the significance of estrogen-induced cholestasis in female patients with protracted jaundice following ERCP and removal of intra-ductal stones. After oral estrogens are discontinued, a short course of steroids needs to be considered.

Regulation of bile acid metabolism-related signaling pathways by gut microbiota in diseases

Over the past decade,there has been increasing attention on the interaction between microbiota and bile acid metabolism.Bile acids are not only involved in the metabolism of nutrients,but are also important in signal transduction for the regulation of host physiological activities.Microbial-regulated bile acid metabolism has been proven to affect many diseases,but there have not been many studies of disease regulation by microbial receptor signaling pathways.This review considers findings of recent research on the core roles of farnesoid X receptor(FXR),G protein-coupled bile acid receptor(TGR5),and vitamin D receptor(VDR)signaling pathways in microbial–host interactions in health and disease.Studying the relationship between these pathways can help us understand the pathogenesis of human diseases,and lead to new solutions for their treatments.

Bile-ology: from bench to bedside

Bile acids(BAs)are originally known as detergents essential for the digestion and absorption of lipids.In recent years,extensive research has unveiled new functions of BAs as gut hormones that modulate physiological and pathological processes,including glucose and lipid metabolism,energy expenditure,inflammation,tumorigenesis,cardiovascular disease,and even the central nervous system in addition to cholesterol homeostasis,enterohepatic protection and liver regeneration.BAs are closely linked with gut microbiota which might explain some of their crucial roles in organs.The signaling actions of BAs can also be mediated through specific nuclear receptors and membranebound G protein-coupled receptors.Several pharmacological agents or bariatric surgeries have demonstrated efficacious therapeutic effects on metabolic diseases through targeting BA signaling.In this mini-review,we summarize recent advances in bile-ology,focusing on its translational studies.