Embryology of Extra‐ and Intrahepatic Bile Ducts,the Ductal plate

In the human embryo, the first anlage of the bile ducts and the liver is the hepatic diverticulum or liver bud. For up to 8 weeks of gestation, the extrahepatic biliary tree develops through lengthening of the caudal part of the hepatic diverticulum. This structure is patent from the beginning and remains patent and in continuity with the developing liver at all stages. The hepatic duct (ductus hepaticus) develops from the cranial part (pars hepatica) of the hepatic diverticulum. The distal portions of the right and left hepatic ducts develop from the extrahepatic ducts and are clearly defined tubular structures by 12 weeks of gestation. The proximal portions of the main hilar ducts derive from the first intrahepatic ductal plates. The extrahepatic bile ducts and the developing intrahepatic biliary tree maintain luminal continuity from the very start of organogenesis throughout further development, contradicting a previous study in the mouse suggesting that the extrahepatic bile duct system develops independently from the intrahepatic biliary tree and that the systems are initially discontinuous but join up later. The normal development of intrahepatic bile ducts requires finely timed and precisely tuned epithelial–mesenchymal interactions, which proceed from the hilum of the liver toward its periphery along the branches of the developing portal vein. Lack of remodeling of the ductal plate results in the persistence of an excess of embryonic bile duct structures remaining in their primitive ductal plate configuration. This abnormality has been termed the ductal plate malformation. Anat Rec, 291:628–635, 2008. © 2008 Wiley‐Liss, Inc.     

The fine structure and histochemistry of human bile duct in obstruction and choledocholithiasis

Biopsies from the common bile ducts from seven patients undergoing surgery for biliary obstruction due to stones or malignancy were studied histochemically and electron microscopically. The surface of the bile duct is lined by a tall epithelium which extends into diverticula. Apically, they contain some neutral and sialated mucosubstances. Fucosyl residues were found in the Golgi apparatus and along the apical cell membrane. The latter is lined by microvilli. There was a well-developed rough endoplasmic reticulum and Golgi apparatus and a small number of apical secretory droplets. Large numbers of lipid droplets were present basally in some cells. Lipid-containing macrophages were also seen intra-epithelially and in the lamina propria. This suggests a possible pathway for lipid transport. The glands were lined by cuboidal cells, some containing much mucus--sulphated, sialated, and neutral with a basal nucleus. A well-developed endoplasmic reticulum and Golgi apparatus were found with abundant secretory droplets. The glandular epithelium contained lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin. These may play a protective role. The lamina propria contained scattered smooth muscle cells amongst the fibroblasts and inflammatory cells.     

Differences in gallstone structure in primary common bile duct lithiasis and gallbladder lithiasis

Summary Some differences between gallbladder lithiasis and primary common bile duct lithiasis are described. Microbiological cultures and biochemical analyses were carried out on the bile of two groups of patients: 27 suffering from gallbladder and 5 from primary common duct lithiasis. The microstructure and composition of gallstones were also examined by polarized light microscopy and X-ray diffraction. Women predominated in gallbladder lithiasis but not in primary common duct lithiasis group (P<0.05) and body weight was higher in the former group (P<0.02). Primary common duct lithiasis patients had a higher, although not significant, incidence of duodenal diverticulosis (P=0.15), and a higher incidence ofE. coli-positive cultures in bile (P<0.001). No significant difference in the biochemical composition of the bile was found between the groups. Brown pigment stones predominated in primary common duct lithiasis, while cholesterol stones did in gallbladder and secondary common duct lithiasis (P<0.0001). Stones formed in the gallbladder generally show linear, radial growths of cholesterol crystals, while those from the common duct present a polystratified, concentric deposition of microgranules composed mainly of pigmentary salts.These differences should be taken into account as additional criteria in the differential diagnosis between primary and secondary common duct lithiasis, as the classical criteria for diagnosing of the former greatly underestimate its actual incidence. The distinction between primary and secondary common duct lithiasis is of practical significance, since each entity requires different treatment.Abbreviations CBD common bile duct - CBDL common bile duct lithiasis - ERCP endoscopic retrograde cholangiopancreatography - GBL gallbladder lithiasis - HDL high density lipoproteins - PCBDL primary common bile duct lithiasis - SCBDL secondary common bile duct lithiasis - SGOT serum glutamic-oxalacetic transaminase - SGPT serum glutamic-pyruvic transaminase     

Chemical Characterization of Macrophage Cytotoxicity Factor,Macrophage Migration Inhibitory Factor,T-Helper Cell-Replacing Factor and Colony-Stimulating Factor from Culture Supernatants of Concanavalin A-Stimulated Murine Spleen Cells

Supernatants from Concanavalin A-stimulated murine spleen cells were subjected to hydrophobic interaction chromatography on phenyl-Sepharose. Macrophage cytotoxicity factor (MCF), macrophage migration inhibitory factor (MIF), T-helper cell-replacing factor (TRF) and colony-stimulating factor (CSF) were bound at high ionic strength and were released stepwise at low ionic strength. CSF thus could be separated from MCF, MIF and TRF and the bulk of other proteins. Chromatography of pools containing MCF, MIF and TRF on Sephadex did not lead to a separation of the three activities which were all found in a molecular weight range of 25.000-55.000. Isoelectric focusing of these pools in pH range from 4 to 9 gave two peaks for MCF at pH 8.2 and 7.2, whereas MIF activity focused from pH 4.5 to 5.5. TRF activity was found in a single sharp peak at pH 5.3. The results demonstrate that the four biological activities can be distinguished on a chemical basis and are accessible for purification and chemical characterization.     

Vimentin expression of newly formed rat bile duct epithelial cells in secondary biliary fibrosis

Summary The intermediate filament profile and the growth fraction of hepatocytes and bile duct epithelial cells were studied in a rat model of biliary fibrosis secondary to common bile duct ligation and scission. Strong vimentin expression was observed in epithelial cells of newly formed bile ductules, while normal liver contained only few weakly positive bile duct epithelial cells. All epithelial cells reacted with a pan-cytokeratin antibody. A monoclonal antibody specific for human cytokeratin 7 selectively reacted with both normal and newly formed bile duct epithelial cells. The intermediate filament profile of hepatocytes was constant, showing no changes during proliferation or in periportal areas adjacent to excessive bile duct formations. The proliferation-associated antigen detected by the antibody Ki-67 was present in many hepatocytes, homogeneously distributed in the lobules, but was seen only in a small proportion of the epithelial cells of the newly formed bile ducts. We conclude that vimentin may serve as an indicator for cellular reorganization in the bile duct system, and that the epithelial cells of newly formed bile ductules in this particular model of secondary biliary fibrosis were most likely to be derived from an outgrowth of the biliary duct system and recruitment of preductular epithelial cells. No morphological or immunohistological evidence suggesting a derivation from hepatocytes by ductular metaplasia or from oval cells was obtained.     

Differential activation of hepatitis B DNA polymerase by detergent and salt

Three patterns of activity were evident when the differential activation of the DNA polymerase associated with serum Dane particles by nonionic detergent and salt was investigated. The patterns were obtained by plotting the increase in enzyme activity mediated by the detergent Nonidet P-40 (NP-40) in increasing concentrations of KCl compared to the activity observed in the absence of detergent. The pattern of differential activity of hepatitis B (HB) DNA polymerase in detergent and salt was altered by subjecting the HBAg preparations to shearing forces. Hepatitis B DNA polymerase activity was stable even in NP-40 concentrations as high as 10%. In addition to hepatitis B DNA polymerase, DNA polymerase activated by calf thymus DNA was found in pellets containing Dane particles. The latter DNA polymerase activity was also activated by NP-40 and was not decreased by DNAse; this DNA polymerase coprecipitated with hepatitis B antigen (HBAg) upon addition of anti-HBs. However, the DNA polymerase activated by calf thymus DNA was inhibited by 0.4 M KCl. Electron microscopic observations of serum Dane particles in 0.4 M KCl showed no alterations of morphology of these particles when compared to particles in low-salt buffer. The data indicated that KCl activated HB DNA polymerase by a different mechanism from that of shear or NP-40, which removed the surface antigen coat from the Dane particles.     

胆总管“T”形管引流少见并发症及其防治

本文报道在施行胆总管探查、T形管引流的病例中,遇到的“拔除T形管导致急性弥漫性胆汁性腹膜炎;胆汁引流量过多,食物返流入T形管;蛔虫阻塞T形管;结石阻塞T形管”等五种少见的并发症,并结合病例对其发生原因,紧急处理和预防措施进行探讨。     

The influence of bile salts on the absorption in vitro and in vivo of propranolol

The lipophilicity of propranolol is increased by some bile salts which form ion-pairs. In the presence of taurodeoxycholate, the logarithm of the apparent partition coefficient (log P) of propranolol is increased. Moreover, the apparent diffusion constants in vitro of propranolol as ion-pairs at pH 3.0–6.0 are about 5–6 times higher than those of propranolol alone.

The area under the curve values of plasma concentration—time profiles of propranolol, following its oral administration to rabbits together with taurodeoxycholate, are about 1.4 times higher than those after administration of propranolol alone. Moreover, after the admistration of propranolol with taurodeoxycholate the plasma concentration rises more rapidly, with a point of inflection between 0.5 and 1.5 h, than after administration of propranolol alone.

Taurodeoxycholate does not modify the first-pass effect of propranolol in rabbits following intravenous and intraportal administration. The absorption of an oral dose of propranolol in the presence of taurodeoxycholate increases from 70% to 100%, due to the higher lipophilicity of the ion-pair. The plasma concentration—time curves suggest the hypothesis that greater absorption of the ion-pair occurs mainly in the upper region of the gastrointestinal tract.     

Assessing the Impact of Salt Reduction Initiatives on the Chronic Disease Burden of Singapore

Globally, many countries are facing an increasing burden of chronic disease due to ageing populations, of which cardiovascular disease forms a large proportion. Excess dietary sodium contributes to cardiovascular disease risk and requires intervention at a population level. This study aimed to quantify the impact of several salt reduction initiatives on population health over a 30-year horizon using GeoDEMOS, a population model from Singapore. Four interventions were modelled in four demographic groups in 2020 for a total of 16 intervention scenarios. The effect of 0.5, 2.0, and 4.0 g/day reductions in daily salt consumption, along with adherence to the World Health Organization guidelines of a maximum of 5.0 g of salt each day, was modelled in the entire population, including the overweight and obese, the elderly, and diabetics. In each scenario, the number of averted incident cases of acute myocardial infarction and stroke, along with the disability-adjusted life years up to 2050, was monitored. We found 4.0 g/day reductions in salt consumption were the most effective when implemented across the entire population, resulting in 24,000 averted incident cases of cardiovascular disease and 215,000 disability-adjusted life years over 30 years. This is a large figure when compared with the 29,200 projected annual incident cases of cardiovascular disease in 2050. When targeted at specific high-risk demographic groups, the largest effects were observed in the overweight and obese, with the same intervention yielding 10,500 averted incident cases of cardiovascular disease and 91,500 disability-adjusted life years. Quantifying the benefits of salt reduction initiatives revealed a significant impact when administered across the entire population or the overweight and obese. Health promotion efforts directed toward sustainably reducing salt consumption will help to lower the chronic disease burden on the healthcare system in years to come.     

Mirizzi综合征18例外科治疗体会

目的：提高临床上对Mirizzi综合征的认识,避免胆道损伤。方法：对经手术证实的18例Mirizzi综合征的临床资料进行回顾性分析。结果：术前明确诊断者仅3例。行单纯胆囊切除11例,胆囊切除、胆管壁瘘口修补3例,胆囊切除、瘘口修补、T型管引流3例,胆囊切除、肝总管空肠Roux-en-y吻合术1例。随访11例平均时间5年,无胆道狭窄情况。结论：为避免胆道损伤,应结合病史、体检、化验及影像学检查进行全面综合分析,以提高术前确诊率,在手术时要认真对待,根据术中情况选择合理术式。