A Tissue-Engineered Artificial Bile Duct Grown to Resemble The Native Bile Duct

The aim of this study was to fabricate an artificial bile duct for the development of a new treatment for biliary diseases. Eighteen hybrid pigs were implanted with a bile duct organoid unit (BDOU) made of a bioabsorbable polymer. Twelve of the transplanted BDOUs had been seeded with autologous bone marrow cells (BMCs) in advance. Six animals, the controls, were grafted with the scaffold alone with no BMCs seeded. The common bile duct was cut, the hepatic cut end of the native common bile duct was anastomosed to the BDOU and the other end was anastomosed to the duodenum. The controls underwent a similar operation. The neo-bile duct was removed at pre-determined time points and investigated histologically. All 18 recipient pigs survived until their sacrifice at 6 weeks, 10 weeks or 6 months. Histological examination revealed incomplete epithelialization of the neo-bile duct at 6 weeks and 10 weeks after transplantation. At 6 months, the organoid exhibited a morphology almost identical to that of the native common bile duct. No differences were found between the controls and BMC-seeded pigs. These results show that the artificial bile duct thus fabricated can serve as a substitute for the native bile duct.     

柯萨奇病毒诱发实验性多发性肌炎的初步研究

分别用不同量的柯萨奇病毒Ｂ１、２、３感染和兔肌匀浆加完全弗氏佐剂免疫正常豚鼠；拟建立多发性肌炎模型。结果发现：０．１ｍｌ毒力为１０－５ＴＣＩＤ５０柯萨奇病毒Ｂ１感染豚鼠组，３周后出现多发性肌炎症状。肌酶谱异常与其它组有明显差异，病理检查证实为多发性肌炎改变。单纯兔肌匀浆免疫对照组未发病。提示柯萨奇病毒Ｂ１感染及感染的病毒量与多发性肌炎的发病相关     

Enhanced Intestinal Absorption of Oxytocin Peptide Analogues in the Absence of Pancreatic Juice in Pigs

Purpose. The present investigation was done to study the intestinal absorption of three oxytocin peptide analogues and to elucidate the role of pancreatic juice on their absorption. Methods. In conscious chronically catheterized pigs (6–8 weeks of age) plasma concentration of the peptides, [Mpa¹, D-Tyr(Ethyl)², Thr⁴, Orn⁸]-oxytocin (F314), [Mpa¹, D-Tyr(Ethyl)², Val⁴, D-Arg⁸]-oxytocin (CAT), and [Mpa¹, D-Tyr(Ethyl)², Thr⁴, Orn⁸, desGly⁹, carba⁶]-oxytocin (F327) after intraduodenal administration, during presence or diversion of the pancreatic juice via a pancreatic duct catheter, were determined by radioimmunoassay. The stability of the peptides to degradation was determined in vitro by incubation with activated pancreatic juice, chymotrypsin or trypsin, followed by reversed phase HPLC analyses. Results. All peptides were absorbed with a bioavailability of about 0.5% in the presence of pancreatic juice, but increased to 1.0%, 2.1%, and 13.5% for F314, CAT, and F327, respectively, when the pancreatic juice was diverted from the intestine. After incubation with pancreatic juice 95% of F314, 98% of F327, and 100% of CAT was found intact. When incubated with trypsin CAT remained intact while F314 and F327 were degraded by 54% and 46%, respectively. Incubation with purified chymotrypsin did not degrade the test peptides. Conclusions. The results indicate that the increased absorption of peptides observed under conditions of diverted pancreatic juice cannot only be explained by the absence of pancreatic enzymes, but also by changed absorptive properties in the gastrointestinal tract.     

用猪肝细胞型混合生物人工肝支持系统治疗肝衰竭的初步研究

目的 对培养猪肝细胞型混合生物人工肝支持系统治疗肝衰竭的可行性进行初步评价。方法 采用自行研制的以新生实验小型猪肝细胞为基础的混合生物人工肝支持系统，对5例慢性重型肝炎患者进行体外人工肝支持，综合评价其临床疗效和安全性。结果 5例患者经混合人工肝支持后，肝衰竭均得到不同程度的控制，表现为临床症状和肝衰竭相关指标好转，肝性脑病改善。最终2例好转出院，1例经肝移植存活，2例 死亡，死亡原因与不良反应无关。结论 猪肝细胞型混合生物人工肝系统可用作重型肝炎肝衰竭的辅助支持和治疗。     

猪肾近端小管的超微结构

目的 研究猪肾近端小管的超微结构。方法 树脂包埋一超薄切片、透射电子显微镜技术。结果 猪肾近端小管可分S1、S2、S3和S4段构成，其中S1、S2段构成了近端小管曲部，S3、S4段构成了近端小管直部。本文对各段细胞超微结构特点进行详细的描述。结论 猪肾近端小管的超微结构与人肾近端小管最接近。     

On the mechanism of increased potassium conductance by the potassium channel opener BRL 34915 in Isolated ventricular myocytes

The potassium conductance increased by BRL 34915 (BRL, cromakalim) was studied in single guinea pig ventricular myocytes by using a whole cell voltage-clamp technique. In control voltage-clamp recordings, the late current-voltage relation showed a distinct inward rectification. BRL (1–100 μM) shortened the action potential and diminished or abolished inward rectification but had no effect on the slope conductance and currents flowing during hyperpolarizing clamp steps. BRL did not decrease the slow inward current but accelerated the time constant of activation and amplitude of the outward current. Cd markedly decreased (0.2 mM) or abolished (0.4–0.6 mM) the slow inward current and BRL induced a faster outward shift of late current to a greater value. Glybenclamide (10 μM), a blocker of ATP-sensitive K⁺ channels, had little effect of its own on action potential, membrane currents, and I-V relation. However, in the presence of BRL, glybenclamide abolished BRL effects on action potential and currents and restored inward rectification. It is concluded that the mechanism by which BRL shortens the action potential is a faster growth of an outward current due to the reduction or abolition of the inward rectification of an ATP-dependent potassium channel. The reduction in force in non-isolated tissues appears to be an indirect result of the action potential shortening and not of a decreased slow inward current.     

Testing for skin sensitization according to the notification procedure for new chemicals: the Magnusson and Kligman test

The notification procedure for new chemicals in the European Union (called the Chemicals Act in Germany) requires a skin sensitization test when the amount of a new chemical produced exceeds 100 kg/year. The preferred test is that of Magnusson and Kligman; more than 90% of the tests submitted are performed with it. Though the Magnusson and Kligman test is described in the literature, and in the test guidelines of the European Union and of the OECD, discrepancies do occur in the performance of the test between test laboratories. In this paper, recommendations are given for standardized performance of the Magnusson and Kligman test.     

Pertussis toxin and N-ethylmaleimide inhibit histamine- but not calcium ionophore-induced endothelium-dependent relaxation

Summary Endothelium-dependent relaxation of the guinea pig pulmonary artery induced by histamine was inhibited by preincubation of the tissue with 10 M N-ethylmaleimide (NEM) for 10 min, whereas the endothelium-dependent relaxation induced by the calcium ionophore A 23187 was not affected by NEM. Pretreatment of the preparations with 0.2–1 g/ml pertussis toxin for 120 min inhibited concentration-dependently the histamine-induced relaxation. In contrast, endothelium-dependent relaxation in response to the calcium ionophore A 23187 was not affected by pertussis toxin. Since NEM and pertussis toxin are thought to interfere with membrane located GTP binding proteins, it is suggested that such a coupling protein is involved in the signal transduction of the histamine receptor leading to endothelium-dependent relaxation.A preliminary report of these results was presented at the autumn Meeting of the Deutsche Pharmakologische Gesellschaft, 1986 Send offprint requests to G. Weinheimer at the above address     

A macrophage inflammatory protein homolog encoded by guinea pig cytomegalovirus signals via CC chemokine receptor 1

Cytomegaloviruses encode homologs of cellular immune effector proteins, including chemokines (CKs) and CK receptor-like G protein-coupled receptors (GPCRs). Sequence of the guinea pig cytomegalovirus (GPCMV) genome identified an open reading frame (ORF) which predicted a 101 amino acid (aa) protein with homology to the macrophage inflammatory protein (MIP) subfamily of CC (β) CKs, designated GPCMV-MIP. To assess functionality of this CK, recombinant GPCMV-MIP was expressed in HEK293 cells and assayed for its ability to bind to and functionally interact with a variety of GPCRs. Specific signaling was observed with the hCCR1 receptor, which could be blocked with hMIP −1α in competition experiments. Migration assays revealed that GPCMV-MIP was able to induce chemotaxis in hCCR1-L1.2 cells. Antisera raised against a GST-MIP fusion protein immunoprecipitated species of ∼12 and 10 kDa from GPCMV-inoculated tissue culture lysates, and convalescent antiserum from GPCMV-infected animals was immunoreactive with GST-MIP by ELISA assay. These results represent the first substantive in vitro characterization of a functional CC CK encoded by a cytomegalovirus.