Bladder smooth muscle cell phenotypic changes and implication of expression of contractile proteins (especially caldesmon) in rats after partial outlet obstruction

BACKGROUND: The purpose of the present study was to investigate morphological changes in bladder smooth muscle of rats with partial outlet obstruction. We investigated smooth muscle cell phenotypic changes and implication of synthetic phenotype in contractility decrease and bladder compliance after bladder outlet obstruction. METHODS: Partial bladder outlet obstruction was introduced in female rats. Bladder were removed at 1, 3, 6, 10 and 20 weeks after the obstruction. Temporal pattern of changes in bladder mass, light microscopic pathogenesis and phenotypic expression of the bladder smooth muscle cells in the electron micrographs were investigated. Expression of contractile protein was also investigated by the immunoblotting method. RESULTS: Marked increase in bladder mass with marked thickening of smooth muscle layer was observed at 1 week after obstruction. The ratio of myocytes exhibiting contractile and synthetic phenotypes was almost constant until 6 weeks after the obstruction, but thereafter, synthetic phenotypes gradually increased and the ratio (synthetic/contractile phenotype) was 1.5-fold at 20 weeks after the obstruction. Caldesmon was most markedly expressed after the obstruction among contractile proteins examined by the immunoblotting method. CONCLUSION: Phenotypic changes were confirmed in bladder smooth muscle, and the decrease of the ratio of contractile phenotype was observed after long-term obstruction of the bladder outlet. Among the contractile proteins in the bladder smooth muscle cell, caldesmon was considered a reliable marker for predicting the pathogenetic conditions of the bladder.     

Primary carcinoid tumor of the testis with teratoma metastatic to the para-aortic lymph node

A primary testicular carcinoid tumor with teratoma metastasized to the para-aortic lymph node. After inguinal orchiectomy, serum and urinary levels of 5-hydroxyindoleacetic acid (5-HIAA) were found to be elevated. Chemotherapy consisting of cisplatin, etoposide and bleomycin was not effective on the metastatic lesions. Retroperitoneal lymphadenectomy normalized the levels of 5-HIAA. The patient is alive without recurrence 25 months after the retroperitoneal lymphadenectomy.     

13C-phenylalanine breath test correlates with liver fibrosis in postoperative biliary atresia

BACKGROUND: Values derived from the (13)C-phenylalanine breath test (PBT) may serve as an index for liver fibrosis and clinically predictive readings for liver diseases in adults. In the present study the PBT was conducted in postoperative biliary atresia (BA) children to evaluate phenylalanine metabolism in the liver, and the results based on biochemical data, especially the index on liver fibrosis, were compared with PBT findings. METHODS: Hepatofunctional evaluations were conducted in 10 postoperative BA children with moderate (group B; n = 4) and severe (group A; n = 6) liver dysfunction, and the PBT results were compared with those of 13 normal healthy children (group C). Subjects were orally given single-bolus (13)C-phenylalanine at 3.5 mg/kg (maximum dosing: 100 mg) in the morning. Time-related exhaled gas was periodically collected until 120 min after dosing. The (13)CO(2) levels were monitored with gas chromatography-mass spectrometry before and after administration, and the (13)C excretion rate, (13)C cumulative excretion and time of maximum (13)C excretion rate were monitored accordingly. RESULTS: Total bile acid, hyaluronic acid, type IV collagen 7S, total bilirubin or albumin and the PBT findings were significantly correlated. The PBT findings in group A were significantly lower those of group B, indicating that phenylalanine metabolism was markedly attenuated in the former. CONCLUSION: The PBT values correlated well with liver fibrosis in postoperative BA children. Because PBT is a non-invasive approach, results from this method may serve as a useful and reliable index for post-surgical monitoring of children operated on for liver fibrosis.     

Reversibility of organic anion-induced cholestasis: Association with compensatory hypersecretion of biliary phospholipid and protein in the dog

Abstract The effect of a concomitant infusion of organic anions, structurally related phthaleins, on bile flow was studied in anaesthetized dogs. A combination of rose bengal and sulfobromophthalein was found to uniquely and synergistically produce an acute, reversible form of intrahepatic cholestasis (< 10% of control level). This phenomenon was not observed with the administration of those individual organic anions at concentrations previously associated with the induction of intrahepatic cholestasis. The infusion of either a micelle forming bile salt, sodium taurocholate, or a non-micelle forming bile salt, sodium dehydrocholate, rapidly reversed the intrahepatic cholestasis (within 20 min after bile salt infusion). During the choleretic phase immediately following the bile salt infusion, a transient but marked hypersecretion, a disproportionately increased output in relation to that of bile acids, of biliary phospholipid (176% of control level by taurocholate and 138% of control level by dehydrocholate), and an even more striking amount of biliary protein hypersecretion were observed (392% of control level by taurocholate and 357% of control leverl by dehydrocholate). Although the significance of these new post-cholestatic observations requires clarification, it is suggested that the intrahepatic cholestasis induced by organic anions reflects a reversible defect in the mechanism(s) involved in transcellular transport.     

An estimation of human bile metastability: Clinical application of a sensitive cholesterol crystal growth assay

The formation of cholesterol monohydrate crystal initiates cholesterol gallstone formation. The nucleation time (NT), a light microscopy method, is used currently to estimate human bile metastability. Recently, a cholesterol crystal growth (CCG) assay utilizing photometric turbidity to quantitate cholesterol crystallization was developed using model bile systems. The object of this study was to determine whether this novel CCG assay was applicable to the quantitative assessment of native human bile metastability. Human gall-bladder bile samples were collected from patients undergoing cholecystectomy. There were five patients with cholesterol gallstone and five stone-free patients. A significant correlation between the onset time measured by the CCG assay and the NT observed by light microscopy was found in our modified assay condition where interference by bilirubin was negligible (P < 0.01). Also, the growth rate measured by the CCG assay significantly correlated with the NT (P < 0.05). These results indicate that the CCG assay is applicable to quantitative assessment of human bile metastability reflected by cholesterol crystal nucleation and that the cholesterol crystal growth is also conveniently estimated by this method.     

Clinical significance of hepatitis G virus infection in patients on long-term haemodialysis

Infection with the newly discovered hepatitis G virus (HGV) was analysed in 163 patients on long-term haemodialysis to clarify its prevalence and clinical significance. Hepatitis G virus RNA in serum was measured by polymerase chain reaction with primers corresponding to the putative non-structural 5’ region. Of the 163 patients, three (1.8%) were positive for hepatitis B surface antigen, 40 (24.5%) were positive for hepatitis C virus (HCV)-RNA and 16 (9.8%) were positive for HGV-RNA. Five of the 16 patients with HGV-RNA were also positive for HCV-RNA. Patients with HCV and HGV coinfection had undergone a longer duration of haemodialysis (P=0.001) and had higher units of transfusion (P=0.031) compared with those without hepatitis virus infection. Transfusion history was significantly higher (P=0.039) in patients with only HGV infection than in those without hepatitis virus infection. Hepatitis C virus RNA concentration was higher (P=0.032) in patients with HCV and HGV coinfection than in those with HCV infection only, but alanine aminotransferase (ALT) levels were similar between these two groups. In conclusion, about 10% of patients on haemodialysis were infected with HGV and the infection was closely associated with transfusion history.     

Lack of hepatic benefit by oxygen inhalation during vasopressin infusion in patients with cirrhosis

Vasopressin has been found to impair hepatic function in patients with cirrhosis. The aim of this study was to investigate whether oxygen inhalation could improve hepatic function during vasopressin infusion. Vasopressin (0.3 iu/min) was infused into eight patients with cirrhosis for 50 min. During the first 30 min they were ventilated by room air and for the following 20 min by oxygen (approximate 50% of FiO2). The extra oxygen inhalation caused a typical increase in arterial (+7%, P less than 0.01), portal venous (+8%, P less than 0.05), and hepatic venous (+9%, P less than 0.01) oxygen content. No effect was noted in arterio-hepatic venous and portal venous-hepatic venous oxygen content difference in comparison with the values after vasopressin alone. The hepatic perfusion remained unchanged. These results suggest that the extra oxygen did not increase hepatic oxygen uptake. Similarly, intrinsic clearance of indocyanine green did not improve. It is concluded that oxygen supplement in this setting has no hepatic benefit in patients with cirrhosis.     

Neuropeptide Y: Immunocytochemical localization to and effect upon feline pial arteries and veins in vitro and in situ

Plexuses of nerve fibres containing neuropeptide Y (NPY)-like immunoreactivity invest pial arteries belonging to the circle of Willis, pial arterioles, occasionally penetrating arterioles and large veins. A more sparse supply of NPY-like fibres are observed around pial veins and venules. The NPY-immunoreactive fibres are located within the adventitia or at the adventitia-media border. Only occasional fibres are present in cerebral vessels of animals in which the superior cervical ganglion has been removed one week previously. Administration of NPY resulted in strong, concentration-dependent contractions of isolated feline middle cerebral arteries whereas administration of avian pancreatic polypeptide (APP) elicited weak contractions. In chloraloseanaesthetized cats, perivascular microapplication of NPY in situ resulted in marked concentration-dependent contractions of cerebral pial arterioles (34.7±6.6%; maximum decrease in calibre with NPY. Perivascular administration of NPY resulted in the constriction of pial veins but the magnitude of the venous calibre reductions was smaller than the response of arterioles at each reductions was smaller than the response of arterioles at each concentration examined. APP did not elicit contraction of pial arterioles or veins during in situ conditions. The pharmacological and immunocytochemical results strongly indicate the existence of a novel perivascular neuronal system containing NPY, which mediates contraction of cerebral blood vessels and NPY is colocalized with NA in sympathetic nerves.     

Pharmacokinetics:Pharmacokinetic Differences Between Lansoprazole Enantiomers in Rats

Because limited information is available about potential differences between the pharmacokinetics and pharmacodynamics of the enantiomers of lansoprazole, the enantioselective pharmacokinetics of the compound have been investigated in rats. There was a noticeable difference between the serum levels of the enantiomers of lansoprazole and of their metabolites, 5-hydroxylansoprazole enantiomers, after oral administration of the racemate (50 mg kg^?1) to rats. C_max (maximum serum concentration) and AUC (area under the serum concentration-time curve) for (+)-lansoprazole were 5–6 times greater than those for (—)-lansoprazole, whereas for (+)-5-hydroxylansoprazole both values were significantly smaller than those for the (—) enantiomer. CL_tot/F values (where CL_tot is total clearance and F is the fraction of the dose absorbed) for (+)-lansoprazole were significantly smaller than those for the (—) enantiomer. There was no significant difference between the absorption rate constants of the lansoprazole enantiomers in the in-situ absorption study. The in-vitro protein-binding study showed that binding of (+)-lansoprazole to rat serum proteins was significantly greater than for the (—) enantiomer. The in-vitro metabolic study showed that the mean metabolic ratio (45.9%) for (—)-lansoprazole was significantly greater than that (19.8%) for the (+) enantiomer in rat liver microsomes at 5.6 μM lansoprazole. These results show that the enantioselective disposition of lansoprazole could be a consequence of the enantioselectivity of plasma-protein binding and the hepatic metabolism of the enantiomers.