Research in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie最新文献

Background: The effect of selective bile duct obstruction (SBDO) on hepatic reserve function of the bile duct obstructed (BDO) and nonobstructed freely draining (FD) lobes of the liver is obscure.

Methods: The bile duct branches draining from the left lateral and median lobes of the liver were ligated for 4 and 10 days in rats, and hepatic reserve functions in BDO and FD lobes were assessed by microsomal cholesterol 7 alpha-hydroxylase activities and by hepatic adenine nucleotide and energy charge levels. The values were compared with those in sham-operated control liver. Cholesterol 7 alpha-hydroxylase activities were determined by gas-liquid chromatography-mass spectrometry, and hepatic adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) levels with high-pressure liquid chromatography.

Results: The histological examination of the BDO lobes showed proliferation and formation of new bile ductules and fibrous connective tissue linking portal areas. Microsomal cholesterol 7 alpha-hydroxylase activities, hepatic energy charge and adenine nucleotide levels did not differ between FD and BDO lobes, and the values were similar to those in the sham-operated liver.

Conclusions: Selective bile duct obstruction shows no adverse effects on microsomal and mitochondrial functions in either BDO or FD lobes of the liver.

Studies were carried out to determine the antifertility and reversibility effect of pyrimethamine (PYR) in adult male mice. The parameters mainly included sperm count and motility, fertility, histoarchitecture of testis and testicular cell kinetics quantitatively following oral administration of PYR (50 mg/kg body weight per day) for 30 days. The same parameters were also studied in PYR-treated animals which were allowed to recover for 45 days (recovery group). The results suggest that sperm motility as well as counts were significantly decreased in PYR-treated animals, and the fertility rate fell to zero. Testicular histology as well as germ cell kinetics were altered. However, in the animals of the recovery group, all the parameters studied were more or less similar to those of control animals. The study demonstrates the antifertility as well as reversible efficacy of PYR.

Natural suppressor (NS) activity is mediated by several kinds of cell lineages in bone marrow. We demonstrated that a NS cell, clone 7-31, was obtained after limiting dilution with bone marrow culture supplemented with WEHI supernatant. Clone 7-31, was capable of non-specific suppression of the generation of cytotoxic T lymphocytes without major histocompatibility complex restriction. Suppression of cytotoxic thymus-dependent lymphocyte (CTL) generation was also induced with a cell-free supernatant from the 7-31 cells. Interleukin-2 (IL-2) containing concanavallin-A-conditioned medium could not reverse the suppression. The supernatant did not inhibit the proliferation of IL-2-dependent CTLL-2 cells and rapidly growing tumour cells and fibroblasts. Thus, this bone marrow suppressor cell produces a soluble factor that inhibits the generation of CTL in vitro, and prolongs the acceptance of skin allografts in in vivo.

Matrix metalloproteinases (MMP) are among the key enzymes responsible for the proteolytic destruction of articular cartilage during chronic rheumatic diseases. Articular cartilage is one potential target for drugs designed to inhibit the activity of MMPs in order to stop or to slow down the proteolytic destruction of the extracellular matrix of cartilage. The purpose of this study was to investigate the effect of the synthetic inhibitor of MMPs U-24522 for its ability (1) to inhibit in vitro the activity of MMP-proteoglycanases; (2) to modulate the morphology and viability of cartilage explants; and (3) to modify the biosynthesis and release of proteoglycans from articular cartilage explants. U-24522 dose-dependently inhibited the activity of MMP-proteoglycanases and significantly reduced the release of proteoglycans from interleukin-1 treated bovine articular cartilage explants when tested at concentrations ranging from 10(-4) to 10(-9) M. This hydroxamic acid derivative proved not to be harmful to chondrocyte viability and cartilage morphology. In addition, U-24522 had no effect on the rate of proteoglycan biosynthesis of interleukin-1 treated cartilage explants and increased the percentage of newly synthesized proteoglycans to form macromolecular aggregates. Thus U-24522 combines direct inhibitory potential on the activity of MMP-proteoglycanases with the inhibition of interleukin-1 stimulated proteoglycan loss from articular cartilage explants without affecting the morphology, viability and biosynthesis of proteoglycans of bovine articular cartilage explants.

We have studied the function of partial orthotopic liver transplantation in the rat by evaluating prothrombin time (PT), liver blood flow, basal and glucose-stimulated insulin secretion and glucose tolerance, and the reticuloendothelial function (RES) in hepatectomized rats subjected to partial liver transplantation. A graft corresponding to 68% of a normal liver was transplanted to totally hepatectomized rats. Comparison was made between control rats and rats subjected to 32% liver resection. PT was not significantly different in the transplanted group compared with liver-resected and control rats. Laser Doppler flowmetry showed that at 28 days after surgery, blood flow had increased in the transplanted livers. Furthermore, on the third day after transplantation, basal plasma insulin was increased and the plasma insulin response to glucose was exaggerated, suggesting reduced insulin action and impaired insulin degradation. Finally, uptake of radioactive-labeled E. coli bacteria, as a measure of RES function, was not compromised in transplanted animals. Based on these results, we conclude that reduced-size liver transplant in out-bred rats results in fast normalization of liver function after surgery although, immediately after surgery, glucose intolerance is seen.

The vasomotor effects of the endothelins (ETs) are mediated by activation of receptor subtypes termed ETA and ETB. The present study aimed to characterize the interaction of ETA and ETB receptor activation in the cerebral circulation. Ring segments obtained from rat basilar artery were used for measurement of isometric force under resting tension or following precontraction with prostaglandin F2 alpha. In some segments, the endothelium was removed mechanically. In precontracted arteries, ET-1 elicited contraction only. In the presence of the ETA receptor antagonist, BQ-123 (10(-5) M), however, ET-1 induced a concentration-related relaxation with a pD2 value of 8.93 +/- 0.16 (mean +/- SEM, n = 15). The relaxant action was abolished following preincubation with an ETB receptor antagonist, IRL-1038 (3 x 10(-6) M), or with a nitric oxide synthase inhibitor, NG-nitro-L-arginine (10(-5) M). These results indicate that the relaxation was mediated by ETB receptor activation coupled to the release of nitric oxide. Under resting tension, ET-1 elicited concentration-related contraction (pD2: 8.03 +/- 0.04, n = 37). In arteries devoid of a functional endothelium, the concentration-effect curve was shifted to the left yielding a pD2 value of 8.88 +/- 0.11 (n = 31). Similarly, in endothelium-intact arteries contraction to ET-1 was augmented following nitric oxide synthase inhibition or ETB receptor blockade with 3 x 10(-6) M BQ-788 (pD2: 8.94 +/- 0.18, n = 19). The results suggested that, in the isolated rat basilar artery, ET-1 induced coactivation of the contraction-mediating ETA receptor and the relaxation-mediating ETB receptor. The coactivation resulted in opposing vasomotor effects, but the contraction covered relaxation under normal conditions. However, force development by ET-1 was suppressed by its endothelium-dependent relaxant action.

One cause of a false positive limulus test after surgery or hemodialysis has been identified as extrinsic (1-->3)-beta-D-glucan which was derived from surgical gauze or cellulose dialyzer. However, there have been no investigations concerning intrinsic factors and the presence of (1-->3)-beta-D-glucan in mammalian organs. In this study, (1-->3)-beta-D-glucan in homogenate of various rat organs and stool was measured by a Gluspecy test (G test) using factor G, which specifically reacts with (1-->3)-beta-D-glucan. In small intestine and lung, large amounts of factor G-activating substance were observed and identified as (1-->3)-beta-D-glucan by a digestion study using end-(1-->3)-beta-D-glucanase. However, only very small amounts of (1-->3)-beta-D-glucan were found in the kidney, spleen, vena cava, aorta, thymus, heart and liver. In serum and plasma, no (1-->3)-beta-D-glucan was observed. On the other hand, extremely large amounts of (1-->3)-beta-D-glucan were found in stool. Minute amounts of (1-->3)-beta-D-glucan were observed in a variety organs except for the small intestine and lung. High levels of (1-->3)-beta-D-glucan found in the small intestine might be traced to contamination by stool in the small intestine, and such levels in the lung might derive from macrophages which have trapped (1-->3)-beta-D-glucan in the air.

Contractile responses were studied in isolated tubal segments of branches of the rat portal vein (diameter 300 microns) and hepatic artery (diameter 200 microns) 1, 3 and 6 weeks after total porto-systemic shunt operation (PCS). 5-Hydroxytryptamine contracted hepatic arteries concentration-dependently, whereas it produced only weak and inconsistent contractions in portal veins. Vasopressin effectively contracted hepatic arteries, but had no effect on portal veins. Both vessel types responded to prostaglandin F2 alpha with contractions, although the drug potency was relatively low. The responses to these agents were not changed significantly in hepatic arteries or portal veins of PCS rats compared with controls at any of the postoperative time intervals. In both portal veins and hepatic arteries noradrenaline produced contraction-dependent contractions, portal veins being 3 times more sensitive to noradrenaline than hepatic arteries. PCS did not change the nor-adrenaline sensitivity in hepatic arteries, whereas it increased the noradrenaline sensitivity in portal veins after 1, but not after 3 or 6 weeks. This effect was enhanced by cocaine, suggesting a partial sympathetic denervation of branches of the portal vein as well as a complete reinnervation within 3 weeks. Furthermore, the results of this study indicate no influence in any vessel type on the response to several vasoactive agents after depriving the liver of splanchnic venous blood.

The senescence-accelerated mouse (SAM) manifests most of the features of function and morphology in the senile lung with aging. However, little is known about the effects of age and cigarette smoke on alterations of the lung in SAM. In the present study, we examined the effects of chronic cigarette smoke inhalation and age on the function and morphology of lungs in two strains of SAM, SAMP2 (senescence-prone strain) and SAMR1 (senescence-resistant strain), from 6 months of age (young) and 18 months of age (aged). After 4 weeks of cigarette smoke inhalation, a small but significant airspace along with a leftward shift of the pressure-volume (P-V) curve was observed in young SAMP2, but not in SAMR1. However, the airspace size of young SAMP2 with cigarette inhalation was smaller than that in aged SAM with air inhalation, suggesting that the effect of age may be greater than that of the small burder of tobacco smoke on the lung alterations in SAMP2. In the aged SAM, there were no differences in function and structure between tobacco-exposed and air-exposed mice. Because the changes in the lungs of young SAMP2 exposed to cigarette smoke were partly simulated with age-related alterations in human lung, and because age-dependent changes of lungs were clearly investigated in SAMP2, this strain may be an interesting animal model for investigating the effects of age and/or cigarette smoke on alterations in lung structure and function.

T-tube-related bile leakage is a considerable problem in liver transplantation but rather rare in surgery of biliary lithiasis. To investigate the effect of T-tube insertion method and material on the intraperitoneal T-tube tract, we performed a choledochotomy and insertion of T-tube (four of silicone, seven of latex, four of silicone with a latex sheath around the long arm) for 2 weeks on 15 piglets (choledochotomy group), and sutured a transected bile duct over a T-tube stent in nine piglets (five silicone, four latex), inserted similarly as in liver transplantations, for 6 weeks. Sixteen patients underwent cholectochotomy and T-tube drainage with a latex T-tube (n = 8) and latex-sheathed silicone T-tube (n = 8) for a median 9 (7-21) days. Histological examination of T-tube tracts in piglets was made, and complications after T-tube removal in the latex T-tube group were compared with those in the latex-sheathed silicone T-tube group. In piglets, latex T-tubes induced better tracts than silicone T-tubes (P < 0.05). Piglets in the choledochotomy group had tracts superior to those in the anastomotic stent group (P < 0.05). There was one bile leakage in the latex T-tube group, and none in the latex-sheathed silicone T-tube group. We conclude that T-tube tract development is affected by both the material and the insertion method of T-tubes. A silicone T-tube with a latex sheath around the long arm may also be a good choice for T-tube material in liver transplantation.