The authors studied the lung injury induced by endotoxemia and the effects of proteolytic agent on the lung changed by endotoxemia. Sprague-Dawley rats were intraperitoneally administrated with a single dose of endotoxin (4 mg/kg, E. coli 025 : B6 lipopolysaccharide) or with endotoxin and gabexate mesilate (200 mg/kg), a proteolytic agent, concomitantly. Rats of each group were scarificed at 9, 18, and 27 hours after injection. Light and electron microscopic examination were done. The results obtained were summarized as follows: Light microscopic exmination revealed congested capillaries and neutrophilic infiltration in both groups. Electron microscopic findings were interstitial and alveolar neutrophilic infiltration, endothelial swelling with increased pinocytotic vesicles and cytoplasmic process formation, and interstitial edema. Decrease of osmiophilic bodies in the type II pneumocytes had appeared at 9 hours after endotoxin injection. These changes were increased in severity at 18 hours and 27 hours after endotoxin injection. In the group of concomitant treatment of gabexate mesilated and endotoxin, there was no edema at 9 hours after injection. After 18 hours welling of endothelial cell and interstitial edema had appeared. However, the severity of the edema was markedly decreased. Type II pneumocytes showed well preserved osmiophilic bodies. According to these results, it is considered that administration of gabexate mesilate can significantly redeced the lung injury induced by endotoxemia.
Rats ; Animals

The enhancing potential of anatoxin a (AFB1) and D-galactosamine (DGA) on development of preneoplastic glutathione S-transferase placental form positive (GST-P+) hepatic foci was examined using an in vivo mid-term assay system based on two-stage concept of hepatocarci-nogenesis. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) intraperi-toneally, and thereafter. with an interval of 2 weeks, AFBl at a graded concentration (0.06, 0.012, 0.0024, 0.00048, and 0.000096 mg/kg i.g.) and DGA (100 mg/kg i.p.) were administered for 6 weeks and then sacrificed. All rats were subjected to a two-thirds partial hepatectomy to induce a potent growth stimulus to DEN-altered hepatocytes at the week 3. The modifying potential was scored by comparing the number and the area (mm2) per cm2 of GST-P+ foci in the liver with those of the corresponding control group given DEN alone. AFBl (at a graded concentration between 96 ng/kg and 60 microgram/kg) exerted a strong promoting effect oil induction of GST-P+ foci with both the number and the area. The logarithmic dose of AFBl and the potency to promote hepatocarcinogenesis were in dose-dependent relationship. DGA, a known necrogenic chemical to cause periportal necrosis and stimulate hepatocellular proliferation. also revealed the increase in the area of GST-P+ foci. although its enhancing potentia1 was 1ess profound than that of AFBl. The results suggest that DGA is also a useful proliferative stimulus m improve the medium-termdetection of unknown carcinogens.
Rats ; Animals

No abstract available.
Animals ; Rats*

Ion irradiation is a very promising tool to modify the chemical structure and physical properities of polymers. This study was aimed to evaluate the cellular adhesion to ion beam-irradiated surface of biodegradable poly-llactide(PLLA) membrane. The PLLA membrane samples were irradiated by using 35 KeV Ar+ to fluence of 5x10(13), 5x10(14) and 5x10(15)ion/cm2. Water contact angles to control and each dose of ion beam-irradiated PLLA membranes were measured. Cultured fetal rat calvarial osteoblasts were seeded onto control and each dose of ion beam-irradiated PLLA membranes and cultured. After 24 hours, each PLLA membranes onto which osteoblasts attached were examined by scanning electron microscopy(SEM). Osteoblasts were removed from each PLLA membrane and then, the vitality and the number of cells were calibrated. Alkaline phosphatase of detached cells from each PLLA membranes were measured. Ion beam-irradiated PLLA membranes showed no significantly morphological change from control PLLA membranes. In the measurement of water contact angle to each membrane, the dose range of ion beam employed in this study reduced significantly contact angles. Among them, 5x10(14) ion/cm2 showed the least contact angle. The vitalities of osteoblastes detached from each membranes were confirmed by flow cytometer and well attached cells with their own morphology onto each membranes were observed by SEM. A very strong improvement of the cell adhesion and proliferation was observed for ion beam-irradiated surfaces of PLLA membranes. 5x10(14)ions/cm2 exhibited the most strong effect also in cellular adherence. ALPase activities also tended to increase in ion beam-irradiated membranes but statistical differences were not found. These results suggested that ion beam irradiation is an effective tool to improve the adhesion and spreading behaviour of the cells onto the biodegradable PLLA membranes for the promotion of membrane-tissue integration.
Rats ; Animals

To clarity the effect of biliary obliteration on copper metabolism of rat liver and on the hepatic morphology, 0.5% cuppuric sulfate was administered intraperitoneally for 42 days following ligation of the common bile duct (CBD) of Sprague-Dawley rats. The blood copper concentration, the hepatic copper content and the accumulation patterns of copper and copper binding protein in the liver were examined and compared with those of the simple CBD ligation group and the simple copper over loaded group. CBD ligation induced marked proliferation of bile ductular structures which, after expanding the portal tracts, invaded and divided the hepatic lobules. There was, however, no excess fibosis beyond what needed to support the new ductules. The blood copper concentration and the hepatic copper content were increased by copper overload with or without CBD ligation, particularly incases with CBD ligation. Liver cell necrosis did not occur by the overloaded copper alone in rats. The hepatic copper and copper binding protein were accumulated at periportal liver cells in the group of coppe overload after CBD ligatio, whereas they began to appear at perivenular hepatocytes in the simple copper overloaded group. In conclusion, it is suggested that CBD ligation does not induce excess fibrosis or liver cirrhosis in rat as far as during our experimental period, but affect significantly on copper metabolism by intrahepatic redistribution of the copper and the copper binding proteins.
Rats ; Animals

Author performed this experiment to define the most important factor preventing the intimal thickening. An endothelium of abdominal aorta in the rat was denuded by two different wires having same caliver. The degree of injury was limited to the endothelial cells in one, and extended to the internal elastic lamina in another. The results showed that at 72 hours, in the case of superficial injury, the entire injury site was covered by new regenerating cells, but in the case of disruption of the internal elastic lamina, the migrating smooth muscle cell completely reached into the intima and resulted in intemal thickening. Similar findings persisted to 1 week later. Above results suggest the most important factor preventing the intimal thickening in endothelial injury is the depth of the injury which limited within the endothelial cells without extending into the internal elastic lamina and medial smooth muscle cells.
Rats ; Animals

To evaluate the ultrastructural changes and the mechanism causing liver injury by lead, light and electron microscopic(LM and EM) examination using Timm sulphide silver method(TSM) was done. Sprague-Dawley rats were divided into a control and 3 experimental groups. The experimental groups were orally administered 0.5% lead acetate(LA). Group 1 received a one time dose of 10 ml of LA by gastric intubation. Groups 2 and 3 continuously received LA instead of drinking water. The control group was composed of 3 rats in each group which did not receive any treatment. Rats of group 1, 2 and 3 and control were sacrificed at 1/2, 1, 1 1/2 hours, 2 days, and at 1, 2, 4, 6 and 8 weeks later, except group 3. Before sacrifice, they were perfused with 0.1% sodium sulphide and 2.5% glutaraldehyde through the abdominal aorta for TSM. The liver was taken for LM and EM examinations. Blood lead concentration began to increase from the 2nd day up to 3.29 microgram/ml at 2nd week, and the urinary delta-ALA level showed a steady increase from the 2nd day. LM and EM examination of liver revealed that absorbed lead granules in group 1 were transported into sinusoidal spaces, Kupffer cells, and the hepatocytes within 1 hour and then disappeared 1/2 hour thereafter. In group 2 deposited lead was found in the hepatocytic cytosol bound to mitochondria. That in turn inhibited mitochondrial respiration with resultant mitochondrial swelling at the 1st week and thereafter at 6th week myelin figure formation and condensation of mitochondria, and peroxisomes were increased at 8th week. Based on these results it can be concluded that a transient intake of subletal dose of LA is biotransformed completely by periportal hepatocytes within 1 1/2 hours, but excessively accumulated lead can induce liver cell injury due to lipid peroxidation of membrane by direct toxic effect of lead and by products of lipid peroxidation. We postulate that lead acetate triggers presumably primarily mitochondrial membrane injury and then other organellar changes may play a role in disturbance of a network of interacting of key events capable of causing cell death.
Rats ; Animals

The purpose of this study was to investigate the morphologic changes of the bile canaliculi and its associated structures of the liver induced by common bile duct ligation(CBDL) in the rat. The canalicular surface and lateral surface of the dry-fractured hepatocytes was studied with scanning electron microscopy at 1~6 weeks post ligation. The first week after CBDL, the bile canaliculi were dilated. The microvilli were increased in number and the lumens contained granular materials After 2 weeks or more, the bile canaliculi were dilated to a variable degree, and with irregularity, measuring from 1.5 to 5 micrometer in diameter, and in the advanced stage, the canaliculi showed blunting and the disappearance of microvilli. Some canaliculi had sprouting side branches. At 4~6 weeks post-ligation, the lateral surface of the hepatocytes also showed some irregularity and a tortuous appearance, and numerous small sized microvillous projections were formed. The tubular structures of the proliferated SER distributed adjacent to the lateral surface of the hepatocytes, and the direct connection of a tubular structure and the cytoplasmic membrane was observed. These results suggest that the deformity and loss of microvilli of bile canaliculi reflect the disturbance of bile secretion from the hepatocytes. And prolonged obstruction of bile flow may result in bile excretion via the lateral surface of hepatocytes.
Rats ; Animals

To investigate the microvascular changes in primary pulmonary hypertension, the lungs of 24 Sprague-Dawley rats were treated by an intraperitoneal injection of 2% monocrotaline(MCT) solution and then examined with scanning electron microscopy(SEM) after microvascular corrosion casting. Histologic examination revealed significant medial thickening in the small to medium-sized pulmonary arteries. Scanning electron microscopic findings of the normal lungs showed two kinds of microvascular structures. One showed a well-fortned three-dimensional basket structure of uniform flat-tubular alveolar capillaries, which were connected to each other in a T or Y shape or at right angles. The other revealed a two-dimensional reticular sheet of round tubular branches mainly in the bronchial artery-supplying regions. The MCT-treated groups(remodelling) showed apparent changes in both kinds of microvasculatures in comparison to the normal group but the more prominent change was found in Lbe bronchial artery microvasculature showing the dense thick encasement around large pulmonary arteries. Alveolar microvasculature of the pulmonary artery revealed individually enlarged angular appearance, with generally deformed alveolar architecture. Quantitatively, the significant enlargement of diameter and intercapillary distance appeared in both microvasculatures of MCT-induced rat lungs, but the density was increased only in the bronchial artery microvasculature. In conclusion, our three-dimensional microvascular study of the MCT-treated rat lungs demonstrates a new morphologic finding of vascular remodeling in primary puhnonary hypertension, which is thought to play an important vascular role in the pathogenesis in addition to interstitial fibrosis.
Rats ; Animals

To investigate the tubular major histocompatibility complex(MHC) expression and inflammatory phenotypes in tubulointerstitial nephritis, Lewis rats were inununized with azobenzen-earsonate-tyrosine in complete Freund adjuvant and challenged either foot pad or kidney, either by subcapsular injection or by ex vivo perfusion. The rats were sacrificed 2, 3, 5, 10 and 15 days after antigenic challenge. Foot pad swelling was significant at the antigenic challenge site (151.8 vs 6.8 x 10(-2) mm) at 24 hours. Tubulointerstitial nephritis was induced by both methods and the inflammatory infiltrate which first appeared on day 2, became prominent at day 5, then gradually subsided in ex vivo perfused rats, while inflannnation started on day 3 in subcapsular injected rats. The major site of inflammation was in the cortex and outer stripe of the outer medulla, with predominance of mononuclear cells throughout the course. The inflammatory cells showed mainly OX8 and ED1 positivity with OX19, W3/25 and CD5 positivity in minority. RT1B expression was diffuse in the cytoplasm of proximal tubules at day 2 and 5. These results suggest the involvement of cell mediated immunity in this experimental model, and the possibility that tubular epidielial cells process antigen and then become targets in immune injury.
Rats ; Animals