No abstract available.
Animals ; Rats*

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

Although there have been many reports about the importance of the spleen's role in hepatic fibrogenesis, the exact mechanism is still uncertain. The author designed this study to evaluate splenic function on hepatic fibrogenesis. The degree of hepatic fibrosis and the population of splenocyte subsets were studied in the experimental animal model with fibrosis produced by injecting normal swine serum intra-peritoneally into Sprague-Dawley rats. The animals were divided into three groups; group A was subjected to injection of swine serum only, group B swine serum and complete Freund's adjuvant and group C swine serum and cyclosporin A. The experimental hepatic fibrogenesis by swine serum was augumented by coinjection with the adjuvant and inhibited by cyclosporin A. The study of the splenocyte subset revealed increased percentages of spienic B cell and CD4+ cell and a decreased percentage of CD8+ cell, and these changes of splenocyte subset were also augumented by the adjuvant and inhibited by cyclosporin A. The percent of monocytes was not significantly altered, although a tendancy of early decrease by the adjuvant was noted.
Rats ; Animals

Since the role of excitatory amino acids such as glutamate and aspartate and their receptors mediating cellular injury through various mechanisms were known in hypoxic-ischemic injury and associated diseases of central nervous system, blocking agents for transmitter release or receptors have been tried to reduce the cellular damages and subsequent sequelae experimentally. Several in vitro studies suggested two kinds of glutamate neurotoxicity: (1) rapid toxicity due to influx of sodium or chloride with resultant cellular edema and consequent damage, which is associated with N-methyl-D-Aspartate(NMDA) as well as non-NMDA receptors, (2) calcium mediated delayed toxicity associated mainly with NMDA receptor. This study was conducted to investigate the role of rapid toxicity in hypoxic-ischemic injury. Early lesions of 30 minutes to 24 hours after hypoxic-ischemic insult were examined by autoradiography with radiolabelled glutamate and kainitic acid (KA) as well as light and electron microscopy. Late changes were evaluated on formaldehyde-acetic acid-methanol(FAM) fixed brain 1 week after the insult. Cornus ammonis(CA) l of hippocampus showed the highest density of NMDA receptors, which was decreased constantly from 2 hours to 24 hours. In contrast, CA3 of hippocampus showed the highest density of KA receptors, which was the lowest at 6 hour and increased thereafter. Light microscopic examination showed the worst changes during 30 minutes to 6 hours. After 1 week, most of the cases showed degeneration of neurons and CAI and CA3 did not show the difference. Electron microscopic examination showed marked degenerative changes of neurons as well as neuropils starting from 30 minutes after the insult. In conclusion, rapid toxicity mediated by non-NMDA(KA) receptor seen in CA3 lead to permanent damage in 1 week old lesion.
Rats ; Animals

The authors studied the formation of giant mitochondria in liver cell. The Sprague Dawley rats were sacrificed following intervals; 5, 10, 20, 30, and 60 minutes after intraperitoneal injection of hydrazine in the amount of 200 microliter/kg. And the extracted liver tissues were examined with light and electron microscopes. The results obtained were summarized as follow; Light microscopically, there is little difference between control and experimental groups. Electron microscopically, elongated, bizzare shaped mitochondria are appears 5 minutes after hydrazine injection. Those show attenuated portion, Y, U, or C shaped feature suggesting fusion or budding mitochondria. The number of giant mitochondria is decreased after 10 minutes group and rarely present in 60 minutes group. The results suggest in this experiment that the formation of giant mitochondria is kind of reversible change and it is different from the mitochondrial swelling of cellular injury. Intermitochondrial fusion and mitochondrial budding may be related with the formation of giant mitochondria.
Rats ; Animals

No abstract available.
Animals ; Rats*

The cholestasis are defined as blockade or secretory distrubance of bile and appearance of bile in hepatocytes, Kupffer cells and biliary passages, usually associated with dilated bile canaliculi. Intra-and extraheptic cholestasis were induced by 17-ethinyl estradiol, or chlorpromazine hydrochloride and by ligation of bile duct to investigate the mechanism of the hepatic injury, ultrastructural changes of liver and alterations of liver function. The results obtained were as follows. 1) Functional and histological changes of intra-and extrahepatic cholestasis differed in various experimental groups. The liver weight is increased in 17-ethinyl estradiol treated group and ligation of bile duct group (5.6+/-0.15, P<0.001, 5.3+/-0.19 gm/100 gm body weight, P<0.001). The common features of intra-and extrahepatic cholestasis were double membrane bounded amorphous vesicular material infiltrations in the cytoplasm of hepatocyte, partial loss of microvilli of bile canaliculi, anf focal thickening of pericanalicular ectoplasm on electron microscopy. 2) Intrahepatic cholestasis induced by 17-ethinyl estradiol show significantly increased serum level of alkaline phosphatase and total bile aicd (134.0+/-16.82 IU/L, 29.5+/-4.68 umol/l). Kupffer cell proliferation and focal cytoplasmic degradation with myelin figures are characteristic features on electron microscopy. Chlorpromazine hydrochloride induced intrahepatic cholestasis show increased serum level of AST, ALT, Cholesterol and bilirubin (156.9+/-11.32, 49.0+/-2.83 IU/L, 59.3+/-6.73 mg/dl, 1.8+/-.043 mg/dl). Inflammatory cell infiltration, chiefly lymphocytes and esoinophils are seen in periportal area. Prominent vesiculation and vacuolations of smooth endoplasmic reticulum are characteristic feature on electron microscopy. 3) Extrahepatic cholestasis induced by ligation of bile duct show increase serum level of AST, ALT, GGT, cholesterol, total bile acid, and bilirubin (290.2+/-50.24, 171.5+/-47.17, 159.3+/-24.54, 33.7+/-1.47 IU/L, 86.6+/-9.18 mg/dl, 246.6+/-27.34 umol/l, 13.9+/-0.83 mg/dl). Light microscopically, morphologic alterations are feathery degeneration of hepatocytes, proliferation of bile ducts, bile infarct and prominent intracytoplasmic lipid droplets. Electron microscopically, electron dense acidophilic body, bile casts and complete loss of microvilli are seen in dilated bile canaliculi. Also noted are hypertrophy of cannalicular ectoplasm. Finely granular materials are infiltrated in degenerative cytoplasm.
Rats ; Animals

This study was performed to investigate the effect of endotoxin to the CCl4-induced liver injury. Twelve Sprague-Dawley rats were intraperitoneally injected 1.6 g/kg CCl4 as control group. Another 24 rats were orally administrated 300 mg/kg of neomycin at 16 and 3 hours prior to CCl4 injection as experimental group. Twelve among them were intraperitoneally infected 1.0 mg/kg of endotoxin(E-Coli, 0111:B4, No L-2630, lipopolysaccharide, Sigma, USA) and CCl4 simultaneously for offsetting neomycin effect. The rats were sacrificed at 1, 4, 10, and 24 hours after CCl4 injection. The liver tissues from all experimental groups were observed by light and electron microscopy. The results obtained were summarized as follows: In the CCl4 only group, the hepatocytes revealed sweling of ER and mitochondria with many lipid droplet in the cytoplasm. Focal cellular necrosis was seen at the later phase. The Kupffer cells were activated and showed many cytoplasmic processes, secondary lysosomes, and vaculoles. The endothelial cells were edematous. Several neutrophils, platelets, and microthrombi were scattered in the sinusoid. In the neomycin-CCl4-endotoxin administrated group, both hepatocytic destruction and intrasinusoidal microthrombi formation were more pronounced. In the neomycin pretreated group, the hepatocytes revealed mild cellular destruction without necrosis. There is no intrasinusoidal microthrombi. According to these results, it would be concluded that the small dosage of gastrointestinal tract-derived endotoxin affects to the liver injury caused by CCl4. The synergistic effects of CCl4 and gastrointestinal tract-derived endotoxin which can not be detoxified by damaged Kupffer cells, may be more important in the pathogenesis of CCl4-induced liver injury.
Rats ; Animals

This study was carried out to investigate the mechanisms of interstitial pulmonary fibrosis of rats after the intratracheal administration of bleomycin. Both lungs after bleomycin injection were examined by light and electron microscopy. The results are as follows: Light microscopically, 1 or 2 weeks after bleomycin injection acute and chronic inflammatory infiltrates and edema in the interstitium and alveolar spaces were observed. Proliferation of alveolar type II pneumocytes was also found at 4 to 6 weeks after bleomycin injection, chronic inflammatory infiltrates with interstitial fibrous thickening were noted. Electron microscopically, the number of type II pneumocytes and irregular lamellar bodies were increased and blunted microvilli were noted at 2 weeks. 4 to 8 weeks, proliferation of fibroblasts with deposition of abundant collagen fibrils in the thickened interstitium revealing irregular or collapsed alveolar spaces were observed. Based on these findings, it can be concluded that bleomycin-induced interstitial pulmonary fibrosis is considered to pass from an early acute inflammation of the interstitium and alveolar spaces to an interstitial fibroblast proliferation and collagen deposition to the length of the period after injection.
Rats ; Animals