Ultrastructural study of the effects of amiodarone on the liver tissue was performed. Rats were fed with amiodarone containing diet and were sacrificerd at 1st, 3rd, 4th, 5th and 8th weeks of experiment. Charateristic lisosomal inclusion bodies were appeared form first week, which were more prominent and increased in size at the 5th and 8th week of experiment. These inclusion bodies were found in hepatocytes, Kupffer cells, bile duct epithelial cells and fibroblasts but most prominent in hepatocytes. The lysosomal inclusion bodies could be divided into four types; those characterized by (1) dense bodies with packed crystaloid contents, (2) multilamellated bodies, (3) irregular shaped bodies with varying electron density and 4. dense bodies containing stacks of fine membranous structures. All types were found in all experimental groups. But the type 1 and 2 were predominent at early stage, while type 3 and 4 were more prominent at later stage According to these findings, the formation of the lysosmal inclusion body was a characteristic change in derangement of phospholipid metabolism. And amiodarone could induce disturbance of phospholipid metabolism in all kinds of cells in liver tissue.
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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.
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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.
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OBJECTIVE: The acidic saline animal model of pain has been suggested to mimic fibromyalgia (FM). In this model, repeated intramuscular (IM) injections of acidic saline produce a widespread hyperalgesia that persists without evidence of significant peripheral tissue damage or inflammation, and is believed to be centrally maintained. We examined the changes of pain-related neurotransmitters in specific brain regions of this model after deep-sea water (DSW) drinking. METHODS: Rats were injected with 100microliter of acidic saline (pH 4.0) at days 0 and 5 into the left gastrocnemius muscle. Control rats received identical injections of physiological saline (pH 7.2) on the same schedule. Two acidic saline rats were given DSW from 1 week following the last IM injection to sacrifice. All rats were sacrificed on day 20. All regions of interest were examined for the changes of pain-related neurotransmitters with immunohistochemistry. RESULTS: Preliminary results showed that compared to controls, acid injected rats demonstrated strong expression of serotonin in red and raphe nucleus. Acid injected rats showed significant reductions of the serotonin expression in red and raphe nucleus after DSW drinking. CONCLUSION: IM acid injections increased the expression of serotonin in red and raphe nucleus of rats. The overwhelming reduction of serotonin expression in the nuclei after DSW drinking suggests DSW might be helpful for pain and anxiety. These preliminary data support the validity of acidic saline treatment as a model of FM, and provide a foundation for future analyses of specific brain regions that contribute to this syndrome.
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Diaphragm is though to play the most role in breathing and has a substantially greater proportion of slow oxidative and fast glycolytic fibers, and low proportion of fast oxidative fibers. The respiratory muscle, diaphragm, has the functional characteristics of slow speed of contraction, high resistance to fatigue and the ability to respond to intermittent ventilatory loads, for example of exercise. In the present study, the characteristics of the metabolism (depletion and repletion) of glycogen and the structural changes of diaphragm during depletion and repletion of glycogen were observed in rats. For comparison, the red gastrocnemius muscle which has a greater proportion of fast oxidative glycolytic (FOG) and slow oxidative (SO) fibers, and low proportion of fast glycolytic (FG) fiber, was also studied. The glycogen concentration of diaphragm in overnight fasted rats was 2.30+/-0.14mg/gm wet weight. The values of glycogen concentration at 60, 90 and 120minutes of treadmill exercise loaded rats was significantly decreased compared to that of the overnight fasted rats. There was no significant difference among the glycogen concentration of diaphragm at 60, 90 and 120minutes of exercises. The glycogen concentration of diaphragm was decreased to 1.12+/-0.17 from 2.30+/-0.14mg/gm wet weight by treadmill exercise. The glycogen depletion rats of diaphragm during exercise was faster than that of red gastrocnemius in both of the first 60minutes and 120minutes duration of exercise. The glycogen repletion of diaphragm after intragastric glucose administration by stomach tube was studied in control and exercise groups. The glycogen concentration was significantly increased after glucose administration in both of the control and exercise groups. All of the concentration of exercise group at 60, 120 and 180minutes after glucose administration was significantly higher than those of control group. In conclusion, one of the characterics of diaphragm in glycogen metabolism is fast glycogen depletion during exercise, and slowness of glycogen repletion after glucose ingestion in rats.
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Amiodarone, an antiarrhythmic drug, may exert pulmonary toxicity in some patients but the pathogenesis is not clear. This study was carried out to investigate the pathogenetic mechanism of pulmonary injury induced by amiodarone at dose of 100 mg/kg/day given to rats by intraperitoneal injection for 3 weeks. And the preventive effects of concomitantly injected steroid (10 mg/kg/day) on amiodarone induced pulmonary injury was also studied using bronchoalveolar lavage, light microscopy and transmission electron microscopy. The results obtained were summarized as follows: Mild lymphocytosis of bronchoalveolar lavage fluid was found in all experimental groups. Intracytoplasmic lamellar body formation was found in all types of pulmonary cells and type II pneumocytes revealed the earliest abnormal lamellar body formation. The capillary endothelial cells showed cellular swelling and detachment from underlying basement membrane at early phase of experiment and the edema of alveolar wall and interstitium were noted. Interstitial fibrosis and proliferation of type II pneumocytes were noted at late phase. The lungs of steroid injected groups revealed accumulation of lamellar bodies in all types of pulmonary cells but interstitial fibrosis was not occurred. These findings support the concept that amiodarone is responsible for a drug-induced phospholipidosis and directly toxic to pulmonary endothelial and epithelial cells. And steroid may regress the progression of amiodarone induced pulmonary injury.
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The purpose of this study was to investigate the inhibitory role of vitamin A with respect to activation of Ito cells in fibrosis of the rat liver induced by common bile duct ligation(CBDL). The liver was examined by immunohistochemical staining for a-smooth muscle actin,the known marker of activated Ito cells, and light and electron microscopy after CBDL andCBDL with intraperitoneal injection of retinoic acid (Sigma, USA) 1 mg/Kg in 3 times per week. The results were sumrrlerized as follows: After CBDL, the bile ductules were markedly proliferated in the periportal areas extending toterminal hepatic veins. Interstitial fibrosis and inflammatory cell infiltration appeared, however,cholestasis was minimal. Retinoic acid treatment with CBDL decreased bile ductular proliferationand interstitial fibrosis compared to CBDL only. After CBDL, proliferated and activated Ito ceIs showing positive reaction in smooth muscle actin were present in the periductular andperisinusoidal areas, and areas of increased interstitial fibrosis. Activated ito cells weredecreased in number after CBDL with vitamin A treatment. Electron microscopically,intracytoplasmic fat droplets and the cytoplasmic processes of Ito cells were decreased afterCBDL. Myofibroblasts were frequently appeared in the interstitial fibrosis after CBDL. But,intracytoplasmic fat droplets of Ito cells were well preserved, and myofibroblasts were found lessfrequently after CBDL with vitamin A treatment. The results suggest that vitamin A plays an inbitory role in the activation and fibrogenesis ofIto cells after CBDL.
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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.
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No abstract available.
Animals ; Rats*

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.
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