The toxicity and adrenostatic effect of o,p'-DDD, a derivative of the insecticidal DDT, on the adrenal cortex were well known. It known that the toxicity was based on the blocking of steroid biopsynthesis when cholesterol was converted to pregnenolone. Lysodren(R) was also known to be capable of producing a regression of adrenocortical carcinoma and its metastases, and this drug became one of useful choice for the treatment of unoperable adrenocortical carcinomas. Recently, fine structural effect of o,p'-DDD on the adrenocortical carcinoma show that the mitochondria is the primary target organelle. o,p'-DDD was dissolved in corn oil and it was orally administered for 28 days to investigate the ultrastructural effects of zona fasciculata of rat adrenal cortex. The results obtained were as follow: 1) The body weight was decreased after feeding o,p'-DDD. 2) Light microscopic examination showed no remarkable change except increased fine lipid droplets of zona fasciculata in group I (o,p'-DDD 75 mg/kg feeding). Moderately increased intracytoplasmic lipid droplets and pyknotic nuclei bearing membrane indentations were seen in group II (o,p'-DDD 150 mg/kg feeding). Large sized lipid droplet aggregates, pyknotic nuclei with severe nuclear membrane indentations and karyorrhexis in focal area were evident in group III. 3) Immunohistochemical staining for ACTH in pituitary gland showed increasing number of ACTH secretory cell and increasing intensity of staining property according to the dosage of o,p'-DDD. 4) Ultrastructural examination showed increased intracytoplasmic lipid droplets and mild increased peroxisome. There was no remarkable ultrastructural changes in mitochondria in group I. Moderately increased lipid droplets and clusters formation, compressed mitochondria, partial disappearance of mitochondrial cristae, increased peroxisome and nuclear membrane indentations were seen in group II. In group III, nuclear membrane showed prominent indentation. Numberous cytoplasmic vacuolation, double membrane ring in mitochondria, disappearance of mitochondrial cristae, myelin figure formation in mitochondrial matrix, and fatty changes in mitochondrial matrix were seen. These findings showed that the primary target organelle of attack by o,p'-DDD on zona fasciculata of adrenal gland in rat is mitochondria and it was developed from double ring formation in mitochondrial matrix.
Rats ; Animals

In an attempt ultrastructural study of alcohol-induced gastric mucosal change, we selected sixty Sprague-Dawley rats. The rats were administrated with 4 ml of 10% and 40% ethanol enterically and examined by light and electron microscopy. Light microscopically, the thickness of the mucus layer of both 10% and 40% ethanol groups was decreased. The antral mucosa revealed focal inflammatory infiltrates, disturbed glandular arrangements, and significant decrease of mucosal thichness and proper glands. On scanning electron microscopy, flattened or swollen mucosal epithelium and irregularly distributed gastric pits were seen in both experimental groups, and these changes were more severe in the groups of higher concentration and longer duration. On transmission electron microscopy, mitochondrial abnormalities with myelin-like materials and dilatation of endoplasmic reticulum and cytoplasmic blebs were observed. Also the mucus cells show significantly decreased mucus globules, increased fat vacuoles, and large autophagic vacuoles. These alterations were similar to those produced by ethanol in the liver and small intestine. This study indicates that, prolonged administration of ethanol induced chronic gastritis, especially chronic atrophic gastritis.
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

No abstract available.
Animals ; Rats*

No abstract available.
Animals ; Rats

To investigate the mechanism of monocrotaline-induced pulmonary arterial hypertension, authors performed immunohistochemical study using antibody to von Willebrand factor(vWF), cell kinetic study using 5-bromodeoxyuridine and ultrastructural study after single subcutaneous injection of monocrotaline(MCT) to Wistar rats. The results of this study demonstrated that the expression of vWF by pulmonary endothelial cells was markedly increased from day 3 until 2 months after MCT injection. The labeling index of pulmonary microvessel endothelium began to increase after six days and was maximal on the third weeks, and thereafter it remained slightly increased above basal level. Electron microscopic study revealed attachment of inflammatory cells an platelets to endothelium from 6 hours and degranulation of attached platelets 24 hours after MCT injection. Evidences of endothelial injury began to appear from 12 hours after MCT injection. Evidences of endothelial injury began to appear from 12 hours and was maximal after 48 hours. From the third day, ultrastructural change of cell regeneration and hypertrophy began to appear and was continuosly observed until 2 months. In addition, we evaluated the changes in the number of pulmonary neuroendocrine cells using antibody to gastrin releasing peptide but it demonstrated no change until 2 months suggesting no role of neuroendocrine cells in the development of pulmonary hypertension of Wistar rats at early stage. In conclusion, the results indicate that pulmonary hypertension by MCT injection is due to increased vascular resistance caused by vasoconstriction and hyperplasia of endothelium with musculariz ation of the pulmonary arterioles induced by endothelial dysfunction and some biologic substances released form endothelium and platelets.
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

No abstract available.
Animals ; Rats*

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

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