• Journal of Korean Neurosurgical Society
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• v.42 no.1
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• pp.20-26
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• 2007

Objective : We present the difference of histopathologic changes of the internal elastic lamina (IEL) and collagen III in the superficial temporal artery (STA) between aneurysmal patients and non-aneurysmal patients. Also, the pathologic data with clinical features by comparative methods to validate the risk factor of the intracranial aneurysm are presented. Methods : Samples of the STA were harvested form 38 patients including aneurysmal and non-aneurysmal patients undergoing craniotomy. Paraffin-embedded sections were examined, using hematoxylin and eosin, van Giebson and mouse anti-collagen III staining techniques. Histopathological observations were ana lysed and correlated with clinical features such as presence of aneurysm, hypertension, age, and sex. Results : Twenty-seven patients had the intracranial aneurysm. Of these 24 patients were 50 years old or older. Nineteen patients had a history of hypertension. Twenty patients were female. Histopathological study demostrated the derangement of IEL and the deficiency of type III collagen were prominent in aneurysmal patients (p < 0.05). Fifty years old or older patients did not show correlation with the deficiency of type III collagen, but with the derangement of IEL (p < 0.05). The female sex was not correlated with the derangement of IEL but with the deficiency of type III collagen (p < 0.05). However, Hypertension was not correlated with these pathologic data. Conclusion : Patients with intracranial aneurysms have severe histopathologic changes of the arterial wall showing the derangement of IEL and the deficiency of type III collagen. In the clinico-pathologic study, the advanced age and female sex were considered as risk factors of the intracranial aneurysm.

• The Korea Journal of Herbology
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• v.27 no.4
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• pp.1-7
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• 2012

Objectives : In this study, we investigated the effect of KOB, a polyherbal medicine for allergic rhinitis and its main herb, Astragali Radix on allergic responses in ovalbumin (OVA)-induced Allergic rhinitis(AR) mice. Methods : Sprague Dawley (SD)-rats were orally administrated with KOB (500 mg/kg), Astragali Radix water extract (ARW, 100 mg/kg) or anti-histamine drug, dosodium cromoglycate (50 mg/kg) as a reference drug, and then intraperitoneally injected with compound 48/80 (8 mg/kg). Rats were measured the mortality and serum levels of histamine. BALB/c mice were orally administrated with KOB (500 mg/kg), ARW (100 mg/kg) or anti-histamine drug, Ketotifen (10 mg/kg) as a reference drug, followed by sensitization and challenge of OVA. Mice were measured the serum levels of histamine and IgE, and observed histopathological changes of nasa mucosa H&E staining. Results : KOB and ARW significantly decreased the mortality and the serum levels of histamine in compound 48/80-induced anaphylatic rats. KOB and ARW also decreased the serum levels of histamine and IgE in OVA-induced AR mice, and inhibited histopathological changes of nasal mucosa with inflammation and the eosinophils infilteration. Conclusions : These data suggest that KOB has a strong anti-allergic effect through the inhibitory property of Astragali Radix, the main component of KOB against allergic responses in allergic rhinitis.

• BMB Reports
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• v.40 no.6
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• pp.1039-1049
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• 2007

Overdoses of acetaminophen cause hepato-renal oxidative stress. The present study was undertaken to investigate the protective effect of a 43 kDa protein isolated from the herb Cajanus indicus, against acetaminophen-induced hepatic and renal toxicity. Male albino mice were treated with the protein for 4 days (intraperitoneally, 2 mg/kg body wt) prior or post to oral administration of acetaminophen (300 mg/kg body wt) for 2 days. Levels of different marker enzymes (namely, glutamate pyruvate transaminase and alkaline phosphatase), creatinine and blood urea nitrogen were measured in the experimental sera. Intracellular reactive oxygen species production and total antioxidant activity were also determined from acetaminophen and protein treated hepatocytes. Indices of different antioxidant enzymes (namely, superoxide dismutase, catalase, glutathione-S-transferase) as well as lipid peroxidation end-products and glutathione were determined in both liver and kidney homogenates. In addition, Cytochrome P450 activity was also measured from liver microsomes. Finally, histopathological studies were performed from liver sections of control, acetaminophen-treated and protein pre- and post-treated (along with acetaminophen) mice. Administration of acetaminophen increased all the serum markers and creatinine levels in mice sera along with the enhancement of hepatic and renal lipid peroxidation. Besides, application of acetaminophen to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. It also reduced the levels of antioxidant enzymes and cellular reserves of glutathione in liver and kidney. In addition, acetaminophen enhanced the cytochrome P450 activity of liver microsomes. Treatment with the protein significantly reversed these changes to almost normal. Apart from these, histopathological changes also revealed the protective nature of the protein against acetaminophen induced necrotic damage of the liver tissues. Results suggest that the protein protects hepatic and renal tissues against oxidative damages and could be used as an effective protector against acetaminophen induced hepato-nephrotoxicity.

• Toxicological Research
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• v.20 no.3
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• pp.263-272
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• 2004

This study was to investigate single and repeated-dose toxicities of DFA IV, a new candidate of nutraceutical which has preventive effect on anemia and osteoporosis. In single-dose oral toxicity study, the test article were administered once by gavage to rats at dose level of 0, 2,000 and 5,000 mg/kg. No dead animal, abnormal sign and abnormal necropsy finding was found in control and treated groups. Thus the approximate lethal dose of DFA IV was considered to be higher than 5,000 mg/kg in rats. In four week repeated dose oral toxicity study, the test article was administered once daily by gavage to rats at dose levels of 0, 500, 1,000 and 2,000 mg/kg. No abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, hematological findings, necropsy findings, organ weights and histopathological findings. In urinalysis, specific gravity was increased in 2,000 mg/kg groups of male rats. In serum biochemical analysis, creatine phosphokinase was increased in all treatment groups of male rats. These increases in urine specific gravity and serum creatine phosphokinase activity were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, four week repeated oral dose of DFA IV to rats did not cause apparent toxicological change at the dose of 500, 1,000 or 2000 mg/kg body weight. Thus it is suggested that no-observed-adverse-effect level (NOAEL) of DFA IV in rats would be 2,000 mg/kg/day body weight.

• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.126-133
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• 2006

Thioacetamide (TA) is well known hepatotoxic and hepatocarcinogenic agent. TA also diminishes the contents of hepatic cytochrome P450 and inhibits the enzyme activity of the hepatic mixed function oxidases. TA metabolite, thioacetamide-s-oxide, is further transformed into a still unknown highly reactive metabolite that binds to macromolecules. In this study, we focused on TA-induced gene expression at hepatotoxic dose. Mice were exposed to two levels (5 mg/kg or 50 mg/kg i.p.) of TA, sampled at 6 or 24 h, and hepatic gene expression levels were determined to evaluate dose and time dependent changes. We evaluated hepatotoxicity by serum AST and ALT level and histopathological observation. Mean serum activities of the liver leakage enzymes, AST and ALT, were slightly increased compare to control. H & E and PAS evaluation of stained liver sections revealed TA-associated histopathological finding in mice. Centrilobular eosinophilic degeneration was observed at high dose-treated mice group. Hepatic gene expression was analyzed by QT clustering. Clustering of high dose-treated samples with TA-suggests that gene expressional changes could be associated from toxicity as measured by traditional biomarkers in this acute study.

• The Journal of Internal Korean Medicine
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• v.31 no.1
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• pp.66-78
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• 2010

Objective : This study was designed to investigate the possibility of AR for chronic renal injury. Methods : The author first investigated the expression levels of DNA by inducing of chronic renal injury. Then, the author investigated the effects of AR on chronic renal injury induced by combination treatment with Adriamycin and cisplatin in terms of changes in body weights and renal tissues, urine volume, BUN and creatinine levels, creatinine clearance and histopathological changes in renal tissues. Total expression levels of 546 genes were elevated or lowered by induction of chronic renal injury. Genes of which whose expression levels were elevated by induction of chronic renal injury were related to the PPAR signaling pathway and fatty acid mechanism, etc. Genes of which expression levels were lowered by induction of chronic renal injury were related to the neuroactive ligand-receptor signaling pathway. Results : Oral administration of AR restored renal mass which was reduced by induction of chronic renal injury. AR also restored creatinine clearance and lowered serum BUN level. In histopathological observation, the AR group has a tendency to prevent tissue damages as shown in the chronic renal injury group. Conclusions : AR can be used to treat patients with chronic renal injury although further study will be needed to elucidate the exact mechanisms in the efficacy of AR on chronic renal injury.

• Biomolecules & Therapeutics
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• v.4 no.1
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• pp.19-31
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• 1996

This study was performed to determine the subacute toxicities of SKI306X, an antiinflammatory herbal extract, in rats. SKI306X was administered orally to rats once a day for 4 weeks at doses of 0.3, 1.0, and 3.0 g/kg/ day. Each group consisted of 20 male and 20 female rats, including 5 male and 5 female rats per group for an interim study at the end of 2-week administration and for a 2-week recovery study, respectively. Throughout the study, all rats survived and no adverse clinical signs were observed. Although male rats treated with high dose (3.0 g/kg/day) of SKI306X showed slight loss of body weight (approximately 5%) in comparison with control animals during the administration period, their body weight loss was normally restored during the recovery period. No significant change was found in all hematological parameters of SKI306X-treated groups except for the decreased number of red blood cells in all female groups at the interim study. Statistically significant changes were observed in several blood enzyme levels of SKI306X-treated groups; however, most of these significant changes were within normal range and statistically significant values did not show dose-related responses. In SKI306X-treated groups, the absolute and relative weights of liver, heart, and stomach were statistically different from those of control group, but these differences disappeared at the end of recovery period and also drug-related gross and histopathological findings in these organs were not found. No other drug-related gross and histopathological findings were observed. It is concluded from the results of this study that non-toxic dose of SKI306X was estimated to be between 0.3 and 1.0 g/kg/day and the maximum tolerated dose of SKI306X was assumed to be higher than 3.0 g/kg/day.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.1039-1045
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• 2005

In order to evaluate the in vivo synergic effect of Eunkyo-san which was a traditional poly-herbal formula has been used in the treatment of respiratory diseases in Korea, with quinolone antibiotics, ciprofloxacin (CPFX), the viable bacterial number and histopathological changes were monitored after experimental respiratory infection with S. pneumoniae ATCC 6303. The obtained results were as follows: In CPFX groups, the viable bacterial numbers were significantly decreased compared to that of control group and these were more dramatically decreased compared to that of single treatment with CPFX, respectively in concomitant treated groups with Eunkyo-san. In control group, severe infiltration of inflammatory cells, hemorrhage and hypertrophy of alveolar linings were demonstrated at microscopical levels. However, these abnormal histopathological changes were significantly decreased compared to that of control group in CPFX groups, and these were more dramatically decreased compared to that of single treatment with CPFX, respectively in concomitant treated groups with Eunkyo-san. In CPFX groups, the LSA (luminal surface of alveoli $\%$) were significantly increased compared to that of control group and these were more dramatically decreased compared to that of single treatment with CPFX, respectively in concomitant treated groups with Eunkyo-san. According to these results, it is considered as the in vivo antibacterial activity of CPFX was dramatically increased by concomitant use of Eunkyo-san against S. pneumoniae ATCC 6303 infection of respiratory tract.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.753-759
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• 2005

In order to evaluate the in vivo synergic effect of Eunkyo-san with quinolone antibiotics, rufloxacin (RUFX), the viable bacterial numbers and histopathological changes were monitored after experimental respiratory infection with Klebsiella peumoniae NCTC 9632. The obtained results were as follows : In RUFX group, the viable bacterial numbers were significantly decreased compared to those of control group and these were more dramatically decreased compared to those of single treatment with RUFX, respectively in concomitant treated groups with Eunkyo-san. In control group, severe infiltration of inflammatory cells, hemorrhage and hypertrophy of alveolar linings were demonstrated at microscopical levels. However, these abnormal histopathological changes were significantly decreased compared to those of control group in RUFX group, and these were more dramatically decreased compared to those of single treatment with RUFX, respectively in concomitant treated groups with Eunkyo-san. In RUFX group, the LSA% (luminal surface of alveolar%) were significantly increased compared to those of control group and these were more dramatically decreased compared to those of single treatment with RUFX, respectively in concomitant treated groups with Eunkyo-san. According to these results, it is considered that in vivo antibacterial activity of RUFX group was dramatically increased by concomitant use of Eunkyo-san against K. pneumoniae NCTC 9632 infection of respiratory tract.

• Korean Journal of Veterinary Research
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• v.33 no.2
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• pp.309-320
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• 1993

Guinea pigs were cutaneously inoculated with Trichophyton verrucosum var album, that is a common causative fungus of dermatophytosis in cattle. The developmental process of lesions, clinical and histopathological changes and reisolations of the fungi were studied to evaluate the pathogenicity of Trichophyton verrucosum var album in guinea pigs. Results obtained through the experiments were summarized as follows : 1. The incidence of infection of the clipping group was 13(86%) of 15 animals, and that of the plucking group was 14(93%) of 15 animals. In both of the clipping and plucking groups, visible cutaneoas lesions were developed between 4 and 7 days post inoculation(p.i.). The spreading and the climax stages persisted for 4 to 11 and 6 to 12 days, respectively. 2. In macroscopic observations, formation of various degree of erythemas and scales over the inoculated skin sites were observed in the spreading stage. In the climax stage, exudative changes and dark red crusts were formed as typical circular lesions. In the healing stage, the lesions revealed shedding of crust, alopecia and hair regrowth. 3. In histopathological observations, infiltration of inflammatory cells, hyperplasia, microabscesses and keratinous-hyaloid materials of epidermis were observed in the spreading stage. Hyphal invasion was primarily observed at the level of epidermis and pilosebaceous ducts. In the climax stage, the infected epidermis was thick with severe hyperplasia, hyperkeratosis and acanthosis. The microabscesses with fungal hyphae, folliculitis and hyperplasia of external root sheath were observed in the dermis. The fungal hyphae were observed only in the tissues of hair follicles, that were internal root sheath, cuticle, the keratinized portions of cortex and medulla 4. In reisolation of the inoculated fungus, all trials for ten animals showed positive cultures until 25 days p.i.. Afterward, the reisolation rates were gradually decreased, showing all negative after 40 days p.i..