CJ-50002 is an oral vaccine against V.vulnificus infection composed of whole cell lysate of V. vulnificus. The general pharmacological properties of CJ-50002 were evaluated in various animals and in vitro system. CJ-50002 at oral doses of 0.2, 2 and 20 mg/kg had no effect on general behavior in mice, chromo- and electro-convulsions in mice, writhing syndrome induced by acetic acid in mice, body temperature in rats, charcoal meal propulsion in mice and urine and electrolytes excretion in rats. However, oral administration of CJ-50002 at dose of 20 mg/kg prolonged the hexobarbital-inuced sleeping inducing time in mice. In anesthetized dogs, CJ-50002 showed no effect on blood pressure, heart rate and ECG but decreased the respiratory rate and femoral blood flow at dose of 20 mg/kg. p.o. CJ-50002 had no effect on the contractile response of the isolated guinea pig ileum to various spasmogen at concentrations of 0.2, 2 and 20 $\mu\textrm{g}$/ml, respectively. Since these pharmacological effects of CJ-500o2 were observed at dose much greater than those in clinical use (approximately 0.16 mg/kg, p.o.), it is likely that this vaccine may be relatively free of undesirable effects in clinical practice.
General pharmacological properties of LB-00014, an erythropoietin which was produced by recombinant DNA technique in Biotech Research Institute, LG Chemical Ltd. were examined. The administration of LB-00014 (60, 600, 6000 IU/kg, iv) in mice had no effect in general behavior and central nervous system, and no influences on normal body temperature, writhing syndromes induced by 0.7% acetic acid solution and chemoshock produced by strychnine and pentetrazole solution. LB-00014 (60, 600, 6000 IU/kg, iv) given to anesthetized rabbits showed no effect on blood pressure of carotid artery and respiration rates, and it did not influence the responses produced by injection of acetylcholine or epinephme. The administration of LB-00014 (601, 600, 6000 IU/kg, iv) in rats had no effect on the plasma prothrombin time, activated partial thromboplastin time and hemolytic action. The platelet aggregation induced by collagen in human plasma was not influenced by LB-00014 (10, 100, 1000 lU/kg, iv). It showed no direct effect at 100 and 1000IU/m1 in isolated stomach fundus and uterus of rats and ileum of guinea-pig, and it also had no inhibition of contraction produced by acetylcholine, oxytocin, serotonin and histamine in the above-mentioned preparations. It did not influence gastric secretion, pH and acid output at 6000 IU/kg, iv in rats, but showed a significant increase in intestinal propulsion of mice at 6000 IU/kg, iv. Its administration (60, 600, 6000 lU/kg, iv) caused no effect on urine and electrolyte excretion in rats. These results indicate that LB-00014 does not exsert any of serious pharmacological effects.
Kim, Young-Ok;Chung, Hye-Joo;Chung, Seung-Tae;Kim, Jin-ho;Park, Jae-Hyun;Kil, Kwang-Sup;Cho, Dae-Hyun
Archives of Pharmacal Research
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v.22
no.2
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pp.143-150
/
1999
melatonin (MLT), N-acetyl-5-methoxytryptamine, is mainly secreted by the pineal gland. The ultraviolet (UV), infrared (IR) and 1H-NMR spectra of irradiated and non-irradiated MLT were measured, and phototoxicity tests of MLT, anthracence (positive control) and sodium lauryl sulfate (SLS, negative control) were performed. The methods employed include both in vitro test such as MTS assay using the human fibroblast cell and yeast growth inhibition assay using Candida albicans and in vivo method using the skin of guinea pig. UV absorption spectra and 1H-NMR spectra of MLT were changed by UVA (365 nm, 15 J/$\textrm{cm}^2$), but IR spectra of MLT were not changed. The fifty percent inhibitory concentration (IC50) ratio (UV-/UV+) of MLT was 10. The inhibition zone of irradiated-paper disks treated with MLT was not observed. According to the results of histophathological examination, no pathologic lesion was observed in the non-irradiated group, but slight degeneration of keratinocytes in the epidermis, homorrhage and vasodilation in dermis were observed in the irradiated group. These results indicated that the molecular structure of MLT is altered by UVA to unidentified photoproducts and a moderate phototoxicity of MLT is predicted.
Ha, Yong-Ho;Yu, Sung-Un;Kim, Dong-Sup;Lim, Se-Jin;Choi, Young-Wook
YAKHAK HOEJI
/
v.42
no.1
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pp.39-45
/
1998
Kojic acid, antimelanogenic agent, has been widely used in cosmetics to lighten the skin color. However, it has skin irritancy and instability against pH, temperature and light. To overcome these problems and optimize the molecular structure of kojic acid (KA), a prodrug, kojic acid monostearate(KMS), has been synthesized to modify the topical drug delivery in the point of sustained release of the parent drug via enzymatic hydrolysis during skin absorption. The prodrug was tested for enzymatic hydrolysis with cytosolic fraction of hairless mouse, skin. From the in vitro skin permeation study through hairless mouse skin, we found that KMS was retained in the skin and generated KA continuously by the skin esterase cleavage. In addition, topical formulations of o/w type creams and polyolprepolymer-containing cream were further tested for whitening effects using in vivo yellow skin guinea pig model.
Background : The herbicide paraquat can cause severe lung injury and fibrosis in experimental animals. In this study we have investigated the changes in lung endothelin-1(Et-1) levels and immunohistochemical localization in relation to treatment with cyclophosphamide and methylprednisolone in paraquat induced pulmonary fibrosis in guinea pigs. Material and methods : 29 male Hartley guinea pigs were divided into 4 groups. Group I was normal control. Paraquat was instilled into the lung of guinea pig of group II, III and IV unilaterally. Group II was treated with cyclophosphamide and methylprednisolone. Group III was treated with methlprednisolone. Group IV was not treated. The degree of fibrosis was evaluated by H-E stains and Masson's trichrome stains and cell activity was assessed by Et-1 immunohistochemical stains. Statistical evaluation was performed using the Kruskawallis oneway analysis. Results : Paraquat induced an increase in numbers of fibroblasts and total amount of lung collagen in Group IV compared to the normal controls. There was no significant difference in total numbers of fibroblasts between any of paraquat instilled groups, but there was significant increase in total amount of collagen in Group IV compared to group II and III (p<0.05). The treatment of cyclophosphamide and methyprednisolone suppressed the growths of both fibroblasts and collagen, but this suppression was stastically significant only in the case of collagen Et-1 immunoreactivities of bronchial epithelium, type II pneumocytes, endothelial cells and fibroblast in group II and III were decreased compared to those in group IV. Conclusion : These results demonstrate that Et-1 is an important contributing factor in the pathogenesis of pulmonary fibrosis. Et-1 is synthesized and released by bronchial epithelium, Type II pneumocyte, endothelial cells, alveolar macrophages and fibroblasts. Especially they are associated with alveolar macrophage and fibroblasts. We conclude that combined therapy of cyclophosphamide and methylprednisolone are more effective in the control of Et-1 expression and collagen deposition.
Histopathological study has been carried out to elucidate the protective effect of Korean red ginseng water extract (KRG-WE) on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced acute toxicity in male guinea pigs. Forty male guinea pigs ($200{\pm}20g$) were divided into 4 groups: normal controls (group 1) received vehicle and saline; group 2 (single TCDD-treated) received TCDD (5 ${\mu}g/kg$, single dose) and saline; group 3 received KRG-WE (200 mg/kg, i.p.) for 2 weeks starting 1 week before TCDD-exposure; group 4 received same dose of KRG-WE for 7 days from the day of TCDD-exposure. Weights of liver, testis, kidney, spleen and lung of the TCDD-exposed guinea pigs were significantly decreased. Thymus was severely shrunken, thereby could not be distinguished from adipose tissue in group 2 animals. Focal interstitial inflammation and fibrosis were observed from the lung parenchyma of group 2 animals. Furthermore, moderate swelling of hepatocyte, diffused aggregates of hemosiderin-laden macrophages from the Prussian blue stained spleen, marked decrease in spermatogenesis, and pyknotic and degenerative changes in the renal tubules were observed from intestinal organs of group 2 animals. On the other hand, histopathological damage was moderately to markedly alleviated in groups 3 and 4, but pretreatment of KRG-WE was more effective than the simultaneous treatment. In particular, TCDD-induced testicular atrophy was significantly attenuated by KRG-WE (p<0.01). From these results, it could be suggested that Korean red ginseng might be a useful herb that prevented TCDD-induced toxicity on liver, testis, kidney and spleen.
The purpose of this study was to investigate the effect of electromagnetic field in orthodontic tooth movement, and the optimal application period of electromagnetic field to initiate tooth movement. Eighty male Hartley guinea pigs were utilized in this study. Laterally directed orthodontic force was applied to the maxillary central incisors. Half sine-wave pulsed electromagnetic field(HSPEMP) was applied to experimental group during 10 days. According to the period of application of HSPEMP(4 hours, 8 hours, 12 hours a day), they were divided into the three sub-groups The obtained results were as follows; 1. In case of application of HSPEMF during 4 hours a day, there was no significant difference in the final amount of orthodontic tooth movement between the experimental and the control group. 2. In case of application of HSPEMF during 8 and 12 hours a day, there was a significant increase in the final amount of orthodontic tooth movement since the eighth day, the sixth day respectively. 3. In comparison with the case of application of HSPEMF during 8 hours a day, there was a significant increase in the final amount of orthodontic tooth movement at the seventh day and the eighth day in case of application of HSPEMF during 12 hours a day.
The effect of genistein on melanin synthesis was studied using in vitro and in vivo model. Genistein inhibited melanin synthesis in cultured melan-a cells dose dependently. Tyrosinase activity was decreased by genistein treatment in melan-a cells, but genistein did not inhibit tyrosinase directly. Genistein did not affect the expression of tyrosinase in melan-a cells. Genistein inhibited the activity of ${\alpha}$-glucosidase in virtro and the glycosylation of tyrosinase in melan-a cells. The resulting unsaturated glycosylation of tyrosinase makes it unstable and disturb correct transportation. To further clarify the effect of genistein on the melanogenesis, we established UVB-induced hyperpigmentation on the shaved backs of brown guinea pigs. The animals were exposed to UVB radiation once a week for three consecutive weeks. Genistein (1 and 2%) or vehicle alone as a control were then topically applied to the hyperpigmented areas daily. Genistein showed significant lightening effect on the UVB-induced hyperpigmentation in five weeks. Depigmenting effect was prominent in 2% genistein treatment with Fontana-Masson staining. In conclusion, genistein may be a useful agent for skin whitening.
In order to observe the responses of the periodontal tissue on the tension side following the experimental tooth movement, 35 Guinea pigs were divided into the control group (5 animals) and 6 experimental groups (3 movement groups and 3 retention groups) consisting of each 5 animals. The experimental tooth movement of Guinea pig's upper incisors installing open helical loop were carried out by rendering continuous force : 5g (1st groups) 35g (2nd groups), 100g (3rd groups), respectively for 7 days. 3 movement groups (15 animals) were sacrificed soon after the continuous force, and 3 retention groups (15 animals) were sacrificed after the retention period of another 7 days. The following results were obtained from the observation of the surrounding tissues of teeth on the tension side through light microscopy any transmission electron microscopy. 1. The vessel walls in the experimental groups were thinner than those of the control group, the number of blood vessel had the tendency to increase. The greater the strong force applied to each group, the more the destruction of cells and fibers was found and the more the number of the red blood cell of vessel outside appeared. 2. New collagen fibers were produced from fibroblasts in the 1st groups (light force), but were produced rather less in the 2nd groups (medium force) and the 3rd groups (heavy force). 3. In the forming patterns of the new alveolar bone of the 3rd groups (heavy force), the bone trabeculae were formed towards the direction of the force to be applied, but the new alveolar bone in the 1st groups (light force) was produced evenly throughout the all surfaces of the alveolar bone rather than the patterns of bone trabeculae ; therefore, the patterns of new alveolar bone were observed differently according to the magnitude of the force applied. 4. In the retention group, it was observed that the collagen fibers were produced from the osteoblasts in the marginal areas of the periodontal ligaments being widely opened and were deposited on the alveolar bone surface but the production of collagen fibers from the osteoblasts in the other area of the periodontal ligaments was almost ceased, and a rest line on the new alveolar bone surface was found.
Kim, Pil-Sun;Lee, Tae-Jong;Kim, Yang-Hee;Kim, Jung-Si
Journal of the Korea Academia-Industrial cooperation Society
/
v.12
no.10
/
pp.4378-4384
/
2011
In order to evaluate the anti-oxidative capabilities of Angelica dahurica Radix ethanol extract (ADEE), we analyzed the contents of polyphenol and flavonoid compounds and the electron donating ability from ADEE. For animal experimentation, the test agent was topically applied to the artificial tanning spots which were induced by 1,500 mJ/$cm^2$ of ultraviolet B radiation on the backs of brown guinea pigs weighing approximately 450~500g. The test agent of $30{\mu}{\ell}$ was applied (6areas per group) twice a day, five days a week, for five weeks. On completion of the experiment, the animals were sacrificed under anesthetization, and the artificial tanning spots were obtained by biopsy punch and stained with H&E to observe the histological change in the epidermis and dermis. As a result, the contents of polyphenol and flavonoid compounds in ADEE were 20.7mg/g and 19.5mg/g respectively. As the for electron-donating capability of ADEE, it was observed that ADEE displays a dose-dependent antioxidative capacity of 14.8% and 19.8% at the concentration of 500 and 1000 ${\mu}g/m{\ell}$ respectively. Tissue staining with H&E revealed that the epidermis of the control group was slightly thicker than that of the other groups. However no inflammation or any other undesirable effect on the skin tissue due to ADEE was observed. These results indicate that ADEE is of value as a natural antioxidant.
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