• Korean Journal of Veterinary Research
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• v.40 no.3
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• pp.575-585
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• 2000

This study was performed to observe the influence of host immune response on the chemotherapy of mice experimentally infected with Fasciola hepatica. Following immunosuppression with prednisolone or immunoenhancement with Freund's complete adjuvant(FCA), mice were experimentally infected with 3 Fasciola hepatica metacercariae and treated with closantel at 1 week post infection. In the group of mice infected with metacercariae alone, 2 mice of 10 were dead at 10 weeks post infection(20% mortality), and adult flukes were recovered from the liver and the peritoneal cavity of the remaining 8 mice(100% infectivity). In the group of mice treated with prednisolone and infected with metacercariae, 8 of 10 mice died before euthanasia with a mean time of death earlier than the control group (p<0.05). In the group of immunosuppressed mice infected with metacercariae and treated with closantel 20mg/kg, 4 of 10 mice died before sacrifice. In the group of mice infected and treated with closantel 20mg/kg, mortality and infectivity was 10% and 30%, respectively. Similar results were observed in mice infected and treated with closantel 5mg/kg which resulted in 10% and 50% mortality and infectivity, respectively. These results indicated that the efficacy of closantel treatment was decreased in immunosuppressed mice, while the pathogenicity was increased. In immunoenhanced mice infected with metacercariae, on the other hand, the efficacy of chemotherapy with both 5mg/kg or 20mg/kg closantel resulted in only 10% infectivity. The results shown in this study strongly suggest that a close interaction between chemotherapy against F hepatica with closantel and the host immune system exists. Considering that fascioliasis is a zoonosis, treatment regimen against the infection to immunosuppressed patients may require a concurrent prescription of an appro-priate immuno-enhancing adjuvant.

• Journal of Pharmacopuncture
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• v.2 no.1 s.2
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• pp.93-109
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• 1999

To investigate effects of Achyranthis Radix herbal-acupuncture on adjuvant arthritis in rats, the edema rate, the number of WBC, the quantity of total protein, albumin and globuline in the blood serum and histological test of the muscular tissue were measured in the arthritis part. 1. After elicitating arthritis of Sprague dawley(SD) rats by injection of Freund's complete adjuvant for 2 weeks, normal saline was injected for the Exp. I group and Achyranthis Radix herbal-acupuncture was injected for the Exp. II group during 30days. Selected point was $D\acute{u}b\acute{i}(ST_{35})$ in both the groups. And then the volume of the paw were checked. The volume of the paw was $0.84{\pm}0.14mm$ in the Exp. I group and $0.47{\pm}0.11mm$ in the Exp.II group, the swelling of the paw was restricted significantly in the Exp. II group(p<0.05). 2. The number of WBC was $10.34{\pm}0.14(10^3/ml)$ in the normal group and $37.47{\pm}5.46(10^3/ml)$ in the Exp. I group. It was $21.24{\pm}2.58(10^3/ml)$ in the Exp. II group. This fact showed that the group Exp. II with Achyranthis Radix herbal-acupuncture was more effective than the Exp. II group in the treatment of arthritis(p<0.05). 3. The content of the total protein in the blood serum was $6.14{\pm}0.43g/dl$ in the normal group, $7.95{\pm}0.94g/dl$ in the Exp. I group, and $6.41{\pm}0.68g/dl$ in the Exp. II group. There was no significance in total protein between the Exp. II group and the Exp. I group from the statistical analysis. 4. The content of albumin in the blood serum was $2.94{\pm}0.13g/dl$ in the normal group, $2.01{\pm}0.48g/dl$ in Chang Tong-young the Exp. I group and $3.15{\pm}0.27g/dl$ in the Exp. II group. This fact showed that the Exp. II group had significant increase in the serum albumin from the statistical analysis compared with the Exp. I group. 5. The content of the globulin in the blood serum was $3.19{\pm}0.48g/dl$ in the normal group, $4.70{\pm}1.26g/dl$ in the Exp. I group and $3.26{\pm}0.57g/dl$ in the Exp. II group. There was no significance in the serum globulin between the Exp. II group and Exp. I group from the statistical analysis. 6. In histological finding, because of severe inflammatory reaction, remarkably irregular tissue and large amount of inflammatory cells were found in the Exp. I group. But the Exp. II group showed small amount of inflammatory cells, the refrained inflammatory state and even recovering state.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.1
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• pp.79-95
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• 2011

Objectives : This study was to investigate the antiarthritic effect of Hwallak-dan(Huoluo-dan) on the complete freund's adjuvant(CFA)-induced arthritis in Lewis rats. Methods : Arthritis was induced by intradermal injection of CFA into base of tail. Experimental groups divided into normal(n=10), control(n=10) and treated(n=10) group. Animals of control group received normal saline for twenty days, treated group received extracts Hwallak-dan(Huoluo-dan) for same duration, light mineral oil only injected non-arthritic rats were served as normal group. The incidence of arthritis and arthritic index were observed after treatment. Body weight, paw edema volume and thickness of ankle joint were measured at 0, 11, 14, 17, 20 days after treatment. White blood cell(WBC) counts in blood were analysed at 20 days after treatment and tumor necrosis $factor-{\alpha}(TNF-{\alpha})$, $interleukin-1{\beta}(IL-1{\beta}$), IL-6 contents in paw exudate were analysed by ELISA at 20 days after treatment. Histopathology on the ankle joint were performed at 20 days after treatment. Results : 1. Incidence of arthritis of treated group was 60% and control group was 100% at 20 days after treatment. 2. Arthritic index of treated group was significantly decreased compared with control group at 20 days after treatment. 3. Paw edema volume and thickness of ankle joint of treated group was significantly decreased compared with control group at 20 days after treatment. 4. Total WBC of treated group was significantly decreased compared with control group at 20 days after treatment. 5. Neutrophils of treated group was significantly decreased compared with control group at 20 days after treatment. 6. $TNF-{\alpha}$ content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 7. $IL-1{\beta}$ content content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 8. IL-6 content content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 9. Histopathological arthritic index of treated group was significantly decreased compared with control group at 20 days after treatment. Conclusions : These results indicate that Hwallak-dan(Huoluo-dan) has inhibitory effect on the development and progression of CFA-induced arthritis in rats.

• Korean Journal of Veterinary Research
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• v.25 no.1
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• pp.7-17
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• 1985

Many investigators have been pursuing various attempts so far to produce hepatitis B surface antigen(HBsAg) vaccines using the techniques such as isolation from plasma of chronic HBsAg carrier, recombinant DNA technique or preparation of synthetic peptides specific for immunogenic determinants. Hepatitis B virus can not grow on any cell lines by the tissue culture technique at the present time. The plasma of chronic HBsAg carrier is expensive and its source is limited. The HBsAg from the recombinant DNA technique gave still very low yield. Another approach, therefore, has been initiated to develop a synthetic hepatitis B virus vaccine. The possible use of several distinct synthetic vaccines in prophylaxis can be facilitated by availability of full synthetic immunogens. Peptides synthesized for potential application as antiviral vaccines have been mostly tested in the form of conjugates with carrier proteins, although the free synthetic peptide can be immunogenic. To understand basic knowledges on the antigenicity and immunogenicity of a synthetic peptide specific for major immunogenic determinant of HBsAg, a nonapeptide, $H_2N^{139}Cys-Thr-Lys-Pro-Thr-Asp-Gly-^{146}Asn-Aba$ COOH, which corresponds to HBsAg amino acid residues 139 to 147, was synthesized by the Merrifield's solid-phase method with a slight modification. The antigenicity and immunogenicity of this specific synthetic peptide were examined comparing with purified plasma-derived natural HBsAg. The results obtained are as follows; 1. The peptide synthesized showed the identical amino acid composition to the theoretical value. The degree of purification and molecular weight were acertained by methods of high performance liquid chromatography and mass spectrometry. 2. Using m-maleimidobenzoyl-N-hydroxysuccinimide ester as a conjugating agent, the synthetic peptide was conjugated to rabbit albumin and ${\gamma}$-globulin, tetanus and diphtheria toxoids, and keyhole limpet hemocyanin. Their conjugation yields were 8.3, 9.5, 15.8, 13.5, and 11.2%, respectively. 3. The natural HBsAg was purified from plasma of chronic HBsAg carrier. By the electron microscopic observation of the purified natural HBsAg preparation, no Dane particles were observed and the preparation showed negative DNA polymerase activity. 4. Antigenicity of the synthetic peptide and the plasma-derived natural HBsAg was determined by competition radioimmunoassay using $^{125}I$-natural HBsAg. Their 50% inhibitions appeared as $90{\mu}g/ml$ and $0.12{\mu}g/ml$ for the synthetic peptide and the natural HBsAg, respectively. This indicates that the former was about 750-fold less antigenic than the latter. 5. Immunogenicity of the synthetic peptide was determined by administering the peptide-carrier conjugates into rabbits with and without Freund's complete adjuvant. Regardless the carrier proteins and adjuvant, positive immune responses to the synthetic peptide were observed. The higher antibody titers, however, were shown in the groups administered with Freund's complete adjuvant. 6. Immunizing dose 50% in mice of the various peptide-carrier conjugates was 5.47, 6.00, 65.16, 31.25 and $13.03{\mu}g/dose$ for rabbit albumin and ${\gamma}$-globulin, tetanus and diphtheria toxoids, and keyhole limpet hemocyanin, respectively, while the natural HBsAg showed $0.65{\mu}g/dose$. 7. It was postulated that homologous proteins prefer to heterologous ones as the carriers.

• Toxicological Research
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• v.14 no.3
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• pp.307-313
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• 1998

Dimethyl dimethoxy biphenylate (DDB) is an agent used to treat hepatits. DDB-S (DDB-soluble), a new DDB derivative, was synthsized to increase water solubility of the original DDB. In the present study, the antigenic potential of DDB-S was examined by active systemic anaphylaxis (ASA), passive cutaneous anaphylaxis (PCA) and passive hemagglutination (PHA) tests. The experimental groups consist of a low dosage group, a high dosage group, he group emulsified with Freund's complete adjuvant (FCA, ASA test) or an alum (PCA and PHA tests) and the macromolecule conjugate group emulsified with FCA or an alum. In the ASA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus FCA showed severe anaphylactic responses. In the heterologous PCA test using mice and rats, positive responses were not detected in any of the experimental groups. In the PHA test, all experimental groups showed negative responses whereas the positive control group given ovalbumin plus an alum showed 512~2048 PHA titers. These results demonstrated that DDB-S does not have any antigenic potential. These can be utilized as a part of preclinical data for the development of DDB-S as an intravenous injection.

• YAKHAK HOEJI
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• v.49 no.2
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• pp.140-146
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• 2005

Candida albicans, a polymorphic fungus, causes systemic and local infections. Recent reports show that the fungus is a main etiological agent for the arthritis. For trea tment, antifungal drugs and/or rheumatoid drugs are used, but resistance and side effects limit application of the drugs. In search of new sources for treatment of the fungal arthritis, we choose Egb 761 (extract of Ginkgo leaves 761), one of the most popular over-the-counter herbal medicines. The Egb 761 contains two major ingredients such as terpene and flavonoid. In the present study, we examined if the terpene portion of Egb 761 had anti-inflammatory activity against C.albicans-caused arthritis. The terpene was extracted with combination of methanol and water from the Egb 761, followed by gel-permeation chromatography. Presence of terpene was determined by the Salkowski colorimetric method and HPLC analysis. For an animal model of inflammation induction, mice were given an emulsion form of C.albicans cell wall mixed with Complete Freund's Adjuvant (CFA) by footpad-injection. Results showed that intraperitoneal administration of the water-soluble portion that contained terpene and flavonoid reduced the inflammation. Whereas the terpene had anti-inflammatory activity, flavonoid portion had no such activity, For determination of possible mechanism of the activity, the terpene seemed to be suppression of nitric oxide (NO) production from LPS-treated macrophages. Taken together the Ginkgo terpene may have anti-inflammatory effect against C.albicans-caused arthritis, possibly by blocking NO production.

• Toxicological Research
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• v.14 no.3
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• pp.459-463
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• 1998

The antigenicity of intralipidos was investigated in guinea pig, mice and rats. Antigenicity tests-active systemic anaphylaxis (ASA), passive systemic anaphylaxis (PSA), passive cutaneous anaphylaxix (PCA) of this materials were performed. The results were followed: 1. After sensitizaion with YPL, YPL+intralipidos, and intralipidos, emulsified with complete Freund's adjuvant (CFA), guinea pigs didn's show any anaphylatic shock symptom in the ASA test, 2. These materials didn't show any anaphylatic shock symptom in the PSA test, 3. After sensitization with antisera of YPL, YPL+intralipidos, and intralipidos sensitized mice, blue spots were not observed on the hypodermis of back of rats in the PCA test. From the results of this investigation, the antigenicity of YPL, intralipidos was negative under the present experimental condition.

• YAKHAK HOEJI
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• v.56 no.1
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• pp.20-25
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• 2012

In Northeast Asia, Paeoniae Radix has been used in treatments of inflammation-causing diseases such as arthritis for many centuries. Paeoniflorin, one of the principle bioactive monoterpene glucosides from the paeony root, is reported to be mostly responsible for the effectiveness of the treatments. However, the anti-inflammatory effect of a monoterpene, paeoniflorigenone (PFG) which partially has the moiety of paeoniflorin minus a glucose structure is unknown. Thus, the aim of this work was to investigate anti-inflammatory activity of PFG. For the investigation, PFG activity on the NO (nitric oxide) production from LPS-stimulated macrophages, and the anti-inflammatory effect was tested in the animal model of septic arthritis caused by Candida albicans, a major etiological agent for septic arthritis. For induction of the arthritis, mice were administered with an emulsion of C. albicans cell wall (CACW) mixed with Complete Freund's Adjuvant (CFA) via footpad-injection (Day 0); PFG at a dose of 0.5 or 1 mg/mouse (25 or 50 mg/kg of body-weight) was given to the animals on Day 3, 6, and 9; footpads were scored for arthritis. Moreover, the PFG effect on proliferation of T-lymphocyte that causes aggravation of arthritis was additionally tested. Data resulting from those tests showed that PFG inhibited the NO production from the stimulated macrophage in a dose dependent manner (P<0.05), indicating that PFG is an anti-inflammatory. To confirm the in-vitro results, anti-inflammatory activity of PFG was determined against C. albicans-caused septic arthritis. Data showed that PFG-treatment reduced footpad-swelling which indicates that PFG has anti-arthritic effect (P<0.05), which is therapeutic. The anti-arthritic effect appeared to be mediated by PFG suppression of T-cell proliferation. Ultimately, PFG, a monoterpene component, has anti-inflammatory activity analogous to paeoniflorin. The anti-inflammatory activity treats the septic arthritis due to a pathogenic fungus C. albicans.

• Journal of Korean Medicine Rehabilitation
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• v.15 no.2
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• pp.55-65
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• 2005

Objectives : Mahwangkanghwal-tang(Mahuangqianghuo-tang;MKT) is a prescription that treat clinically arthritis. The purpose of this study is to investigate effects of MKT extract on the adjuvant arthritis in pathological rats induced by Freund's complete adjvant($0.2m{\ell}/kg$). Methods : Experimental groups were divided into 4 groups ; Normal group were administered DDW $1.0m{\ell}$ to normal rats for 14 days, Control group were administered DDW $1.0m{\ell}$ to arthritic rats for 14 days, Sample A group were administered MKT $300m{\ell}/kg$ $1.0m{\ell}$ to arthritic rats for 14 days, Sample B group were administered MKT $500m{\ell}/kg$ $1.0m{\ell}$ to arthritic rats for 14 days. The present author observed body weight, inhibitory effect of edema, analgesic effects by hot plate, WBC, RBC, hemoglobin, hematocrit, platelet, total serum protein level and total serum cholesterol level. Results : 1. All sample group were increased body weight compared with control group, sample B group were significantly increased body weighty compared with control group. 2. All sample group significantly inhibited the rated of paw edema compared with control group. 3. All sample group significantly prolongated the escaping time compared with control group, sample B group significantly prolongated the paw licking time compared with control group. 4. All sample group were significantly decreased WBC compared with control group, sample B group were significantly decreased RBC compared with control group. 5. All sample group ware decreased hemoglobin and hematocrit compared with control group. 6. All sample group ware increased total serum cholesterol compared with control group, sample B group were significantly decreased platelet compared with control group. 7. All sample group ware significantly decreased total serum protein level compared with control group. 8. All sample group ware increased total serum cholesterol compared with control group, sample B group were significantly increased total serum cholesterol level compared with control group. Conclusions : We thought that Mahwangkanghwal-tang(Mahuangqianghuo-tang) could be used for curing rheumatoid arthritis, anti-inflammatory effect was somewhat better in much than small dosage.

• Journal of Acupuncture Research
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• v.25 no.4
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• pp.1-9
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• 2008

Objectives : This study was to investigate the effect of low frequency electroacupuncture according to acupoints combination on NOS positive neurons in the PAG and Hippocampus of Rat with adjuvant induced Rheumatoid arthritis. Methods : Arthritis was induced by intradermal injection of FCA into base of tail. Experimental group were divided into 6 group ; Normal, Control, $ST_{36}$, $SP_9$, $ST_{36}+SP_9$, and NA. Normal group was injected with normal saline and not treated electroacupuncture. Control group was injected with FCA and not treated electroacupuncture. ST36 group was injected with FCA and treated by 2 Hz electroacupuncture at $ST_{36}$. $SP_9$ group was injected with FCA and treated by 2 Hz electroacupuncture at $SP_9$. $ST_{36}+SP_9$ group was injected with FCA and treated by 2 Hz electroacupuncture at $ST_{36}+SP_9$. NA group was injected with FCA and treated by 2 Hz electroacupuncture at non acupoint. Each groups were evaluated by the number of NOS-positive neurons in PAG and hippocampus by using an image analyzer and a microscope. Results : 1. The number of NOS-positive neurons of the NA group were significantly decreased in the CA2-3. 2. The number of NOS-positive neurons of the ST36 group were significantly decreased in the PAG and CA2-3. 3. The number of NOS-positive neurons of the SP9 group were significantly decreased in the PAG and DG 4. The number of NOS-positive neurons of the ST36+SP9 group were significantly decreased in the PAG, CA1 and DG. Conclusions : It is expected that low frequency electroacupuncture can be used a treatment of rheumatoid arthritic pain and that treatment of electroacupuncture at combined acupoints is more efficient than treatment of low frequency electroacupuncture at one acupoint.