1. Name of the centre

Title : Developments of Therapeutic Models on East-West Integrated Medicine
Primary inverstigator : Yun-Ho Lee, OMD.
Department of Acupuncture & Moxibustion,
College of Oriental Medicine, Kyung Hee University

This team aims at development the therapeutic models for arthritis by the East-West Integrated Medicine at the East-West Arthritis Center, and to develope pain control model by East-West Integrated Medicine at the East-West Pain Clinic.

In the first year, we carried out ① clinical study of bee venom for therapeutic models of rheumatoid arthritis at the East-West Arthritis Center in our hospital. Bee venom therapy has been used for the treatment of rheumatoid arthritis in traditional oriental medicine. A double-blind, randomized controlled trial was performed to evaluate the efficacy of the bee venom treatment with control of Methotrexate in 72 patients for three months.
In addition to this clinical trial, this group confirmed ② anti-rheumatic effects after bee venom treatment at the Zusanli point on type II-collagen induced arthritis in DBA/1 mice. The effect of bee venom herbal acupuncture was confirmed that inhibit the production of proinflmmatory cytokines such as TNF-α and IL-1β, and also inhibit the proliferation of synovial cells and the invasion of chronic inflmmation cells on the joint space of CIA mice.

In the second year, it is planned that the clinical control model will be developed in the treatment of central pain by East-West Integrated Medicine.

This work was supported by grant KRF-2001-005-F00025 from Center of Research Institute Program in the Korea Research Foundation

Primary investigator : Sabina Lim, OMD.
Department of Meridian and Acupoint,
College of Oriental Medicine, Kyung Hee University

This part intends to find new herbal medicine including herbal prescription and herbal acupuncture for the treatment of arthritis and neuropathic pain, and to develope a ultrasonic therapeutic system on non-invasive meridian points.

In the first year, the research went forward with ① screening of herbal medicine to develope therapeutic agents for rheumatoid arthritis(RA) in vitro and in vivo. RA is an autoimmune disorder of unknown etiology that is characterized by progressive joint destruction, deformity, disability and premature death in most patients. In results, several herbal medicine showed acute anti-inflammatory and anti-nociceptive effects on carrageenan induced paw edema. Among them, KHM-10, a herbal medicine exhibited chronic anti-inflammatory and anti-nociceptive effects on complete Freund's adjuvant-induced arthritis in Rats through paw edema, mechanical hyperalgesia, thermal hyperalgesia, ankle flexion test. These herbal medicine may be a promising therapy for the long-term treatment of rheumatoid arthritis. Bee venom inhibited cell proliferation and COX-2 espression at dendate gyrus in rats on the acetic acid-induced hyperalgesia.
On the other hand, ② effects of herbal medicine was also screened for neuropathic pain control, and some of them suppressed this pain.
③ Ultrasonic therapeutic system was developed on non-invasive meridian points.

In the second year, it is planned to elucidate the action mechanisms of these herbal medicine in vitro, and in vivo. In addition, it will be tried to make new herbal prescription for arthritis and pain control.

This work was supported by grant KRF-2001-005-F00024 from Center of Research Institute Program of the Korea Research Foundation.

(1) Title : Effects of acupuncture on alterations of immune responses evoked by
hypothalamus lesions
Primary investigator : Byung-Il Min, MD.
Department of Physiology, College of Medicine,
Kyung Hee University

The Institute has got fund from the 'Korea Science And Engineering Foundation' in September 2002 as a 3rd year government research project, which is a 3-year program. The research result of 2nd year is as follows;

This study was performed as described previously. Briefly, the hypothalamic lesion was made by the electrical conduction with concentric bipolar electrode on the lateral hypothalamic area(LHA) in the Sprague-Dawley rats. The changes of serum concentration of cytokines (IL-2, INF-?) were measured by ELISA assay. In order to evaluate the messenger RNA(mRNA) involved in acupuncture effect on the immune modulation, the level of mRNA were determined by microarray assay using the total RNAs extracted from the hypothalamus and spleen respectively. The results were as follows;

The NK cell activity of electroacupuncture(EA) group was significantly higher than those of control and sham group. The EA stimulation of ST36 acupoint enhanced splenic NK cell activity in the rats through increment of IFN- ? and IL-2 secretion. These results suggested that LHA is a major mediating center for the modulation of NK cell activity induced by EA. Subsequently, microarray assay revealed that mRNAs relating NK cell activity(protein-tyrosine-phospatase mRNA, protein-tyrosine phosphatase (SHP-1) mRNA, VCAM-1, protein-tyrosine kinase, CD94 mRNA) were expressed in the rat spleen after EA stimulation.

This Work is Supported by grant No. R01-2000-000-00170-0 form the Basic Research Program of the Korea Science and Engineering Foundation.

(2) Title : The absorption and metabolic pathways of antimalarial drugs with
stereoselectivity
Primary investigator : Kyoung-Ah Kim, PhD.
East-West Medical Research Institute, Kyung Hee University

To determine whether the absorption of the antimalarial drugs is affected by p-glycoprotein, an efflux pump, and to evaluate which metabolic pathway(s) is involved in the disposition of antimalarial drugs.
Recently, resistant to antimalarial drugs to treat malaria and treatment failure have become critical problem in endemic area of malaria including Africa and Asia. However, there has been no clear demonstration how to cause resistant to antimalarial therapy. For this, we hypothesize significant lower blood concentrations of antimalarial drugs might induce failure to treatment of malaria. So, we intend to demonstrate the metabolic pathways of antimalarial drugs and to show the absorption of antimalarial drugs from intestine is affected by p-glycoprotein, an efflux pump.

With these results, we confirm that the role of CYPs in the metabolic pathways of antimalarial drugs, and their absorption through drug transporter, p-glycoprotein. These results will show the possible mechanism(s) of drug resistance caused by reduced drug concentrations in blood, resulted from drug-drug interaction and genetic polymorphism in drug-metabolizing enzyme(s). In addition, we estimate the discrepancy between two enantiomers of drugs on the metabolism by CYPs and the absorption through p-glycoprotein for reducing the toxicity of drugs and treatment failure and for possible resistant to the treatment of antimalarial drugs. In addition, these experiment result in increase in their efficacy as antimalarial drugs to treat malaria and showing direction what kind of antimalarial drugs should be developed.

This Work is Supported by grant No. R03-2002-000-00028-0 form the Basic Research Program of the Korea Science and Engineering Foundation.

The purpose of this study is to examine the genetic polymorphism associated with rheumatoid arthritis by Sasang constitution. This study is planned to detect the susceptibility of the patients diagnosed by rheumatoid arthritis to Sasang Constitution and its association with specific genetic polymorphism. In order to analyze the susceptibility of rheumatoid arthritis to Sasang Constitution, two hundreds rheumatoid arthritis patients and two hundreds matched controls are assessed with QSCCⅡ question for Sasang constitution. Then the frequencies of patients by Sasang constitution are compared to those of control, which are statistically analyzed and adjusted by age, sex, smoking status and BMI. On the basis of the results during the first year, specific constitution which are expected to be related to rheumatoid arthratis are studied by lifestyle (smoking and overweight, e.g.) and the hazardous environment for health, in detail. Also, the genetic polymorphism(GSTs and NAT2) associated with rheumatoid arthritis according to Sasang constitution are analyzed with RFLP-PCR in patients with rheumatoid arthritis and control.
The genetic polymorphism associated with rheumatoid arthritis are used as its susceptibility marker and further as basic data to prevent the risk factors of rheumatoid arthritis

This Work is Supported by grant No. R03-2002-000-00033-0 form the Basic Research Program of the Korea Science and Engineering Foundation.

Principle investigator of the Vision 2000 Project is Professor Jin-Woo Kim, head of this institute. It was initiated in July 2000, admitted, supported and proceeded by the Kyung Hee University task force team. All research was carried out through cooperation between western medicine, oriental medicine and pharmacy. Research team received funds from university $167,000/year.

- Pain and Neuroscience Team

Title : Studies of therapeutic modalities and new drugs on the east-west medicine
Primary Investigator : Sabina Lim, OMD.
Department of Meridian and Acupoint,
College of Oriental Medicine, Kyung Hee University

During the first year, this group investigated ① the efficacy of East-West medical therapeutic model on chronic arthritis and rheumatoid arthritis, ② the efficacy of East-West medical therapeutic model on post-stroke central pain, ③ the toxicity and anti-inflammatory effects of the selected herbal medicines, ④ experiment for the role of herb and acupuncture on cellular toxicity and COX-2 expression and ⑤ analgesic and anti-inflammatory effects of medicinal herbs. ⑥ The animal model of neuropathic pain was established for the study of analgesic effects of herbal medicine and acupuncture. ⑦ this group also investigated the neuroprotective effects of Woohwangchungshimhwan (牛黃淸心丸).

On the basis of the results of the first year, five research groups was made in the second year as follows.

In group 1, The effects of herbal medicines were screened in vitro to find the potential therapeutics for the treatment of arthritis and pain. A lot of herbal medicine showed inhibitory effects of COX-2 expression and NO production on Raw 264.7 cells.
In group 2, Development of oral therapeutics will be carried out for the treatment of arthritis and pain. Several herbal medicines were also selected as effective candidate, KHM-02 markedly inhibited inflammatory and nociceptive effects on carrageenan induced paw edema in Rats and on adjuvant-induced chronic arthritis.
In group 3, Development of the therapeutic modalities will be conducted for arthritis and pain using herbal acupuncture.
In group 4, Development of the patch will be conducted for the treatment of arthritis and pain. The antiinflammatory effects of herbal medicine was tested in vitro and in vivo for patch or cream. In other words, lots of herbal medicine exhibited enzyme activities on hyaluronidase and trypsin in vitro, and acetic acid-induced hyperalgesia in vivo.

These research will be also continuing in 2003. In group 5, the toxicity test will be planning for the selected herbal medicine from group 1-4.

(2) The 2nd team - In the second year, it is planning to elucidate the action mechanism of this herbal medine in vitro, and in vivo. In addition, it will be tried to make new herbal prescription for arthritis and pain control.

(2) The 2nd year of research on 'The absorption and metabolic pathways of
antimalarial drugs with stereoselectivity' will be continued.

(3) The 2nd year of research on 'The study of the genetic polymorphism associated with rheumatoid arthritis by Sasang constitution' will be continued.

The 2nd year of research on 'Studies of therapeutic modalities and new drugs on the east-west medicine' will be continued.