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Compilation of 104 Experimental Theses on the Antitumor and Immuno-activating therapies of Oriental Medicine (한의학의 항종양 면역치료에 관한 연구 -1990년 이후 발표된 실험논문을 중심으로-)

  • Kang Yeon Yee;Kim Tai Im;Park Jong Ho;Kim Sung Hoon;Park Jong Dai;Kim Dong Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.1-24
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    • 2003
  • This study was done to compile 104 experimental theses which are related to the antitumor and immuno-activating therapies between February 1990 through February 2002. Master's and doctoral theses were dassified by schools, degrees, materials, effects, experimental methods of antitumor and immunoactivity, and results. The following results were obtained from this study : 1. Classifying the theses by the school, 34.6% were presented by Daejeon University, 29.8% by Kyung-hee University and 11.5% by Won-kwang University. Of all theses, 51.0% were aimed for the doctoral degree and 43.3% were for the master's degree. All of three universities have their own cancer centers. 2. Classifying the theses by herb materials, complex prescription accounted for 60.3%, single herb accounted for 24.8% and herbal acupuncture accounted for 14.2%. Considering the key principles of the traditional medicine, complex prescription was much more thoroughly studied than single herb prescription. The results showed that the complex prescription had both antitumor activity and immuno-activating activity, which might reflects on multi-activation mechanisms by complex components. 3. Classifying the theses by the efficacy of herbs examined, in single herb, invigorating spleen and supplementing was 35.5%, expelling toxin and cooling was 29.0%, activating blood flow and removing blood stasis was 12.9%. In herbal acupuncture, invigorating spleen and supplementing was 52.9%, expelling toxin and cooling was 29.4%. In complex prescription, pathogen-free status was 41.9%, strengthening healthy qi to eliminate pathogen was 35.5%, strengthening healthy qi was 22.6%. It is presumed that the antitumor and immunoactivating therapy based on syndrome differentiation is the best way to develop oriental oncology. 4. Classifying the theses by antitumor experiments, cytotoxic effect was 48.1 %, survival time was 48.1 % and change of tumor size was 42.3%. Survival rate was not necessarily correlated with cytotoxicity. These data reflect the characteristic, wholistic nature of the oriental medicine which is based on BRM (biological response modifier). 5. Classifying the theses by immunoactivating experiments, hemolysin titer was 51.0%, hemagglutinin titer was 46.2% and NK cell's activity was 44.2%. In the future studies, an effort to elucidate specific molecular and cellular mechanisms of cytokine production in the body would be crucial. 6. Classifying the theses according to the data in terms of antitumor activity, 50% was evaluated good, 24.0% was excellent, and 15.5% have no effect. In an evaluation of immuno-activating activity, 35.9% was excellent and 18.0% showed a little effect. The index point, as described here, may helps to use experimental data for clinical trials. Changes in index points by varying dosage implicate the importance of oriental medical theory for prescription. 7. In 167 materials, IIP (immunoactivating index point, mean : 3.12±0.07) was significantly higher than AIP(antitumor index point, mean : 2.83±0.07). These data demonstrate that the effect of herb medicine on tumor activity depends more on immunoactivating activity than antitumor activity. This further implies that the development of herbal antitumor drugs must be preceded by the mechanistic understanding of immunoactivating effect. 8. After medline-searching tumor and herb-related articles from NCBI web site, we conclude that most of the studies are primarily focused on biomolecular mechanisms and/or pathways. Henceforth, we need to define the biomolecular mechanisms and/or pathways affected by herbs or complicated prescriptions. 9. Therefore, the most important point of oriental medical oncology is to conned between experimental results and clinical trials. For the public application of herbal therapy to cancer, it is critical to present the data to mass media. 10. To develop the relationship of experimental results and clinical trials, university's cancer clinic must have a long-range plan related to the university laboratories and, at the same time, a regular consortium for this relationship is imperative. 11. After all these efforts, a new type herbal medicine for cancer therapy which is to take care of the long-term administering and safety problem must be developed. Then, it would be expected that anti-tumor herbal acupuncture can improve clinical symptoms and quality of life (QOL) for cancer patients. 12. Finally, oriental medical cancer center must be constructed in NCC (National Cancer Center) or government agency for the development of oriental medical oncology which has international competitive power.

Effects of HapKok (LI-4) , SamUmGyo (SP-6) Acupuncture on Uterine Motility and Cyclooxygenase-2 Manifestation in Rats (합곡(合谷), 삼음교(三陰交) 자침(刺鍼)이 백서(白鼠) 자궁(子宮) 운동(運動) 및 Cyclooxygenase-2 발현(發現)에 미치는 영향(影響))

  • Lee, Byung-Chul;Lee, Ho-Sub;Kim, Kyung-Sik;Lee, Geon-Mok;Na, Chang-Soo;Kim, Jung-Sang;Hwang, Woo-Jun
    • Journal of Acupuncture Research
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    • v.17 no.2
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    • pp.187-208
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    • 2000
  • By the activation of ovary hormone, many morphological changes occur in the epithelial cell lines and muscle cells in rat uterus. These two cells in uterus are important to the implantation of embryo, maintaining pregnancy and starting parturition. One important change associated with the morphological change of these two cells in uterus is the change on prostaglandin(PG) metabolism. Its presence and synthesis in endometriurn and myometrium in uterus affects estrous cycle and the start of embryo implantation in uterus. It also performs as an important modulator in parturition. So the abnormally weak expression of PG causes difficulty during labor and over-expression causes pre-term labor. PG biosynthesis starts from either free or liberated arachidonic acids from membrane phospholipid by phospholipase. Such arachidonic acids are converted into PG catalyzed by Cyclooxygenase. Under normal physiological condition, Cyclooxygenase-1(COX-1) having 602 units of amino acids controls the synthesis of PG. It acts as a local hormone regulating vasomodulation of blood flow, flexible muscle movement, increasing the blood permeability and contributing the protective role in preserving integrity of the stomach lining and Cyclooxygenase-2 (COX-2) is induced by the inflammation, pregnancy and increased its expression until parturition. Lipid metabolite like PG is located in uterine and expression of COX-2 increased with pregnancy. Increased expression of COX proteins in epithelial cells and myometrial cells are told to increase the muscle contractility in uterus but decreased right after the labor in rat. It is a good sign indicating that COX proteins are deeply related to the start of labor. Currently, Several studies report the use of PG and COX-2 inhibitor as medication for controlled abortion or to prevent pre-term labor but they entail various side-effects. Our study proposed to suggest use of acupuncture as an another mediator to control abortion or pre-term labor without causing unnecessary side-effects by those medicines. Two acupuncture sites, LI-4 & SP-6 were selected due to their known efficacy. From the immunohistochemical staining of COX-2, normal expression of COX-2 protein in nonpregnant SD rat's uterus revealed that COX-2 protein was primarily detected in the lumina epithelial lining and in the epithelial cell lining contacting the stromal cells. High resolution optical microscopic scanning revealed distinguishable staining in the myometrial mucosa. LI-4 acupuncture administered nonpregnant rat's uterus showed strong expression for COX-2 in endometrium contacted with lumina epithelial lining of rat uterus and in myometrial mucosa. Stromal cells showed more staining than untreated nonpregnant rat's uterus and stronger staining in stromal cells contacting myometrial layer compared to untreated nonpregnant rat's uterus. SP-6 acupuncture administered nonpregnant rat's uterus showed weak expression for COX-2 in myometrial layers and stromal cells but no staining was visible in lumina epitheliai and glandular epithelial cells. Few stromal cells and myometrial mucosa were positively stained for COX-2. Pregnant SD rat's uterus was also immunostained for COX-2 expression after 18 days of pregnancy. Unlike to untreated nonpregnant rat's uterus, luminal epithelial cells were not positively stained for COX-2 but stronger staining for COX-2 was revealed in stromal cells. LI-4 acupunctured SD rat's uterus had very strong expression of COX-2 in luminal epithelial lining. Few stromal cells showed stronger positive COX-2 staining and myometrial layers also showed more expression than untreated pregnant rat. SP-6 acupuncture administered pregnant SD rat's uterus showed positive expression of COX-2 in epithelial cells of luminal mucosa layer but weaker than that of LI-4 acupuncture treatment's case. However, strong positive staining was revealed in stromal mucosa and myometrial layers. Virgin SD rat's uterus motility index during LI-4 acupuncture was 66.52 % (Prob〉T = 0.0197) compared to its motility before the acupuncture treatment but the motility index was slighdy elevated up to 79.58 % (Prob〉T = 0.1175) after the acupuncture. During the SP-6 acupuncture treatment for 30 minutes, uterus motility index was 90.52 % (Prob〉T = 0.1832) showing lesser decrement but consequently reached similar motility index decreasal to 79.95 % (Prob〉T = 0.0215) after the acupuncture treatment as LI-4 showed. LI-4 acupuncture tend to be a quick treatment to reducing the uterus motility in a virgin rat but eventually both two acupuncture administration created very similar reduction of uterus motility seeing the index after the both acupunctures. The uterus movement monitored during the LI-4 acupuncture administered for 30 minutes, Pregnant SD rat showed decreased motility down to 77.90 % (Prob〉 T = 0.0076) compared to uterus motility before the acupuncture and it continuously decreased down to 71.81 %(Prob〉T = 0.0214) after the removal of needle. The statistical analysis using paired t-test showed significance difference for both two motility indexs at =0.05. SP-6 acupuncture administered to pregnant SD rat also had similar pattern of decreasing uterus motility index down to 74.70 % (Prob〉T = 0.1730) during the initial 30 minutes acupuncture administration and it was continuously lowered to 71.52 % (Prob〉T = 0.0155) after the acupuncture. The paired t-test resuit for SP-6 suggest prompt response of uterus motility index to the SP-6 acupuncture treatment but consequently reached same level of inducing the motility reduction as LI-4 at =0.05 level.

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Popliteal Artery Entrapment Syndrome -One case report - (슬와동맥 포착증후군 - 1예 보고 -)

  • Oh Jae-Yun;Lee Seock-Yeol;Lee Chol-Sae;Lee Seung-Jin
    • Journal of Chest Surgery
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    • v.39 no.10 s.267
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    • pp.791-794
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    • 2006
  • Popliteal artery entrapment syndrome is a rare disorder and lead to claudication and disturbance of blood flow from the results of an abnormal relationship of the popliteal artery to the gastrocnemius muscle, a fibrous band or the popliteus muscle in a young male population. The specific diagnosis is difficult, In most cases, surgical treatment provides a definitive diagnosis of the lesion and is necessary for the patient's recovery. A 34-years-old male was admitted complaining of claudication and pain on left leg. Ankle-brachial index, vascular sonography, CT-angiogram and MRI revealed an occlusion of proximal popliteal artery of left leg. The patient was confirmed as a popliteal artery entrapment syndrome (type IV) that the popliteal artery was entrapped by a fibrous band around the popliteus muscle in the operative fold. Completely occluded fibrotic popliteal artery was removed, and interposition with ipsilateral greater saphenous vein graft was done. After surgery, symptoms of the patient have improved.

Real-time Vessel Navigation Using Indocyanine Green Fluorescence during Robotic or Laparoscopic Gastrectomy for Gastric Cancer

  • Kim, Mina;Son, Sang-Yong;Cui, Long-Hai;Shin, Ho-Jung;Hur, Hoon;Han, Sang-Uk
    • Journal of Gastric Cancer
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    • v.17 no.2
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    • pp.145-153
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    • 2017
  • Purpose: Identification of the infrapyloric artery (IPA) type is a key component of pylorus-preserving gastrectomy. As the indocyanine green (ICG) fluorescence technique is known to help visualize blood vessels and flow during reconstruction, we speculated that this emerging technique would be helpful in identifying the IPA type. Materials and Methods: From August 2015 to February 2016, 20 patients who underwent robotic or laparoscopic gastrectomy were prospectively enrolled. After intravenous injection of approximately 3 mL of ICG (2.5 mg/mL), a near-infrared fluorescence apparatus was applied. The identified shape of the IPA was confirmed by examining the actual anatomy following infrapyloric dissection. Results: The mean interval time between ICG injection and visualization of the artery was 22.2 seconds (range, 14-30 seconds), and the mean duration of the arterial phase was 16.1 seconds (range, 9-30 seconds). The overall positive predictive value (PPV) of ICG fluorescence in identifying the IPA type was 80% (16/20). The IPA type was incorrectly predicted in four patients, all of whom were obese with a body mass index (BMI) of more than $25kg/m^2$. Conclusions: Our preliminary results indicate that intraoperative vascular imaging using the ICG fluorescence technique may be helpful for robotic or laparoscopic pylorus-preserving gastrectomy.

Effects of Single Leg Ankle Balance Exercise and Neck Stabilization Exercise on Neck Alignment, Muscle and Vascular Thickness in Adults with Forward Head Posture (한발 서기 발목 균형 운동과 목 안정화 운동이 전방 머리 자세를 가진 성인의 목 부위 정렬, 근육 및 혈관두께에 미치는 영향)

  • Sam-Won Yoon;Yun-Hwan Kim;Young-Joo Cha
    • Journal of The Korean Society of Integrative Medicine
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    • v.12 no.3
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    • pp.71-81
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    • 2024
  • Purpose : In this study, we compared the effects of ankle, McKenzie, and cervical stabilization exercises in individuals with a forward head posture. Outcome measures investigated included the neck disability index, craniovertebral angle (CVA), cranial rotation angle (CRA), and thickness of the longus colli muscle (LC) and carotid artery (CA) post-intervention. Methods : The study included 20 individuals with a forward head posture, who were assigned to an experimental group (EG, individuals performed ankle exercises) or control group (CG, individuals performed McKenzie and cervical stabilization exercises). The EG intervention was specifically designed to enhance proprioception in the ankle joint and strengthen the ankle muscles to improve overall stability and function. In contrast, CG interventions aimed to improve neck muscle balance and cervical spine alignment. Paired t-tests were used to analyze intragroup changes and independent t-tests to determine intergroup differences pre-and post-intervention. The significance level for all statistical tests was set at α=.05. Results : We observed significant post-intervention improvements in both groups, specifically, in the CVA, CRA, and LC and CA thickness (p<.05). These results indicate that ankle, McKenzie, and cervical stabilization exercises were useful for neck posture correction, improved muscle balance, and enhanced blood flow to the neck. Conclusion : This study underscores the positive effects of ankle, McKenzie, and cervical stabilization exercises in individuals with a forward head posture. Our study highlights the benefits of these exercises for posture correction and overall neck health and the clinical effectiveness and usefulness of ankle exercises as an important intervention to improve forward head posture.

Impact of Pulmonary Vascular Compliance on the Duration of Pleural Effusion Duration after Extracardiac Fontan Procedure (수술 전 폐혈관 유순도가 심장 외 도판을 이용한 Fontan 수술 후 늑막 삼출 기간에 미치는 영향)

  • Yun Tae-Jin;Im Yu-Mi;Song Kwang-Jae;Jung Sung-Ho;Park Jeong-Jun;Seo Dong-Man;Lee Moo-Song
    • Journal of Chest Surgery
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    • v.39 no.8 s.265
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    • pp.579-587
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    • 2006
  • Background: Preoperative risk analysis for Fontan candidates is still less than optimal in that patients with apparently low risks may have poor surgical outcome; prolonged pleural drainage, protein losing enteropathy, pulmonary thromboembolism and death. We hypothesized that low pulmonary vascular compliance (PVC) is a risk factor for prolonged pleural effusion drainage after the Fontan operation. Material and Method: A retrospective review of 96 consecutive patients who underwent the Extracardiac Fontan procedures (median age: 3.9 years) was performed. Fontan risk score (FRS) was calculated from 12 categorized preoperative anatomic and physiologic variables. PVC $(mm^2/m^2{\cdot}mmHg)$ was defined as pulmonary artery index $(mm^2/m^2)$ divided by total pulmonary resistance $(W.U{\cdot}/m^2)$ and pulmonary blood flow $(L/min/m^2)$ based on the electrical circuit analogue of the pulmonary circulation. Chest tube indwelling time was log-transformed (log indwelling time, LIT) to fit normal distribution, and the relationship between preoperative predictors and LIT was analyzed by multiple linear regression. Result: Preoperative PVC, chest tube indwelling time and LIT ranged from 6 to 94.8 $mm^2/mmHg/m^2$ (median: 24.8), 3 to 268 days (median: 20 days), and 1.1 to 5.6 (mean: 2.9, standard deviation: 0.8), respectively. FRS, PVC, cardiopulmonary bypass time (CPB) and central venous pressure at postoperative 12 hours were correlated with LIT by univariable analyses. By multiple linear regression, PVC (p=0.0018) and CPB (p=0.0024) independently predicted LIT, explaining 21.7% of the variation. The regression equation was LIT=2.74-0.0158 PVC+0.00658 CPB. Conclusion: Low pulmonary vascular compliance is an important risk factor for prolonged pleural effusion drainage after the extracardiac Fontan procedure.

Active hexose correlated compound potentiates the antitumor effects of low-dose 5-fluorouracil through modulation of immune function in hepatoma 22 tumor-bearing mice

  • Cao, Zhiyun;Chen, Xuzheng;Lan, Lan;Zhang, Zhideng;Du, Jian;Liao, Lianming
    • Nutrition Research and Practice
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    • v.9 no.2
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    • pp.129-136
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    • 2015
  • BACKGROUND/OBJECTIVES: A variety of immunomodulators can improve the efficacy of low-dose chemotherapeutics. Active hexose correlated compound (AHCC), a mushroom mycelia extract, has been shown to be a strong immunomodulator. Whether AHCC could enhance the antitumor effect of low-dose 5-fluorouracil (5-FU) via regulation of host immunity is unknown. MATERIALS/METHODS: In the current study Hepatoma 22 (H22) tumor-bearing mice were treated with PBS, 5-FU ($10mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.p), or AHCC ($360mg{\cdot}kg^{-1}{\cdot}d^{-1}$, i.g) plus 5-FU, respectively, for 5 d. $CD^{3+}$, $CD^{4+}$, $CD^{8+}$, and NK in peripheral blood were detected by flow cytometry. ALT, AST, BUN, and Cr levels were measured by biochemical assay. IL-2 and $TNF{\alpha}$ in serum were measured using the RIA kit and apoptosis of tumor was detected by TUNEL staining. Bax, Bcl-2, and TS protein levels were measured by immunohistochemical staining and mRNA level was evaluated by RT-PCR. RESULTS: Diet consumption and body weight showed that AHCC had no apparent toxicity. AHCC could reverse liver injury and myelosuppression induced by 5-FU (P < 0.05). Compared to mice treated with 5-FU, mice treated with AHCC plus 5-FU had higher thymus index, percentages of $CD^{3+}$, $CD^{4+}$, and NK cells (P < 0.01), and ratio of $CD^{4+}$/$CD^{8+}$ (P < 0.01) in peripheral blood. Radioimmunoassay showed that mice treated with AHCC plus 5-FU had the highest serum levels of IL-2 and $TNF{\alpha}$ compared with the vehicle group and 5-FU group. More importantly, the combination of AHCC and 5-FU produced a more potent antitumor effect (P < 0.05) and caused more severe apoptosis in tumor tissue (P < 0.05) compared with the 5-FU group. In addition, the combination of AHCC and 5-FU further up-regulated the expression of Bcl-2 associated X protein (Bax) (P < 0.01), while it down-regulated the expression of B cell lymphoma 2 (Bcl-2) (P < 0.01). CONCLUSIONS: These results support the claim that AHCC might be beneficial for cancer patients receiving chemotherapy.

Effect of Propranolol on Portal Vein Pressure in Patients with Chronic Liver Disease: Evaluation by Perrectal Portal Scintigraphy (만성 간질환에서 Propranolol의 문맥압 감소 효과: 경직장 문맥 신티그라피를 이용한 평가)

  • Rho, Young-Ho;Han, Shin;Kim, Hak-Su;Yoon, Su-Jin;Kim, Yun-Kwon;Kim, So-Yon;Kim, Yeong-Jung;Cho, Min-Koo;Park, Byong-Yik;Lee, Gwon-Jun
    • The Korean Journal of Nuclear Medicine
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    • v.33 no.4
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    • pp.388-397
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    • 1999
  • Purpose: Propranolol is known to decrease portal pressure by reducing blood flow of portal vein. Perrectal portal scintigraphy with Tc-99m pertechnetate has been introduced to evaluate the portal circulation and early diagnosis of liver cirrhosis. We evaluated the effects of propranolol on portal circulation by using per-rectal portal scintigraphy. Materials and Methods: We analyzed the portal hemodynamics by per-rectal portal scintigraphy in 51 patients with liver cirrhosis, 10 chronic hepatitis and 10 normal subjects. 38 patients with cirrhosis underwent per-rectal portal scintigraphy before and after propranolol medication. Perrectal portal scintigraphy was performed after per-rectal administration of 370 MBq of Tc-99m pertechnetate. The shunt index was calculated as the ratio, expressed as a percentage of heart radioactivity to the sum of heart and liver radioactivity during the first 30 seconds. Results: The shunt index in 40 patients with cirrhosis ($59.8{\pm}27.2%$) was significantly higher than that of normal control ($5.0{\pm}1.2%$. p<0.01) and chronic hepatitis ($11.4{\pm}3.5%$, p<0.01). Shunt index was significantly different according to Child's classification and the degree of esophageal varix (p<0.01). After propranolol medication, shunt index was significantly decreased from $59.9{\pm}27.3%$ to $51.3{\pm}15.3%$ (p<0.01) in 38 patients with liver cirrhosis. There was no significant difference of the amount of shunt index reduction after propranolol according to Childs' classification and the degree of esophgageal varix. Conclusion : The effect of propranolol on portal circulation was demonstrated as decreasing shunt index on per-rectal portal scintigraphy in patients with liver cirrhosis. Per-rectal portal scintigraphy may be useful to evaluate the portal circulation and to predict the effect of propranolol in patients with liver cirrhosis.

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Effects of Omahwan(OMH) on CD4+, CD8+ T cell and Immune Organ Index in Rat (오마환(烏麻丸)이 백서(白鼠)의 혈액내(血液內) CD4+, CD8+ T cell 및 면역기관(免疫器官) 장기지수(臟器指數)에 미치는 영향(影響))

  • Lee Song-Shil;Lee Sang-Jae;Kim Kwang-Ho
    • Journal of Society of Preventive Korean Medicine
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    • v.5 no.1
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    • pp.76-89
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    • 2001
  • OMH which is known for its properties of recruiting vitality, is composed of Polygonum multiflorum Thunb. and Sesamum indicum DC.. This formula is known to possess the properties of recruiting vitality, blackening white hair and expanding life span. 16-week-old SD-Rats were treated with OMH for 16 days. After 24 hours, the rats were treated with MTX(Mthotrexate is oral administrated for 4 days(1mg/kg/day), in order to lower immunity. Then, These rats were classified in to groups, the N-16 group(not specially tested), the Control group(MTX), the OMH-L group(2.5% OMH+MTX)&the OMH-H group(10% OMH+MTX) and 6 rats were assigned to each group. After 18 hours from MTX treatment the organ index of the rats from each group Thymus and Spleen were measured. The percentage of CD+4, CD8+ T cell were measured and compared by flow cytometer. 1) Rats from the OHM-L&OMH-H group showed higher organ indexes of the Thymus and Spleen compared to the rats from the Control Group. This proves that OMH possesses the properties to mitigate degenerations of immunity($F_{thymus}=20.162,\;F_{spleen}=5.882$, ANDVA, p<0.05). 2) The rats from the two OMH groups showed higher rates of CD4+ T cell counts compared to the control group(F=26.906, ANOVA, p<0.05). CD8+ T cell showed lower rates compared to the Control group, but showed no differences within the two OMH groups(F=1.254, ANOYA, p>0.05). CD4+/CD8+ showed higher rates in the two OMH groups compared to the control group which can be thought as a proof that OMH prevents depression of immune response(F=10.554, ANOVA, p<0.05). In this test 16 week-old rats were used, which can be considered as the middle and prime age of the human being. These rats were treated with OMH which ended up showing properties of mitigating degeneration of immune responses and maintaining T-cell rates within the blood. It was possible to study that OMH possesses the properties to increase immune responses.

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Effects of Diltiazem on Isoproterenol-induced Myocardial Cell Wounding in the Rabbit (Isoproterenol 투여로 유발된 심근세포 손상에 미치는 diltiazem의 영향)

  • Kim, Hyun;Chang, Dae-Yung;Rah, Bpng-Jin;Kim, Ho-Dirk
    • Applied Microscopy
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    • v.27 no.2
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    • pp.121-130
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    • 1997
  • It has been demonstrated that majority of cells in the mammalian body such as myocytes and epithelial cells of skin and intestine respond to mechanical force or environmental factors and exhibit partial disruption of cell membrane, i. e., cell wounding, even in a physiological condition. Myocardial cells are rather apt to be wounded than other cells since they are definitely exposed to mechanical stress by contraction-relaxation and blood flow. However, the mechanism how myocardial cells protect themselves against cell wounding is not yet clarified. On this background, the present study was performed to elucidate whether albumin leakage is related to cell wounding and to assess whether diltiazem, a potent calcium channel blocker, is beneficial in isoproterenol-induced cell wounding in the heart. Hearts isolated from New Zealand White rabbits ($1.5\sim2.0kg$ body weight, n=20) were perfused with Tyrode solution by Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to bolus administration of isoproterenol and diltiazem as following order: $1.6{\mu}M$ isoproterenol at zero min (the beginning point): $16{\mu}M$ diltiazem at 20min; $1.6{\mu}M$ isoproterenol at 25min; $16{\mu}M$ isoproterenol at 45 min; $160{\mu}M$ diltiazem at 65 min; $16{\mu}M$ isoproterenol at 70 min. During all experiments, the left ventricular function was recorded, albumin leakage in the coronary effluents was analyzed by electrophoresis and Western blot, and myocardial cell membranes were examined by conventional transmission electron microscopy. Data were analyzed by t-test and linear regression test. Isoproterenol significantly increased the inotropic and chronotropic contractions, coronary flow, and frequency of arrhythmia, however, diltiazem did not influence on hemodynamics except decrease in the frequency of arrhythmia and a slight decrease in contractility. Isoproterenol also resulted partial disruption of myocardial cell membrane and inclose in albumin leakage, while diltiazem pretreatment showed number of electron-dense plaques in the cell membrane and a tendency of decrease in albumin leakage. These results indicate that albumin leakage may be an indirect index of cell wounding in the heart and diltiazem nay be beneficial to protect myocardial cells against isoproterenol-induced cell wounding. It is likely that diltiazem promotes resealing process of the cell membrane.

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