• Title/Summary/Keyword: internal medicine

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Expression of the Peroxisome-proliferator-activated $Receptor-{\gamma}$ in Human Gastric Cancer (위암에서 $PPAR-{\gamma}$ 발현의 임상적 의의)

  • Cho, Dong-Hui;Kang, Sung-Gu;Park, Sang-Su;Yoon, Jin;Kim, Il-Myung;Yoon, Seong-Min;Lee, Yun-Kyung;Lee, Yong-Jik;Yang, Dae-Hyun;Cho, Ik-Hang;Shin, Dong-Gue
    • Journal of Gastric Cancer
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    • v.6 no.4
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    • pp.250-256
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    • 2006
  • Purpose: Recently, interest in peroxisome-proliferator-activated receptors (PPAR) has increased, although clinical studies of the effect of $PPAR-{\gamma}$ expression on gastric cancer have not been reported yet. In this study, we investigated the role of $PPAR-{\gamma}$ expression in gastric cancer patients. Materials and Methods: One hundred twenty-eight (128) samples of both gastric cancer and normal tissues were obtained from 128 patients who had undergone at a curative gastrectomy at Seoul Medical Center from Jan. 2001 to Dec. 2005. $PPAR-{\gamma}$ expression was determined by using immunohistochemical staining, and the results were analyzed. The statistical analysis was based on clinicopathological findings and the differences in survival rates. Results: The mean age of the patients was 6n, and the male : female ratio was 1.9 : 1. $PPAR-{\gamma}$ expression was significantly higher in cancer tissues than in normal tissue (81.3% vs. 57.0%, p<0.001). There was insignificant difference between well and moderately differentiated types and poorly differentiated types in terms of the expression of $PPAR-{\gamma}$ (87.0% vs. 74.6%, P=0.074). In the univariate analysis the survival rate was significantly increased when $PPAR-{\gamma}$ was expressed in normal tissue (P=0.003). In the multivariate analysis, only the UICC TNM staging had significance related to the survival rate. Conclusion: The rate of $PPAR-{\gamma}$ expression was higher in cancer tissue than it was in normal tissue from gastric cancer patients. In the univariate analysis, $PPAR-{\gamma}$ expression in normal tissue had significance with respect to survival, but the multivariate analysis showed no such significance. Thus, we should further evaluate more cases to determine whether or not such a significance exists.

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The Immunological Effect of Mistletoe Extract on Gastric Cancer Patients (미슬토 추출물(Mistletoe Extract)이 위암환자의 수술 후 면역기능에 미치는 효과)

  • Yang, Sung-Woo;Shin, Dong-Gue;Kim, Il-Myung;Yoon, Seong-Min;Lee, Yong-Jik;Heo, Su-Hak;Kim, Tae-Hee
    • Journal of Gastric Cancer
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    • v.7 no.3
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    • pp.167-173
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    • 2007
  • Purpose: Mistletoe (Viscum album L.) extract is one of the most widely used agents in alternative cancer therapeutic regimens in Europe. This study was conducted to determine the effect of mistletoe extract on immune function in gastric cancer patients. Materials and Methods: Ten patients that had undergone a curative gastrectomy were enrolled in the prospective study. ABNOBAviscum $Q^{(R)}$ was injected subcutaneously three times a week from postoperative-day 7 to week 16 with an increasing dose. All of the patients simultaneously received chemotheraphy with mitomycin, oral 5-FU and a cisplatin regimen. The WBC count, differential count, lymphocyte/WBC ratio and the level of cytokines (IL-$1{\beta}$, IL-2, IL-6, IFN-$\gamma$, TNF-$\alpha$) were checked in the peripheral blood preoperatively, at postoperative week 8 and at postoperative week 16. Results: The WBC and neutrophil counts significantly decreased after treatment on week 8 and week 16 (P=0.001), but the total eosinophil count was slightly increased (P=0.15). The total lymphocyte count also decreased during treatment but the lymphocyte/WBC ratio was slightly increased without statistical significance (P=0.91). The cytokine levels did not significantly change during treatment. Conclusion: It is somewhat difficult to determine the direct effect of mistletoe therapy on immune function as the effect may be compromised by the concurrent chemotherapy. It can be assumed that the slightly increased lymphocyte/WBC ratio and eosinophil count may be a result of the immunomodulatory effect of the mistletoe extract.

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Influences of Histamine on Permeability across Blood-brain Barrier (혈액-뇌장벽 투과성에 대한 히스타민의 영향)

  • Kim, Kee-Jin;Shin, Dong-Hoon
    • The Korean Journal of Physiology
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    • v.2 no.2
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    • pp.33-43
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    • 1968
  • Histamine, 0.5 mg as histamine base in 4 ml of normal saline solution, was injected into rabbits anesthetized with nembutal and the mean blood pressure was kept in the range of $52{\sim}80\;mmHg$ for over one hour by supplemental additions. Following the injection of the test substances, 300 mg of urea and 200 mg of antipyrine intravenously, serial blood samples were obtained from the femoral artery and the internal jugular vein at $0.5{\sim}3$ minutes interval. The decreasing patterns in the concentrations of arterial and venous blood plasma samples were compared with each other. The ratio of the concentration of brain tissue to that of the final arterial plasma was also studied. By these measures the degrees of penetration of the test substances in the brain in the control and in the histamine treated rabbits were observed. The concentrations of antipyrine and urea in the arterial blood plasma were decreasing exponentially with respect to the time elapsed. The venous concentrations were anticipated to increase initially and to cross the arterial concentration curve in the point of equlibrium between the plasma and the tissue. On the contrary to the expectation venous concentration also revealed the decreasing tendency similar to that of arterial plasma. The similarity between these two curves, arterial and venous, would be atributable to the fact that the cerebral blood flow rate was large enough and the rising phase in the venous concentration curve was instantly over before serial blood samples were taken. Inspite of some similarity in the decreasing tedency in both concentration curves there were appreciable discrepancies between the arterial and venous plasma which would reflect the situation far from the equlibria among several compartments in the brain. Changes in plasma potassium levels caused by the injection of histamine or bleeding were observed, too. Using 8 rabbits as the control and 12 rabbits for the histamine treated group following results were obtained: 1. Both of the concentration curves, arterial and venous, declined rapidly at_first and slowly later on and approached same equilibrium concentration with the passage of time after a single injection. The time at which attained the same concentration was $2.0{\pm}0.54\;min.$ in the control and $4.3{\pm}1.92\;min.$ in the histamine treated group with respect to antipyrine. On the other hand in the case of urea they were $2.4{\pm}0.59\;min.$ in the control and $4.4{\pm}1.31\;min.$ in the histamine group, respectively. In the histamine treated group enlarged spaces for distribution of test substances were postulated. 2. The concentration of antipyrine in the brain tissue water revealed no significant differences between the control and experimental groups, showing $212{\pm}40.2\;mg/l$ in the control and $206{\pm}64.1\;mg/l$ in the histamine treated group. On the other hand urea revealed higher value in the histamine treated group than in the control, showing an enhanced penetration of urea into the tissue after injection of histamine. Urea concentration in the brain water was $32.3{\pm}3.36\;mg%$ in the control and $39.2{\pm}4.25\;mg%$ in the histamine treated group. 3. The distribution ratio of antipyrine in the brain tissue was very close to unity in the histamine treated animals as well as in the control. 4. The average of the distribution ratio of urea in the control animals was 0.77 and it showed the presence of blood-brain barrier with regard to urea. However in the histamine treated animals the distribution ratios climbed up to 0.86 and they were closer to unity than in the control animals. Out of 12 cases 5 were greater than 0.9 and 8 exceeded 0.85. It appeared that histamine enhanced the penetration of urea through the barrier. 5. Histamine injection and or hemorrhage caused an elevation of the concentration of potassium in plasma. In the event that histamine and hemorrhage were applied together the elevation of potassium exceed the elevation seen at the histamine alone. There was no evidence that the leakage of potassium from the brain tissue was dominant in comparison with the general leakage from the whole body.

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Occlusive Complications after Lower Limb Arterial Bypass Surgery (하지동맥 재건술 후 폐쇄성 합병증에 대한 임상적 고찰)

  • Kim Jong Won;Chung Sung Woon
    • Journal of Chest Surgery
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    • v.38 no.2 s.247
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    • pp.152-156
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    • 2005
  • Background: Occlusive complications after arterial revascularization are difficult to treat and have high recurrence rate. This study was performed to establish an effective treatment modality and to evaluate the factors affecting the occlusive complications by analysis of clinical data. Material and Method: During the period of 5 years. 33 patients (55 reoperations) were studied at the Department of Thoracic and Cardiovascular Surgery, Pusan National University Hospital following 173 arterial revascularization surgeries. The clinical characteristics, operating methods, the time intervals of reoperation, used graft, and the results of treatment were evaluated retrospectively. Result: All the patients were men except one and the mean age was 63.5 years old. The mean time internal from first operation to reoperation was 11.9 months. The cause of arterial occlusive diseases were 28 atherosclerosis and 5 Burger's diseases, Associated diseases were Hypertension $(57.6\%)$, Diabetes mellitus $(33.3\%)$, heart failure $(18.2\%)$, and so on. The mean rate of reoperation was 1.67 times and the most common type of first operation was femoro-popliteal bypass grafting $(57.6\%)$. The graft that used revascularization surgery were 25 cases of PTFE and 6 case were Dacron. There was no statistical difference between two groups. The kinds of reoperations were thrombectomy in 20 cases, angioplasty 18 cases, re-bypass surgery in 13 cases, and lumbar sympathectomy in 4 cases. The results of reoperation were 15 cases of functional recovery, 7 cases of limb salvage, 5 cases of above-knee amputation. 3 cases of below-knee amputation and 3 deaths. Conclusion: The main cause of occlusive complications are occlusion of inflow or outflow artery. Treatments were different according to the first operation methods and graft used. The most frequent time of reoperation was within one year after the first operation. We believe that graft surveillance especially during the first year is very important factor in observing the patient. We can look forward to improving limb salvage rate to perform additional treatment such as radiological interventions and lumbar sympathectomy.

Radiation Therapy for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis (간문맥종양혈전증을 동반한 간세포암에서의 방사선 치료)

  • Park, Seung-Gyu;Kim, Jin-Hee;Byun, Sang-Jun;Kim, Ok-Bae;Hwang, Jae-Seok;Oh, Young-Kee;Choi, Tae-Jin
    • Radiation Oncology Journal
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    • v.29 no.1
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    • pp.36-43
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    • 2011
  • Purpose: To evaluate the effectiveness of radiation therapy (RT) for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and to analyze the prognostic factors. Materials and Methods: From December 2004 to April 2009, 70 patients who had HCC with PVTT were treated with RT at Keimyung University Dongsan Medical Center. Nineteen patients whose total dose was below 30 Gy and one patient who underwent liver transplantation were excluded. The remaining 50 patients (45 males, 5 females; median age 55 years) were analyzed. According to the LCSGJ TNM stage, there were 27 patients (54.0%) with stage III and 23 (46.0%) with stage IV. Total dose of 30~54 Gy was administered (median 45). Thirty patients (60.0%) were treated with concurrent chemoradiation therapy (CCRT). The median follow-up duration was from 13.5 months (range, 3 to 70 months). Results: The median survival time from the start of RT was 9 months. One-year and 2-year overall survival rates were 24.9% and 11.2%, respectively. At the follow-up time, three patients (6.0%) displayed no evidence of disease. Seven patients (14.0%) were alive with disease, and 40 (80.0%) patients had expired due to disease progression. CCRT was associated with worse survival than RT alone (p=0.034), Response to RT (p=0.037), CLIP stage (p=0.017), and TNM stage (p=0.041) were statistically significant prognostic factors. There was no radiation-induced liver disease. Conclusion: RT is an effective and safe modality for HCC with PVTT. Further studies such as prospective randomized trials are needed to confirm the role of RT for HCC with PVTT.

Therapeutic Endoscopy-related Gastrointestinal Bleeding and Thromboembolic Events in Patients Using Warfarin or Direct Oral Anticoagulant (와파린 및 새로운 경구용 항응고제를 복용하는 환자에서의 치료 내시경과 관련된 위장관 출혈 및 혈전색전증의 위험)

  • Na, Hee Kyong
    • The Korean Journal of Gastroenterology
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    • v.72 no.5
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    • pp.271-273
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    • 2018
  • 내시경 시술 전 일시적으로 항응고제를 중단하는 것은 위장관 출혈의 위험과 혈전색전증의 위험 사이에 적절한 균형을 잡기 어렵기 때문에 논란의 여지가 많다. 와파린은 새로운 경구용 항응고제(direct oral anticoagulant agent, DOAC)보다 임상의에게 더 친숙하고, 효과를 쉽고 빠르게 전환시킬 수 있다는 장점이 있지만 복잡한 약역동학 특징과 좁은 치료적 범위 때문에 관리가 어렵다. 반면, DOAC는 약물의 모니터링 및 용량 조절 없이 정해진 용량으로 처방이 가능하며, 빠르게 작용하고, 반감기가 짧아 관리가 쉽지만 해독제가 없다는 단점이 있다. 이전 연구들에서 DOAC를 복용한 환자들은 와파린을 복용한 환자들보다 시술과 관련되지 않은 위장관 출혈의 위험이 높았다고 보고한 바 있다. 하지만 시술과 관련된 위장관 출혈 위험에 대하여는 알려진 바가 없는 실정이다. 미국이나 유럽 내시경 가이드라인들에서는 저위험 내시경 시술을 받는 환자들에서는 와파린과 DOAC를 유지하도록 권고하고 있으며, 고위험 시술의 경우에는 와파린를 사용하는 환자들에서 헤파린 교량 요법(heparin bridging)을 시행하도록 권고하고 있다. 임상적으로 DOAC를 사용하는 환자들 또한 혈전색전증을 예방하기 위하여 헤파린 교량 요법을 시행해볼 수 있는데, 와파린 및 DOAC의 헤파린 교량 요법과 관련된 출혈 및 혈전색전증 위험의 차이 또한 명확하지 않다. 따라서 저자들은 1) 와파린과 DOAC 치료를 받는 환자들에서의 출혈, 혈전색전증 및 사망의 위험을 비교하고자 하였으며, 2) 13종류의 고위험 내시경 시술 중에서 시술별 위험을 비교하고, 3) 헤파린 교량 요법이 합병증의 발생을 증가시키지 않는지 확인하고자 본 연구를 진행하였다. 일본 대규모 국가 입원 환자 데이터베이스를 이용하여 2014년 4월부터 2015년 5월까지 시술 전 와파린 또는 DOAC(rivaroxaban, apixaban, dabigatran, edoxaban)를 복용하고, 13종류의 고위험 내시경 시술을 시행받은 20세 이상의 성인 환자 총 16,977명을 확인하였다. 고위험 시술은 용종 절제술, 내시경 점막절제술, 내시경 점막하박리술, 협착 부위의 풍선확장술, 내시경 지혈술, 내시경 정맥결찰술, 내시경 주사 경화요법, 내시경 괄약근절개술, 내시경 초음파 유도하 미세침 흡인 검사, 경피적 위루술을 포함하였다. 일대일 성향 점수 매칭 분석(propensity score matching, 나이, 성별, 체질량 지수, 기저 질환, 병원의 규모, 시술의 종류, 약물의 종류를 매칭)을 시행하여 와파린군과 DOAC군에서 시술 위장관 출혈 및 혈전색전증, 사망의 발생을 비교하였다. 또한 경구항혈전제와 헤파린 교량 치료 시행 유무에 따라, DOAC 단독군, 와파린 단독군, DOAC와 헤파린 교량 요법군, 와파린과 헤파린 교량요법군으로 나누어, 하위군(subgroup) 분석을 시행하였다. 5,046쌍이 성향 점수 매칭 분석에 포함되었으며, 와파린군에서 DOAC군보다 통계적으로 의미 있게 위장관 출혈의 비율이 높았다(12.0% vs. 9.9% p=0.02). 혈전색전증 발생률(5.4% vs. 4.7%)과 입원중 사망률(5.4% vs. 4.7%)은 양 군에서 의미 있는 차이는 없었다. DOAC 종류별로 나누어 하위군 분석을 시행하였을 때, 와파린군은 rivaroxaban군에 비하여 위장관 출혈의 비율이 높았으며, rivaroxaban군, dabigatran군에 비하여 혈전색전증의 비율이 높았고, 입원 중 사망률에서는 의미 있는 차이는 없었다. 내시경 시술의 종류로 보정하였을 때 위장관 출혈 및 혈전색전증, 사망률은 DOAC 단독으로 치료한 환자에서보다 와파린과 헤파린 교량 요법(bridging) 또는 DOAC과 헤파린 교량 요법을 시행한 환자에서 높았다. 시술 종류 중에서는 위루관 삽입술에 비하여 내시경 점막하박리술, 내시경 점막절제술 및 내시경 정맥류결찰술, 내시경 주사경화요법을 시행한 환자에서 위장관 출혈의 위험이 가장 높았으며, 하부 내시경 점막절제술, 하부 용종 절제술, 내시경적 유두괄약근절제술 또는 내시경 초음파 유도하 미세침 흡인 검사는 중등도 위험을 보였다.

Dietary behaviors and nutritional status according to the bone mineral density status among adult female North Korean refugees in South Korea (한국에 거주하고 있는 북한이탈주민 여성의 골밀도에 따른 식생활과 영양상태)

  • Kim, Su-Hyeon;Lee, Soo-Kyung;Kim, Sin-Gon
    • Journal of Nutrition and Health
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    • v.52 no.5
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    • pp.449-464
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    • 2019
  • Purpose: North Koreans could be at higher risk for their bone health because of previous periods of severe famine and the continuing low availability of food. This study determined the bone mineral density (BMD) status and its relationship with dietary behaviors and nutrient intake of North Korean refugees (NKR) in South Korea (SK). Methods: This cross-sectional study analyzed 110 female NKR from a NORNS cohort of a non-probability sample of adult NKR in Seoul. BMD examined by DEXA was used to divide participants into the normal group (NG) and the non-normal group (NNG) according to the WHO guideline. A self-administered questionnaire included questions on age, the socioeconomic situation in North Korea (NK) and SK, the food security in NK and SK, and the health behaviors, dietary behaviors, and food frequency questionnaire administered in SK. A one-day 24-hr recall was conducted and the results were analyzed by using CanPro. SPSS was used to analyze whether BMD and related dietary behaviors and nutrient intakes differed according to the groups. Results: NG (62.7%) was significantly younger and had a lower abdominal obesity score than NNG (p < 0.001). While 14.5% of NG reported experiencing menopause, all of NNG reported experiencing menopause. The NG more frequently consumed the dairy group of foods (9.6 times a week) than did the NNG (4.8 times a week) after the statistics were adjusted for age (p < 0.007). The NG consumed significantly more animal protein and animal calcium than did the NNG (p = 0.01, p = 0.009, respectively). Calcium intake was low with 49.3% of NG, and 78.0% of the NNG reported consuming calcium lower than the estimated average requirement. Only calcium showed an index of nutrient quality lower than one in both groups. Conclusion: These results showed that NKR women and possibly all North Korean women are at high risk for bone health and they consumed low levels of bone-related nutrients, and this should be considered for the nutrition policy for NKR and North Korea.

Shoulder Replacement Arthroplasty after Failed Proximal Humerus Fracture (상완골 근위부 골절의 치료 실패 후 견관절 치환술)

  • Park, Jin-Young;Seo, Beom-Ho;Lee, Seung-Jun
    • Journal of the Korean Orthopaedic Association
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    • v.54 no.2
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    • pp.110-119
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    • 2019
  • Proximal humerus fracture can be defined as a fracture that occurs in the surgical neck or proximal part of the humerus. Despite the appropriate treatment, however, various complications and sequelae can occur, and the treatment is quite difficult often requiring surgical treatment, such as a shoulder replacement. The classification of sequelae after a proximal humerus fracture is most commonly used by Boileau and can be divided into two categories and four types. Category I is an intracapsular impacted fracture that is not accompanied by important distortions between the tuberosities and humeral head. An anatomic prosthesis can be used without greater tuberosity osteotomy. In category I, there are type 1 with cephalic collapse or necrosis with minimal tuberosity malunion and type 2 related to locked dislocation or fracture-dislocation. Category II is an extracapsular dis-impacted fracture with gross distortion between the tuberosities and the humeral head. To perform an anatomic prosthesis, a tuberosity osteotomy should be performed. In category II, there are type 3 with nonunion of the surgical neck and type 4 with severe tuberosity malunion. In type 1, non-constrained arthroplasty (NCA) without a tuberosity osteotomy should be considered as a treatment. On the other hand, reverse shoulder arthroplasty (RSA) should be considered if types 1C or 1D accompanied by valgus or varus deformity or severe fatty degeneration of the rotator cuff. In general, the results are satisfactory when NCA is performed in type 2 sequelae. On the other hand, RSA can be considered as an option when there is no bony defect of the glenoid and a defect of the rotator cuff is accompanied. In type 3, it would be effective to perform internal fixation with a bone wedge graft rather than shoulder replacement arthroplasty. Recent reports on the results of RSA are also increasing. On the other hand, recent reports suggest that good results are obtained with RSA in type 3. In type 4, RSA should be considered as a first option.

Therapeutic Angiogenesis by Intramyocardial Injection of pCK-VEGF165 in Pigs (돼지에서 pCK-VEGF165의 심근내 주입에 의한 치료적 혈관조성)

  • Choi Jae-Sung;Han Woong;Kim Dong Sik;Park Jin Sik;Lee Jong Jin;Lee Dong Soo;Kim Ki-Bong
    • Journal of Chest Surgery
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    • v.38 no.5 s.250
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    • pp.323-334
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    • 2005
  • Background: Gene therapy is a new and promising option for the treatment of severe myocardial ischemia by therapeutic angiogenesis. The goal of this study was to elucidate the efficacy of therapeutic angiogenesis by using VEGF165 in large animals. Material and Method: Twenty-one pigs that underwent ligation of the distal left anterior descending coronary artery were randomly allocated to one of two treatments: intramyocardial injection of pCK-VEGF (VEGF) or intramyocardial injection of pCK-Null (Control). Injections were administered 30 days after ligation. Seven pigs died during the trial, but eight pigs from VEGF and six from Control survived. Echo-cardiography was performed on day 0 (preoperative) and on days 30 and 60 following coronary ligation. Gated myocardial single photon emission computed tomography imaging (SPECT) with $^{99m}Tc-labeled$ sestamibi was performed on days 30 and 60. Myocardial perfusion was assessed from the uptake of $^{99m}Tc-labeled$ sestamibi at rest. Global and regional myocardial function as well as post-infarction left ventricular remodeling were assessed from segmental wall thickening; left ventricular ejection fraction (EF); end systolic volume (ESV); and end diastolic volume (EDV) using gated SPECT and echocardiography. Myocardium of the ischemic border zone into which pCK plasmid vector had been injected was also sampled to assess micro-capillary density. Result: Micro-capillary density was significantly higher in the VEGF than in Control ($386\pm110/mm^{2}\;vs.\;291\pm127/mm^{2};\;p<0.001$). Segmental perfusion increased significantly from day 30 to day 60 after intramyocardial injection of plasmid vector in VEGF ($48.4\pm15.2\%\;vs.\;53.8\pm19.6\%;\;p<0.001$), while no significant change was observed in the Control ($45.1\pm17.0\%\;vs.\;43.4\pm17.7\%;\;p=0.186$). This resulted in a significant difference in the percentage changes between the two groups ($11.4\pm27.0\%\;increase\;vs.\;2.7\pm19.0\%\;decrease;\;p=0.003$). Segmental wall thickening increased significantly from day 30 to day 60 in both groups; the increments did not differ between groups. ESV measured using echocardiography increased significantly from day 0 to day 30 in VEGF ($22.9\pm9.9\;mL\;vs.\;32.3\pm9.1\;mL;\; p=0.006$) and in Control ($26.3\pm12.0\;mL\;vs.\;36.8\pm9.7\;mL;\;p=0.046$). EF decreased significantly in VEGF ($52.0\pm7.7\%\;vs.\;46.5\pm7.4\%;\;p=0.004$) and in Control ($48.2\pm9.2\%\;vs.\;41.6\pm10.0\%;\;p=0.028$). There was no significant change in EDV. The interval changes (days $30\~60$) of EF, ESV, and EDV did not differ significantly between groups both by gated SPECT and by echocardiography. Conclusion: Intramyocardial injection of pCK-VEGF165 induced therapeutic angiogenesis and improved myocardial perfusion. However, post-infarction remodeling and global myocardial function were not improved.

Studies on the Mechanism of Contraction by Substance P in Rabbit Ileum (Substance P에 의한 가토 회장평활근의 수축기전에 대한 연구)

  • Jo, Se-Hun;Jung, Jin-Sup;Lee, Sang-Ho
    • The Korean Journal of Physiology
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    • v.18 no.2
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    • pp.151-162
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    • 1984
  • The mechanism of the contractile response of longitudial muscle of rabbit ileum to substance P (SP) has been investigated. The contractions in rabbit ileum under various conditions were recorded isometrically The following results were obtained. 1) The contractions by SP increased according to concentrations. SP·induced contraction was not sustained but faded rapidly at $10^{-7}M$. The response to the commutative addition of SP was decreased in comparison to the response to separate administration of each concentration . 2) The response to $10^{-8}M$ SP after 5 min application cf $10^{-7}M$ SP was increased with increasing the time interval between the administration of $10^{-7}$ and $10^{-8}M$ SP. 3) The treatment of rabbit ileum by $10^{-7}M$ SP for 5 min didn't decrease the response to $10^{-6}M$ acetylcholine. 4) $10^{-6}M$ atropine had no effect of the contractile response to $10^{-7}M$ SP. The response to $10^{-7}M$ SP was normal or subnormal in the presence of 3 mM tetraethylammonium(TEA). 5) 100k solution, $10^{-4}M$ ouabain, and Na-free solution inhibited the response to $10^{-8}M$ SP and 3 mM TEA completely, and to $10^{-7}M$ SP incompletely. 3 mM TEA induced a considerable contraction in K-free solution, but $10^{-8}M$ SP didn't induce the contraction. $10^{-6}M$ norepinephrine decreased the contractile responses to SP and TEA. 6) The contractile response to $10^{-7}M$ SP was dependent on the extracellular $Ca^{2+}$ concentrations to 1.8 mM. 7) The contractile response to $10^{-7}M$ SP remained 15% of the maximal response after bathing the ileum in a Ca-free solution for 2.5 min. 8) The responsiveness to SP was completely lost within 10 min of bathing in Ca-free solution, but was restored by the exposure to $Ca^{2+}$. The restorative effect of $Ca^{2+}$ depended on the concentration of $Ca^{2+}$, and on time for which the tissue exposed to this $Ca^{2+}$ concentration. These results suggest that there are two mechanisms of the action by which the low concentrations of substance P causes the contraction of intestinal smooth muscle: the reduction of K conductance and a mechanism dependent on the extracellular $Ca^{2+}$, and that high concentration of SP may elicit a contraction by releasing $Ca^{2+}$ from an intracellular store, which is not as sensitive to removal of extracellular $Ca^{2+}$ or as easily accessible to EGTA as the extracellular space of the muscle. The location of this store is not known; it may be associated with the internal side of the cell membrane.

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