독시사이클린 나노입자가 함유된 치주용 키토산 스트럽의 제조 및 특성

송경숙,양재헌,김영일,정규호 한국약제학회 2001 Journal of Pharmaceutical Investigation Vol.31 No.4

Local drug delivery by using biocompatible polymers has been developed in the treatment of periodontitis for many years. In the field of dental therapy, doxycycline is usually a first choice because of its broad-spectrum antibiotic activity. The strip releases antibiotics for a week, and the polymer should be degradable after a week. In this study, we prepared and evaluated the chitosan strips and nanoparticle strips containing doxycycline hydrochloride, and studied their antiacterial activity, dissoultion, and degrability in vitro. The weight of cast strip containing a 5 mg of doxycycline hydrochloride and a 45 mg of chitosan polymer was 57.67±0.17 mg. The release rate of doxycycline hydrochloride from the strip was measured by HPLC. The drug released from chitosan strip and nanoparticle strip was shown to be 50 ㎍/ml, in first 24 hours. In antibacterial test showed growth inhibitory activity after 24 hrs anaerobic incubation. In vitro degradability showed demolished weight of 93.74±0.08% chitosan strip, 82.48±1.29% chitosan nanoparticle strip, 2.47±1.99% polycarprolactione strip (control). These results showed that, with this doxycycline hydrochloride strip, it is feasible to obtain a sustained release of the drug within the periodontal pocket for seven days which may be improve for local drug delivery system for treatment of periodontal disease.

표피 종양에서 Epidermal Growth Factor Receptor의 발현 비교

송준영,이규석,정재봉 啓明大學校 醫科大學 1994 계명의대학술지 Vol.13 No.4

Epidermal growth factor(EGF) and transforming growth factor alpha(TGFα) are important keratinocyte mitogens. Their effect are mediated by a cell membrane receptor(EGFR), quantitive and qualitive abnormalities of which may be responsible for deranged keratinocyte proliferation and differentiation. We have therefore examined EGFR expression immunohistochemically in a variety of benign and malignant epithelial neoplasms using monoclonal antibodies to the extracellular and intracellular receptor domains, In benign tumor(seborrheic keratosis), there was an ordered pattern of EGFR expression. In malignant tumors(basal and squamous cell carcinoma), there was loss of membrane labelling and cytoplasmic accumulation of the receptor. In premalignant prolifertation(Bowen's disease), there was loss of membrane receptor with absent cytoplasmic EGFR. In slot-blot analysis, the levels of EGFR mRNA in sguamous cell carcinoma and basal cell carcinoma revealed 3 fold elevation when compared to normal skin. We suggest that dysregulation of the EGFR may be important in the development of cutaneous epithelial malignancies.

지속성 외래 복막투석 환자에서 염증 지표와 고해상도 B 모드 경동맥 초음파 소견의 연관성에 관한 연구

송현용,송영수,안철우,강신욱,최규헌,하성규,이현철,이호영,한대석 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.2

배 경 : 저알부민혈증 및 C-반응 단백(C-reactive protein, CRP)이 증가된 지속성 외래 복막투석 환자의 사망률이 높은 정확한 이유는 밝혀져 않다. 혈액투석 환자에서처럼 복막투석 환자에서 저알부민혈증 및 염증반응이 심혈관계 질환 위험인자 인지 알아보고자 하였다. 방 법: 비당뇨병성 말기 신부전, 지속성 외래 복막투석 환자 93명의 심혈관계 질환 위험인자들과 복막 투과 특성 및 알부민, CRP 등의 염증지표에 따라 고해상도 초음파를 이용한 경동맥내막-중간막 두께, 내막-중간막 면적, 플라크의 유무 등을 단면적으로 비교하였다. 결 과: 복막 투과 특성은 고투과막군 14명, 중간 고투과막군 38명, 중간 저투과막군 31명, 저투과막군 10명으로 각 군간의 경동맥 내막-중간막 두께, 플라크 유무 및 내막-중간막 면적의 차이는 없었다. 기존 관상동맥 질환 환자는 8예(8.6%)로 내막-중간막 두께는 관상동맥 질환이 없는 환자보다 증가되었고(0.79±0.21 vs 0.60±0.11 mm, p<0.05) 플라크 형성은 더 많이 보이나 통계적 유의성은 없었다(75.0 vs 63.5%, p>0.05). 혈청 알부민치와 경동맥 내막-중간막 면적은 역상관관계를 보였다(r=-0.27, p<0.05). 저알부민혈증 환자(혈청 알부민 <3.5 g/dL)는 정상 알부민혈증 환자보다 내막-중간막 두께가 증가되었고(0.67±0.15 vs 0.61±0.12 mm, p<0.05), 플라크도 유의하게 많았다(68.0 vs 55.8%, p<0.05). 혈청 CRP치와 경동맥 내막-중간막 면적은 양의 상관관계가 있었으며(r=0.21, p<0.05) CRP가 높은 환자(≥0.8 mg/dL, n=18)에서플라크가 많이 관찰되었으나(65.8 vs 50.0%, p<0.05) 경동맥 내막-중간막 두께 및 내막-중간막면적은 양군간에 차이가 없었다. 다변량 회귀 분석상 경동맥 내막-중간막 두께에 영향을 미치는 인자는 고령, 높은 CRP, 기존 심혈관계질환, 낮은 혈청 알부민 순이였다. 결 론 : 복막투석 환자에서 고해상도 초음파를 이용한 경동맥 내막-중간막 두께 측정은 심혈관계 질환 유무 예측의 비침습적 검사가 될 수 있고 저알부민혈증 및 높은 CRP과 같은 만성염증 지속상태가 복막투석 환자에서 죽상 동맥 경화증의 발생을 증가시킨다고 가정할 수 있다. Background : Continuous ambulatory peritoneal dialysis(CAPD) patients with low albumin(LA) and signs of inflammation reflected by increased C-reactive protein(CRP) level have an increased mortality, but the mechanism of this phenomenon is not clear yet. Methods : To answer whether LA and inflammation also enhance cardiovascular risk in CAPD patients, we performed cross sectional study measuring carotid artery intima-media thickness(IMT), calculated intima-media area(cIM area) and the presence of plaque by high-resolution B-mode ultrasonography in 93 non-diabetic CAPD patients. Results : Patients with coronary artery disease (CAD, n=8) had significantly increased IMT(0.79± 0.21 mm vs. 0.60±0.11 mm, p<0.05) and higher prevalence of carotid plaques(75.0% vs. 63.5%) compared to the non-CAD patients. Significant inverse correlation was observed between serum albumin (SA) level and cIM area(r=-0.27, p<0.05). Those patients with LA(SA <3.5 g/dL) had significantly increased IMT compared to non-LA patients(0.67±0.15 mm vs 0.61±0.12 mm, p<0.05). Prevalence of carotid plaques was also significantly higher in LA patients (68.0% vs. 55.8%, p<0.05). CRP level revealed a significant positive correlation with cIM area(r=0.21, p< 0.05). Patients with high CRP(≥0.8 mg/dL, n=18) had higher prevalence of carotid plaques (65.8% vs. 50.0%, p<0.05) compared to those patients with CRP <0.8 mg/dL, but IMT and cIMT area were not different. By multivariate logistic regression analysis, old age, high CRP, history of CAD and low SA were the independent risk factors affecting IMT. Conclusion : Our study strongly suggests that low albumin and chronic inflammatory state of CAPD patients could be associated with increasing atherosclerotic cardiovascular disease. (Korean J Nephrol 2002;21(2):285-294)

말기 신부전 환자에서 투여 경로에 따른 유전자 재조합 인 Erythropoietin(Epokine^(�))의 효과와 안정성에 대한 연구 : 제 4상 연구 A Phase 4 Single Center Study

송현용,윤향숙,강신욱,최규헌,하성규,이호영,한대석 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.2

목 적 : 국내 독자적 기술로 첫 개발된 유전자 재조합 인 에리트로포에틴(Epokineⓡ)의 투여방법에 따른 유효성과 안정성을 알아보고자 하였다. 방 법 : Epokineⓡ을 주당 100-150 U/kg, 주 2회, 12주간 피하 주사하여 목표 또는 안정된 혈색소치 유지 후 무작위로 피하 및 정맥 주사군으로 나누어 12주간 혈액투석 및 복막투석 환자13명, 28명에서 유효성, 안정성을 분석하였다. 결 과 : 양군에서 혈색소치와 헤마토크릿은 Epokineⓡ 투여 2주 후부터 증가, 혈색소치가 혈액투석 환자는 투여 전 7.3 g/dL, 투여 12주 9.5 g/dL, 24주 10.6 g/dL로, 복막투석 환자는 6.8g/dL에서 12주 10.2 g/dL, 24주 10.8 g/dL로 증가하였다. 양군에서 교정 망상적혈구수(%)는투여 1주 후부터 전 기간동안 증가하였다. 혈청 내 철분, ferritin치는 양군에서 투여 2주 후부터감소, 총 철분 결합능은 투여 2주 후부터 증가하였다. 12주째 혈액투석 환자에서 많은 Epokineⓡ용량이 필요했으나(142.2±20.5 vs 117.3±33.6 U/kg/wk, p<0.001) 24주 후 양군의 용량차이는 없었다(123.6±41.5 vs 99.2±49.3 U/kg/wk, p>0.05). 혈액투석 환자에서 피하 주사가Epokineⓡ 투여용량이 더 적었으나(97.4±15.4 vs 145.4±2.9 U/kg/wk, p<0.002) 복막투석 환자는 차이가 없었다(93.0±60.2 vs 105.4±9.7 U/kg/wk, p>0.05) 연구기간 중 9명(18.8%)에서혈압강하제 추가가 필요한 혈압상승, 근육통 동반 상기도 감염 유사증상 및 두통 등의 부작용이 있었다. 대부분 자연소실 혹은 대증요법으로 치유되었고 2명이 부작용으로 탈락하였다. 결 론 : 말기 신부전 환자의 빈혈 개선에 사용하는 Epokineⓡ의 효과는 복막투석 환자에서 더 좋았으며 투여 경로는 정맥주사보다 피하주사가 높음을 알 수 있었다. Background : We evaluated the clinical efficacy and safety of recombinant human erythropoietin(Epokine^(ⓡ)). Methods : A comparative prospective study of intravenously and subcutaneously administrated Epokine^(ⓡ) conducted 13 patients performing hemodialysis and 28 patients performing continuous ambulatory peritoneal dialysis with end-stage renal disease. Epokine^(ⓡ) was given initially at a dosage of 100 unit/kg, subcutaneously, two times a week. The patients had achieved stable or more than 10 g/dL of hemoglobin level for 12 weeks and then we randomized switching intravenously or subcutaneously administrated Epokine^(ⓡ) for another 12 weeks. Results : Hemoglobin(g/dL) and hematocrit(%) increased significantly from baseline levels beginning from 2 weeks after Epokine^(ⓡ) administration. In HD patients, hemoglobin increased significantly from 7.3 to 9.5 after 12 weeks and to 10.6 after 24 weeks. In CAPD patients, hemoglobin increased significantly from 6.8 to 10.2 after 12 weeks and then 10.8 after 24 weeks(p<0.05). Corrected reticulocyte count(%) was significantly increased from baseline levels beginning from 1 week after Epokine^(ⓡ) administration and continuously increased during study period in both group. Serum ferritin and serum iron decreased significantly and total iron binding capacity increased significantly after 2 weeks. At 12 weeks, HD patients were significantly needed more dosage of Epokine^(ⓡ) than CAPD patients(142.2±20.5 vs 117.3±33.6 U/kg/wk, p<0.001), but at 24 weeks, the dosage was not different(123.6±41.5 vs 99.2±49.3 U/kg/wk, p> 0.05). In HD patients, intravenously administrated Epokine^(ⓡ) group was more dosage than subcutaneously group(97.4±15.4 vs 145.4±2.9 U/kg/wk, p< 0.002), but CAPD patients were not different by administration method(93.0±60.2 vs 105.4±9.7 U/kg/ wk, p>0.05). The 9 cases(18.8%) were suffered from headache and flu-like syndrome, but these side effects were not severe and disappeared from conventional therapy. Conclusion : Epokine^(ⓡ) administration is safe and effective in treating anemia of ESRD patients and subcutaneously administration is significantly more effective than intravenously. (Korean J Nephrol 2002;21(2):190-198)

정상인과 정신지체인,다운증후군 환자에서 치주질환 원인균의 출현율

이해송,김선미,최남기,오종석,강미선,임희정,양규호 대한소아치과학회 2006 大韓小兒齒科學會誌 Vol.33 No.3

Adriamycin 백서자궁경부 기질내 교원섬유에 미치는 영향

김원규,백태경,송석근 漢陽大學校 環境科學硏究所 1993 環境科學論文集 Vol.14 No.-

Adriamycin은 Streptomyces peucetius var. caesius에서 추출한 항균성 항암제로서 세포내의 핵산과 결합하여 핵산 및 단백질의 합성을 억제하므로 종양세포의 증식을 억제하는 화학요법제이다. 그러나 adriamycin은 암환자에게 투여하면 종양세포 뿐 아니라 정상세포에도 손상을 초래하여 여러가지 부작용을 일으키므로 저자는 adriamycin을 백서에 투여하면 자궁경부내 섬유모세포의 단백질 합성이 억제되어 교원섬유의 양 및 분포에 변화가 야기될 것으로 사료되어 체중 200mg 내외의 Wistar계 자성 백서를 질도말법으로 발정주기를 확인하고 백서 체중 kg당 5mg의 adriamycin을 5일간 복강내에 투여하였으며, 희생시키기 직전 다시 발정주기를 확인한 후 경동맥사혈로 희생하고 개복하여 자궁경부를 적출하였다. 적출한 자궁경부는 두께 6㎛의 연속절편을 만들어 일반적인 자궁경부 조직의 변화를 관찰하기 위하여 hematoxylin 및 eosin 염색을 새행하였고 교원섬유의 관찰을 위하여 van Gieson 염색을 시행하여 다음과 같은 결과를 얻었다. 1. Adriamycin 투여군 백서 자궁경부의 상피세포층은 대조군 백서 자궁경부의 상피세포층에 비하여 위축되었다. 2. Adriamycin 투여군 백서 자궁경부 기질내 교원섬유의 van Gieson 염색에 대한 반응은 모든 발정주기에서 감소하였다. 3. Adriamycin 투여군 백서 자궁경부 기질내 교원섬유의 분포는 대조군 백서 자궁경부 기질내 교원섬유 분포의 치밀도에 비하여 감소하였다. 이상의 결과를 종합한 바 백서에 adriamycin을 투여하면 자궁경부의 상피세포 및 섬유모세포에 독성으로 작용하여 상피세포층이 위축되고 교원섬유의 van Gieson 염색반응 정도 및 분포의 치밀도가 감소하는 것으로 사료된다. It is well known that adriamycin, an anthracycline antibiotics isolated from Streptomyces peucetius var. caesius inhibits DNA and RNA synthesis and exhibits a significant antitumor activity against various tumors. Although adriamycin is very effective against tumor cell proliferation, it may also damage the normal cells of the body and develop the toxic effects during treatment of cancer patients. In this experiment, the authors studied the effect of adriamycin on the rat uterine cervix, observing the changes in content and distribution of collagen fibers in the uterine cervix of the rat. Fourty female Wistar strain rats, weighing about 200gm and exhibiting normal estrous cycle, were used as experimental animals. After confirmaiton of estrous cycle by mean of vaginal smear, the animals of experiment and control groups were injected intraperitoneally with 5mg/kg of adriamycin diluted in 0.2ml of distilled water and with 0.2ml of normal saline for 5 days, respectively. On the 5th day after administration of adriamycin and normal saline the expeimental animals were sacrificed by carotid exsanguination. The obtained cervix uteri was fixed in 10%. neutral buffered formalin solation(pH 7.2) and paraffin sections, 6㎛ in thickness, were made. Histological preparations were prepated by way of hematoxylin and eosin stain for the general changes of uterine cervix, and van Gieson's stain for the changes of collagen fibers in rat uterine cervix. The results obtained were as follows : 1. Epithelial cells in the adriamycin treated uterine cervix were atrophied. 2. Reaction of collagen to van Gison's stain in the adriamycin treated uterine cervix was decreased at all stages of estrous cycle. 3. The distribution of collagen in the adriamycin treated uterine cervix was less compact than the control uterine cervix. Consequently, it is suggested that the atrophy of epithelial layer, a decreased reaction to van Gieson's stain, and less compact distribution of collagen fibers may be resulted from cytotoxic effect of adriamycin on the eptihelial cells and fibroblasts in the rat uterine cervix.

구진상괴사성 결핵진 3례

손보성,송준영,정재봉,김병천,이상숙,류영욱,이규석 啓明大學校 醫科大學 1994 계명의대학술지 Vol.13 No.4

Papulonecrotic tuberculid is an eruption of necrotizing papules, particularly affecting the extremities and occurring in more or less symmetrical crops, and responding to antituberculosis therapy. Individual lesions heal with scarring. Histologically, vascular involvement is seen in early lesions. Late lesions are divided into two forms. In superficial forms, wedge shaped area of necrosis forms in epidermis and upper dermis. Epithelial and lymphoid cells gather around its periphery. In deep forms, with no epidermal change, granulomatous changes surrounded by well defined palisading histiocyte and lymphoid, epithelioid cells are seen. In mid-dermis and perivascular area, vessel shows vasculitis. In the first case, leukocytoclastic vasculitis and early granuloma formation were seen. In the second case, palisading granuloma formation was seen. In the third case, tuberculoid granuloma formation was seen. We report three cases of papulonecrotic tuberculid showing three different stages of histological finding, in individual cases.

우측 귓바퀴 뒷면에 발생한 혈관평활근종 1예

박수정,송현정,김주용,김창덕,김창욱,이규석 대한피부과학회 2006 大韓皮膚科學會誌 Vol.44 No.4

표재성 피부 지방종성 모반 2례

홍진표,송준영,김병천,이규석 啓明大學校 醫科大學 1986 계명의대학술지 Vol.5 No.2

Nevus lipomatosus cutaneus superficialis is very rare malformation consisting of multiple or solitary papules usually occuring on the lower trunk or glutesl regions. Microscopically it reveals groups of ectopic fat cell nests within the dermis. The authors observed two cases of typical nevus lipomatosus cutanes superficaialis. The first case was a 30-year-old female who has had asymptomatic, soft, skin colored and huge confluent tomor masses on the left buttock for 10 years; the second case was a 21-year-old male who has had multipel, soft, skin colored papules on the right buttock for 10 years. The author, made diagnosis of nevus lipomatosus cutaneus superficialis from characteristic clinical and histopathological findings. Related literature was briefly reviewed for the discussion.

Streptomyces exfoliatus가 생성되는 mutanase에 의한 인공치태 억제 작용

오종석,정진,송도원,양규호 大韓小兒齒科學會 1997 大韓小兒齒科學會誌 Vol.24 No.2

Streptomyces exfoliatus 의 mutan 분해 능력에 영향을 미치는 인자에 대해 알아보고자 blue mutan을 이용한 실험을 실시하여 다음과 같은 결과를 얻었다. Blue mutan이 들어있는 배지에서 Streptomyces exfoliatus에 의한 투명대를 봄으로써 mutanase의 분비를 확인할 수 있었다. Blue mutan이 들어있는 여러 종류의 배지 중에서 minimal essential agar 상에서 Streptomyces exfoliatus가 투명대를 형성하였다. Minimal essential broth의 pH가 7.0일때 pH가 5.5나 8.5일 때보다 blue mutan이 잘 분해되었으며, 배양 온도가 37。c때 32。나 42。때보다 잘 분해되었다. (P<0.05). Minimal essential broth에서의 blue mutan의 분해는 CaCl₂농도가 증가할 수록 (p<0.05), KCI 농도가 10mM일때 증가하였으나, MgCl₂ 농도는 0.1M에서 6.4mM의 범위에서 비슷하였다. Streptomyces exfoliatus배양 상청액을 0.5% yeast extract와 10% sucrose를 첨가한 2배의 BHI broth에 가한 경우 교정용 wire상에서의 Streptococcus mutans에 의한 인공치태 형성이 유의성있게 억제되었다 (p<0.05). 이상의 결과를 종합하면 Streptomyces exfoliatus에서 생성되는 배양 상청액내의 mutanase가 인공치태 형성에 억제 작용이 있다는 것을 확인할 수 있었다. The main component of dental plaque is the mutan containing the a-1,3 bond. The following results were obtained by using a blue mutan to assess the factors affecting the mutandigesting activity of Streptomyces exfloiatus isolated from soil. A clear zone was produced by mutanase-producing Streptomyces exfoliatus on the minimal essential agar containing blue mutan. Streptomyces exfoliatus digested more blue mutan in the minimal essential broth at pH 7.0 than at pH5.5 or 8.5 Streptomyces digested more blue mutan at 37。c than at 32。c or 42。c (p<0.05). When the concentration of CaCl₂was increased in the minimal essential broth, the digestion of the blue mutan was increased (p<0.0.). The optimal concentration of KCI was 10mM to digest blue mutan, but a similar amount of blue mutan was digested at the range of 0.1mM to 6.4mM of MgCl₂. When the culture supernatant of Streptomyces exfoliatus was mixed with 2X brain heart infusion broth containing 0.5% yeast extract and 10% sucrose, less artificial plaque was formed by Streptococcus mutans on the orthodontic wire (p<0.05). These results indicated that the secretion of mutanase was identified in culture supernatant of mutan-digesting Streptomyces exfoliatus, suppressing the formation of artificial plaque by Streptococcus mutans.