설치류의 [18F]Mefway에서 뇌 섭취에 기여하는 P-glycoprotein의 효과

Dept. of Medicine/박사I. INTRODUCTION Efflux transporters in brain capillary endothelial cells impede xenobiotics, including therapeutic drugs and PET radioligands. Of these, P-gp (P-glycoprotein) and Bcrp (Breast cancer resistance protein) are prominent efflux pumps. P-gp is colocalized with Bcrp on the luminal membranes of brain capillary endothelial cells, and they have partly overlapping substrate specificities that include a wide range of compounds. Thus, to investigate the effects of P-gp, it is required to evaluate the impact of Bcrp. The aim of this study was to determine whether the brain uptake of [18F]Mefway is influenced by the action of P-gp and Bcrp in rodents. II. MATERIALS AND METHODS To effectively suppress in vivo defluorination, fluconazole (OneFlu, JW Pharmaceutial, Seoul, Korea) was used. [18F]Mefway was applied to the pharmacological inhibition rats and genetically disrupted mice. In rats, blocking of P-gp activity was performed by tariquidar (TQD). For the pharmacological inhibition experiments male Sprague-Dawley (n = 3 for each group) rats were used. For genetic disruption, male Mdr1a/b(-/-), Bcrp1(-/-), Mdr1a/b(-/-)Bcrp1(-/-), and wild-type (WT) mice were used (n = 4 for each group). III. RESULTS Pretreatment of TQD results in 160% higher hippocampal uptake compared with control rats. In genetically disrupted mice, a maximal brain uptake value of 3.2 SUV in the triple knockout mice (Mdr1a/b(-/-)Bcrp1(-/-) was comparable to that of the double knockout mice (Mdr1a/b(-/-)) and two-fold those of the wild type and Bcrp1(-/-) knockout mice. The differences of binding values were statistically insignificant between control and experimental groups. The brain-to-plasma ratios for triple knockout mice were also 2-5 times higher than those for other groups. IV. CONCLUSION In PET, chemical knockout P-gp disruption induced considerable increase of brain uptake of [18F]Mefway compared with control group or wild type. This result was substantiated by ex vivo experiments showing high brain-to-plasma ratios for P-gp disrupted mice. In conclusion, [18F]Mefway is modulated by P-gp, and not by Bcrp in rodents. I. 목적 뇌 모세혈관 내피 세포에서 유출 운반자들은 치료 약물들과 PET 방사성 리간드들을 포함한 생체이물질들을 방해한다. 이들 중에서 P-glycoprotein (P-gp)와 breast cancer resistance protein (Bcrp)는 가장 중요한 유출 운반자들이다. P-gp는 뇌 모세혈관 내피 세포의 관강내막에 Bcrp와 함께 발현이 되어 있으며 일부 기질 특이성을 공유하고 있다. 따라서 P-gp의 효과를 알아보기 위해서는 Bcrp의 효과를 알아볼 필요성이 있다. 본 연구의 목적은 설치류의 [18F]Mefway에서 P-glycoprotein (P-gp)와 breast cancer resistance protein (Bcrp)의 뇌섭취에 관련된 효과를 알아보고자 하였다. II. 대상 및 방법 탈불소화를 효과적으로 억제시키기 위하여 fluconazole (OneFlu, JW Pharmaceutial, 서울, 대한민국)를 사용하였다. [18F]Mefway를 약물학적으로 억제시킨 쥐와 유전적으로 변형시킨 생쥐에게 적용을 하였다. 쥐에서는 tariquidar(TQD)를 이용하여 P-gp 기능을 억제 시켰다. 약물학적으로 억제시키는 실험을 위해서는 수컷 Sprague-Dawley (각 그룹 당 세 마리) 쥐를 사용하였다. 유전적 변형을 위하여서는 수컷 Mdr1a/b(-/-), Bcrp1(-/-), Mdr1a/b(-/-)Bcrp1(-/-), 그리고 대조군 생쥐가 사용되었다 (각 그룹 당 네 마리). III. 결과 TQD를 전처치함으로써 대조군 쥐와 비교 시 해마의 뇌 섭취가 160% 증가되었다. 유전적으로 변형된 생쥐에서, 최대 뇌 섭취가 3.2 SUV인 삼중 유전자 결손 생쥐 (tKO, Mdr1a/b(-/-)Bcrp1(-/-) 와 비교 시 이중 유전자 결손 생쥐 (dKO, Mdr1a/b(-/-)) 와 최대 뇌 섭취가 비슷하였으며 대조 군과 Bcrp1(-/-) 유전자 결손 생쥐와 비교 시 두 배 높은 최대 뇌 섭취를 보였다. 대조 군과 실험 군간의 결합 가치의 차이는 통계적으로 의미가 없는 것으로 나타났다. [18F]Mefway 농도의 뇌와 혈장간 비율은 다른 그룹과 비교 시 삼중 유전자 결손 생쥐에서 2.5배 높은 것으로 확인되었다. IV. 결론 PET에서 화학적으로 P-gp 결여된 경우 대조군과 비교시 [18F]Mefway의 뇌에서 섭취도가 매우 많이 증가되었다. 이러한 결과는 P-gp 결손 생쥐에서도 높은 뇌-혈장간 비율을 보인 실험 결과에서도 입증되었다. 결론적으로 [18F]Mefway는 설치류에서 Bcrp가 아닌 P-gp에 의해서 조절이 된다.ope

Haemodynamic events and localised parenchymal changes following transcatheter arterial chemoembolisation for hepatic malignancy: interpretation of imaging findings.

Following transcatheter arterial chemoembolisation (TACE), the appearances on CT or MR images are largely related to the chemical and ischaemic insults to the portal tract. Understanding the mechanism of TACE-induced changes is essential for radiologists in order to determine the therapeutic effect as well as to distinguish these changes from recurrent tumours. This pictorial review illustrates the haemodynamic and substantial parenchymal changes related to TACE for hepatic malignancy.ope

Value of the US BI-RADS final assessment following mastectomy: BI-RADS 4 and 5 lesions

BACKGROUND: Clinical examination is not entirely sufficient for evaluation of the postoperative site for follow-up of patients with mastectomy. A few studies have reported that postoperative follow-up US evaluation allows early detection and proper management of local tumor recurrence. PURPOSE: To evaluate the diagnostic performance of the American College of Radiology (ACR) ultrasonographic (US) Breast Imaging Reporting and Data System (BI-RADS) categories 4 and 5 breast lesions at the mastectomy site. MATERIAL AND METHODS: Our institutional review board approved this study and waived the need for informed consent. We retrospectively reviewed the consecutive post-mastectomy US exams for palpable and non-palpable lesions in the post-mastectomy chest wall that were categorized as BI-RADS 4 (subcategorized 4a, 4b, and 4c) or 5 between January 2007 and April 2010. The positive predictive value (PPV) for final assessment was evaluated. RESULTS: From 2681 post-mastectomy US examinations, we obtained a study population of 50 patients with 50 lesions (20 palpable, 30 non-palpable). There were nine (45%) malignancies among the palpable lesions and six (20%) malignancies among the non-palpable lesions. The palpability showed no significant correlation with malignancy in overall subcategorization (P >0.05). The PPVs of categories 4 and 5 were 14.3% for category 4a, 62.5% for category 4b, 100% for category 4c, and 100% for category 5. CONCLUSION: The ACR US BI-RADS categorization of 4a, 4b, 4c, and 5 for breast lesions at the mastectomy site is a feasible method for predicting local recurrence. All lesions should be managed according to US characteristics during evaluation of local recurrence at the mastectomy site, regardless of palpability.ope

Initially non-diagnostic ultrasound-guided fine needle aspiration cytology of thyroid nodules: value and management.

BACKGROUND: Ultrasound (US)-guided fine needle aspiration cytology (FNAC) is an accurate, reliable, and simple method to identify a thyroid nodule as benign or malignant. However, non-diagnostic cytology results for thyroid nodules are a major limitation of US-guided FNAC. PURPOSE: To investigate the incidence of thyroid cancer among cases with non-diagnostic results on FNAC and to provide suggestions for the management of thyroid nodules that are initially non-diagnostic by FNAC according to ultrasonographic findings. MATERIAL AND METHODS: From July 2006 to December 2009, 10,317 thyroid nodules in 6684 consecutive patients underwent US-guided FNAC at our institute. Among these, 871 thyroid nodules (8.4%) were diagnosed as non-diagnostic on initial cytologic evaluation and 196 underwent a second or third FNAC. Twenty-seven thyroid nodules (18.9%) underwent surgery, while 116 thyroid nodules were cytologically confirmed as benign with no remarkable change on follow-up US were included. We retrospectively reviewed the US findings for a total of 143 thyroid nodules (123 benign nodules and 20 malignant nodules). The US features that we compared included composition, echogenicity, margin, calcifications, shape, and underlying echogenicity. RESULTS: In total, thyroid cancer was diagnosed in 20 nodules (14.0%). The size of the nodule was significantly associated with malignancy (P < 0.05). Most of the sonographically probable benign nodules were found to be benign (97.6%). Suspicious nodules on US were thyroid cancer in 43.2% of cases. Marked hypoechogenicity, microlobulated or irregular margin, microcalcifications, and taller-than-wide shape were significant US findings that correlated with malignancy (P < 0.05). The diagnostic performance of ultrasound for initially non-diagnostic thyroid nodules was as follows: sensitivity of 90.0%, specificity of 65.0%, positive predictive value of 29.5%, and negative predictive value of 97.6%. CONCLUSION: In terms of management of thyroid nodules with non-diagnostic FNAC cytology, US evaluation is a feasible and useful method for predicting malignancy.ope

Hermann Cohen 의 Kant 해석

Hermann Cohen에 의하면 Kant는 그의 학적 활동의 초기에 Newton에 의해 원리의 체계로 정초된 자연과학을 알게 되었다. 그리고 자연과학에서 인식일반의 이상을 이해하게 되었다. 이러한 이상의 사상안에는 인식의 체계에 대한 이상화한 것의 관계가 있다. 이 관계를 Kant는 물론 그 완전한 의미로 파악할 수는 없었다. 그가 개별적 자연과학을 통해서 철학적 문제제기에 도달한 것이 아닌 한, 그러했다. 이와 반대로 일단 철학적 시점이 파악된 후에, 이상으로서 요구되는 인식의 사실이 학적 이성에 관계되고 학적 이성에 기초되었다는 방식으로 이 관계가 이상의 사상에서 타당으로 나아갔다. 이러한 관계안에서 인식일반의 체계의 통일이 사유되었다. Newton의 과학이 이러한 관계안에서 고정됨으로써, 이 Newton의 과학을 인식의 이상으로서 요구하고, 다른 과학들의 정위를 이 Newton의 과학에서 고찰하는 것이 이제 철학적으로 중요한 의미를 가졌을 것이다

"Alois Riehl Kantinterpretation"

Naeh der Meinung A. Riehls ist die Frage der Vernunftkritik Kants eine Frage nach ler Erkenntnis. Jedoch erfordert sie zu ihrer Beantwortung keine vollständige "'Theorie ler menschlichen Erkenntnis." Die Aufgabe ist beschränkt auf die Erkenntnis a priori; das viele "Empirische und Sinnliche" bleibt außer Betracht. Die für die ganze Untersuchung maßgebliche Formulierung lautet: Wie sind synthetische Urteile apriori möglich? Und zwar zielt die Möglichkeitsfrage nicht auf die zu ermöglichende Wirklichkeit, sondern auf die zu begründende objektiye Gültigkeit solcher Urteile. Alois Riehl betont mehrfach, das Problem Kants sei ein Iediglich erkenntnistheoretisches Problelm. Auf die Erkenntnis gehe die kritische Frage, nicht auf die Existenz. Dennoch ist der Denker an der Seinsweise des Dinges an sich lebhaft interessiert. Das könnte schon darum verständlich scheinen, weil sich im kritischen System die Frage nach der Erkenntnis nicht von der nach der Gegenständlichkeit trennen läßt, und weil bei dieser der Ausblick auf das Ding-an-sich Problem nahe liegt. Tatsächlich reißt Riehl aber Erkenntnis des Gegenstandes und Gegenstand der Erkenntnis in einer Weise auseinander, die diese Erklärung nicht zuläßt. Vielmehr ist hier an das Problem zudenken, in dessen Erörterung Riehl überhaupt zur kritischen Fragestellung geführt wird: An das der Möglichkeit der positiven Wissenschaften. Der Punkt, an dem Riehls Interpretation völlig versagt, ist demnach die Begründung ler Erfahrungsgegenstädlichkeit, ihre Begründung nämlich im streng kritishen Sinnc

갑상선 결절의 초기 비진단적 초음파 유도하 미세침흡인술 결과의 평가와 처리

Dept. of Medicine/석사[한글] [영문]I.INTRODUCTIONThe management of patients with thyroid fine-needle aspiration biopsy (FNAB) specimens that are nondiagnostic cytologic results still remains problematic. Aims of this study were to investigate the incidence of thyroid cancer among the initially nondiagnostic cases of FNAB and to compare the final cytopathologic results between probably benign and suspicious nodules in ultrasonography (US) with suggesting the management of initially nondiagnostic thyroid nodules at FNABs.II.MATERIALS AND METHODSFrom July 2006 to December 2009, 10,317 thyroid nodules in 6,684 consecutive patients underwent US-guided FNAB. Among them, 871 thyroid nodules (8.4%) that were diagnosed as nondiagnostic at initial cytologic evaluation and 196 thyroid nodules underwent subsequent second or third FNAB. Twenty-seven thyroid nodules (18.9%) were underwent surgery and 116 thyroid nodules were considered as benign which were cytologically confirmed as benign and showed no remarkable change at follow-up US. US findings of total 143 thyroid nodules (123 benign nodules and 20 malignant nodules) in 138 patients (M: F = 20: 118; mean age, 50.5 years) were retrospectively reviewed. US features were including internal composition, echogenicity, margin, calcifications, shape and underlying echogenicity.III.RESULTSIn total, thyroid cancers were diagnosed in 20 nodules (14.0%, 19 papillary carcinomas and one minimally invasive Hurthle cell cancer). Lesion size varied from 3 to 40mm (mean, 10.4mm). Fourteen lesions were palpable and the others were incidentally found. The size of lesion was significantly associated with malignancy (P < 0.05). Only two sonographically probable benign nodules revealed malignancy (2.4%). Suspicious nodule on US showed thyroid cancer in 43.2%. Markedly hypoechogenicity, microlobulated or irregular margin, microcalcifications and taller-than-wide shape were significant US findings that correlated with malignancy (P < 0.05). Diagnostic performance of ultrasound of initially nondiagnostic thyroid nodules was calculated as follow: sensitivity 90.0%, specificity 65.0%, positive predictive value 29.5 %, and negative predictive value 97.6%.IV.DISCUSSION Malignancy rates of thyroid nodules which were showed non-diagnostic result in FNAB was 14.0% in our study. Considering the management of thyroid nodules with nondiagnostic FNAB cytology, the US evaluation is a feasible method and useful in predicting malignancy. V.CONCLUSIONAlthough nondiagnostic cytologic result at initial FNAB, repeat FNAB is needed for sonographically suspicious nodules, due to 14% of malignancy rates in nondiagnostic thyroid nodules. However, follow-up US is more recommended rather than repeat FNAB for sonographically probably benign nodules. Sonographic findings of thyroid nodules with nondiagnostic results at FNABs are useful method to plan the management.ope

르네상스 시대의 철학

Agrippa는 신 Platon 주의와 유태교의 Kabbala의 신비설을 결합한 Reuchlin의 영향을 받았다. 또 중세의 철학자이며 신비론자인 Raymundus Lullus의 영향을 받았다. Agrippa에 의하면 우주는 모든 부분에 있어서 작용의 통일적인 연관을 가진다. 그는 우주를 셋으로 나누는 고래의생각을 받아들이고 있다 즉 1) 지상세계(지 · 수 · 불 · 풍의 세계) 2)성 즉 천의(himmlische Welt) 3) 천사의 예지적 세계(intelligible welt) 또는 관념적인 세계(ideelle Welt)로써, 이 세 세계에서 작용의 원리는 동일하다. 현실적 생기현상에 신의 의사가 그것에 침입한다는 것은 생각되지 않는다. 일체의 사물이나 힘은, 하나의 완결적인 세계 연관을 이루고 있다. 따라서 인간은 자기 내부에 사물의 힘과 가까운 것을 자각하면 할수록 점점 더 자연에 영향을 미칠 수가 있다. 그리하여 인간은 자연을 지배할 수 있다