Clostridium difficile에 의한 설사의 예후인자

김준형,김희정,구남수,김영근,최준용,신소연,박윤선,김연아,김명수,정수진,최희경,송영구,이경원,김준명 대한감염학회 2007 감염과 화학요법 Vol.39 No.2

배경 : Clostridium difficile에 의한 설사(Clostridium difficile associated diarrhea; CDAD)는 임상 경과가 다양하다. 최근에 유럽과 북미에서 C. difficile 감염의 발생률이 증가하고 고전적 치료에 잘 반응하지 않으며 이환률이 증가하였고, 이러한 원인이 새로운 균주의 탄생에 기인한다고 보고되었다. CDAD의 예후에 영향을 미치는 세균성 요인과 숙주 요인을 확인하기 위해 본 연구를 진행하였다. 재료 및 방법 : 2002년 8월부터 2003년 12월까지 CDAD가 진단된 20세 이상인 환자들을 대상으로 후향적 Cohort 연구를 하였다. 세균성 요인을 확인하기 위해 cdt A, cdtB, tcd A, tcd A rep 그리고 tcd B 유전자(binary toxin)를 확인하였다. 설사가 치료 시작 후 11일 이상 지속되거나, 2달 이내에 재발하거나, 수술 혹은 다른 시술이 필요한 경우, 사망한 경우 예후가 좋지 않은 것으로 정의하였다. 결과 : 총 115예에서 toxin을 생성하는 C. difficile가 동정되었으며, Toxin A와 toxin B 모두 양성인 균이 91예, toxin B만 양성인 균이 24예였다. Toxin A 생성 여부가 예후에 영향을 미치지 않았지만, 제산제를 사용한 환자에서 그렇지 않은 환자에 비해 toxin B만 양성인 균이 많이 동정되었다(P<0.05). 예후가 좋지 않은 경우는 39예(33.9%)였고 76예(66.1%)에서 예후는 양호하였다. 단변량 분석에서 70세 이상의 고령, 남성, 증상 발현 후 사용한 항생제의 개수 사용, 증상 발현 후 carbapenem, aminoglycoside, glycopeptide 사용, 당뇨 및 뇌졸중 병력이 있는 경우, 그리고 높은 Charlson index가 불량한 예후 인자로 확인되었다. 그러나 독립적인 예후 인자를 조사했을 때에는70세 이상의 고령(odds ratio=3.378, P=0.009), 증상 발현후 carbapenem 사용(odds ratio 7.210, P<0.001)이 예후에 중요한 영향을 미치는 요소로 확인되었다. 결론 : 70세 이상의 고령과 증상 발현 후 carbapenem 사용이 CDAD 독립적인 불량한 예후인자이다. Background : Clostridium difficile associated diarrhea (CDAD) has a wide range of clinical manifestations. The prognostic factors of CDAD are not fully understood. Materialsand Methods : A retrospective cohort study of 115 patients with CDAD from Aug. 2002 to Dec. 2003 was conducted to evaluate prognostic factors of CDAD. Bacteriologic factors were determined by detecting the binary toxin gene, tcd A, tcd A rep and tcd B gene. Poor prognosis was defined as diarrhea more than 10 days even with classic treatment, recurrence, death, and moribund discharge. Results : Approximately 79% of isolated strains were toxin A+/B+ strains and 21% were toxin A-/B+ strains. There was no difference in prognosis between toxin A+ and toxin A- strains. 39 (33.9%) cases showed poor prognosis and 76 (66.1%) cases showed good prognosis. Univariate analyses revealed that the poor prognostic factors were old age over 70 years old, male, the number of antibiotics used after onset of symptom, the administration of carbapenems, aminoglycosides, glycopeptides after onset of symptom, history of DM and stroke, and high Charlson comorbidity index. Multiple logistic regression analysis identified old age over 70 years old (odds ratio=3.378, P=0.009) and the administration of carbapenems after onset of symptom (odds ratio 7.210, P<0.001) as the independent poor prognostic factors. Conclusion : Old age over 70 and the administration of carbapenems after onset of symptom were the poor prognostic factors for CDAD caused by none-binary toxin producing strains.

Exploration of the metal coordination region of concanavalin A for its interaction with human norovirus

Kim, D.,Lee, H.M.,Oh, K.S.,Ki, A.Y.,Protzman, R.A.,Kim, D.,Choi, J.S.,Kim, M.J.,Kim, S.H.,Vaidya, B.,Lee, S.J.,Kwon, J. IPC Science and Technology Press 2017 Biomaterials Vol.128 No.-

Rapid methods for the detection and clinical treatment of human norovirus (HuNoV) are needed to control foodborne disease outbreaks, but reliable techniques that are fast and sensitive enough to detect small amounts of HuNoV in food and aquatic environments are not yet available. We explore the interactions between HuNoV and concanavalin A (Con A), which could facilitate the development of a sensitive detection tool for HuNoV. Biophysical studies including hydrogen/deuterium exchange (HDX) mass spectrometry and surface plasmon resonance (SPR) revealed that when the metal coordinated region of Con A, which spans Asp16 to His24, is converted to nine alanine residues (mCon A<SUP>MCR</SUP>), the affinity for HuNoV (GII.4) diminishes, demonstrating that this Ca<SUP>2+</SUP> and Mn<SUP>2+</SUP> coordinated region is responsible for the observed virus-protein interaction. The mutated carbohydrate binding region of Con A (mCon A<SUP>CBR</SUP>) does not affect binding affinity significantly, indicating that MCR of Con A is a major region of interaction to HuNoV (GII.4). The results further contribute to the development of a HuNoV concentration tool, Con A-immobilized polyacrylate beads (Con A-PAB), for rapid detection of genotypes from genogroups I and II (GI and GII). This method offers many advantages over currently available methods, including a short concentration time. HuNov (GI and GII) can be detected in just 15 min with 90% recovery through Con A-PAB application. In addition, this method can be used over a wide range of pH values (pH 3.0 - 10.0). Overall, this rapid and sensitive detection of HuNoV (GI and GII) will aid in the prevention of virus transmission pathways, and the method developed here may have applicability for other foodborne viral infections.

간호대생과 의대생의 간호사 이미지 비교

구민진,김수영,방정민,서아영,양희진,윤소람,이윤재,이재은,이지연,정윤경,최수정 이화여자대학교 간호과학대학 2014 이화간호학회지 Vol.- No.48

Purpose: This study aims to analyze the difference in the perception that nursing students and medical students have regarding the image of nurses. Method: The sampling group for this study was made up of 111 nursing students and 117 medicine students, conducted from the 19th August 2013 to 3rd September 2013. The tool used for this study is the “Nurse Image Scale”. The data is analyzed using the SPSS 21.0 program, technical stats, t-test and ANOVA with Scheffe test. Result: There was a notable difference in the results(t=6.94, p<001), with the average image perception score of nurses at 3.84±0.34 amongst nursing students being higher than the 3.50±0.38 amongst Medicine students. The average score of the 4 areas tested, “Qualification of a Nurse”, “Role of a Nurse”, “Social Participation of a Nurse” and “Interpersonal Skills of a Nurse” were all marked higher by the nursing students than the medicine students. The average score became notably higher as the period of practice became shorter with nursing students (F=4.21, p=.043). Furthermore, the average score for the “Qualification of a Nurse” was notably higher as the period of practice became shorter (F=3.98, p=.049). Medical students gave an average score for the “Qualification of a Nurse”(F=3.72, p=.027) and the “Interpersonal Skills of a Nurse”(F=4.11, p=.019) which was relative to the development of a nurse’s image, while the average score for the “Role of a Nurse” was notably higher with a longer period of practice(F=6.65, p=.011). Conclusion: The results of this study suggest that the image perception of a nurse can vary depending on the experience in period of practice. Therefore, together with this study conducted with nursing students and medicine students, there is a need for further studies conducted on image perception of nurses with various experience in period of practice.

Descending thin limb of the intermediate loop expresses both aquaporin 1 and urea transporter A2 in the mouse kidney

Kim, W. Y.,Lee, H. W.,Han, K. H.,Nam, S. A.,Choi, A.,Kim, Y. K.,Kim, J. Springer Science + Business Media 2016 Histochemistry and cell biology Vol.146 No.1

<P>A new intermediate type of Henle's loop has been reported that it extends into the inner medulla and turns within the first millimeter beyond the outer medulla. This study aimed to identify the descending thin limb (DTL) of the intermediate loop in the adult C57Bl/6 mouse kidney using aquaporin 1 (AQP1) and urea transporter A2 (UT-A2) antibodies. In the upper part of the inner stripe of the outer medulla (ISOM), AQP1 was expressed strongly in the DTL with type II epithelium of the long loop, but not in type I epithelium of the short loop. The DTL of the intermediate loop exhibited weak AQP1 immunoreactivity. UT-A2 immunoreactivity was not observed in the upper part of any DTL type. AQP1 expression was similar in the upper and middle parts of the ISOM. UT-A2 expression was variable, being expressed strongly in the DTL with type I epithelium of the short loop, but not in type II epithelium of the long loop. In the innermost part of the ISOM, AQP1 was expressed only in type III epithelium of the long loop. UT-A2-positive and UT-A2-negative cells were intermingled in type I epithelium of the intermediate loop, but were not observed in type III epithelium of the long loop. UT-A2-positive DTLs of the intermediate loop extended into the UT-A2/AQP1-negative type I epithelium in the initial part of the inner medulla. These results demonstrate that the DTL of the intermediate loop is composed of type I epithelium and expresses both AQP1 and UT-A2. The functional role of the DTL of the intermediate loop may be distinct from the short or long loops.</P>

Molecular Identification of the Soybean Aphid on the Primary Host, Rhamnus davurica in Korea

Hyojoong Kim,Yeyeun Kim,Kim A. Hoelmer,Seunghwan Lee 한국응용곤충학회 2009 한국응용곤충학회 학술대회논문집 Vol.2009 No.05

The soybean aphid, Aphis glycines Matsumura 1917, is well known as a soybean pest in the world. Recently, it has been introduced to North America causing serious damage in U.S. As a cooperative research with USDA-ARS, we have investigated A. glycines in soybean fields, and also examined the colonies on the overwintering host Rhamnus davurica in order to find its natural enemies. It was generally reported that A. glycines has host alternation between the soybean, Glycine max (summer host) and the Dahurian buckthorn, Rhamnus davurica (winter host) in East Asia. However, it was very difficult to identify the soybean aphid, A. glycines, from R. davurica due to the co-existance of at least three Aphis species and the seasonal polymorphisms of each species (e.g, gynopara, ovipara, and male). For species identification, we tested 3 molecular markers, mitochondrial COI, COII, and nuclear EF1α, for 14 collected samples (7 samples from G. max and 7 samples from R. davurica). As a result, we found two different species, A. gossypii and other Aphis sp., are mixed together with A. glycines on R. davurica. We report the biology of A. glycines in Korea, and present species identification using molecular phylogenetic approach.

A형 간염의 자연항체와 예방접종을 통한 항체 생성률의 역가 비교분석

권원현,김경화,조경아,문기춘,김정인,이인원,Kwon, Won Hyun,Kim, Kyung Hwa,Cho, Kyung A,Moon, Ki Choon,Kim, Jung In,Lee, In Won 대한핵의학기술학회 2013 핵의학 기술 Vol.17 No.2

2008년부터 A형 간염 환자들이 급속히 증가하고 본원에 내원하여 건진을 받는 대부분의 수검자들이 A형 간염(IgG) 항체 생성 유무에 관심이 많아지며 검사 건수가 증가하였다. 그에 따라 항체 검사결과가 cut-off값에 걸리는 검체가 많아져 원인을 분석하였더니 대부분 A형 간염 예방접종을 한 수검자들이었다. 이에 저자들은 건강증진센터에서 설문조사를 통하여 자연면역을 획득한 수검자들 그룹과 본원에서 A형 간염 예방접종(1차, 2차)을 실시한 직원들 그룹으로 나누어 검사를 시행하였고 cut-off값을 기준으로 항체 생성률과 그에 대한 역가를 비교하고 진단검사의학과와 핵의학과에서 사용하는 진단 시약간에 항체 생성률과 그에 대한 역가를 비교해 보고자 했고, 2012년 8월 한 달 동안 건진 수검자 185명을 설문조사하여 자연면역을 획득한 119명과 본원에서 예방 접종을 실시한 직원들을 대상으로 1차 접종자 53명, 2차 접종자 59명으로 대상을 분류했다. 항체 생성률은 cut-off값 1을 기준했을 때 0.90-1.10 (${\pm}$), 0.60-0.89 (1+), 0.30-0.59 (2+), 0.01-0.29 (3+)로 나누어 역가를 비교하고, 같은 기준으로 제조사별 백신 접종 후 항체 생성률에 대한 역가를 비교평가 해 보았다. 그 결과, 건진 수검자 중 자연 면역을 획득한 수검자는 cut-off값 1을 기준했을 때, 0.90-1.10 (${\pm}$)가 0%, 0.60-0.89 (1+)가 0%, 0.30-0.59 (2+)가 4.2%, 0.01-0.29 (3+)가 96%로 역가가 <0.60 ($${\geq_-}2+$$)가 100%였다. 그리고 예방접종을 실시한 직원들의 항체 생성률은 1차 접종자 중 ${\pm}$가 59.1%, 1+가 18.1%, 2+가 18.1%, 3+가 4.6%로 총 45.3%였고, 역가는 $${\geq_-}$$ 0.60 ($${\leq_-}1+$$)가 77.3%였다. 2차 접종자의 항체 생성률은 ${\pm}$가 1.9%, 1+가 15.4%, 2+가 36.54%, 3+가 46.2%로 총 88.1%였고 역가는 <0.60 ($${\geq_-}2+$$) 82.7%가 였다. 또한 제조사별로 비교 하였을 때 1차 접종자의 항체 생성률은 BNIBT 20.8% (${\pm}24.5%$), GB 15.7% (${\pm}7.8%$), RIAKEY 94.3% (${\pm}3.8%$), ROCHE 83% (${\pm}0%$), Abbot 73.1% (${\pm}5.8%$)였고, 2차 접종자의 항체 생성률은 BNIBT 86.4% (${\pm}1.7%$), GB 88.5% (${\pm}1.9%$), RIAKEY 100% (${\pm}0%$), ROCHE 98.3% (${\pm}0%$), Abbot 98.2% (${\pm}0%$)였다. 즉 자연면역 항체가 예방접종에 의한 항체보다 역가가 높다는 것을 알 수 있었고, 1차 접종 후 보다는 2차 접종 후 검사를 시행했을 때 항체 생성률과 역가가 대부분 높아짐을 알 수 있었다. 따라서 결과 보고시 negative, index (${\pm}$), weak positive (1+), positive (2+), strong positive (3+)로 역가를 나누어 보고를 하거나 결과값에 index값을 같이 적어서 결과를 상세히 보고한다면 과거결과와 비교도 가능할 것이다. 또 제조사별 비교 시 1차 예방접종 후의 항체 생성률과 역가에서 시약간에 많은 차이를 보이고 있었고, 매년 예방 접종률이 높아지고 있는 시점에서 이러한 차이를 줄이기 위해서 각 제조사들은 민감도나 재현성에 더 주의를 기울여야 하겠고, 자연면역항체와 예방접종을 통한 항체간에 생길 수 있는 미지의 차이를 감안하여 검사자들이 사용하는 시약을 신뢰할 수 있도록 더 연구하고 개발해야 할 것이다. Purpose: Since 2008, hepatitis A patients was rapidly increasing. So, Most of the health checkup examinees were interested in whether hepatitis A antibody was a lot. thereby The number of tests was increasing. In recent years, Antibody test results in the range of cut-off values were increased. According to the cause analysis, most examinees had a hepatitis A vaccine. This study was conducted to classify hepatitis A antibody as natural antibody and antibody after vaccination and compared the titer for seroconversion rate based on cut-off values. Materials and Methods: For a month in August 2012, First, We surveyed 185 health examinees and classified 119 health examinees who had acquired natural antibody. Second, for employees who were inoculated against hepatitis at our hospital, We classified into 53 primary inoculators and 59 secondary inculators. when the standard of cut-off value was 1, The seroconversion rate was compared the titer divided by 0.90-1.10 (${\pm}$), 0.60-0,89 (1+), 0.30-0.59 (2+), 0.01-0.29 (3+) and we compared the titer for seroconversion rate by each manufacturer after vaccination. Results: When the standard of cut-off value was 1, the titer of 119 health examinees who had acquired natural antibody was 0.90-1.10 (${\pm}$): 0%, 0.60-0.89 (1+): 0%, 0.30-0.59 (2+): 4.2%, 0.01-0.29 (3+): 96% and the titer of <0.60 ($${\geq_-}2+$$) was 100%. The titer of 53 primary inoculators was 0.90-1.10 (${\pm}:59.1%$), 0.60-0.89 (1+): 18.1%, 0.30-0.59 (2+): 18.1%, 0.01-0.29 (3+): 4.6% and the seroconversion rate was 45.3%. The titer of $${\geq_-}0.60$$ ($${\leq_-}1+$$) was 77.3%. The titer of 59 secondary inoculators was 0.90-1.10 (${\pm}:1.9%$), 0.60-0.89 (1+): 15.4%, 0.30-0.59 (2+): 36.54%, 0.01-0.29 (3+): 46.2% and the seroconversion rate was 88.1%. The titer of <0.60 ($${\geq_-}2+$$) was 82.7%. When we compared the titer for seroconversion rate by each manufacturer after vaccination, the seroconversion rate of 53 primary inoculators was BNIBT: 20.8% (${\pm}:24.5%$), GB: 15.7% (${\pm}:7.8%$), RIAKEY: 94.3% (${\pm}:3.8%$), ROCHE: 83% (${\pm}:0%$), ABBOTT: 73.1% (${\pm}:5.8%$) and the seroconversion rate of 59 secondary inoculators was BNIBT : 86.4% (${\pm}:1.7%$), GB: 88.5% (${\pm}:1.9%$), RIAKEY: 100% (${\pm}:0%$), ROCHE: 98.3% (${\pm}:0%$), ABBOTT: 98.2% (${\pm}:0%$). Conclusion: The study show that the titer of natural immune antibodies is higher than the titer of vaccination and the titer of secondary inoculation is mainly higher than the titer of primary inoculation. Consequently, if we know the titer of hepatitis A antibodies, it will help to give resullt reports. And then, when we compared the titer and the seroconversion rate by each manufacturer, There was a very distinct difference. As the test subjects inoculate against hepatitis A (HAV), it is considered BNIBT, GB will occur false negative rate and RIAKEY, ROCHE, ABOTT will occur false positive rate.

Thermal and X-ray diffraction analysis studies during the decomposition of ammonium uranyl nitrate

Kim, B. H.,Lee, Y. B.,Prelas, M. A.,Ghosh, T. K. Springer Netherlands 2012 Journal of radioanalytical and nuclear chemistry Vol.292 No.3

<P>Two types of ammonium uranyl nitrate (NH<SUB>4</SUB>)<SUB>2</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>4</SUB>·2H<SUB>2</SUB>O and NH<SUB>4</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>3</SUB>, were thermally decomposed and reduced in a TG-DTA unit in nitrogen, air, and hydrogen atmospheres. Various intermediate phases produced by the thermal decomposition and reduction process were investigated by an X-ray diffraction analysis and a TG/DTA analysis. Both (NH<SUB>4</SUB>)<SUB>2</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>4</SUB>·2H<SUB>2</SUB>O and NH<SUB>4</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>3</SUB> decomposed to amorphous UO<SUB>3</SUB> regardless of the atmosphere used. The amorphous UO<SUB>3</SUB> from (NH<SUB>4</SUB>)<SUB>2</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>4</SUB>·2H<SUB>2</SUB>O was crystallized to γ-UO<SUB>3</SUB> regardless of the atmosphere used without a change in weight. The amorphous UO<SUB>3</SUB> obtained from decomposition of NH<SUB>4</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>3</SUB> was crystallized to α-UO<SUB>3</SUB> under a nitrogen and air atmosphere, and to β-UO<SUB>3</SUB> under a hydrogen atmosphere without a change in weight. Under each atmosphere, the reaction paths of (NH<SUB>4</SUB>)<SUB>2</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>4</SUB>·2H<SUB>2</SUB>O and NH<SUB>4</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>3</SUB> were as follows: under a nitrogen atmosphere: (NH<SUB>4</SUB>)<SUB>2</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>4</SUB>·2H<SUB>2</SUB>O → (NH<SUB>4</SUB>)<SUB>2</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>4</SUB>·H<SUB>2</SUB>O → (NH<SUB>4</SUB>)<SUB>2</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>4</SUB> → NH<SUB>4</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>3</SUB> → A-UO<SUB>3</SUB> → γ-UO<SUB>3</SUB> → U<SUB>3</SUB>O<SUB>8</SUB>, NH<SUB>4</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>3</SUB> → A-UO<SUB>3</SUB> → α-UO<SUB>3</SUB> → U<SUB>3</SUB>O<SUB>8</SUB>; under an air atmosphere: (NH<SUB>4</SUB>)<SUB>2</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>4</SUB>·2H<SUB>2</SUB>O → (NH<SUB>4</SUB>)<SUB>2</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>4</SUB>·H<SUB>2</SUB>O → (NH<SUB>4</SUB>)<SUB>2</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>4</SUB> → NH<SUB>4</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>3</SUB> → A-UO<SUB>3</SUB> → γ-UO<SUB>3</SUB> → U<SUB>3</SUB>O<SUB>8</SUB>, NH<SUB>4</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>3</SUB> → A-UO<SUB>3</SUB> → α-UO<SUB>3</SUB> → U<SUB>3</SUB>O<SUB>8</SUB>; and under a hydrogen atmosphere: (NH<SUB>4</SUB>)<SUB>2</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>4</SUB>·2H<SUB>2</SUB>O → (NH<SUB>4</SUB>)<SUB>2</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>4</SUB>·H<SUB>2</SUB>O → (NH<SUB>4</SUB>)<SUB>2</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>4</SUB> → NH<SUB>4</SUB>UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>3</SUB> → A-UO<SUB>3</SUB> → γ-UO<SUB>3</SUB> → α-U<SUB>3</SUB>O<SUB>8</SUB> → UO<SUB>2</SUB>, NH<SUB>4</SUB> UO<SUB>2</SUB>(NO<SUB>3</SUB>)<SUB>3</SUB> → A-UO<SUB>3</SUB> → β-UO<SUB>3</SUB> → α-U<SUB>3</SUB>O<SUB>8</SUB> → UO<SUB>2</SUB>.</P>

A rationally designed small molecule for identifying an <i>in vivo</i> link between metal–amyloid-β complexes and the pathogenesis of Alzheimer's disease

Beck, Michael W.,Oh, Shin Bi,Kerr, Richard A.,Lee, Hyuck Jin,Kim, So Hee,Kim, Sujeong,Jang, Milim,Ruotolo, Brandon T.,Lee, Joo-Yong,Lim, Mi Hee Royal Society of Chemistry 2015 Chemical Science Vol.6 No.3

<▼1><P>An <I>in vivo</I> chemical tool designed to target metal–Aβ complexes and modulate their activity was applied to the 5XFAD mouse model of Alzheimer’s disease (AD) demonstrating the involvement of metal–Aβ in AD pathology.</P></▼1><▼2><P>Multiple factors, including amyloid-β (Aβ), metals, and reactive oxygen species (ROS), are involved in the development of Alzheimer's disease (AD). Metal ions can interact with Aβ species generating toxic oligomers and ROS <I>in vitro</I>; however, the involvement of metal–Aβ complexes in AD pathology <I>in vivo</I> remains unclear. To solve this uncertainty, we have developed a chemical tool (<B>L2-b</B>) that specifically targets metal–Aβ complexes and modulates their reactivity (<I>i.e.</I>, metal–Aβ aggregation, toxic oligomer formation, and ROS production). Through the studies presented herein, we demonstrate that <B>L2-b</B> is able to specifically interact with metal–Aβ complexes over metal-free Aβ analogues, redirect metal–Aβ aggregation into off-pathway, nontoxic less structured Aβ aggregates, and diminish metal–Aβ-induced ROS production, overall mitigating metal–Aβ-triggered toxicity, confirmed by multidisciplinary approaches. <B>L2-b</B> is also verified to enter the brain <I>in vivo</I> with relative metabolic stability. Most importantly, upon treatment of 5XFAD AD mice with <B>L2-b</B>, (i) metal–Aβ complexes are targeted and modulated in the brain; (ii) amyloid pathology is reduced; and (iii) cognition deficits are significantly improved. To the best of our knowledge, by employing an <I>in vivo</I> chemical tool specifically prepared for investigating metal–Aβ complexes, we report for the first time experimental evidence that metal–Aβ complexes are related directly to AD pathogenesis.</P></▼2>

A study of nerve agent model organophosphonate binding with manganese-A₂B-corrole and -A₂B₂-porphyrin systems

Kim, K.,Kim, I.,Maiti, N.,Kwon, S.J.,Bucella, D.,Egorova, O.A.,Lee, Y.S.,Kwak, J.,Churchill, D.G. Pergamon Press 2009 Polyhedron Vol.28 No.12

Herein the synthesis and binding studies of novel trans-A<SUB>2</SUB>B-corrole and trans-A<SUB>2</SUB>B<SUB>2</SUB>-porphyrin derivatives are presented in comparing manganese(III)-organophosphonate (OP) binding (e.g., M<SUP>n+</SUP>←O?PR(OR)<SUB>2</SUB>) capabilities. H<SUB>3</SUB>(PFP-VC) [PFP-VC=5,15-di(pentafluorophenyl)-10-(3-vinylphenyl)corrolate] was synthesized by way of literature procedures and was characterized by a variety of 2-D NMR spectroscopic techniques and single-crystal X-ray diffraction. These compounds represent the first example of 3-vinyl-phenyl-containing meso-substituted corroles or porphyrins. Mn(PFP-VC) (3) was treated separately with (CH<SUB>3</SUB>CH<SUB>2</SUB>O)<SUB>2</SUB>P?O(C<SUB>3</SUB>H<SUB>6</SUB>NMe<SUB>2</SUB>), (C<SUB>4</SUB>H<SUB>9</SUB>O)<SUB>2</SUB>P?O(Me), (C<SUB>2</SUB>H<SUB>5</SUB>O)<SUB>2</SUB>P?O(CH<SUB>2</SUB>COCH<SUB>3</SUB>), (CH<SUB>3</SUB>CH<SUB>2</SUB>O)<SUB>2</SUB>P?O(Me), to give 1:1 adducts, as determined by UV-Vis spectroscopy (Job Plot), giving a red shift; Ph<SUB>3</SUB>P?O, was also found to bind, but very weakly. The trans-A<SUB>2</SUB>B<SUB>2</SUB>-porphyrin analogue Mn(PFP-VP) (4) was also prepared by way of a literature procedure; related binding studies gave 1:1 organophosphonate-Mn(PFP-VP) adducts (Job Plot). A clean blue shift occurred for the Mn-porphyrins at higher organophosphonate loadings (K<SUB>a</SUB> values: 6.7 (0.9)-11.9 (0.4)M<SUP>-1</SUP>). DFT geometry optimizations of O?P(OMe)<SUB>2</SUB>Me binding and formal Mn-O or P-O cleavage products in the unsubstituted neutral Mn-corrolato and -porphyrinato systems with a range of metal-based spin states revealed greatest stability in formal phosphoryl oxygen binding (energies: 11-13kcal/mol) for the Mn-corrole (singlet); the Mn-porphyrin (sextet) was also quite stable.

Viral genome RNA degradation by sequence-selective, nucleic-acid hydrolyzing antibody inhibits the replication of influenza H9N2 virus without significant cytotoxicity to host cells

Kim, A.,Lee, J.Y.,Byun, S.J.,Kwon, M.H.,Kim, Y.S. Elsevier/North-Holland 2012 Antiviral research Vol.94 No.2

Influenza A virus infection is a great threat to avian species and humans. Targeting viral proteins by antibody has a limited success due to the antigen drift and shift. Here we present a novel antibody-based antiviral strategy of targeting viral genomic RNA (vRNA) for degradation rather than neutralizing viral proteins. Based on the template of a sequence-nonspecific nucleic acid-hydrolyzing, single domain antibody of the light chain variable domain, 3D8 VL, we generated a synthetic library on the yeast surface by randomizing putative nucleic acid interacting residues. To target nucleocapsid protein (NP)-encoding viral genomic RNA (NP-vRNA) of H9N2 influenza virus, the library was screened against a 18-nucleotide single stranded nucleic acid substrate, dubbed asNP<SUB>18</SUB>, the sequence of which is unique to the NP-vRNA. We isolated a 3D8 VL variant, NP25, that had ~15-fold higher affinity (~54nM) and ~3-fold greater selective hydrolyzing activity for the target substrate than for off targets. In contrast to 3D8 VL WT, asNP<SUB>18</SUB>-selective NP25 constitutively expressed in the cytosol of human lung carcinoma A549 cells does not exhibit any significant cytotoxicity and selectively degrades a reporter mRNA carrying the target asNP<SUB>18</SUB> sequence in the stable cell lines. NP25 more potently inhibits the replication of H9N2 influenza virus than 3D8 VL WT in the stable cell lines. NP25 more selectively reduces the amount of the targeted NP-vRNA than 3D8 VL WT from the early stage of virus infection in the stable cell lines, without noticeable harmful effects on the endogenous mRNA, suggesting that NP25 indeed more specifically recognizes to hydrolyze the target NP-vRNA of H9N2 virus than off-targets. Our results provide a new strategy of targeting viral genomic RNA for degradation by antibody for the prevention of influenza virus infection in humans and animals.