This work was supported by the Korea Ministry of Environment (MOE) as part of the "The advancement of scientific research and technological development in environmental science program (E315-00015-0414-2)."

관리 세트에서 튜브 1. 준비 참고 정확하게 약물 흡수에 튜브 길이 차이의 효과를 제거하는 절단 공정을 수행한다. <ol><li> 마커를 사용하여 튜브형과 튜브의 단부에 라벨 (예를 들면, PVC, 폴리 우레탄 (PU)을 폴리올레핀 (PO)). </li><li> 이러한 커넥터와 바늘 커버 모든 분리 액세서리를 제거합니다. </li><li> 날카로운 면도날을 사용하여 깨끗한 가장자리를 확인 드립 챔버의 연결에서 길이 1m에 튜브를 잘라. </li></ol> 약물 주입 2. 희석 참고 : 주입 된 약물 솔루션을 용기로 유리 병 (1 L)를 사용합니다. 정확하게 희석 단계를 수행합니다. 시판 제제의 조성을 확인하고, 전체 실험 세트의 동일한 배치 번호를 사용한다. <ol><li> 약물 이름 (예를 들어, 다이아 제팜 또는 타 크롤리 무스)와 라벨 병. </li><li> 약물 주입 희석5 % 포도당 용액의 5 밀리그램에서 / mL의 디아제팜 주사 (2 100 mL의 5 % 덱 스트로스 용액에 다이아 제팜 주입 mL)과 5 mg 내지 / mL의 타 크롤리 무스 주사 10 μg의 / mL의에 100 μg의 / mL의에 ( 5 % 덱 스트로스 용액 100 ㎖)에 주입 타크로리무스 200 μL. 참고 : 임상 사용량에 따라 약물과 용매의 시험 농도를 설정합니다. </li><li> 부드럽게 균질 약물 용액을 수득 소용돌이에 의해 병에 희석 용액을 혼합한다. </li><li> 유리를 사용하여 황색 유리 병에 수집 희석 용액 (1 ~ 10 mL)을 실린더를 졸업했다. </li><li> 단계 4에 기재된 바와 같이, 농도를 확인한다. 참고 : 시작 지점에서 농도로 약물의 이러한 농도를 사용합니다. </li></ol> 3. 운동 흡착 연구 주입 펌프를 사용하여 주 : 의한 튜브의 경도 수착 측정에 앞서, 펌프를 사용하는 튜브 따라 유량을 확인한다. 정확한 시점과 사용 GLA에서 샘플을 수집SS 병 및 유리 병은 저장 중에 추가로 약물 흡수를 방지합니다. 도 2에 도시 된 바와 같이 시험한다. 약물이 감광성이있는 경우 빛에 약액을 보호합니다. 세중의 실험을 수행합니다. <ol><li> 기포를 생성하지 않고, 주사기를 사용하여 튜브에 약물 희석액을 미리로드. <ol><li> 주사기에 튜브의 한쪽 끝을 연결합니다. </li><li> 병에 약액에 상기 튜브의 다른 쪽 끝을 넣는다. </li><li> 튜브가 완전히 약액 충전 될 때까지 주사기 플런저를 후퇴. </li></ol></li><li> 주입 펌프로 튜브를 설치합니다. <ol><li> 주입 펌프의 문을 열고 해제 레버를 누릅니다. </li><li> 주입 펌프에 미리로드 된 튜브를 삽입하고 똑바로 유지. </li><li> 설치 후, 튜브의 단부에 주사기를 제거한다. </li><li> 화학적 내성 붕 규산염 유리 튜브의 끝을 넣어 약물 오디오 솔루션을 수집하기 위해 실린더를 졸업이온은 튜브를 통과 한 후. </li></ol></li><li> 투여 세트의 튜브의 유형에 따라 유량 (PVC, PU, 또는 PO) 및 약물을 설정 (예를 들면, 디아제팜 1 ㎖ / 분, 타크로리무스 10 ㎖ / H). </li><li> 실온에서, 다양한 시점에서 황색 바이알에 샘플을 수집한다. <ol><li> 0.05에서 0.30, 0.55, 1.05 시간을 1 ML의 다이아 제팜 샘플을 수집합니다. </li><li> , 1.05에서 2.05, 3.05 및 4.05 시간을 10 ML의 타 크롤리 무스의 샘플을 수집합니다. </li></ol></li></ol> 약물 4. 분석하여 고성능 액체 크로마토 그래피 (HPLC) 주 : 약물 분석 용 HPLC 추천 방법은 참고 문헌 1, 8, 9에 기재되어있다. 다른 방법 (10), (11) 시료 전처리 후 탠덤 질량 분석 (MS / MS)와 면역를 사용합니다. 세중의 실험을 수행합니다.<ol><li> 약물을 달아 원액으로서 1 ㎎ / ㎖의 농도로 유기 용매에 용해들을. <ol><li> 때문에 5 % 덱 스트로스에서 다이아 제팜의 낮은 용해도에 다이아 제팜 원액을위한 용매로 메탄올을 사용합니다. </li><li> 때문에 5 % 포도당에 타 크롤리 무스의 낮은 용해도에 타 크롤리 무스의 원액을위한 용매로 아세토 니트릴을 사용합니다. </li></ol></li><li> 주식 솔루션을 희석하여 표준 용액을 준비합니다. <ol><li> , 0.3125 메탄올로 디아제팜 스톡 희석액 0.625, 1.25, 2.5, 5.0, 10.0, 20.0 μg의 / ㎖. </li><li> 5 % 덱 스트로스와 타크로리무스 스톡 희석액 2.5, 5.0, 10.0, 15.0, 20.0 μg의 / ㎖. </li></ol></li><li> UV 검사 1, 8, 9로 HPLC 방법을 이용하여 표준 분석. 주 : 약물 분석에 적합한 검출 방법 (UV, 형광 등)를 사용합니다. <ol><li> 스탠의 10 μL를 주입dards는 C (18) 열 (250mm × 1.5 mm, 5 μm의)을 갖춘 UV 검출과의 HPLC 시스템에. 분석 조건은 표 1을 참조하십시오. </li><li> 특이성 및 선형성 1, 8, 9를 확인합니다. <ol><li> 특이성을 위해, 약물을 식별 (이 크로마토 그램에서 다른 피크로부터 분리되었는지, IE) 약물 피크를 모니터링한다. </li><li> (피크 면적 결과 농도에 정비례 여부 IE) 보정 범위에서 선형성을 확인한다. </li></ol></li><li> 교정 곡선을 얻습니다. <ol><li> 표준 1, 8, 9의 크로마토 그램에서 피크 면적 값에 비해 농도에 따라 그래프를 작성합니다. </li><li> 예를 들어 (교정 곡선 R 2 선형 회귀 방정식을 구 </em&gt; Y = AX + B, X : 약물, Y의 농도 피크 면적) 1, 8, 9. </li></ol></li></ol></li><li> 그들이 보정 범위 내에 있도록 적절히 타크로리무스위한 디아제팜 또는 5 % 덱 스트로스 메탄올로 흡착 ​​연구 중 샘플을 희석 직접 HPLC 시스템으로 희석 한 시료의 10 μL를 주입. </li></ol> 약물 농도와 흡착 레벨 5. 계산 <ol><li> 검량선 (미지의 x 및 공지 Y)를 사용하여 샘플의 약물 농도를 계산한다. </li><li> 다음 식을 이용하여 약물의 흡수 레벨을 계산한다 : <img alt="식 (1)" src="/files/ftp_upload/55086/55086eq1.jpg" /> 여기서, S : 수착 수준 (%) CO : 주사 희석 한 후 약물 농도 (μg의 / ㎖) CP : 튜브를 통과 약물 농도 (μg의 / ㎖) </li></ol>

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The authors have nothing to disclose.

관리 세트에 대한 약물 흡수는 정맥 주사 약물 전달에 예상치 못한 약물 손실의 원인이다. 흡착 동안 약물은 일반적으로 주입의 초기 단계에서 튜브 고분자 재료로 분할된다; 흡착 평형에 도달 한 후, 약물의 전달 양이 1 안정화된다. 약물의 흡수 수준을 평가하고 최소로 할 것. 약물 흡수에 대한 여러 평가 방법은 이러한 펌프 방법과 똑 방법으로서 연구되어왔다. 드립 방식에 비...

투여 세트는 스파이크, 드립 챔버 튜브 루어 어댑터 (커넥터) 및 보호 바늘 커버로 구성된다. 이러한기도 체크 밸브, 조절 클램프 인라인 필터 캡 (주입구)와 Y-관 및 바늘 등의 다른 보조 역시 투여 세트에 부착 될 수있다. 튜브에 약물 흡수는 주사제 1의 전달에서 중요한 문제입니다. 수착은 중합체 표면에 약물 및 중합체 매트릭스에 약물이 흡수의 흡착을 설명한다. 투여 세트의 튜브 약물 흡수 예측할 약물 손실이 발생하고 어려운 전달 약물 농도를 제어 할 수있다. 고분자 튜브에 약물 흡수 따라서 몸에 주사 약물의 정확한 전달에 큰 장애물이다. 그러나 관리 세트에서 튜브에 약물 흡수의 평가에 대한 표준 방법 또는 규제 가이드 라인이 없다. <html> 투여 세트의 튜브 약물 흡수의 수준은 다양한 평가 방법 1, 2, 3, 4, 5를 이용하여보고되었다. 시험 방법 및 모델 약물 흡수 평가의 핵심 요소입니다. 펌프 방법 1, 3, 드립 방식 -4,5- 널리 흡착 시험에 사용되었다. 일반적으로, 펌프에있어서의 주입 상태 낮은 농도와 낮은 유량으로 약물의 경우에 사용되어야한다. 및 관리 비 PVC 계 튜브는 3, 2, 1로 설정 - 다양한 평가 방법을 사용하여, 약물 흡수의 많은 연구는 폴리 염화 비닐 (PVC)에 대해보고 된&gt; 5. 많은 흡착 약물 투여 세트의 튜브 약물 흡수 가능성이 있는지 여부를 조사하기 위해 선택 될 수있다. 디아제팜 (도 1A) 1, 2, 타크로리무스 (도 1B) 5 글리세린 2 및 3 PVC- 높은 흡착 비 PVC 계 튜브 대표적인 약물 스포린이다. 튜브에 약물 흡수의 평가를 들면, 유량 및 약물 농도 시험 조건은 선택된 약물 1, 6, 7의 임상 사용에 기초한다. 디아제팜의 경우 100 μg의 / ㎖의 고농도 간질 중첩증 (1)의 처리에 대한 초기 투여 량을 모방 1 mL / 분의 유속으로 사용되었다. 10 μg의 / ㎖ 타크로리무스 들어, 농도10 ㎖ / h의 유량으로 공급 하였다. 덱 스트로스 용액 (5 %)에서 약물 주입의 희석에 사용하고, 튜브 길이 1m로 고정 하였다. 유리 병, 바이알 실험 및 저장 중에 추가로 흡착을 ​​방지하기 위해 사용되어야한다. 본 연구에서는 펌프의 방법을 사용하여, 모델 약물, 디아제팜 및 타크로리무스와 운동 흡착 연구를 실시 하였다. 이 프로토콜의 구체적인 내용은, 튜브 준비에서 흡착 평가, 이전에 설명했다. 약물 흡수를 평가하는 방법은 이미 주사제 약물의 성질을 확인하고에 투여 세트와 주사의 임상 적 사용을 권장하는데 사용 된 경우에 따라 1, 2, 3, 4, 5, 6, 7. 이 프로토콜은 표준으로 사용될 수있다투여 세트의 흡착 평가 방법. 튜브 약물 흡수의 평가를위한 국제 표준 약물 전달의 안전성 및 효능을 보장하기 위해 필요할 수있다.

<table>
	<tbody>
		<tr>
			<td>PVC IV sets</td>
			<td>Becton Dickinson 
			(BD) Co. Ltd. (Franklin Lakes, NJ, USA)</td>
			<td></td>
			<td>Internal diameter: 2.54 mm</td>
		</tr>
		<tr>
			<td>PU IV sets</td>
			<td>Tianjin Hanaco Medical (THM) Co.Ltd. 
			(Tianjin, China)</td>
			<td></td>
			<td>Non-PVC 
			Internal diameter: 2.54 mm</td>
		</tr>
		<tr>
			<td>Non-PVC Polyolefin IV sets</td>
			<td>Polyscientech, Co. Ltd (Anseong, Korea)</td>
			<td></td>
			<td>Non-PVC [PE elastomer/PP elastomer/PB elastomer(25/50/25, weight ratio) blend] 
			Internal diameter: 2.54 mm</td>
		</tr>
		<tr>
			<td>Syringe</td>
			<td>Korea Vaccine Co. Ltd. (Seoul, Korea)</td>
			<td>KOVAX-SYRINGE 1 mL 26G 1/2&#34;</td>
			<td></td>
		</tr>
		<tr>
			<td>Daewon diazepam injection</td>
			<td>Daewon Pharma. Co. Ltd. (Hwaseong, Gyunggi, Korea)</td>
			<td></td>
			<td>1 mg/mL, total 2 mL 
			Batch No.: P003 
			Composition: diazepam, propylene glycol, ethanol, benzyl alcohol, sodium benzoate, bezoic acid, water for injection</td>
		</tr>
		<tr>
			<td>Tacrobel injection</td>
			<td>Chong Keun Dang, Co. Ltd. (Seoul, Korea)</td>
			<td></td>
			<td>5 mg/mL, total 1 mL 
			Batch No.: AG002 
			Composition: tacrolimus hydrate, polyoxyl 60 hydrogenated castor oil (HCO-60), dehydrated alcohol</td>
		</tr>
		<tr>
			<td>5% Dextrose</td>
			<td>JW Pharmaceutical (Seoul, Korea)</td>
			<td>500 mL</td>
			<td></td>
		</tr>
		<tr>
			<td>5% Dextrose</td>
			<td>Daehan Pharmaceutical (Seoul, Korea)</td>
			<td>200 mL</td>
			<td>Bottle (glass)</td>
		</tr>
		<tr>
			<td>Amber vials</td>
			<td></td>
			<td>20 mL</td>
			<td>Glass</td>
		</tr>
		<tr>
			<td>Terumo infusion pump</td>
			<td>Terumo (Medical Corp., USA)</td>
			<td>TE-135</td>
			<td></td>
		</tr>
		<tr>
			<td>HPLC system with UV detector</td>
			<td>Agilent (Santa Clara, CA, USA)</td>
			<td>Agilent 1260</td>
			<td></td>
		</tr>
		<tr>
			<td>CAPCELL PAK C18 column&#160;</td>
			<td>Shiseido (Japan)</td>
			<td>90404</td>
			<td>1.5 mm x 250 mm, 5 &#956;m</td>
		</tr>
		<tr>
			<td>Diazepam</td>
			<td></td>
			<td></td>
			<td>From Daewon Pharma. Co., Ltd.</td>
		</tr>
		<tr>
			<td>Tacrolimus</td>
			<td>Teva Czech industries&#160; (Czech Republic)</td>
			<td></td>
			<td>From Chong Keun Dang, Co. Ltd.</td>
		</tr>
		<tr>
			<td>Acetonitrile</td>
			<td>Burdick and Jackson Co., Ltd. (MI, USA)</td>
			<td>3/1/9017</td>
			<td></td>
		</tr>
		<tr>
			<td>Methanol</td>
			<td>Burdick and Jackson Co. Ltd. (MI, USA)</td>
			<td>AH230-4</td>
			<td></td>
		</tr>
		<tr>
			<td>Water</td>
			<td>Burdick and Jackson Co. Ltd. (MI, USA)</td>
			<td>3/1/4218</td>
			<td></td>
		</tr>
		<tr>
			<td>Sodium dihydrogen phosphate</td>
			<td>Sigma (St. Louis, MO, USA)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Phosphoric acid</td>
			<td>Sigma (St. Louis, MO, USA)</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

evaluation of drug sorption to pvc- and non-pvc-based tubes in administration sets using a pump

관리 세트는 몸에 약물의 직접 응용 프로그램에 전달 도구와 스파이크, 드립 챔버, 튜브, 루어 어댑터 (커넥터) 보호를위한 바늘 커버, 및 기타 액세서리로 구성된다. 투여 세트의 튜브 약물 흡수는 안전성과 효능면에서 중요한 문제이다. 약물 흡수는 투여 세트의 품질에있어서 중요한 인자이지만, 튜브에 약물 흡수의 조절에 대한 표준화 된 평가 방법은 없다. 여기서는 투여 세트의 튜브로 약물 흡수에 대한 평가 프로토콜을 설명한다. 폴리 염화 비닐 (PVC)로 이루어지는 관 - 비 PVC 계 고분자 재료는 길이 1m로 절단 하였다. 다이아 제팜과 타 크롤리 무스는 모델 약물로 사용되었다. 운동 흡착 연구는 이러한 약물의 임상 적 사용에 따라 약물의 농도 및 유량을 선택했다. 유리 병에서 각 약제의 희석 후에, 희석 된 약액은 튜브를 통해 전달 된관리의 펌프를 사용하여 설정합니다. 샘플은 적절한 시점에서 호박색 튜브에 수집하고, 약물은 고성능 액체 크로마토 그래피를 이용하여 분석 하였다. 투여 세트의 튜브 약물 농도 및 흡수 수준을 계산 하였다. 관리 세트의 품질을 보장하기 위해 허용 기준이 권장됩니다.

관리 세트의 튜브에 흡착는 역학적 모델 약물, 다이아 제팜 (그림 1a) 및 타 크롤리 무스를 사용하여 측정 하였다 (그림 1b), 펌프 방식 (그림 2). 희석 약제 (도 2a) (도 2B)는 주입 펌프 (도 2C)를 이용하여 일정한 유량 PVC- 비 PVC 계 튜브에 통과시켰다. 유리 병은 투여 세트 튜브의 삽입을 허용하도록 약...

Watch this Scientific Journal Video about Evaluation of Drug Sorption to PVC- and Non-PVC-based Tubes in Administration Sets Using a Pump at JoVE.com

Evaluation of Drug Sorption to PVC- and Non-PVC-based Tubes in Administration Sets Using a Pump

우리는 펌프 모델 약물 (디아제팜 및 타 크롤리 무스)을 사용하여 약 흡착 평가하는 방법을보고한다. 투여 세트의 튜브에서 고성능 액체 크로마토 그래피, 약물 농도 및 수착 레벨을 사용하여 약물 분석 후 계산된다.

약 흡착의 평가 PVC- 및 관리에 튜브를 비 PVC 기반 펌프를 사용하여 세트

Administration sets are delivery tools for the direct application of drugs into the body and are composed of a spike, a drip chamber, tubes, Luer adapters ...

evaluation-drug-sorption-to-pvc-non-pvc-based-tubes-administration

Research

JoVE Journal

Medicine

10.5K 조회수.  Yonsei University.  우리는 펌프 모델 약물 (디아제팜 및 타 크롤리 무스)을 사용하여 약 흡착 평가하는 방법을보고한다. 투여 세트의 튜브에서 고성능 액체 크로마토 그래피, 약물 농도 및 수착 레벨을 사용하여 약물 분석 후 계산된다. 

비디오: Evaluation of Drug Sorption to PVC- and Non-PVC-based Tubes in Administration Sets Using a Pump

Evaluation of Cancer Stem Cell Migration Using Compartmentalizing Microfluidic Devices and Live Cell Imaging

In the last 40 years, the United States invested over 200 billion dollars on cancer research, resulting in only a 5% decrease in death rate. A major obstacle for improving patient outcomes is the poor understanding of mechanisms underlying cellular migration associated with aggressive cancer cell invasion, metastasis and therapeutic resistance1. Glioblastoma Multiforme (GBM), the most prevalent primary malignant adult brain tumor2, exemplifies this difficulty. Despite standard surgery, radiation and chemotherapies, patient median survival is only fifteen months, due to aggressive GBM infiltration into adjacent brain and rapid cancer recurrence2. The interactions of aberrant cell migratory mechanisms and the tumor microenvironment likely differentiate cancer from normal cells3. Therefore, improving therapeutic approaches for GBM require a better understanding of cancer cell migration mechanisms. Recent work suggests that a small subpopulation of cells within GBM, the brain tumor stem cell (BTSC), may be responsible for therapeutic resistance and recurrence. Mechanisms underlying BTSC migratory capacity are only starting to be characterized1,4.
Due to a limitation in visual inspection and geometrical manipulation, conventional migration assays5 are restricted to quantifying overall cell populations. In contrast, microfluidic devices permit single cell analysis because of compatibility with modern microscopy and control over micro-environment6-9.
We present a method for detailed characterization of BTSC migration using compartmentalizing microfluidic devices. These PDMS-made devices cast the tissue culture environment into three connected compartments: seeding chamber, receiving chamber and bridging microchannels. We tailored the device such that both chambers hold sufficient media to support viable BTSC for 4-5 days without media exchange. Highly mobile BTSCs initially introduced into the seeding chamber are isolated after migration though bridging microchannels to the parallel receiving chamber. This migration simulates cancer cellular spread through the interstitial spaces of the brain. The phase live images of cell morphology during migration are recorded over several days. Highly migratory BTSC can therefore be isolated, recultured, and analyzed further. 
Compartmentalizing microfluidics can be a versatile platform to study the migratory behavior of BTSCs and other cancer stem cells. By combining gradient generators, fluid handling, micro-electrodes and other microfluidic modules, these devices can also be used for drug screening and disease diagnosis6. Isolation of an aggressive subpopulation of migratory cells will enable studies of underlying molecular mechanisms.

A compartmentalizing microfluidic device for investigating cancer stem cell migration is described. This novel platform creates a viable cellular microenvironment and enables microscopic visualization of live cell locomotion. Highly motile cancer cells are isolated to study molecular mechanisms of aggressive infiltration, potentially leading to more effective future therapies.

Compartmentalizing 마이크로 유체 장치와 라이브 세포 이미징을 사용하여 암 줄기 세포 마이그레이션 평가

In the last 40 years, the United States invested over 200 billion dollars on cancer research, resulting in only a 5% decrease in death rate. A major ...

연구

의학

Femoral Arterial and Venous Catheterization for Blood Sampling, Drug Administration and Conscious Blood Pressure and Heart Rate Measurements

In multiple fields of study, access to the circulatory system in laboratory studies is necessary. Pharmacological studies in rats using chronically implanted catheters permit a researcher to effectively and humanely administer substances, perform repeated blood sampling and assists in conscious direct measurements of blood pressure and heart rate. Once the catheter is implanted long-term sampling is possible. Patency and catheter life depends on multiple factors including the lock solution used, flushing regimen and catheter material. This video will demonstrate the methodology of femoral artery and venous catheterization of the rat. In addition the video will demonstrate the use of the femoral venous and arterial catheters for blood sampling, drug administration and use of the arterial catheter in taking measurements of blood pressure and heart rate in a conscious freely-moving rat. A tether and harness attached to a swivel system will allow the animal to be housed and have samples taken by the researcher with minimal disruption to the animal. To maintain patency of the catheter, careful daily maintenance of the catheter is required using lock solution (100 U/ml heparinized saline), machine-ground blunt tip syringe needles and the use of syringe filters to minimize potential contamination. With careful aseptic surgical techniques, proper catheter materials and careful catheter maintenance techniques, it is possible to sustain patent catheters and healthy animals for long periods of time (several weeks).

Chronic catheterization of blood vessels in the rat is often required for administration of substances, obtain blood sample over a period of time or for direct conscious blood pressure measurements. Femoral arterial catheterization of the rat and corresponding measurements of blood pressure in the conscious animal will be demonstrated.

혈액 샘플링, 마약 관리 및 의식 검사 중 혈압과 심장 박동을 측정 대퇴 동맥혈과 정맥 Catheterization

In multiple fields of study, access to the circulatory system in laboratory studies is necessary. Pharmacological studies in rats using chronically ...

The Measurement and Treatment of Suppression in Amblyopia

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current estimates put the prevalence of amblyopia at approximately 1-3%1-3, the majority of cases being monocular2. Amblyopia is most frequently caused by ocular misalignment (strabismus), blur induced by unequal refractive error (anisometropia), and in some cases by form deprivation.
Although amblyopia is initially caused by abnormal visual input in infancy, once established, the visual deficit often remains when normal visual input has been restored using surgery and/or refractive correction. This is because amblyopia is the result of abnormal visual cortex development rather than a problem with the amblyopic eye itself4,5 . Amblyopia is characterized by both monocular and binocular deficits6,7 which include impaired visual acuity and poor or absent stereopsis respectively. The visual dysfunction in amblyopia is often associated with a strong suppression of the inputs from the amblyopic eye under binocular viewing conditions8. Recent work has indicated that suppression may play a central role in both the monocular and binocular deficits associated with amblyopia9,10 .
Current clinical tests for suppression tend to verify the presence or absence of suppression rather than giving a quantitative measurement of the degree of suppression. Here we describe a technique for measuring amblyopic suppression with a compact, portable device11,12 . The device consists of a laptop computer connected to a pair of virtual reality goggles. The novelty of the technique lies in the way we present visual stimuli to measure suppression. Stimuli are shown to the amblyopic eye at high contrast while the contrast of the stimuli shown to the non-amblyopic eye are varied. Patients perform a simple signal/noise task that allows for a precise measurement of the strength of excitatory binocular interactions. The contrast offset at which neither eye has a performance advantage is a measure of the "balance point" and is a direct measure of suppression. This technique has been validated psychophysically both in control13,14 and patient6,9,11 populations.
In addition to measuring suppression this technique also forms the basis of a novel form of treatment to decrease suppression over time and improve binocular and often monocular function in adult patients with amblyopia12,15,16 . This new treatment approach can be deployed either on the goggle system described above or on a specially modified iPod touch device15.

Amblyopia is a developmental disorder of the visual cortex that is often accompanied by strong suppression of one eye. We present a new technique for measuring and treating interocular suppression in patients with amblyopia that can be deployed using virtual reality goggles or a portable iPod Touch device.

약시의 억제의 측정 및 치료

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current ...

Intranasal Administration of CNS Therapeutics to Awake Mice

Intranasal administration is a method of delivering therapeutic agents to the central nervous system (CNS). It is non-invasive and allows large molecules that do not cross the blood-brain barrier access to the CNS. Drugs are directly targeted to the CNS with intranasal delivery, reducing systemic exposure and thus unwanted systemic side effects1. Delivery from the nose to the CNS occurs within minutes along both the olfactory and trigeminal neural pathways via an extracellular route and does not require drug to bind to any receptor or axonal transport2. Intranasal delivery is a widely publicized method and is currently being used in human clinical trials3.
Intranasal delivery of drugs in animal models allows for initial evaluation of pharmacokinetic distribution and efficacy. With mice, it is possible to administer drugs to awake (non-anesthetized) animals on a regular basis using a specialized intranasal grip. Awake delivery is beneficial because it allows for long-term chronic dosing without anesthesia, it takes less time than with anesthesia, and can be learned and done by many people so that teams of technicians can dose large numbers of mice in short periods. Efficacy of therapeutics administered intranasally in this way to mice has been demonstrated in a number of studies including insulin in diabetic mouse models 4-6 and deferoxamine in Alzheimer's mouse models. 7,8
The intranasal grip for mice can be learned, but is not easy and requires practice, skill, and a precise grip to effectively deliver drug to the brain and avoid drainage to the lung and stomach. Mice are restrained by hand using a modified scruff in the non-dominant hand with the neck held parallel to the floor, while drug is delivered with a pipettor using the dominant hand. It usually takes 3-4 weeks of acclimating to handling before mice can be held with this grip without a stress response. We have prepared this JoVE video to make this intranasal delivery technique more accessible.

A method to intranasally administer drugs to awake mice for the purpose of targeting the brain is described. This method allows for repeat dosing over long periods using intranasal administration of drug without anesthesia, and nose-to-brain delivery with minimal systemic exposure.

깨어 마우스로 CNS의 치료학의 비강 관리

Intranasal administration is a method of delivering  therapeutic agents to the central nervous system (CNS). It is  non-invasive and allows large ...

Evaluation of a Novel Laser-assisted Coronary Anastomotic Connector - the Trinity Clip - in a Porcine Off-pump Bypass Model

To simplify and facilitate beating heart (i.e., off-pump), minimally invasive coronary artery bypass surgery, a new coronary anastomotic connector, the Trinity Clip, is developed based on the excimer laser-assisted nonocclusive anastomosis technique. The Trinity Clip connector enables simplified, sutureless, and nonocclusive connection of the graft to the coronary artery, and an excimer laser catheter laser-punches the opening of the anastomosis. Consequently, owing to the complete nonocclusive anastomosis construction, coronary conditioning (i.e., occluding or shunting) is not necessary, in contrast to the conventional anastomotic technique, hence simplifying the off-pump bypass procedure. Prior to clinical application in coronary artery bypass grafting, the safety and quality of this novel connector will be evaluated in a long-term experimental porcine off-pump coronary artery bypass (OPCAB) study. In this paper, we describe how to evaluate the coronary anastomosis in the porcine OPCAB model using various techniques to assess its quality. Representative results are summarized and visually demonstrated.

This paper describes a novel nonocclusive coronary anastomotic connector in a porcine off-pump coronary artery bypass (OPCAB) model. This easy-to-use coronary connector has intrinsic potential to facilitate minimally invasive OPCAB surgery.

삼위 일체 클립 - - 소설 레이저를 이용한 관상 동맥 문합 커넥터의 평가 돼지 오프 펌프 바이 패스 모델에

To simplify and facilitate beating heart (i.e., off-pump), minimally invasive coronary artery bypass surgery, a new coronary anastomotic connector, the ...

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

The calcineurin inhibitor tacrolimus is the cornerstone of most immunosuppressive treatment protocols after solid organ transplantation in the United States. Tacrolimus is a narrow therapeutic index drug and as such requires therapeutic drug monitoring and dose adjustment based on its whole blood trough concentrations. To facilitate home therapeutic drug and adherence monitoring, the collection of dried blood spots is an attractive concept. After a finger stick, the patient collects a blood drop on filter paper at home. After the blood is dried, it is mailed to the analytical laboratory where tacrolimus is quantified using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in combination with a simple manual protein precipitation step and online column extraction.
For tacrolimus analysis, a 6-mm disc is punched from the saturated center of the blood spot. The blood spot is homogenized using a bullet blender and then proteins are precipitated with methanol/0.2 M ZnSO4 containing the internal standard D2,13C-tacrolimus. After vortexing and centrifugation, 100 &#181;l of supernatant is injected into an online extraction column and washed with 5 ml/min of 0.1 formic acid/acetonitrile (7:3, v:v) for 1 min. Hereafter, the switching valve is activated and the analytes are back-flushed onto the analytical column (and separated using a 0.1% formic acid/acetonitrile gradient). Tacrolimus is quantified in the positive multi reaction mode (MRM) using a tandem mass spectrometer.
The assay is linear from 1 to 50 ng/ml. Inter-assay variability (3.6%-6.1%) and accuracy (91.7%-101.6%) as assessed over 20 days meet acceptance criteria. Average extraction recovery is 95.5%. There are no relevant carry-over, matrix interferences and matrix effects. Tacrolimus is stable in dried blood spots at RT and at +4 &#176;C for 1 week. Extracted samples in the autosampler are stable at +4 &#176;C for at least 72 hr.

Here we describe a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay to quantify the immunosuppressant tacrolimus in dried blood spots using a simple manual protein precipitation step and online column extraction.

LC-MS / MS를 사용하여 건조 혈액 명소에 면역 억제제 타 크롤리 무스의 정량화

The calcineurin inhibitor tacrolimus is the cornerstone of most immunosuppressive treatment protocols after solid organ transplantation in the United ...

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport

Along with their traditional role as detergents that facilitate fat absorption, emerging literature indicates that bile acids are potent signaling molecules that affect multiple organs; they modulate gut motility and hormone production, and alter vascular tone, glucose metabolism, lipid metabolism, and energy utilization. Changes in fecal bile acids may alter the gut microbiome and promote colon pathology including cholerrheic diarrhea and colon cancer. Key regulators of fecal bile acid composition are the small intestinal Apical Sodium-dependent Bile Acid Transporter (ASBT) and fibroblast growth factor-19 (FGF19). Reduced expression and function of ASBT decreases intestinal bile acid up-take. Moreover, in vitro data suggest that some FDA-approved drugs inhibit ASBT function. Deficient FGF19 release increases hepatic bile acid synthesis and release into the intestines to levels that overwhelm ASBT. Either ASBT dysfunction or FGF19 deficiency increases fecal bile acids and may cause chronic diarrhea and promote colon neoplasia. Regrettably, tools to measure bile acid malabsorption and the actions of drugs on bile acid transport in vivo are limited. To understand the complex actions of bile acids, techniques are required that permit simultaneous monitoring of bile acids in the gut and metabolic tissues. This led us to conceive an innovative method to measure bile acid transport in live animals using a combination of proton (1H) and fluorine (19F) magnetic resonance imaging (MRI). Novel tracers for fluorine (19F)-based live animal MRI were created and tested, both in vitro and in vivo. Strengths of this approach include the lack of exposure to ionizing radiation and translational potential for clinical research and practice.

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport

Tools to diagnose bile acid malabsorption and measure bile acid transport in vivo are limited. An innovative approach in live animals is described that utilizes combined proton (1H) plus fluorine (19F) magnetic resonance imaging; this novel methodology has translational potential to screen for bile acid malabsorption in clinical practice.

멀티 플루오르 담즙 산 및 사용<em&gt; 생체</em&gt; 자기 공명 영상은 측정하는 담즙 산 전송

Along with their traditional role as detergents that facilitate fat absorption, emerging literature indicates that bile acids are potent signaling ...

Novel Methods for Intranasal Administration Under Inhalation Anesthesia to Evaluate Nose-to-Brain Drug Delivery

Intranasal administration has been reported to be a potential pathway for nose-to-brain delivery of therapeutic agents that circumvents the blood-brain barrier. However, there have been few reports regarding not only the quantitative analysis but also optimal administration conditions and dosing regimens for investigations of nose-to-brain delivery. The limited progress in research on nose-to-brain pathway mechanisms using rodents represents a significant impediment in terms of designing nose-to-brain delivery systems for candidate drugs.
To gain some headway in this regard, we developed and evaluated two novel methods of stable intranasal administration under inhalation anesthesia for experimental animals. We also describe a method for the evaluation of drug distribution levels in the brain via the nose-to-brain pathway using radio-labeled [14C]-inulin (molecular weight: 5,000) as a model substrate of water-soluble macromolecules.
Initially, we developed a pipette-based intranasal administration protocol using temporarily openable masks, which enabled us to perform reliable administration to animals under stable anesthesia. Using this system, [14C]-inulin could be delivered to the brain with little experimental error.
We subsequently developed an intranasal administration protocol entailing reverse cannulation from the airway side through the esophagus, which was developed to minimize the effects of mucociliary clearance (MC). This technique led to significantly higher levels of [14C]-inulin, which was quantitatively detected in the olfactory bulb, cerebrum, and medulla oblongata, than the pipette method. This appears to be because retention of the drug solution in the nasal cavity was substantially increased by active administration using a syringe pump in a direction opposite to the MC into the nasal cavity.
In conclusion, the two methods of intranasal administration developed in this study can be expected to be extremely useful techniques for evaluating pharmacokinetics in rodents. The reverse cannulation method, in particular, could be useful for evaluating the full potential of nose-to-brain delivery of drug candidates.

Here, we describe two novel methods of stable intranasal administration under inhalation anesthesia with minimal physical stress for experimental animals. We also describe a method for quantitative evaluation of drug distribution levels in the brain via the nose-to-brain pathway using radiolabeled [14C]-inulin as a model substrate of water-soluble macromolecules.

Intranasal administration has been reported to be a potential pathway for nose-to-brain delivery of therapeutic agents that circumvents the blood-brain ...

Implantation of an Isoproterenol Mini-Pump to Induce Heart Failure in Mice

Isoproterenol (ISO), is a non-selective beta-adrenergic agonist, that is used widely to induce cardiac injury in mice. While the acute model mimics stress-induced cardiomyopathy, the chronic model, administered through an osmotic pump, mimics advanced heart failure in humans. The purpose of the described protocol is to create the chronic ISO-induced heart failure model in mice using an implanted mini-pump. This protocol has been used to induce heart failure in 100+ strains of inbred mice. Techniques on surgical pump implantation are described in detail and may be relevant to anyone interested in creating a heart failure model in mice. In addition, the weekly cardiac remodeling changes based on echocardiographic parameters for each strain and expected time to model development are presented. In summary, the method is simple and reproducible. Continuous ISO administered via the implanted mini-pump over 3 to 4 weeks is sufficient to induce cardiac remodeling. Finally, the success for ISO model creation may be assessed in vivo by serial echocardiography demonstrating hypertrophy, ventricular dilation, and dysfunction.

The chronic administration of isoproterenol via an implanted osmotic pump has been used widely to mimic advanced heart failure in mice. Here, we describe detailed methods in surgical mini-pump implantation for the continuous isoproterenol administration over 3 weeks, as well as, echocardiographic assessment for the successful model creation.

마우스에서 심부전을 유도하는 이소프로테레놀 미니 펌프 의 이식

Isoproterenol (ISO), is a non-selective beta-adrenergic agonist, that is used widely to induce cardiac injury in mice. While the acute model mimics ...

Evaluation of Cerebral Blood Flow Autoregulation in the Rat Using Laser Doppler Flowmetry

When investigating the body&#39;s mechanisms for regulating cerebral blood flow, a relative measurement of microcirculatory blood flow can be obtained using laser Doppler flowmetry (LDF). This paper demonstrates a closed skull preparation that allows cerebral blood flow to be assessed without penetrating the skull or installing a chamber or cerebral window. To evaluate autoregulatory mechanisms, a model of controlled blood pressure reduction via graded hemorrhage can be utilized while simultaneously employing LDF. This enables the real time tracking of the relative changes in the blood flow in response to reductions in arterial blood pressure produced by the withdrawal of circulating blood volume. This paradigm is a valuable approach to study cerebral blood flow autoregulation during reductions in arterial blood pressure and, with minor modifications in the protocol, is also valuable as an experimental model of hemorrhagic shock. In addition to evaluating autoregulatory responses, LDF can be used to monitor the cortical blood flow when investigating metabolic, myogenic, endothelial, humoral, or neural mechanisms that regulate cerebral blood flow and the impact of various experimental interventions and pathological conditions on cerebral blood flow.

This article demonstrates the use of laser Doppler flowmetry to evaluate the ability of the cerebral circulation to autoregulate its blood flow during reductions in arterial blood pressure.

레이저 도플러 흐름 측정을 사용하여 쥐에 대뇌 혈액 흐름 자동 조절의 평가

When investigating the body&#39;s mechanisms for regulating cerebral blood flow, a relative measurement of microcirculatory blood flow can be obtained ...