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Microfluidics for interrogating live intact tissues

Microsystems & Nanoengineering 2020年第1期6卷 538-564页

作者： lisa f.horowitz Adan D.Rodriguez Tyler Ray Albert folch Department of Bioengineering University of WashingtonSeattleWA 98195USA Department of Mechanical Engineering University of Hawaiʻi at MānoaHonoluluHI 96822USA

The intricate microarchitecture of tissues–the“tissue microenvironment”–is a strong determinant of tissue *** offers an invaluable tool to precisely stimulate,manipulate,and analyze the tissue microenvironment in live tissues and engineer mass transport around and into small tissue *** control is critical in clinical studies,especially where tissue samples are scarce,in analytical sensors,where testing smaller amounts of analytes results in faster,more portable sensors,and in biological experiments,where accurate control of the cellular microenvironment is *** also provides inexpensive multiplexing strategies to address the pressing need to test large quantities of drugs and reagents on a single biopsy specimen,increasing testing accuracy,relevance,and speed while reducing overall diagnostic ***,we review the use of microfluidics to study the physiology and pathophysiology of intact live tissues at sub-millimeter *** categorize uses as either in vitro studies–where a piece of an organism must be excised and introduced into the microfluidic device–or in vivo studies–where whole organisms are small enough to be introduced into microchannels or where a microfluidic device is interfaced with a live tissue surface(*** skin or inside an internal organ or tumor)that forms part of an animal larger than the *** microfluidic systems promise to deliver functional measurements obtained directly on intact tissue–such as the response of tissue to drugs or the analysis of tissue secretions–that cannot be obtained otherwise.

关键词： fluid drugs testing

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Gastric emptying, postprandial blood pressure, glycaemia and splanchnic flow in Parkinson's disease

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World Journal of Gastroenterology 2016年第20期22卷 4860-4867页

作者： Laurence G Trahair Thomas E Kimber Katerina flabouris Michael horowitz Karen L Jones Discipline of Medicine The University of Adelaide NHMRC Centre of Research Excellence in Translating Nutritional Science to Good Health The University of Adelaide Neurology Unit Royal Adelaide Hospital

AIM: To determine gastric emptying, blood pressure, mesenteric artery blood flow, and blood glucose responses to oral glucose in Parkinson’s ***: Twenty-one subjects (13 M, 8 f; age 64.2 ± 1.6 years) with mild to moderate Parkinson’s disease (Hoehn and Yahr score 1.4 ± 0.1, duration of known disease 6.3 ± 0.9 years) consumed a 75 g glucose drink, labelled with 20 MBq 99mTc-calcium phytate. Gastric emptying was quantified with scintigraphy, blood pressure and heart rate with an automated device, superior mesenteric artery blood flow by Doppler ultrasonography and blood glucose by glucometer for 180 min. Autonomic nerve function was evaluated with cardiovascular reflex tests and upper gastrointestinal symptoms by ***: The mean gastric half-emptying time was 106 ± 9.1 min, gastric emptying was abnormally delayed in 3 subjects (14%). Systolic and diastolic blood pressure fell (P flow and blood glucose (P for both) increased, following the drink. Three subjects (14%) had definite autonomic neuropathy and 8 (38%) had postprandial hypotension. There were no significant relationships between changes in blood pressure, heart rate or mesenteric artery blood flow with gastric emptying. Gastric emptying was related to the score for autonomic nerve function (R = 0.55, P function and a determinant of the glycaemic response to oral glucose.

关键词： Gastric emptying Hypotension Parkinson’ s disease Blood pressure Glucose

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Gender and tachycardia： independent modulation of platelet reactivity in patients with atrial fibrillation

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Journal of Geriatric Cardiology 2016年第3期13卷 202-208页

作者： Nathan EK Procter Jocasta Ball Doan TM Ngo Jeffrey S Isenberg Elaine M Hylek Yuliy Y Chirkov Simon Stewart John D horowitz Basil Hetzel Institute for Translational Research Queen Elizabeth Hospital University of Adelaide Adelaide Australia National Health and Medical Research Council(HMRC) Centre of Research Excellence to Reduce Inequality in Heart Disease Mary MacKillop Institutefor Health Research Australian Catholic University Melbourne Australia Heart Lung Blood and Vascular Medicine Institute Division of Pulmonary Allergy and Critical Care Medicine Department University of Pittsburgh Pitts-burgh Pennsylvania USA Department of Medicine Boston University School of Medicine Boston Massachusetts USA

Background female patients with atrial fibrillation （Af） experience increased risk of thromboembolism compared to males, an observation that is reflected by its inclusion in the CHA2DS2VASc score. New onset Af （often associated with tachycardia） also confers upon patients increased thromboembolic risk. The mechanisms underlying this risk are uncertain, but new onset Af is associated with profound impairment of platelet nitric oxide （NO） signalling. Given that cardiovascular responses to catecholamines are gender-dependent, and that the presence of tachycardia in new onset Af may represent a response to catecholaminergic stimulation, we explored the potential impact of gender and tachycardia on platelet aggregation and NO signalling. Methods Interactions were sought in 87 Af patients between the extent of adenosine diphosphate （ADP）-induced platelet aggregation, the anti-aggregatory effects of the NO donor, sodium nitroprusside, gender, and admission heart rate. The potential impact of platelet expression of thioredoxin-interacting protein （Txnip） was also evaluated. Results Analysis ofcovariance confLrmed the presence of physiological antagonism between platelet ADP and NO responses [f （1, 74） = 12.212, P 〈 0.01 ], while female sex correlated with impaired NO responses independent of platelet aggregability [f （2, 74） = 8.313, P 〈 0.01]. Admission heart rate correlated directly with platelet aggregation （r = 0.235, P 〈 0.05）, and inversely with NO response （r = -0.331, P 〈 0.01）. Txnip expression varied neither with gender nor with heart rate. Conclusions These results indicate, that gender and heart rate are independent determinants of platelet fimction. Prospective studies of the putative benefit of reversal of tachycardia on restoration of normal platelet function are therefore a priority.

关键词： Atrial fibrillation Gender Heart rate Nitric oxide Platelet aggregation

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对单叶函数系数估计的进一步改进

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青海师范大学学报(自然科学版) 1980年第1期 59-62页

作者： David horowitz 左光纪

本文用fitz Gerafd系数不等式得出,如果f（z）=z+a2z2+a3z3+……在单位园内解析单叶的话,则有|a_n|<1.0657n。用于求解出上述问题的方法不能得出比|a_n|<1.0599n更好的结果。

关键词：系数估计函数系数不等式估计式单叶

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你所做即你所是

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作者： (美)本·霍洛维茨(Ben horowitz)

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吉西他滨和拓扑替康治疗有治疗史的卵巢或腹膜癌Ⅰ期试验:一项妇科肿瘤协作组研究

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世界核心医学期刊文摘（妇产科学分册） 2006年第5期2卷 49-49页

作者： fleming G.f Mitchell S horowitz I 李奎

To determine the maximum tolerated dose (MTD) of the combination of gemcitabine and topotecan in women with previously treated epithelial ovarian, peritoneal, or fallopian tube cancer. Methods. Patients with recurrent or persistent cancer after treatment with a platinum and paclitaxel-containing regimen were eligible for this study. Initial treatment was gemcitabine at a dose of 800 mg/m2 on days 1, 8, and 15 and topotecan at a dose of 0.5 mg/m2 on days 2- 5, with cycles repeated every 28 days. Dose escalations were planned first for topotecan (Cohort I, Dose Levels 1- 5) then for gemcitabine (Cohort II, Dose Levels 6- 9) until the MTD was reached. Results. Ten patients received a total of 29 cycles. When none of the first four patients could complete therapy as prescribed due to toxicity, doses for each drug were reduced by 1 day. The next six patients were treated at the modified schedule of gemcitabine days 1 and 8 and topotecan days 2- 4 (Dose Level- 1). Despite this modification, dose-limiting toxicities including neutropenia, thrombocytopenia, and stomatitis occurred at Dose Level- 1, and the study was closed early. Conclusions. At both the initial dose schedule and an attenuated schedule, the combination of gemcitabine and topotecan produced doselimiting toxicities in women with previously treated epithelial ovarian or peritoneal cancer.

关键词：拓扑替康腹膜癌妇科肿瘤剂量限制性毒性剂量水平输卵管癌最大耐受剂量泰素改良方案白细胞

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