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Development and bioequivalence study of potassium chloride extended release tablets

Asian Journal of Pharmaceutical Sciences 2018年第4期13卷 353-359页

作者： Thu Van le Thi Nghiem le Quan hau le University of Medicine and Pharmacy at ho Chi Minh city

The purposes of this study are to prepare the generic extended release tablet of potassiumchloride(PC) 600 mg and to compare the absorption of potassium ion from the experimen-tal tablets to tha. of Kaleorid? LP 600 mg(leo Pharmaceutical Products, Denmark). Car-nauba wax was used as retardant in the matrix core tablets. The core tablets were coatedwith blends of ethyl cellulose(EC) and hydroxypropyl methyl cellulose(hPMC) to modulatethe drug release. Results of a selective two-level, three-factor experiment design revealedtha. a blend of 41.75% of EC and 58.25% of hPMC at 4.5% weight gained could produce thecoated tablets having dissolution profiles similar to those of Kaleorid?. A two-treatment,two-period, two-sequence crossover bioequivalence study was carried out on 24 healthyvolunteers to compare the absorption of potassium ion from experimental tablets to tha.from Kaleorid?. The potassium ion in the urine was measured by a selective electrode of theADVIA 1650 system(Bayer) and used to calculate cumulative urinary excretion and urinaryexcretion rate. Results of 90 percent confidence interval analysis showed tha. the limits fornatural log-transformed cumulative urinary potassium excretion(Ln Ae 0-24) of test productwere in the range of 3.73–3.79 mEq, corresponding to 99.08%–100.92% of Kaleorid ?, respec-tively, and the limits for natural log-transformed maximal potassium excretion rate( R max) oftest product were in the range of 1.72–1.82 mEq/h, corresponding to 97.34%–102.66% of refer-ence product, respectively. Both of them fell within the bioequivalence interval(80%–125%)of reference product, proving tha. experimental product is bioequivalent to Kaleorid ?.

关键词： Potassium chloride Ethyl cellulose hydroxypropyl methyl cellulose Extended release tablet Cumulative urinary excretion Urinary excretion rate

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Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys

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Acta Pharmacologica Sinica 2007年第4期28卷 473-483页

作者： Bernard le FOLL Behavioral Neuroscience Branch Intramural Research ProgramNational Institute on Drug AbuseNational Institutes ofHealthBaltimoreMaryland 21224USA

Aim:Clonidine is an α2adrenoceptor agonist tha. is frequently used to reducewithdrawal symptoms during opioid detoxification in *** long-termeffects of clonidine on withdrawal symptoms and its effects on subsequent drugexposure have not been thoroughly *** aim of the study was todetermine if clonidine administered during morphine withdrawal in rhesus mon-keys produces long-lasting effects on withdrawal symptoms and alters the effectsof subsequently taken drugs of ***:Adult male rhesus monkeyswere treated with increasing doses of morphine for 90 d to induce opiate (narcotic)*** immediate and long-lasting effects of 1 week’s administration ofclonidine were measured via the recording of morphine withdrawal signs and thesubsequent effects of challenge injections of morphine or ***:Monkeys chronically treated with morphine displayed withdrawal signs tha. lasted2 weeks after cessation of morphine administration and displayed sensitized re-sponses to subsequent morphine and cocaine *** significantlyreduced certain morphine withdrawal signs and overall withdrawal score,but theseeffects did not persist upon cessation of clonidine *** to theeffects of morphine and cocaine were significantly reduced in monkeys previ-ously treated with ***:Our results suggest tha. in addition toits short-term alleviating effect on morphine withdrawal signs,clonidine may re-duce subsequent effects of drugs of abuse after prolonged abstinence.

关键词： cocaine withdrawal drug challenge crosssensitization recurrence monkeys

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A NOTE ON SINgULAR INTEgRALS WITh DOMINATINg MIXED SMOOThNESS IN TRIEBEL-LIZORKIN SPACES

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Acta Mathematica Scientia 2014年第4期34卷 1331-1344页

作者： hung Viet le Faculty of Science and Technology Hoa Sen UniversityQuang Trung Software ParkSection 10Ward Tan Chanh HiepDistrict 12Ho Chi Minh CityViet Nam

let h, be a measurable function defined on R^＋ ×R^＋. let Ω ∈ L（log L^＋）^υq （S^n1-1 × S^n2-1）（1≤ υq ≤ 2） be homogeneous of degree zero and satisfy certain cancellation conditions. We show tha. the singular integral Tf（x1,x2）=p.v.∫∫R^n1＋n2 Ω（y′1,y′2）h（｜y1｜,｜y2｜）/｜y1｜^n1｜y2｜^n2 f（x1-y1,x2-y2）dy1dy2maps from Sp,q^α1,α2F（R^n1×R^n2）boundedly to itself for 1 〈 p, q 〈 ∞, α1, α2 ∈R.

关键词： singular integrals Marcinkiewicz integrals mixed smoothness Triebel-Lizorkin spaces

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奇特氟效应:一个有效构筑不敏感含能材料的重要因素

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含能材料 2024年第6期32卷 641-650页

作者：余沛东刘强强丁小勇刘应乐高海翔四川轻化工大学化学与环境工程学院四川自贡643000 北京理工大学重庆研究中心重庆401120 中国农业大学应用化学系北京100193

研究设计、合成并表征了化合物5,7-二(三氟甲基)-2-(二硝甲基)-[1,2,4]三唑[1,5-a]嘧啶(1)。采用差示扫描量热仪、高斯03及EXPLO5 v6.05软件分别测试或计算了其热性能、生成焓和爆轰性能,并通过hirschfeld表面分析、2D指纹图谱、静电势(... 详细信息

研究设计、合成并表征了化合物5,7-二(三氟甲基)-2-(二硝甲基)-[1,2,4]三唑[1,5-a]嘧啶(1)。采用差示扫描量热仪、高斯03及EXPLO5 v6.05软件分别测试或计算了其热性能、生成焓和爆轰性能,并通过hirschfeld表面分析、2D指纹图谱、静电势(ESP)对化合物1和已报道的偕二硝甲基含能化合物进行了对比研究。结果表明,化合物1具有较低的机械感度,其撞击感度>40 J,摩擦感度>360 N,这与已报道的ChON型偕二硝甲基含能化合物的敏感性有很大不同。单晶堆积及分子间作用力的计算结果表明化合物1中的卤键(C—F…X)能够有效打断分子之间O…O相互作用的生成。此外,由于三氟甲基的存在,化合物1展示出较为优越的静电势值和静电势偏移值,从而使其比其它偕二硝甲基含能化合物更加稳定。

关键词：含能材料不敏感炸药偕二硝甲基卤键弱相互作用

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人工流产术前缩短卡前列甲酯给药时间对软化子宫颈效果和围术期安全性影响随机对照研究

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中国实用妇科与产科杂志 2024年第3期40卷 349-353页

作者：张多多赵毅飞申乐金力中国医学科学院北京协和医学院、北京协和医院、国家妇产疾病临床医学研究中心妇产科北京100730 中国医学科学院北京协和医学院、北京协和医院、国家妇产疾病临床医学研究中心麻醉科北京100730

目的探索缩短卡前列甲酯(卡孕栓)在全麻人工流产术(人流)术前的给药时间对软化子宫颈的效果和围术期安全性的影响。方法前瞻性纳入北京协和医院2022年11月至2023年2月行人流负压吸引的早孕期患者120例,术前使用卡孕栓软化子宫颈。随... 详细信息

目的探索缩短卡前列甲酯(卡孕栓)在全麻人工流产术(人流)术前的给药时间对软化子宫颈的效果和围术期安全性的影响。方法前瞻性纳入北京协和医院2022年11月至2023年2月行人流负压吸引的早孕期患者120例,术前使用卡孕栓软化子宫颈。随机分为两组:A组在术前1.5~2.0h给药;B组在麻醉前给药。两组平均用药时间分别为(111.9±23.4)min和(21.5±10.6)min。研究初级结局指标为子宫颈扩张时间;次级结局指标为手术完成指标,包括手术时间、总出血量和7.5号扩宫棒初次通过率,以及围术期不良反应,包括发热、腹痛、恶心、呕吐及便意和腹泻等。结果两组患者在扩宫时间和手术完成指标上差异均无统计学意义,但在麻醉前A组出现的总不良反应率显著高于B组(93.4%vs. 28.8%,P<0.01),其中A组腹痛分数高于B组[(2.8±2.1)分vs.(0.3±0.5)分,P<0.01]。A组术后恶心、呕吐的发生率也显著高于B组(18.3%vs. 6.7%,P=0.04)。结论阴道内放置卡孕栓时间延迟至麻醉前仍然能够充分软化人流手术患者的子宫颈,并减少药物相关不良反应,有助于改善患者就医体验和保障围术期安全。

关键词：人工流产术促子宫颈成熟围术期安全性前列腺素卡前列甲酯

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A new interpretation for formation of orthogonal joints in quartz sandstone

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Journal of Rock Mechanics and geotechnical Engineering 2021年第2期13卷 289-299页

作者： le Li Shaocheng Ji Département des génies Civil Géologique et des MinesÉcole Polytechnique de MontréalMontréalQuébecH3C 3A7Canada

Two vertical and orthogonal systematic joint sets are generally arrayed in a grid pattern on the bedding surface,which are the significant features of flat-lying sandstone *** extensive researches are reported on this topic,many fundamental problems have still not been *** mutually perpendicular opening-mode fractures are an obvious manifestation of effective tensile stresses in two orthogonal directions in the horizontal bedding plane.A good understanding of these orthogonal joint systems is a key to structural analysis,landscape interpretation,and guidance of resolving a number of very practical problems in engineering,mining and hydrologic *** on an anatomic investigation on the orthogonal joints in the Potsdam sandstone of Cambrian age at Ausable Chasm(New York State,USA)and Beauharnois(Quebec,Canada),we proposed tha. the orthogonal joints may result from the auxetic effects of quartz-rich sandstone rather tha. local or regional rotation of the maximum tensile stress(σ_(3))direction by about 90°.The sandstone beds with negative Poisson's ratios are so fascinating tha.,when placed under vertical burial compression and layer-parallel extension in one direction(σ_(3)),it becomes stretched in the transverse direction(σ_(2)),producing two orthogonal sets of mutual abutting and intersecting joints(J1 and J2 normal toσ_(3) andσ_(2),respectively),and both are normal to the bedding *** set J1 is more closely-spaced tha. J2 by a factor of∼3.3,which is correlated with an average Poisson's ratio of−0.3 for the Potsdam sandstone at the time of joint formation.

关键词： Rock fractures Orthogonal joints Sandstone Auxetic effects Potsdam group

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基于神经网络的hEVC帧间预测方法及其硬件研究

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中国集成电路 2024年第4期33卷 75-81页

作者：陶乐溪施隆照福州大学物理与信息工程学院

相比于h.264,高效视频编码标准(hEVC)提出了许多新技术,提高了编码性能,但是也显著提高了编码复杂度。本文从硬件实现的角度出发,对已有的帧间CU划分预测神经网络的结构进行了多方面的优化,使其参数减少了70%,加法和乘法运算分别减少了... 详细信息

相比于h.264,高效视频编码标准(hEVC)提出了许多新技术,提高了编码性能,但是也显著提高了编码复杂度。本文从硬件实现的角度出发,对已有的帧间CU划分预测神经网络的结构进行了多方面的优化,使其参数减少了70%,加法和乘法运算分别减少了60%、58.2%。并对优化后的卷积神经网络参数采用10位定点数方案进行定点化处理,进一步有效减少硬件资源的开支。对比于hEVC参考软件(hM16.5),优化后网络引起的BD-BR和BD-PSNR平均损失为1.718%和-0.056dB,平均节省35%~52%的编码复杂度,并且定点化处理后引起的性能损失可忽略不计。

关键词： hEVC 帧间预测卷积神经网络低复杂度神经网络定点化

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Regulation of cytokine gene expression by orosomucoid in neonatal swine adipose tissue

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Journal of Animal Science and Biotechnology 2016年第3期7卷 403-411页

作者： Timothy g.Ramsay Margo J.Stoll le Ann Blomberg Thomas J.Caperna Animal Biosciences and Biotechnology Laboratory USDA/ARSBeltsville Agricultural Research CenterUSDABeltsvilieMD 20705USA

Background： Porcine adipose tissue expresses orosomucoid（ORM1） mRNA, a protein with anti-inflammatory and immunomodulatory properties. Previous research has demonstrated tha. porcine ORM1 can reduce insulin stimulated glucose metabolism in porcine adipose tissue in vitro. The present study was designed to examine the preweaning ontogeny of ORM1 m RNA abundance in porcine subcutaneous adipose and to determine if ORM1 can regulate m RNA abundance of inflammatory cytokines tha. contribute to insulin resistance in primary cultures derived from neonatal porcine subcutaneous adipose tissue. Cultures were differentiated in vitro and subsequently the adipocyte containing cultures were incubated for 24 h with 0–5000 ng porcine ORM1/m L medium. Cultures were then harvested, total RNA extracted for use in reverse transcription and the m RNA abundance of cytokine m RNA quantified by real-time ***： ORM1 m RNA abundance within neonatal adipose tissue does not change from d 1 to d 21 of age and is a very small fraction relative to liver m RNA abundance. The ORM1 m RNA level in porcine adipocytes and stromalvascular cells are similar（P 〉 0.05）. Treatment with ORM1 did not affect TNFα（tumor necrosis factor α） m RNA level（P 〉 0.05）, while interleukin 6（IL6） m RNA abundance was reduced 32 % at 1,000 ng ORM1/m L（P 〈 0.01）. however,TNFα protein content in the cell culture media was reduced by ORM1 treatment（5,000 ng/m L, P 〈 0.05）, whereas ORM1 had no detectable effect on the media content of IL6（P 〉 0.05）. The reduction of macrophage migration inhibitory factor（MIF） m RNA abundance by ORM1 was dose dependent（P 〈 0.01）. Monocyte chemotactic protein（MCP） m RNA level was reduced 27 % by 1,000 ng ORM1/m L（P 〈 0.05）.Conclusions： The data suggest tha. ORM1 has limited effects TNFα, IL6, MIF or MCP expression at the concentrations tested. Secondly, these cytokines do not appear to contribute to the reported insulin resistance induced by ORM1 in porcine adipose tissue in vitro as an in

关键词： Adipose Cytokines Neonate Orosomucoid Swine

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Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy

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World Journal of gastroenterology 2007年第8期13卷 1195-1203页

作者： Pascal Veillon Christopher Payan hélène le guillou-guillemette Catherine gaudy Franoise Lunel Laboratory of Virology Angers University Hospital 4 rue Larrey 49933 Angers cedex 9 France HIFIH Laboratory UPRES EA 3859 IFR 132 University of Angers rue de Haute Reculée 49045 Angers France Departement of Microbiology EA 3882 Brest University Hospital 2 avenue Foch 29609 Brest cedex France University Francois Rabelais INSERM ERI 19 Faculty of Medecine 10 Boulevard Tonnellé BP 3223 37032 Tours Cedex France

AIM: To evaluate the implication of substitutions in the hepatitis C virus (hCV) non-structural 5A (NS5A) protein in the resistance of hCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the hCV RNA- dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of hCV remains unclear. METhODS: hCV quasispecies were studied by clon- ing and sequencing of sequential isolates from patients infected by hCV genotype 1b. Patients were treated by IFN-α2b for 3 mo followed by IFN-α2b alone or com- bined IFN-R therapy for 9 additional months. Patients were categorized intro two groups based on their re- sponse to the treatments: 7 with sustained virological re- sponse (SVR) (quasispecies = 150) and 3 non-respond- ers (NR) to IFN-R (quasispecies = 106). RESULTS: Prior to treatment, SVR patients displayed a lower complexity of quasispecies tha. NR patients. Most patients had a decrease in the complexity of quasispe- cies during therapy. Analysis of amino acids substitu- tions showed tha. the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate thetwo groups of patients. Moreover, SVR patients displayed more variability in the NS5A region tha. NR patients. CONCLUSION: These results suggest tha. detailed mo- lecular analysis of the NS5A region may be important for understanding its function in IFN response during hCV 1b infection.

关键词： hepatitis C virus Quasispecies NS5A region Interferon sensitivity-determining region V3 domain

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氨氮短期胁迫与恢复对克氏原螯虾的影响

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水产科学 2024年第3期43卷 390-399页

作者：吴乐李嘉尧周文宗成永旭上海海洋大学农业农村部稻渔综合种养生态重点实验室上海201306 上海海洋大学水产科学国家级试验教学示范中心上海201306 上海海洋大学上海水产养殖工程技术研究中心上海201306 上海市农业科学院上海201403

为探究氨氮胁迫与恢复对克氏原螯虾抗氧化和免疫酶活性及组织结构的影响,将体质量(6.33±0.73)g的克氏原螯虾暴露于0、20、40、60、80 mg/L 5个氨氮质量浓度下,比较胁迫48 h时及恢复48 h后,各组肝胰腺、鳃和血清的抗氧化和免疫酶活性以... 详细信息

为探究氨氮胁迫与恢复对克氏原螯虾抗氧化和免疫酶活性及组织结构的影响,将体质量(6.33±0.73)g的克氏原螯虾暴露于0、20、40、60、80 mg/L 5个氨氮质量浓度下,比较胁迫48 h时及恢复48 h后,各组肝胰腺、鳃和血清的抗氧化和免疫酶活性以及各组肝胰腺和肌肉组织结构的变化。试验结果显示:氨氮对克氏原螯虾幼虾24、48、72、96 h的半致死质量浓度分别为359.37、238.09、196.34、162.00 mg/L,安全质量浓度为16.20 mg/L。胁迫48 h后,除20 mg/L试验组外,其余试验组肝胰腺的总超氧化物歧化酶活性较对照组显著增强,80 mg/L组鳃的总抗氧化能力显著降低、过氧化氢酶活性显著增强,80 mg/L组血清的总超氧化物歧化酶活性显著增强;恢复48 h后,60 mg/L组肝胰腺和鳃的丙二醛含量较对照组显著上升,80 mg/L组鳃的过氧化氢酶活性较对照组显著增强,60 mg/L组血清的总抗氧化能力较对照组显著上升,其他试验组酶活性均恢复至对照组水平。氨氮胁迫48 h,随着氨氮质量浓度的升高,肝胰腺管腔逐渐变形、转运泡增大,鳃的呼吸上皮细胞开始脱落、微血管腔受损;恢复48 h后,肝胰腺的组织结构基本恢复正常,40、60、80 mg/L组鳃局部呼吸上皮细胞脱落,微血管腔受损。试验结果表明,20 mg/L质量浓度的氨氮胁迫48 h即会对克氏原螯虾抗氧化和免疫酶及组织结构造成损伤,解除胁迫48 h后可得到修复。克氏原螯虾经40、60、80 mg/L质量浓度的氨氮胁迫48 h后恢复48 h,鳃仍处于应激状态。

关键词：克氏原螯虾氨氮胁迫恢复抗氧化酶免疫酶组织结构

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