UPLC-PDA-ESI-QTOF-MS/MS fingerprint of purified flavonoid enriched fraction of Bryophyllum pinnatum; antioxidant properties,anticholinesterase activity and in silico studies

ContextBryophyllum pinnatum (Lam.) Oken (Crassulaceae) is used traditionally to treat many ailments.ObjectivesThis study characterizes the constituents of B. pinnatum flavonoid-rich fraction (BPFRF) and investigates their antioxidant and anticholinesterase activity using in vitro and in silico approaches.Materials and methodsMethanol extract of B. pinnatum leaves was partitioned to yield the ethyl acetate fraction. BPFRF was isolated from the ethyl acetate fraction and purified. The constituent flavonoids were structurally characterized using UPLC-PDA-MS². Antioxidant activity (DPPH), Fe²⁺-induced lipid peroxidation (LP) and anticholinesterase activity (Ellman’s method) of the BPFRF and standards (ascorbic acid and rivastigmine) across a concentration range of 3.125–100 μg/mL were evaluated in vitro for 4 months. Molecular docking was performed to give insight into the binding potentials of BPFRF constituents against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE).ResultsUPLC-PDA-MS² analysis of BPFRF identified carlinoside, quercetin (most dominant), luteolin, isorhamnetin, luteolin-7-glucoside. Carlinoside was first reported in this plant. BPFRF significantly inhibited DPPH radical (IC₅₀ = 7.382 ± 0.79 µg/mL) and LP (IC₅₀ = 7.182 ± 0.60 µg/mL) better than quercetin and ascorbic acid. Also, BPFRF exhibited potent inhibition against AChE and BuChE with IC₅₀ values of 22.283 ± 0.27 µg/mL and 33.437 ± 1.46 µg/mL, respectively compared to quercetin and rivastigmine. Docking studies revealed that luteolin-7-glucoside, carlinoside and quercetin interact effectively with crucial amino acid residues of AChE and BuChE through hydrogen bonds.Discussion and conclusionsBPFRF possesses an excellent natural source of cholinesterase inhibitor and antioxidant. The material could be further explored for the potential treatment of oxidative damage and cholinergic dysfunction in Alzheimer’s disease.     

艾司奥美拉唑、克拉霉素、阿莫西林短程三联疗法根除幽门螺杆菌

目的:观察艾司奥美拉唑、克拉霉素、阿莫西林短程三联疗法根除幽门螺杆菌(Hp)的疗效。方法:Hp阳性的活动性十二指肠溃疡病人44例,以艾司奥美拉唑20mg、克拉霉素500mg及阿莫西林1000mg,po,bid治疗,疗程7d,7d之后继服法莫替丁20mg,po,bid×3wk。观察Hp根除率、症状缓解和消失率、溃疡愈合率及不良反应。结果:Hp根除率为88%(按完成试验方案分析)和86%(按意图分析),d7症状缓解率为100%、消失率为72%,wk5溃疡愈合率为100%。不良反应发生率为14%,其中1例因皮疹退出。结论:艾司奥美拉唑、克拉霉素,阿莫西林三联短程疗法并后续法莫替丁治疗3wk,是当前治疗Hp阳性的活动性十二指肠溃疡的满意选择之一。     

雷贝拉唑、阿莫西林、加替沙星三联疗法根除幽门螺杆菌的疗效及安全性

目的:评价由加替沙星(400 mg,qd),雷贝拉唑(20 mg,bid),阿莫西林(1 g,bid),疗程7 d的三联方案根除治疗幽门螺杆菌的疗效及安全性。方法:48名幽门螺杆菌感染的患者参与本次研究,受试者均有一次或一次以上含克拉霉素的常规三联治疗史。治疗后四周通过14 C-呼气试验判定根除治疗效果。根除治疗失败的患者通过体外抑菌试验判断幽门螺杆菌对阿莫西林,克拉霉素及加替沙星的药物敏感性。结果:41名患者根除治疗成功[完成治疗分析(PP)和意向治疗分析(ITT)均为85.4%,95%CI:74%～95%]无显著副作用。体外药敏试验显示在7名治疗失败的患者中未出现对加替沙星和阿莫西林的继发耐药。结论:由加替沙星、阿莫西林和雷贝拉唑组成的7 d短程治疗方案,作为根除治疗失败后的补救治疗方案简单有效,耐受性好,依从性高;而且此方案失败后未引起继发耐药性。     

枸橼酸铋钾、克拉霉素和替硝唑治疗慢性胃炎的胃窦粘膜病理学改变

目的 :观察枸橼酸铋钾、克拉霉素和替硝唑三联治疗幽门螺杆菌相关性胃炎胃窦粘膜组织病理学改变。方法 :38例幽门螺杆菌 (Hp)感染的慢性胃炎病人按就诊前后入选 ,分为 2组 ,枸橼酸铋钾三联 (BCT)组和奥美拉唑三联 (OCT)组 ,分别给予口服枸橼酸铋钾 +克拉霉素 +替硝唑和奥美拉唑 +克拉霉素 +替硝唑 ,治疗 1wk。 4wk后检查13 C 尿素呼气试验 ,8mo后复查胃镜和胃粘膜活检。结果 :BCT组Hp根除率为 80 % ,OCT组为 83% ,2组间差异无显著意义 (P >0 .0 5 )。 2组病人治疗后胃粘膜组织慢性炎症、活动性炎症明显减轻 (P <0 .0 5 ) ,粘膜萎缩及肠化生程度无明显变化 (P >0 .0 5 )。BCT组与OCT组间病理学改变差异无显著意义 (P >0 .0 5 )。结论 :幽门螺杆菌感染与胃粘膜炎症反应有关 ,BCT具有较高的幽门螺杆菌根除率 ,并可减轻胃粘膜的炎症反应     

艾司奥美拉唑、克拉霉素和阿莫西林三联疗法根除幽门螺杆菌的疗效

目的 :观察艾司奥美拉唑、克拉霉素和阿莫西林三联疗法根除幽门螺杆菌 (Hp)的疗效 ,以期寻找疗程短、疗效高的方案。方法 :10 1例Hp阳性病人随机分为 3组。治疗 1组 (31例 )予艾司奥美拉唑 2 0mg ,克拉霉素0 .5 g,阿莫西林 1.0 g ,疗程3d。治疗 2组 (35例 )予药物 ,剂量同治疗 1组 ,疗程 7d。对照组 (35例 )予奥美拉唑 2 0mg ,克拉霉素 0 .5 g ,阿莫西林 1.0 g ,疗程 7d。均每日 2次口服。停药 4wk查13C 尿素呼气试验。结果 :治疗1,2组 ,对照组Hp的根除率为 81% ,86 % ,83% ,均P >0 .0 5。不良反应发生率为 9% ,19% ,2 1% ,P >0 .0 5。C/E为 2 .5 2 ,5 .75 ,6 .0 1,治疗 1组药费与疗效比值明显低于治疗 2组及对照组。结论 :艾司奥美拉唑三联疗法是一种安全、高效的根除Hp方案。 3d疗法更为短程、经济。     

雷贝拉唑、阿莫西林和硫糖铝根除幽门螺杆菌的疗效观察

目的观察雷贝拉唑、阿莫西林和硫糖铝三联疗法对根除幽门螺杆菌(HP)的疗效。方法将95例经胃镜检查确诊为十二指肠溃疡活动期,并经快速尿素酶试验和14C-尿素呼气试验,确定为HP阳性的患者分为两组。A组以雷贝拉唑0.01 g(qd),阿莫西林1 g(bid)和硫糖铝1 g(qid)治疗2周;B组以雷贝拉唑0.01 g(qd),阿莫西林1 g(bid)和克拉霉素0.5 g(bid)治疗2周。于用药结束后,第28天复查胃镜,观察溃疡愈合情况并检查HP。结果A组的HP根除率为91.5%,B组为93.8%,两组无显著性差异(P>0.05);A组溃疡的愈合率(93.6%)稍高于B组(89.6%),但无显著性差异(P>0.05)。结论雷贝拉唑、阿莫西林和硫糖铝三联疗法能有效地根除HP,溃疡愈合率高,安全且耐受性好,是一种较理想的HP根除新方案。     

四联与三联疗法在胃溃疡合并幽门螺杆菌感染治疗中的应用效果比较

目的：比较胃溃疡合并幽门螺杆菌（ Hp）感染治疗中四联与三联疗法的应用效果。方法选取六盘水市人民医院2011—2013年收治的胃溃疡合并Hp感染患者86例,按照治疗方案分为三联组（雷贝拉唑+阿莫西林+克拉霉素）和四联组（雷贝拉唑+阿莫西林+克拉霉素+胶体果胶铋）,每组43例。比较两组患者的临床疗效、Hp清除率及不良反应发生率。结果四联组患者总有效率（88.4%）高于三联组（69.8%）（ P<0.05）。四联组患者Hp清除率为86.1%（37/43）,高于三联组的67.4%（29/43）,差异有统计学意义（ P<0.05）;两组患者不良反应发生率比较,差异无统计学意义（ P>0.05）。结论四联疗法治疗胃溃疡合并Hp感染的效果显著,能有效提高Hp清除率,且具有一定的安全性。     

兰索拉唑、阿奇霉素和甲硝唑根除幽门螺杆菌的疗效-费用观察

目的 :观察兰索拉唑、阿奇霉素和甲硝唑短程低剂量三联疗法根除幽门螺杆菌 (Hp)的临床疗效和治疗费用。方法 :将 4 7例病人随机分为 2组 :治疗组 2 4例给兰索拉唑 30mg ,po ,qd× 1wk ,阿奇霉素 5 0 0mg ,po ,qd× 3d ,甲硝唑 4 0 0mg ,po ,bid× 3d。对照组 2 3例给奥美拉唑 2 0mg ,po ,bid× 1wk ,克拉霉素 5 0 0mg ,po ,bid× 1wk ,甲硝唑4 0 0mg ,po ,bid× 1wk。停药 1mo后采用14 C呼气试验复查Hp。结果 :治疗组和对照组Hp根除率分别为 92 %和 91% (P >0 .0 5 ) ;治疗费用为185 .84元和 6 2 3.96元 ;药物不良反应发生率 4 %和9% (P >0 .0 5 )。结论 :兰索拉唑、阿奇霉素和甲硝唑短程低剂量三联疗法根除Hp有较好效果 ,且治疗药品费用低 ,病人依从性好     

雷贝拉唑钠肠溶片在幽门螺杆菌阳性十二指肠溃疡中的疗效、安全性及优势分析

目的:探讨雷贝拉唑钠在幽门螺杆菌阳性十二指肠溃疡患者中的应用效果、安全性及临床优势。方法:将122例十二指肠溃疡患者作为研究对象,所选患者均行¹³C呼吸试验并确定幽门螺杆菌阳性,经随机数字表法将全部患者分为2组,即观察组行"雷贝拉唑钠+阿莫西林克拉维酸钾+甲硝唑"的三联治疗,对照组行"奥美拉唑+阿莫西林克拉维酸钾+甲硝唑"的传统三联治疗,综合比较2组患者溃疡治疗效果、幽门螺杆菌根除情况及药物安全性。结果:经治疗2周后,观察组溃疡愈合率为90.16%,高于对照组(75.41%)(P<0.05);经治疗后2组患者镜下溃疡面积较治疗前均明显缩小(P<0.01);观察组幽门螺杆菌根除率达到95.08%;对照组为81.97%,2组幽门螺杆菌根除率比较差异有统计学意义(P<0.05);2组患者不良反应发生率比较差异无统计学意义(P>0.05);药物经济学方面,观察组C/E值为8.5明显优于对照组。结论:雷贝拉唑钠用于临床治疗幽门螺杆菌阳性十二指肠溃疡具有溃疡愈合率高、幽门螺杆菌根除彻底、安全性高等优势,值得临床推广应用。     

含左氧氟沙星的三种方法根除幽门螺杆菌疗效比较

目的比较含左氧氟沙星的三联疗法、铋剂四联疗法及序贯疗法根治幽门螺杆菌（Hp）的疗效。方法115例Hp阳性患者按时间先后顺序随机分为3组：三联组38例,给予口服兰索拉唑胶囊30mg、阿莫西林克拉维酸钾片685．5mg、左氧氟沙星胶囊200mg,2次／d,治疗7d;四联组38例,予以口服兰索拉唑胶囊30mg、阿莫西林克拉维酸钾片685．5mg、左氧氟沙星胶囊200mg、胶体果胶铋胶囊200mg,2次／d,7d;序贯组39例,前5d口服兰索拉唑胶囊30mg、阿莫西林克拉维酸钾片685．5mg,后5d口服兰索拉唑胶囊30mg、克拉霉素片500mg、左氧氟沙星胶囊200mg,均2次／d。疗程结束后4周复查”C呼气试验检查,评估治疗结果及不良反应。结果三联组完成35例,失访2例,未能按要求服药1例;铋剂四联组完成36例,失访2例;序贯组完成37例,未能按要求服药2例。三联组成功根除29例,按符合方案（PP）分析根除率为82．9％（29／35）,意向性治疗（ITT）分析根除率为76．3％（29／38）;铋剂四联组成功根除32例,PP根除率为88．9％（32／36）,ITT根除率为84．2％（32／38）;序贯组成功根除34例,PP根除率为91．9％（34／37）,ITT根除率为87．2％（34／39）。3组间Hp根除率差异无统计学意义（P〉0．05）。结论含左氧氟沙星的铋剂四联与序贯治疗均有较高的Hp根除率,但从安全性与疗效方面考虑,含左氧氟沙星的铋剂四联疗法可作为Hp初治的首选方案。     

Alpinia zerumbet,a ginger plant with a multitude of medicinal properties: An update on its research findings

In this review, the botany and uses of Alpinia zerumbet (yan shan jiang) are described, and the current knowledge of its phytochemistry, pharmacological properties, and clinical trials is summarized. An important ginger crop in East Asia, A. zerumbet has many uses, both medicinal and non-medicinal. Leaves are used to produce essential oils and herbal teas. Rhizomes are consumed as spices, and stem fibers are made into paper, fabrics, and handicrafts. In Brazil, tea from A. zerumbet leaves is believed to have hypotensive, diuretic, and anti-ulcerogenic properties. This species possesses many medicinal properties due to its chemical constituents, including flavonoids, phenolic acids, phenylpropanoids, kava pyrones, sterols, and terpenoids. Extracts of A. zerumbet display antioxidant, antimicrobial, insecticidal, anthelmintic, tyrosinase and melanogenesis inhibitory, anti-atherogenic, anti-aging, anti-glycation, integrase and neuraminidase inhibitory, lifespan prolongation, hair growth promotion, anticancer, antidepressant, anxiolytic, anti-obesity, analgesic, anti-inflammatory, hypolipidemic, anti-ulcerogenic, anti-platelet, osteoblastic, osteogenic, thrombolytic, and cardiacarrhythmogenic activities. Essential oils of A. zerumbet leaves have antimicrobial, larvicidal, antinociceptive, hypotensive, vasorelaxant, myorelaxant, antispasmodic, antidepressant, anxiolytic, anti-neuraminidase, anti-atherogenic, anti-aging, anti-melanogenic, anti-tyrosinase, cytoprotective, cardiodepressive, antipsychotic, analgesic, anti-inflammatory, and tissue healing activities.Clinical trials conducted in Brazil showed that extracts of A. zerumbet have hypotensive and diuretic effects whereas topical application of the essential oil has positive therapeutic effects on patients with fibromyalgia. Spanning two continents of Asia and South America, A. zerumbetis truly a multi-purpose ginger plant with promising medicinal properties.     

1 例颅内皮氏罗尔斯顿菌合并血流瓦氏葡萄球菌感染患儿的抗感染治疗

目的:探讨 1 例颅内泛耐药皮氏罗尔斯顿菌合并血流瓦氏葡萄球菌感染患儿的抗感染治疗。 方法:从抗感染治疗方案的制定、调整、血药浓度监测、不良反应监护等多个方面对患者实施全流程药学监护。 结果:临床医师完全采纳临床药师的抗感染方案并取得了良好疗效,脑脊液和血液均未再培养出该病原菌。 结论:该抗感染方案安全、有效,临床药师提供的药学服务在临床治疗中发挥着重要作用。     

1例伯基特淋巴瘤患儿化疗后手部皮肤软组织感染治疗方案的优化分析

目的 为伯基特淋巴瘤化疗后手部皮肤软组织感染（skin and soft tissue infection,SSTI）患儿的抗感染治疗提供思路和方法。方法 临床药师对济南市儿童医院收治的1例伯基特淋巴瘤化疗后手部SSTI患儿的抗感染方案进行优化,针对该患儿可能存在的耐甲氧西林金黄色葡萄球菌（methicillin-resistant Staphylococcus aureus,MRSA）感染的初始抗菌药物的选择、后续药物更换,治疗过程中出现严重粒细胞缺乏状态时抗菌药物的选用及哌拉西林他唑巴坦的剂量调整、替考拉宁频次确定等方面提出建议。结果 考虑为MRSA感染时首先选用利奈唑胺,之后根据血小板水平更换为替考拉宁,并确定其频次为前3剂160 mg,输液泵输,q12h,随后剂量为160 mg,输液泵输,qd;当患儿处于严重粒细胞缺乏状态时,选用亚胺培南西司他丁钠及米卡芬净抗感染治疗;根据指南和药动学/药效学理论,调整哌拉西林他唑巴坦剂量为1.2 g,ivgtt,q8h至1.8 g,ivgtt,q8h,并延长其输注时间至3 h。医师采纳上述建议。患儿经积极有效的抗感染、对症支持等治疗后,症状体征明显好转,病情稳定予以出院。结论 临床药师在参与血液肿瘤合并感染的治疗过程中,可以根据患儿的具体病情变化制订个体化治疗方案,提出合理化用药建议。     

The interaction potential of herbal medicinal products: a luminescence-based screening platform assessing effects on cytochrome P450 and its use with devil's claw (Harpagophyti radix) preparations

Objectives Potential interactions between herbal medicinal products and the cytochrome (CYP) P450 system are an important safety concern. We set out to develop a screening panel for assessing such interactions and use it to evaluate the interaction potential of devil's claw. Methods The panel consisted of luminescence‐based inhibition assays for CYP1A2, 2C9, 2C19, 2D6 and 3A4, and a reporter gene (luciferase) assay for pregnane X receptor (PXR) activation and CYP3A4 induction. Caftaric acid and chlorogenic acid, two compounds with strong fluorescence quenching properties, were used to demonstrate the assay's resistance to interference. We tested 10 commercial devil's claw preparations as well as harpagoside and harpagide, two important constituents of devil's claw. Key findings Five preparations were found to weakly inhibit CYP3A4 (IC50 124.2–327.6 µg/ml) and five were found to weakly activate PXR (EC50 10.21–169.3 µg/ml). Harpagoside and harpagide did not inhibit CYP3A4. In agreement with published data, bergamottin, a natural product known to interact with CYP3A4, was shown to inhibit CYP3A4 with an IC50 of 13.63 µm and activate PXR with an EC50 of 6.7 µm . Conclusions Devil's claw preparations are unlikely to have a clinically relevant effect on CYP function. The assay panel proved effective in screening devil's claw preparations, demonstrating its suitability for use with plant extracts. It showed superior sensitivity and resistance to interference.     

箬叶多糖及其衍生物对小鼠艾滋病作用的研究

目的　研究箬叶多糖及其衍生物硫酸酯多糖和硒酸酯多糖对小鼠艾滋病的治疗作用。方法　采用 Ｌ Ｐ Ｂ Ｍ５ 鼠白血病病毒（ Ｍｕ Ｌ Ｖ） 感染 Ｃ５７ Ｂ Ｌ／６ Ｊ 小鼠的方法建立艾滋病模型。结果　硫酸酯多糖５０ ｍｇ·ｋｇ － １·ｄ － １（ｉｐ） 具有较好地抑制小鼠脾肿大、血清 Ｉｇ Ｇ 增高的作用,硒酸酯多糖在两种给药方式中有一定的保护作用。此外,还首次发现感染小鼠出现 Ｇ Ｓ Ｈ Ｐｘ 活力下降,脂质过氧化产物升高,这与 Ｈ Ｉ Ｖ感染的病人的症状是一致的,硒多糖对提高机体的抗氧化功能有较好的作用。多糖经硫酸酯化、硒酸酯化等化学修饰后,活性有不同程度的提高。结论　作为抗氧化剂和免疫增强剂的微量元素硒和多糖类可能对 Ｈ Ｉ Ｖ 感染的病人有一定的治疗作用     

Fosfomycin for the treatment of infections caused by Gram-positive cocci with advanced antimicrobial drug resistance: a review of microbiological,animal and clinical studies

Background: The advancing antimicrobial drug resistance in Gram-positive cocci complicates the selection of appropriate therapy. The re-evaluation of older antibiotics may prove useful in expanding relevant therapeutic options. Objective: We sought to evaluate fosfomycin for the treatment of infections caused by methicillin-resistant staphylococci, vancomycin-resistant enterococci, and penicillin-non-susceptible pneumococci. Methods: We searched in PubMed, Scopus, and the Cochrane Library for studies evaluating the antimicrobial activity of fosfomycin against the above-mentioned pathogens, or the in vivo or clinical effectiveness of fosfomycin for the treatment of infections caused by these pathogens. Results/conclusions: As reported in the identified studies, the susceptibility rate of methicillin-resistant Staphylococcus aureus to fosfomycin was ≥ 90% in 12/22, and 50 – 90% in 7/22 studies; the cumulative susceptibility rate was 87.9% (4240/4892 isolates). The cumulative susceptibility rate of vancomycin-resistant enterococci to fosfomycin was 30.3% (183/604 isolates), and that of penicillin-non-susceptible pneumococci was 87.2% (191/219 isolates). Clinical data show that fosfomycin, primarily in combination regimens, has been associated with clinical success in 28/29 (96.6%) cases of infection (mainly pneumonia, bacteremia, and meningitis) by fosfomycin-susceptible isolates of methicillin-resistant S. aureus. The above data support further research on the role of fosfomycin against infections caused by Gram-positive cocci with advanced antimicrobial drug resistance.     

Treatment with DF 2162, a non-competitive allosteric inhibitor of CXCR1/2, diminishes neutrophil influx and inflammatory hypernociception in mice

BACKGROUND AND PURPOSE: Neutrophil migration into tissues is involved in the genesis of inflammatory pain. Here, we addressed the hypothesis that the effect of CXC chemokines on CXCR1/2 is important to induce neutrophil migration and inflammatory hypernociception. EXPERIMENTAL APPROACH: Mice were treated with a non-competitive allosteric inhibitor of CXCR1/2, DF 2162, and neutrophil influx and inflammatory hypernociception were assessed by myeloperoxidase assay and electronic pressure meter test, respectively, in various models of inflammation. KEY RESULTS: DF 2162 inhibited neutrophil chemotaxis induced by CXCR1/2 ligands but had no effect on CXCL8 binding to neutrophils. A single mutation of the allosteric site at CXCR1 abrogated the inhibitory effect of DF 2162 on CXCL-8-induced chemotaxis. Treatment with DF 2162 prevented influx of neutrophils and inflammatory hypernociception induced by CXCL1 in a dose-dependent manner. The compound inhibited neutrophil influx and inflammatory hypernociception induced by carrageenan, lipopolysaccharide and zymosan, but not hypernociception induced by dopamine and PGE(2). DF 2162 had a synergistic effect with indomethacin or the absence of TNFR1 to abrogate carrageenan-induced hypernociception. Treatment with DF 2162 diminished neutrophil influx, oedema formation, disease score and hypernociception in collagen-induced arthritis. CONCLUSIONS AND IMPLICATIONS: CXCR1/2 mediates neutrophil migration and is involved in the cascade of events leading to inflammatory hypernociception. In addition to modifying fundamental pathological processes, non-competitive allosteric inhibitors of CXCR1/2 may have the additional benefit of providing partial relief for pain and, hence, may be a valid therapeutic target for further studies aimed at the development of new drugs for the treatment of rheumatoid arthritis.     

超细支气管镜、 DP 电子导航、 GS 外周超声小探头、 玫瑰系统联合评价外周 （1/3） 肺感染性病灶的价值

摘要： 目的 评价超细支气管镜、 Direct Path 电子导航系统、 Guide sheath （GS） 外周超声小探头 K201/K203 系统、快速现场评价 （玫瑰系统, ROSE） 即四加技术 （UNRE） 引导下肺活检对外周 （1/3） 肺感染性病灶的诊断价值及安全性。方法 连续纳入 2014 年 4 月 1 日-2015 年 3 月 31 日在天津医科大学总医院就诊的胸部 CT 发现外周 （1/3） 肺感染性病变的患者共 97 例, 将其随机分为四加技术组 49 例及非四加技术组 48 例, 分别行四加技术或非四加技术引导下的经支气管肺活检 （TBLB）, 分别比较四加技术组及非四加技术组的诊断率、 安全性以及不同感染程度患者肺泡灌洗液肺泡巨噬细胞自发荧光强度的差异。结果 四加技术组诊断率明显高于非四加技术组 （81.63% vs 56.25%, χ2 =7.313, P < 0.01）, 病灶包含支气管征亚组四加技术诊断率高于非四加技术组。所有患者均仅在活检时见少许出血, 无咯血、 气胸等并发症发生。处于不同感染状态的患者, 其肺泡灌洗液肺泡巨噬细胞自发荧光强度亦不相同。结论 四加技术引导下肺活检诊断率高、 并发症少, 选择合适的病例能够提高诊断率, 肺泡灌洗液肺泡巨噬细胞自发荧光强度对外周 （1/3） 肺感染性病变的严重程度有提示作用。     

F15063, a potential antipsychotic with dopamine D(2)/D(3) antagonist, 5-HT(1A) agonist and D(4) partial agonist properties: (IV) duration of brain D2-like receptor occupancy and antipsychotic-like activity versus plasma concentration in mice

F15063 (N-[(2,2-dimethyl-2,3-dihydro-benzofuran-7-yloxy)ethyl]-3-(cyclopent-1-enyl)-benzylamine fumarate salt) is a novel potential antipsychotic with dopamine D₂/D₃ blocking properties and agonist activity at 5-HT_1A and D₄ receptors. The pertinent parameter for pharmacological activity of antipsychotics appears to be central D2-like receptor occupancy. However, its duration is not necessarily correlated with drug plasma levels, on which clinical dosing regimens are often based. Thus, we compared in mice the duration of actions of F15063 and haloperidol to (1) inhibit apomorphine-induced climbing and sniffing (behavioural measures of D2-like receptor antagonism) and (2) occupy D2-like receptors in vivo in the striatum and olfactory tubercles (inhibition of [³H]nemonapride binding). Finally, we measured plasma levels of F15063. D2-like receptor occupancy in the striatum remained elevated at 1, 4 and 8 h postadministration, with both F15063 (ID₅₀: 7.1, 3.6 and 16.5 mg/kg p.o., respectively) and the typical antipsychotic, haloperidol (ID₅₀: 1.4, 0.52 and 0.53 mg/kg p.o., respectively). This was paralleled by a protracted inhibition of apomorphine-induced climbing (ED₅₀: 0.9, 2.8 and 3.6 mg/kg p.o., and 0.21, 0.37 and 0.87 mg/kg p.o., respectively, for F15063 and haloperidol). In contrast, after administration of 10 mg/kg p.o. of F15063, its plasma levels decreased rapidly: 15.2, 2.1 and 0.6 ng/ml, 1, 4 and 8 h after administration, respectively. A similar pattern of results was observed when F15063 and haloperidol were administered i.p. and s.c., respectively. To summarise, the time-course of D2-like receptor occupancy and inhibition of apomorphine-climbing (and sniffing) behaviours was similarly long lasting with F15063 and haloperidol. In addition, the durations of action of F15063 and haloperidol in a behavioural model of antipsychotic-like activity were closely correlated to their occupancy of central D2-like receptors, and much longer than their presence in plasma.