白三烯拮抗剂ONO—1078对辣椒素和P物质诱导豚鼠支气管收缩和…

目的：探讨白三烯特异性拮抗剂４氧－８－（对－（４－苯丁氧基）苯甲酰氨基）－２－（（５－四唑基）－４Ｈ－１－苯并吡喃半水合物（ＯＮＯ－１０７８）对气道辣椒素敏感的感觉神经功能的调节作用。方法：观察豚鼠肺内压（ＩＰＰ），伊文思蓝渗出量和离体支气管平滑肌收缩反应，结果：辣椒素（Ｃａｐ，０．０５ｍｇ．ｋｇ＾－１，ｉｖ）Ｐ物质（ＳＰ，１μｇ．ｋｇ＾－１，ｉｖ）和白三烯Ｃ４（ＬＴＣ４，０．５μｇ．ｋｇ＾－１）     

速激肽受体拮抗剂对白三烯C_4诱导豚鼠气道收缩和微血管渗漏的作用

本实验探讨了内源性速激肽是否参与白三烯Ｃ４（ＬＴＣ４）的气道效应．ＬＴＣ４（０．５μｇｋｇ－１，ｉｖ）可增高豚鼠肺内压（ＩＰＰ）和气道内依文思蓝渗出。速激肽ＮＫ－１受体拮抗剂ＣＰ－９６３４５｛（２Ｓ，３Ｓ）－顺式－２－（二苯甲基）－Ｎ－［（２－甲氧苯）－甲基］－１－杂氮双环［２．２．２］辛烷－３－胺｝１ｍｇｋｇ－１，ｉｖ，可减弱ＬＴＣ４诱导的依文思蓝渗出；ＮＫ－２受体拮抗剂ＳＲ－４８９６８｛（Ｓ）－Ｎ－甲基－Ｎ－［４－（４－乙酰氨基－４－苯基哌啶）－２－（３，４－二氯苯基）丁基］苯甲酰胺｝，１ｍｇｋｇ－１，ｉｖ，可抑制ＩＰＰ的增高．白三烯拮抗剂ＯＮＯ－１０７８（０．０３ｍｇｋｇ－１，ｉｖ）可阻断这两种反应．结果说明内源性速激肽增强ＬＴＣ４的气道作用，其中ＮＫ－１受体介导微血管渗漏，ＮＫ－２受体介导支气管收缩．     

4－氧－8－［对－（4－苯丁氧基）苯甲酰氨基］－2－（5－四唑基）－4H－1－苯并吡喃抑制抗原诱导的豚鼠气道收缩及微血管渗漏的作用

在扑尔敏预先处理的致敏豚鼠，白三烯拮抗剂４－氧－８－［对－（４－苯丁氧基）苯甲酰氨基］－２－（５－四唑基）－４Ｈ－１－苯并吡喃（ＯＮＯ－１０７８，０．０３，０．３ｍｇ·ｋｇ－１，ｉｖ）显著抑制抗原引起的肺内压增高，并完全抑制肺内气道中心部和外周部的依文思蓝渗出。肺内压与这两部位的染料渗出量呈正相关，但与气管和主支气管的染料渗出无相关性。在扑尔敏处理的肺条和气管条，ＯＮＯ－１０７８（１μｍｏｌ·Ｌ－１）仅部分抑制抗原诱导的收缩（４５．８％和３３．３％）。结果说明ＯＮＯ－１０７８抑制抗原诱导的气道收缩作用，至少部分通过抑制微血管渗漏，并主要作用在相对外周的气道。     

4—氧—8—1对—（4—苯丁氧基）苯甲酰氨基1—2—（5—四唑基）…

在扑尔敏预先处理的致敏豚鼠，白三烯拮抗剂４－氧－８－［对－４－苯丁氧基）苯甲酰氨基］－２－（５－四唑基）－４Ｈ－１－苯并吡喃（ＯＮＯ－１０７８，０．０３，０．３ｍｇ．ｋｇ＾－１，ｉｖ）显著抑制抗原引起的肺内压增高，并完全抑制肺内气道中心部和外周部的依文思蓝渗出，肺内压与这两部位的染料渗出量呈正相关，但与气管和主支气管的染料渗出无相关性，在扑尔敏处理的肺条和气管条，ＯＮＯ－１０７８仅部分抑制抗原诱导     

Inhibitory effects of S-nitrosocaptopril on vasomotor tone

目的：观察巯亚硝酰卡托普利（ＣａｐＮＯ）和卡托普利（Ｃａｐ）对血管紧张性的影响．方法：记录家兔胸主动脉环张力和大鼠肾动脉灌流压（ＰＰｒ）．结果：ＣａｐＮＯ对苯福林预收缩的内皮完整与去内皮主动脉环，均呈浓度依赖性（３０ｎｍｏｌ·Ｌ－１－１０μｍｏｌ·Ｌ－１，Ｐ＜００１）的舒张作用，而相同浓度的Ｃａｐ作用不显著；ＣａｐＮＯ降低ＰＰｒ的作用亦呈浓度依赖性（１０ｎｍｏｌ·Ｌ－１－１０００ｎｍｏｌ·Ｌ－１，Ｐ＜００１），而Ｃａｐ只在１０００ｎｍｏｌ·Ｌ－１呈显著性变化；Ｎ单甲基左旋精氨酸和左旋精氨酸预处理均不影响ＣａｐＮＯ诱发的降ＰＰｒ作用．结论：ＣａｐＮＯ具有直接降低血管紧张性作用．     

Effects of dl-3-n-butylphthalide on region al cerebral blood flow in right middle cerebral artery occlusion rats

目的：观察ｄｌ３ｎ丁基苯酞（ＮＢＰ）对右大脑右中动脉阻断（ＲＭＣＡＯ）大鼠缺血区局部脑血流（ｒＣＢＦ）的影响．方法：氢清除法动态监测ＲＭＣＡＯ大鼠ｒＣＢＦ变化．结果：ＲＭＣＡＯ后１０ｍｉｎｉｐＮＢＰ（５，１０，２０ｍｇ·ｋｇ－１）可明显增加ｒＣＢＦ（与溶剂对照组相比Ｐ＜００１），４０ｍｉｎ给药有类似作用但作用较弱（与给药前相比Ｐ＜００５），６０ｍｉｎ给药不能增加ｒＣＢＦ（与给药前相比Ｐ＞００５）．此外，ＲＭＣＡＯ前４０ｍｉｎｉｐＮＢＰ也可使ＲＭＣＡＯ后不同时间点ｒＣＢＦ明显增加．尼莫地平（０５ｍｇ·ｋｇ－１，ｉｐ）与ＮＢＰ（１０ｍｇ·ｋｇ－１，ｉｐ）具有相似的作用．结论：ＮＢＰ预防给药或治疗给药能使ＲＭＣＡＯ后减少的ｒＣＢＦ明显增加．     

6β－乙酰氧基去甲托烷呼吸抑制效应

６β－乙酰氧基去甲托烷（６β－ａｃｅｔｏｘｙｎｏｒｔｒｏｐａｎｅ，６β－ＡＮ）是一种新型Ｍ２受体激动剂，兔１０ｕｇ·ｋｇ－１ｉｖ，犬２，５，２０ｕｇ·ｋｇ－１ｉｖ均导致呼吸频率、潮气量、每分通气量明显减少（Ｐ＜０．０５或０．０１），呈剂量依赖关系。ｐＯ２降低，ｐＣＯ２升高。较小剂量给兔０．５，１．０，２．０，４．０ｕｇ·ｋｇ－１ｉｖａ和犬０．２５，０．５，１．０ｕｇ·ｋｇ－１ｉｖａ亦产生与静脉给药相似的呼吸抑制效应。ＡＦ－ＤＸ１１６能拮抗６β－ＡＮ的呼吸抑制作用，ＰＺ则与６β－ＡＮ产生协同作用。表明６β－ＡＮ有呼吸抑制作用，并可能与其激动呼吸中枢Ｍ２受体有关。     

速激肽NK-1受体拮抗剂SR-140333对抗原引起致敏大鼠气道高反应性的影响

为观察速激肽ＮＫ１受体拮抗剂ＳＲ１４０３３３对抗原攻击引起的致敏大鼠气道高反应性的影响，测定了致敏大鼠在抗原攻击前后的基础呼吸频率，对ＭＣｈ的反应性及支气管肺泡灌洗液中的白细胞数量。实验结果显示，致敏大鼠吸入ＯＡ后６ｈ基础呼吸频率增加，并显著增加乙酰甲胆碱（ＭＣｈ）的反应性、ＭＣｈ的－ｌｏｇＰＣ３０值和支气管肺泡灌洗液中的白细胞数量。ｉｐ速激肽ＮＫ１受体拮抗剂ＳＲ１４０３３３（０１ｍｇ·ｋｇ－１）或地塞米松（０５ｍｇ·ｋｇ－１），可明显抑制上述反应，小剂量ＳＲ１４０３３３（００１ｍｇ·ｋｇ－１）仅有部分抑制作用。结果提示抗原攻击可引起致敏大鼠气道高反应性和气道炎症，速激肽ＮＫ１受体拮抗剂可抑制这些反应     

白细胞三烯拮抗剂ONO－1078对豚鼠迷走神经电刺激引起气道痉挛及微血管渗漏作用

阿托品预先处理的豚鼠，电刺激迷走神经（１０Ｈｚ，５ｍｓ，２Ｖ或１０Ｖ，９０ｓ）引起气道阻力增高，气管、主支气管和肺内气道的依文思蓝渗出量增加，并随刺激强度加大而增强。白细胞三烯拮抗剂ＯＮＯ－１０７８（０．０３，０．１ｍｇ·ｋｇ－１，ｉｖ）对气道阻力的增高无明显影响；但显著抑制微血管渗漏，在刺激强度低（２Ｖ）时更明显。结果提示白细胞三烯类参与神经原性炎症时的气道微血管渗漏反应。     

白三烯拮抗剂ONO—1078对电刺激迷走神经辣椒素和P物质引起的…

阐明ＯＮＯ－１０７８（ＯＮＯ，４－氧－８［对－（４－苯丁氧基）苯甲酰氨基］－２－（５－四唑基）－４Ｈ－１－苯并吡喃）对神经原性刺激诱导心血管反应的作用。观察豚鼠心房和心室伊文思蓝渗出以及平均主动脉压变化。在阿托品预先处理后，电刺激迷走神经显著增高伊文思蓝渗出；辣椒素和Ｐ物质也增加染料渗出并降低平均动脉压。     

Alcohol,Age, and Piloting: Judgment,Mood, and Actual Performance

We have previously described acute and carry-over effects of alcohol on young and older pilots' performance. In the present paper we report the effects of alcohol and age on self-assessment of performance and mood in the same study. Young and older pilots flew in a simulator during an alcohol and placebo condition. In the alcohol condition, they flew after reaching. 04 g/dL (.04%) BAL, after. 10% BAL, and then 2,4, 8,24, and 48 h after. 10% BAL (they flew at the same times in the placebo condition). They rated confidence in ability to fly, mood, alertness, and intoxication before each flight, and perceived workload and performance after each flight. As reported in Morrow et al., alcohol had both acute and carry-over effects for 8 h on actual flight performance, with greater acute impairment for older pilots. The present study reports that these older pilots tended to be more aware than the young pilots of acute and carry-over alcohol impairment out to 4 h. By 8 h, however, all pilots were unaware of impairment. Alcohol also had a biphasic effect on mood, which increased on the ascending limb and decreased on the descending limb of the BAL curve.     

Polymorphism, pseudopolymorphism, and amorphism of peracetylated alpha-, beta-, and gamma-cyclodextrins

Polymorphism, pseudopolymorphism, and amorphism of hexakis(2,3,6-tri-O-acetyl)-alpha-cyclodextrin (TAalphaCyD), heptakis(2,3,6-tri-O-acetyl)-beta-cyclodextrin (TAbetaCyD), and octakis(2,3,6-tri-O-acetyl)-gamma-cyclodextrin (TAgammaCyD) were investigated using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffractometry (XRPD), Fourier transform infrared spectroscopy (FTIR) and optical microscopy. An anhydrous and a bi-hydrate crystalline forms of TAalphaCyD, two monotropic anhydrous polymorphs and three pseudopolymorphs (i.e. methanolate, hydrate, and isopropanolate-hydrate) of TAbetaCyD, as well as two monotropic anhydrous polymorphs and isostructural pseudopolymorphs (e.g. hydrate and isopropanolate-hydrate) of TAgammaCyD were isolated and characterized. The amorphous forms of each TACyD were also obtained. Thermal data for desolvation of TAalphaCyD.2H2O and TAbetaCyD.CH3OH were reconciled with their crystal packing features. Melting temperatures and enthalpies of the crystalline forms of each TACyD can be referred to for possible solid-state interactions with drugs.     

Fibroblasts, myofibroblasts, and fibrosis: fact, fiction, and the future

Fibroblasts and their activated phenotype known as myofibroblasts are nonexcitable cells found in all organs of the body. In the heart, fibroblasts, along with the endothelial and smooth muscle cells of the blood vessels, make up approximately 30% of tissue mass. In vitro, myofibroblasts cocultured with cardiac myocytes can propagate electrical signals down cellular strands indicating that under these conditions myofibroblasts are capable of depolarizing enough to maintain electrical propagation. This has obvious implications for cardiac biology if heterocellular coupling between fibroblasts and myocytes were to occur in the intact heart either under normal conditions or during cellular stress. The purpose of this review series is to highlight the newest information on cardiac fibroblasts and myofibroblasts and to review the data on their interactions with cardiac myocytes.     

Smooth-pursuit eye movements,and diazepam,CPZ, and secobarbital

This study examined the effects on smooth-pursuit eye tracking of single doses of CPZ (0.667 and 1.334 mg/kg), diazepam (0.071, 0.142, and 0.284 mg/kg), and secobarbital (100 mg). Only the barbiturate significantly affected the ability to follow a moving target with smooth-pursuit eye movements. In repeated testing of a single subject, 130 mg of secobarbital disrupted smooth-pursuit movements at least until 24 hrs after ingestion.This study was supported in part by grant MH-19477, USPHS, and USFDA contract No. 72-42. Dr. Holzman is the recipient of Research Scientist Award No. K5-MH-70900, USPHS. We express our thanks to Dr. Alfred Heller for helpful comment.     

Lesbian,Gay, Bisexual,and Transgender Youth: Health Concerns,Services, and Care

Abstract

This paper was developed from a presentation made at the FDA/Industry Workshop held at Sandoz Research Institute, East Hanover, New Jersey on November 20, 1986.     

Temperature,pH, salinity,hardness, and particulates mediate nickel toxicity to eubacteria,an actinomycete,and yeasts in lake,simulated estuarine,and sea waters

The survival of some eubacteria, an actinomycete, and yeasts after acute and chronic exposures to nickel (Ni) in lake, simulated estuarine, and sea waters and the influence of environmental factors on Ni toxicity were determined. Nickel toxicity to microbes in marine systems was reduced by increasing the salinity, by decreasing the temperature, and by the incorporation of simulated sediment. The toxicity of Ni to microbes in fresh water was reduced by increasing the pH, by increasing the hardness, and by the incorporation of suspended particulates. Chronic toxicity studies indicated that fresh waters are more sensitive than marine waters to Ni pollution, as microbial survival was greater in marine than in fresh waters stressed with equivalent concentrations of Ni.