体外培育牛黄联合氟哌啶醇治疗大鼠精神分裂症的研究

摘 要 目的：研究体外培育牛黄（CBS）联合氟哌啶醇对精神分裂症模型大鼠行为学的影响并探索其作用机制。方法: 以地卓西平马来酸盐（MK 801）制备大鼠精神分裂症模型。SD大鼠随机分为对照组,模型组,氟哌啶醇组（1.4 mg·kg-1）,氟哌啶醇联合CBS低剂量（50 mg·kg-1）、中剂量（100 mg·kg-1）、高剂量（150 mg·kg-1）组,CBS低剂量（50 mg·kg-1）、中剂量（100 mg·kg-1）、高剂量（150 mg·kg-1）组。用高架十字实验评价各组大鼠焦虑水平的影响,Western blot检测各组大鼠前额皮层c Fos蛋白水平。结果: 高架十字实验结果显示,氟哌啶醇组和联合用药组大鼠开臂次数百分比相比模型组明显增加（P<0.01）,而CBS各剂量组与模型组无显著差异。联合用药中、高剂量组开臂时间百分比显著大于氟哌啶醇组（P<0.05）。CBS和氟哌啶醇均可降低大脑前额皮层中c Fos蛋白含量（P<0.05或P<0.01）;而联合用药各剂量组较氟哌啶醇组c Fos蛋白含量均显著降低（P<0.05）。结论: 通过行为学评价发现,CBS与氟哌啶醇联合使用能协同降低大鼠精神分裂症模型中增高的焦虑水平,这可能与协同降低前额皮层c Fos蛋白含量有关。本研究为临床上两药的联合使用提供了药效学基础,具有一定的参考意义。     

基于AMPK/Sirt1通路延龄草总皂苷对脑缺血再灌注继发肺损伤大鼠的保护作用

摘 要 目的：探讨延龄草总皂苷（TST）对脑缺血再灌注大鼠肺组织的影响及其可能机制。 方法: 选取80只雄性大鼠随机分为8组：假手术组、模型组、阳性对照组（尼莫地平,200 mg·kg-1）、TST低（50 mg·kg-1）、中（100 mg·kg-1）、高（200 mg·kg-1）剂量组、腺苷酸活化蛋白激酶（AMPK）/沉默信息调节因子1（Sirt1）通路抑制剂组(1 mg·kg-1)、TST+AMPK/Sirt1通路抑制剂组(200 mg·kg-1+1 mg·kg-1),每组10只。苏木精 伊红（HE）染色检测大鼠肺组织病理变化;检测各组大鼠氧分压（PaO2）;酶联免疫吸附（ELISA）法检测各组大鼠支气管肺泡灌洗液中炎性因子水平;检测各组大鼠肺组织氧化应激水平。蛋白免疫印迹（Western blot）法检测肺组织AMPK、磷酸化AMPK（p AMPK）、Sirt1蛋白表达水平。 结果: 模型组大鼠肺损伤评分较假手术组高,而阳性对照组与TST不同剂量组均较模型组低（P＜0.05）;模型组大鼠PaO2、氧合指数（OI）、超氧化物歧化酶（SOD）、p AMPK及Sirt1蛋白表达水平均较假手术组低,而阳性对照组与TST组（高剂量）较模型组高,AMPK/Sirt1通路抑制剂组与TST+AMPK/Sirt1通路抑制剂组较TST组低,AMPK/Sirt1通路抑制剂组较TST+AMPK/Sirt1通路抑制剂组低（P＜0.05）;模型组IL-18、IL-1β、TNF-α、IL 6、肺组织湿干质量比、MDA、ROS、Ac NF κB p65蛋白表达水平均较假手术组高,而阳性对照组与TST组（高剂量组）较模型组低,AMPK/Sirt1通路抑制剂组与TST+AMPK/Sirt1通路抑制剂组较TST组高,AMPK/Sirt1通路抑制剂组较TST+AMPK/Sirt1通路抑制剂组高（P＜0.05）;阳性对照组与TST组比较差异均无统计学意义（P＞0.05）。 结论: TST可通过激活AMPK/Sirt1通路并减轻肺组织炎性反应及氧化应激反应进而减缓脑缺血再灌注继发肺损伤。     

绿原酸通过抑制内质网应激改善大鼠糖尿病氧化性肾损伤

摘 要 目的：探讨绿原酸（CGA）对链脲佐菌素（STZ）诱导的糖尿病肾病（DN）大鼠氧化应激的肾脏保护作用及其可能机制。 方法: 将40只大鼠随机分为5组：正常对照组、模型组、 CGA低（5 mg·kg-1）、中（10 mg·kg-1）、高（20 mg·kg-1）剂量组,每组8只。除正常对照组外,其余各组腹腔单次注射STZ（60 mg·kg-1）建立大鼠糖尿病模型。腹腔注射给药,1次/d,连续给药6周。测定大鼠血糖、尿蛋白、尿素氮（BUN）、血清肌酐（SCr）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH Px）、过氧化氢酶（CAT）和超氧化物歧化酶（SOD）水平;免疫印迹法检测内质网应激（ERS）信号通路关键分子[C/EBP同源蛋白（CHOP）、活化转录因子6（ATF6）、磷酸化蛋白激酶R（p PERK）和磷酸化鸡真核生物翻译起始因子2α（p eIF2α）]的蛋白表达水平;RT-PCR检测CHOP、ATF6 和PERK的mRNA表达水平。 结果: 与模型组相比,CGA组血糖、尿蛋白、BUN、SCr、MDA水平、CHOP、ATF6、p PERK、p eIF2α的蛋白表达水平及CHOP、ATF6 和PERK的mRNA表达水平显著降低（P<0.05或P<0.01）,SOD、GSH Px和CAT活性显著提高（P <0.05或P<0.01）,以上作用均呈剂量依赖性。 结论: CGA对STZ诱导的DN大鼠有抗氧化作用,其机制可能与抑制DN内质网应激反应有关。     

不同浓度白头翁皂苷对口腔鳞癌细胞增殖、迁移和钙蛋白酶1、E cadherin、N cadherin蛋白的影响

摘 要 目的：探究白头翁皂苷对口腔鳞癌细胞增殖、迁移及钙蛋白酶1（calpain1）表达的影响。方法: 用0,1.0,2.0,4.0,8.0,12.0 mg·L-1白头翁皂苷处理人口腔鳞癌CAL27细胞。四甲基偶氮唑（MTT）法检测白头翁皂苷对CAL27细胞增殖的影响;细胞划痕实验与Transwell实验检测白头翁皂苷对CAL27细胞迁移与侵袭能力的影响;蛋白质印迹（Western blot）技术检测CAL27细胞calpain1、E cadherin、N cadherin蛋白的表达变化。结果:与空白对照组比较,白头翁皂苷对CAL27细胞的增殖抑制率显著增加（P<0.05）,且具有时间 剂量依赖关系。12.0 mg·L-1白头翁皂苷处理48 h后CAL27细胞细胞形态从长梭形间质样变成鹅卵石状上皮样。随着白头翁皂苷处理浓度的增加,CAL27细胞迁移与侵袭能力逐渐减弱（P<0.05）;CAL27细胞中calpain1、N cadherin蛋白表达水平逐渐降低（P<0.05）,E cadherin蛋白表达水平逐渐升高（P>0.05）。结论:白头翁皂苷可抑制口腔鳞癌CAL27细胞增殖、迁移与侵袭过程,其机制可能与calpain1、N cadherin表达下调、E cadherin表达上调有关。     

丹参提取物改善大鼠重症急性胰腺炎肺损伤模型的ROS-NLRP3炎症小体信号通路机制

摘 要 目的：探讨活性氧簇（ROS） 核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎症小体信号通路在丹参提取物改善急性胰腺炎肺损伤大鼠的作用机制。 方法: 60只SD大鼠随机分组5组：假手术组、模型组、丹参提取物（1.5 g·kg-1）组、ROS抑制剂组[N 乙酰 L 半胱氨酸（NAC）,20 mg·kg-1]、丹参提取物+NAC组（1.5 g·kg-1＋20 mg·kg-1）,每组12只。以逆行胆胰管注射5%牛磺胆酸钠（1 ml·kg-1）法建立急性胰腺炎肺损伤大鼠模型,各组灌胃给药,模型组和假手术组给予等量生理盐水,qd,持续5 d。处死大鼠,测量腹水量、右肺干质量、右肺湿质量,计算湿质量/干质量（W/D）比值,采用苏木精 伊红（HE）染色法对大鼠肺组织病理症状进行Holfbauer评分,以全自动血气分析检测仪检测动脉血中氧分压（PaO2）、二氧化碳分压（PaCO2）、氧合指数（OI）,用酶联免疫吸附（ELISA）法检测血清肿瘤坏死因子 α（TNF α）、白介素 6（IL 6）水平,ROS检测试剂盒检测肺组织中ROS水平,蛋白免疫印迹（Western blot）法检测NLRP3、半胱氨酸蛋白酶 1（caspase 1）、凋亡相关的斑点样蛋白（ASC）表达。 结果: 与假手术组比较,模型组大鼠腹水量、W/D比值、Holfbauer评分、PaCO2、TNF α、IL 6、ROS水平、NLRP3、caspase 1、ASC蛋白表达显著升高（P＜0.05）,PaO2、OI显著降低（P＜0.05）;与模型组比较,各药物处理组大鼠腹水量、W/D、Holfbauer评分、PaCO2、TNF α、IL 6、ROS水平、NLRP3、caspase 1、ASC蛋白表达显著降低（P＜0.05）,PaO2、OI显著升高（P＜0.05）;与丹参提取物组及NAC组分别比较,丹参提取物+NAC组大鼠腹水量、W/D、Holfbauer评分、PaCO2、TNF α、IL 6、ROS水平、NLRP3、caspase 1、ASC蛋白表达均显著降低（P＜0.05）,PaO2、OI显著升高（P＜0.05）。结论: 丹参提取物可以保护急性胰腺炎肺损伤大鼠的肺组织,可能通过下调ROS-NLRP3炎症小体信号实现。     

HPLC法同时测定参莲胶囊中7种生物碱成分的含量

摘 要 目的：建立RP HPLC双波长法同时测定参莲胶囊中氧化苦参碱、槐定碱、氧化槐果碱、苦参碱、槐果碱、粉防己碱、防己诺林碱7种生物碱含量。 方法: 采用Venusil XBP NH2（250 mm×4.6 mm,5 μm）色谱柱,以乙腈 0.01%醋酸铵水溶液为流动相梯度洗脱,流速为1.0 ml·min-1,检测波长为210 nm、280 nm。 结果: 氧化苦参碱、槐定碱、氧化槐果碱、苦参碱、槐果碱、粉防己碱、防己诺林碱线性范围分别为32.07～513.07 μg·ml-1（r=0.998 8）、37.90～606.40 μg·ml-1（r=0.999 2）、23.07～369.07 μg·ml-1（r=0.999 2）、52.37～837.87 μg·ml-1（r=0.999 7）、17.63～282.13 μg·ml-1（r=0.999 1）、5.30～84.80 μg·ml-1（r=0.999 5）、8.87～141.87 μg·ml-1（r=0.999 7）;平均加样回收率（n=9）为100.16%~102.84%（RSD≤2.0%）。5批样品中氧化苦参碱、槐定碱、氧化槐果碱、苦参碱、槐果碱、粉防己碱、防己诺林碱含量依次为9.18~9.69 mg·g-1、9.35~11.74 mg·g-1、6.73~7.09 mg·g-1、15.17~15.96 mg·g-1、5.03~5.33 mg·g-1、1.23~1.97 mg·g-1、2.48~2.74 mg·g-1。 结论: 所建立的多成分分析方法可用于参莲胶囊中7个生物碱成分的含量测定。     

阿帕替尼联合紫杉醇对人宫颈癌HeLa S3细胞裸鼠移植瘤的抑制作用

摘 要 目的：研究阿帕替尼联合紫杉醇对人宫颈癌HeLa S3细胞裸鼠移植瘤的抑制作用及可能的作用机制。 方法: 将HeLa S3细胞接种于裸鼠右肩背部皮下,建立人宫颈癌裸鼠皮下移植瘤模型。将建模成功的40只裸鼠随机分为4组：模型组,阿帕替尼组（200 mg·kg-1）、阿帕替尼联合紫杉醇低（200 mg·kg-1+ 10 mg·kg-1）、高（200 mg·kg-1+ 20 mg·kg-1）剂量组,每组10只。各给药组按剂量腹腔注射给药,模型组腹腔注射等量生理盐水,1次/d,连续给药 14 d。检测裸鼠移植瘤体积和瘤质量,计算抑瘤率;采用TUNEL法检测肿瘤细胞凋亡指数（AI）,Western blot 法检测瘤组织内含半胱氨酸的天冬氨酸蛋白水解酶（caspase） 3、caspase 9、细胞色素C（Cyto C）蛋白表达情况。 结果: 与模型组比较,阿帕替尼组裸鼠的移植瘤体积、瘤质量均显著降低,抑瘤率、细胞AI、caspase 3、caspase 9、Cyto C蛋白表达量均显著增加（P<0.01）;与阿帕替尼组比较,阿帕替尼联合紫杉醇组裸鼠的移植瘤体积、瘤质量显著降低,抑瘤率、细胞AI、caspase 3、caspase 9、Cyto C蛋白表达量显著增加（P<0.01）,且高低剂量组间差异有统计学意义（P<0.01）。 结论: 阿帕替尼联合紫杉醇对人宫颈癌细胞株移植瘤有明显的抑制作用,且优于单独使用阿帕替尼。     

格列美脲对细颗粒物PM2.5诱导的心肌样细胞损伤的保护作用及机制研究

摘 要 目的：探讨格列美脲对细颗粒物空气动力学直径<2.5 μm（PM2.5）诱导的心肌样细胞损伤的保护作用及机制研究。 方法: 采用噻唑蓝（MTT）确定PM2.5的干预浓度;将大鼠心肌样细胞H9c2分为对照组（含血清1640培养基）、PM2.5组（800 mg·L-1）、格列美脲低、中、高剂量组（10,20,40 μmol·L-1的格列美脲＋800 mg·L-1的PM2.5）。培养24 h后检测H9c2细胞中肿瘤坏死因子 α（TNF α）和白细胞介素 1β（IL 1β）含量,同时检测细胞中活性氧（ROS）和细胞凋亡率,检测B淋巴细胞瘤 2（Bcl 2）、Bcl 2 Associated X的蛋白质（Bax）和半胱氨酸天冬氨酸特异性蛋白酶 3（caspase 3）mRNA表达水平。 结果: 随着PM2.5浓度的增加,H9c2细胞增值率降低,在800 mg·L-1时H9c2细胞增值率降到46.28%,故选800 mg·L-1作为PM2.5的干预浓度;与PM2.5组比较,格列美脲各剂量组细胞中TNF α、IL 1β含量、ROS荧光强度、细胞凋亡率、Bax和caspase 3 mRNA的相对表达量显著降低（P<0.05）,Bcl 2 mRNA的相对表达量显著升高（P<0.05）,且呈剂量相关性（P<0.05）。 结论: 格列美脲对细颗粒物PM2.5诱导的心肌样细胞损伤具有保护作用,其机制可能与格列美脲减轻炎症反应和氧化应激、抑制心肌细胞凋亡有关。     

益母草碱对小鼠肝药酶含量的影响

摘 要 目的：研究益母草碱对小鼠肝药酶含量的影响。 方法: 将40只ICR小鼠随机分为5组：空白对照组、益母草碱高（120 mg·kg-1）、中（90 mg·kg-1）、低剂量组（60 mg·kg-1）、阳性对照组（苯巴比妥钠,80 mg·kg-1）,每组8只。益母草碱组灌胃给药,1次/d,连续进行7 d;阳性对照组腹腔注射给药,1次/d,连续进行5 d;空白对照组给予同等体积的生理盐水。检测肝微粒体蛋白、细胞色素P450酶（CYP450）、细胞色素b5（CYPb5）、氨基比林N 脱甲基酶（ADM）、红霉素N 脱甲基酶（ERD）、谷胱甘肽S 转移酶（GST）含量。结果: 与空白对照组相比,益母草碱各剂量组肝微粒体蛋白含量变化不明显（P>0.05）,CYP450、CYPb5、ADM含量显著降低（P<0.01）,中、高剂量组的ERD和高剂量组的GST含量显著降低（P<0.01）。益母草碱各剂量组与阳性对照组相比,以上各指标差异均有统计学意义（P<0.01）。 结论: 益母草碱能明显降低小鼠肝微粒体肝药酶的含量,下调CYP3A和CYP2E1的表达,其作用效果与益母草碱给药剂量相关。     

红景天苷对高同型半胱氨酸诱导的小鼠膀胱胶原沉积及SGK1蛋白表达的影响

摘 要 目的：观察红景天苷对高同型半胱氨酸诱导的小鼠膀胱沉积胶原的影响。方法: 40只清洁级BABLc雄性小鼠适应饲养7 d后,随机分为空白对照组、模型组（1%高蛋氨酸饮水8周）、红景天苷25 mg·kg-1组（0.01%的含红景天苷饮食喂养16周,后给予1%高蛋氨酸饮水8周）和红景天苷50 mg·kg-1组（0.02%的含红景天苷饮食喂养16周,后给予1%高蛋氨酸饮水8周）,每组10只。取膀胱组织,Masson染色检测胶原沉积;Western Blot法检测纤维化相关蛋白 血清和糖皮质激素诱导蛋白激酶 1(Serum and glucocorticoid induced protein kinase, SGK1)表达和免疫组化染色检测膀胱组织白介素 1β (Interleukin 1β, IL 1β)蛋白表达。结果: 与模型组相比,红景天苷50 mg·kg-1可显著抑制高蛋氨酸诱导的膀胱组织胶原沉积和纤维化相关蛋白SGK1及膀胱组织炎症因子IL 1β的表达（P＜0.05）。结论: 红景天苷可减轻高同型半胱氨酸诱导的小鼠膀胱胶原沉积和SGK1蛋白表达,同时抑制膀胱组织IL 1β蛋白表达。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.