多索茶碱与氨茶碱治疗支气管哮喘的效果观察

目的探讨多索茶碱与氨茶碱治疗支气管哮喘的临床效果。方法选择本院2010年1月～2013年1月收治住院的支气管哮喘患者100例,随机分为多索茶碱组和氨茶碱组。在常规治疗的基础上,多索茶碱组患者给予多索茶碱治疗,氨茶碱组患者给予氨茶碱治疗,治疗7d后比较两组患者的肺功能指标及临床疗效。结果多索茶碱组的总有效率高于氨茶碱组,差异有统计学意义（P〈0．05）;多索茶碱组的不良反应发生率低于氨茶碱组,差异有统计学意义（P〈0．05）。结论多索茶碱治疗支气管哮喘效果显著,不良反应发生率低,是一种安全有效的药物,值得临床推广。     

多索茶碱与氨茶碱治疗支气管哮喘临床疗效的对比分析

目的：评价多索茶碱与氨茶碱治疗支气管哮喘的疗效。方法选择100例支气管哮喘患者,将其均分为氨茶碱组与多索茶碱组,分别用氨茶碱和多索茶碱。治疗1周后,比较两组的临床疗效。结果多索茶碱组治疗总有效率为92.0％,高于氨茶碱组治疗总有效率74.0％（P＜0.01）,FEV1、FVC、VC均较对照组改善明显。结论采用多索茶碱治疗支气管哮喘的临床疗效果好。     

氨茶碱与多索茶碱治疗支气管哮喘急性发作的疗效及对患者呼吸功能的影响

目的：观察氨茶碱与多索茶碱治疗支气管哮喘急性发作的疗效及对患者呼吸功能的影响。方法：选取我院收治的支气管哮喘患者65例为研究对象,按照随机数字表法分为氨茶碱组32例和多索茶碱组33例,分别在常规治疗方法的基础上联合多索茶碱或氨茶碱进行治疗。结果：多索茶碱组治疗总有效率为90.9%,氨茶碱组为71.88%,二者差异有统计学意义（P＜0.05）;治疗后多索茶碱组FEV1、FVC及VC等肺通气功能指标改善程度优于氨茶碱组（P＜0.05）;多索茶碱组不良反应发生率明显低于氨茶碱组（P＜0.05）。结论：多索茶碱治疗支气管哮喘临床疗效明显优于氨茶碱,安全性更高。     

黄嘌呤类支气管扩张药--多索茶碱

多索茶碱（1,3二甲基-7-（1,3-二氧环戊基-2-基）-甲基-3,7-二氢-1H-嘌呤-2,6-二酮）是一种不同于目前茶碱类药物的新型黄嘌呤类支气管扩张药,它的茶碱分子结构的N-7位上增加了一个二氧戊环结构。多索茶碱与其它支气管扩张药相比,没有对心脏的直接刺激作用。     

静脉滴注多索茶碱与氨茶碱辅治婴幼儿急性肺炎疗效对比分析

目的观察静脉滴注多索茶碱与氨茶碱辅治婴幼儿急性支气管肺炎止咳平喘的治疗效果对比。方法选择住院肺炎128例。多索茶碱组68例,氨茶碱组60例,两组均给予抗生素,化痰止咳等基础治疗。结果多索茶碱组比氨茶碱组在气喘、咳嗽及肺部体征消退时间,住院天数明显缩短,（P〉0.05）,结论多索茶碱静脉滴注对婴幼儿支气管肺炎有显著的平喘止咳作用,且安全、方便,是辅佐治疗婴幼儿治疗的有效药物。     

多索茶碱治疗支气管哮喘的临床疗效分析

目的探讨多索茶碱治疗支气管哮喘的疗效,用于指导临床治疗。方法选择支气管哮喘患者142例,随机分成治疗组及对照组各71例,将治疗组用多索茶碱治疗与对照组氨茶碱治疗进行疗效比较观察。结果治疗组显效43例,总有效率90．14％;对照组显效28例,总有效率70．43％。治疗组明显优于对照组,经统计学处理差异有显著性（P〈0．05）。结论多索茶碱治疗支气管哮喘具有显著疗效,可以有效控制病情发展,值得临床推广。     

葛根素注射液对多索茶碱在大鼠体内药动学的影响

目的研究葛根素对多索茶碱在大鼠体内药动学的影响。方法采用高效液相色谱（HPLC）法测定12只大鼠单独给药和联合葛根素给药后多索茶碱及其代谢产物茶碱的血浆浓度,采用DAS药动学软件对多索茶碱血浆浓度 时间数据进行非房室模型分析,求多索茶碱在大鼠体内的主要药动学参数,并进行统计分析。结果两组大鼠多索茶碱t1/2差异有统计学意义（P＜0.05）,合并用药组较单独用药组增加了6.65%;CL/F差异有统计学意义（P＜0.05）,合并用药组较单独用药组减少38.00%。单独给药组和合并给药组茶碱AUC（0 8）、Cmax、tmax差异无统计学意义（P＞0.05）,t1/2差异有统计学意义（P＜0.05）,合并用药组较单独用药组增加了35.29%;CL/F差异有统计学意义（P＜0.05）,合并用药组较单独用药组减少了35.29%。结论葛根素能抑制多索茶碱在大鼠体内代谢,且能延长多索茶碱代谢产物茶碱在体内的消除,两药同时使用应注意监测血茶碱浓度。     

支气管哮喘治疗中氨茶碱和多索茶碱的疗效对比评估

目的：探究采用氨茶碱与多索茶碱治疗支气管哮喘的临床效果。方法选取我院收治的支气管哮喘患者80例作为本次的研究对象，所有患者均为2013年1月～2015年1月来我院接受疾病治疗的患者，按照入院顺序分为两组，常规组40例，采用氨茶碱治疗，研究组40例，采用多索茶碱治疗，比较两组患者的临床治疗效果与不良反应情况。结果经过临床治疗后，研究组患者的总有效率明显高于常规组，比较差异显著（ P＜0．05）；且研究组患者的不良反应发生率明显低于常规组，比较差异显著（ P＜0．05）。结论对支气管哮喘患者采用多索茶碱治疗的临床效果显著，总有效率高，不良反应少，患者的临床症状得到明显的改善，值得大力推广并应用。     

多索茶碱与氨茶碱治疗支气管哮喘的临床分析

目的比较分析多索茶碱与氨茶碱治疗支气管哮喘的临床效果。方法我院2012年1月至2013年12月间收治的支气管哮喘患者66例,按照治疗方案分为多索茶碱(34例)和氨茶碱组(32例),比较两组治疗效果及不良反应发生情况。结果多索茶碱组患者的治疗有效率为94.11%,而氨茶碱组有效率为71.88%,氨茶碱有效率比多索茶碱低;多索茶碱组不良反应发生率达11.76%,明显低于氨茶碱组31.25%(P<0.05)。结论支气管哮喘中应用多索茶碱效果优于氨茶碱,且不良反应发生率更低,值得临床推广应用。     

多索茶碱和茶碱缓释片对支气管哮喘的疗效和安全性比较

目的 比较多索茶碱和茶碱缓释片对稳定期哮喘患者的疗效和安全性,为临床用药提供依据。方法 前瞻性入组汉中市中心医院收治的稳定期哮喘患者100例,随机分为观察组（n=50）和对照组（n=50）。观察组给予多索茶碱400 mg,2次/d;对照组给予300 mg茶碱缓释片,2次/d。两组疗程均为6周。观察记录两组患者治疗前后的肺功能指标-1秒用力呼气量（FEV1）,用力肺活量（FVC）,FEV1/FVC（%）,最大呼气流量（PEFR）及不良反应。结果 治疗前,两组患者肺功能指标（FEV1、FVC、FEV1/FVC、PEFR）均无统计学差异;治疗6周后,与治疗前比较,两组患者肺功能FEV1、FEV1/FVC、PEFR均显著提高,但观察组和对照组患者肺功能比较没有统计学差异。对照组患者总不良反应事件发生率显著高于观察组（P<0.05）。结论 茶碱缓释片和多索茶碱均能改善轻度支气管哮喘患者肺功能,但多索茶碱安全性好于茶碱缓释片。     

Simultaneous analysis of mycotoxins in corn flour using LC/MS-MS combined with a modified QuEChERS procedure

The present study was developed to simultaneously quantify different mycotoxins including zearalenone (ZEA), T2-toxin, aflatoxin B1 (AFB₁), deoxynivalenol (DON), and ochratoxin A (OTA) in 30 and 10 corn flour samples collected from local gristmill corn in Ardabil province and local markets in Tehran, respectively. A modified method QuEChERS (quick, easy, cheap, effective, rugged, and safe) in combination with an LC-MS/MS technique was used for sample preparation and measuring the levels of mycotoxins, respectively. Spiked calibration curves based on external and internal standards were used to overcome matrix effects and were reported as linear between 2 and 50?ng g^?1 for aflatoxin B1, T-2 toxin, ochratoxin A; 50 and 1250?ng g^?1 for zearalenone; and 75 and 1800?ng g^?1 for deoxynivalenol. With the aid of spike calibration curves and acidic condition, the absorption of OTA by primary, secondary amine was reduced, and consequently, the percentage of recoveries was improved (in the range of 92.98–103.8). AFB₁, OTA, and ZEA were detected and quantified in 23 (76.6%), 6 (20%), and 14 (46%) of 30 samples, with average contamination of 154.1?ng g^?1, 25?ng g^?1, and 358.7?ng g^?1, respectively. The co-occurrence of AFB₁?+?ZEA and AFB₁?+?OTA?+?ZEA was noted in 20% and 23% of corn samples, respectively. The measured level of contamination for DON and T-2 toxin of corn flour samples did not exceed the maximum tolerated level. Moreover, the estimation of dietary intake of AFB₁, OTA, ZER, DON, and T2-toxin were 5.8, 1.1, 32.1, 5.58, and 0.06?ng per kg body weight per day, respectively.     

Depression linked to higher antibodies production against estrogenized insulin in type 1 diabetes

Depression has been commonly associated with type 1 diabetes (T1D) and insulin covalently modified with catecholestrogens (CEs) was found in serum of these T1D patients. This study aimed to know whether depression link to higher antibodies against estrogenized insulin in T1D.ELISA (direct binding and competition) and quantitative precipitin titration were used to detect antibodies and their affinities against estrogenized insulin in the serum of 66 depressed T1D (DT1D) patients (out of 110 T1D) and 41 control subjects. Antibodies from DT1D patients showed high binding specificity to estrogenized insulin (2-hydroestradiol-insulin; 2-OHE₂-Ins) in comparison to overall T1D patients (p < 0.05) or control subjects (p < 0.001). However, T1D sera demonstrate high recognition to 2-OHE₂-Ins as compared to Ins (p < 0.05) or 2-OHE₂ (p < 0.001). The affinity of antibodies from DT1D and T1D patients was 1.32 × 10^-7 M and 1.43 × 10^-7 M, respectively. Depression linked to higher antibodies production against estrogenized insulin in T1D. Furthermore, depression in T1D generates inflammatory conditions that further increased antibodies production in T1D patients.     

Preparation of pH-dependent modified-release pellets of urapidil to improve its bioavailability

Objective: Modified-release pellets containing urapidil were developed and its in vivo bioavailability was investigated.

Methods: Lactose and MCC were used as the main fillers to prepare drug-layer pellets by the powder layering method using centrifugal granulation, and coated in a fluidized bed coater. Pellets with different drug release characteristics were prepared with a methacrylic acid copolymer aqueous dispersion.

Results: Using commercial German capsules as the reference (R), two coating formulations were selected for tests after optimization: pH-dependent pellets with a ratio of Eudragit^® NE30D/L30D55 of 10:1, a 3% coating level (T₁), and pH-independent pellets with a Eudragit^® NE30D coating level (T₂) of 3.5%. The bioavailability of the pellets (T₁, T₂, containing 30?mg urapidil) was determined in six healthy subjects after oral administration of a single dose, for a period of three weeks, in the form of a crossover design with a wash-out period of one week. The plasma concentrations of urapidil were determined by HPLC with UV detection. The C_max (maximum concentration), T_max, and MRT of T₁ were 311.7?ng/mL, 5.3?h and 8.3?h, respectively. T₁ was bioequivalent to R, with a relative bioavailability 110.9%. The C_max and T_max, of T₂ were 105.3?ng/mL and 13.3?h, respectively, and the relative bioavailability was 72.7%.

Conclusion: The pH-dependent urapidil pellets have a high bioavailability.     

Pharmacokinetics of the antiarrhythmic agent tiracizine: Steady state kinetics in comparison with single-dose kinetics

Serum and urine kinetics of unchanged tiracizine (T), a new class I antiarrhythmic agent, and three metabolites (M1, 2, and 3) were assessed in eight healthy extensive metabolizers after a single oral administration of 50 mg tiracizine and during steady state (50 mg b.i.d.). Additionally, tiracizine-induced ECG changes were measured. Considerable accumulation of M1 and M2 was observed during repeated dosing (M1, C_max,ss = 391.8 ng mL^?1 against C_max,sd = 132.8 ng mL^?1; M2, C_max,ss = 143.2 ng mL^?1 against C_max,sd = 25.8 ng mL^?1). However, significant increases of AUC (AUCτ = 261.9 ng h mL^?1 against AUC_0–∞,sd = 182.9 ng h mL^?1), C_max (C_max,ss = 75.9 ng mL^?1 against C_max,sd = 56.9 ng mL^?1) and t_1/2β (t_1/2β,ss = 4.0 h against t_1/2β,sd = 2.4 h) of the parent compound indicate non-linear kinetics. The significant decrease in renal clearance of all four substances as well as the decrease of non-renal tiracizine clearance with repeated dosing led to the assumption that non-linearity is due to saturable renal excretion and a fall in intrinsic tiracizine clearance. PQ time was prolonged significantly during steady state and culminated at the t_max of the parent compound, whereas there was no change in any ECG parameter after a single-dose administration of 50 mg tiracizine.     

硫酸沙丁胺醇缓释胶囊人体药代动力学和生物利用度

目的　研究健康受试者单剂量和多剂量口服硫酸沙丁胺醇缓释胶囊的人体生物利用度和药代动力学。方法　以英国Glaxo公司生产的硫酸沙丁胺醇控释片为参比制剂,HPLC-UV法测定20名健康男性志愿受试者按交叉试验单剂量和多剂量口服硫酸沙丁胺醇缓释胶囊和控释片后血浆中沙丁胺醇的浓度。结果　单剂量服用硫酸沙丁胺醇缓释胶囊和控释片后,二者的C_max,T_max和T_1/2均无显著性差异,缓释胶囊的相对生物利用度为99.68%±10.27%。多剂量给药达稳态时,缓释胶囊和控释片的C^ss_max,C^ss_min,波动度(DF),均无显著性差异。结论　两种制剂具有生物等效性,缓释胶囊有与控释片相似的缓释特征。     

LC-MS-MS analysis of 2-pyridylacetic acid,a major metabolite of betahistine: application to a pharmacokinetic study in healthy volunteers

1.?A sensitive liquid chromatographic-tandem mass spectrometric assay was developed and validated to determine the major metabolite of betahistine, 2-pyridylacetic acid, in human plasma.

2.?The analyte was extracted from plasma samples by liquid–liquid extraction and analysed using liquid chromatography-tandem mass spectrometry with an electrospray ionization interface. The method has a lower limit of quantitation of 1?ng?ml^?1 for a 0.5-ml plasma aliquot. The intra- and interday precision (relative standard deviation), calculated from quality control (QC) samples, was less than 10%. Accuracy as determined from QC samples was within ±7%.

3.?The validated method was successfully applied to a pharmacokinetic study of betahistine in healthy volunteers. After oral administration of a single dose of 24?mg betahistine mesylate to 20 healthy Chinese male volunteers, C_max was 339.4?ng?ml^?1 (range 77.3–776.4?ng?ml^?1). The t_1/2 was 5.2?h (range 2.0^?1?11.4?h). The AUC_0?t obtained was 1153.5?ng?ml^?1?h (range 278.5–3150.8?ng ml^?1?h). The disposition of the metabolite exhibited a marked interindividual variation.

4.?The plasma concentrations of the parent drug were less than 0.5?ng ml^?1, suggesting that it undergoes almost complete first-pass metabolism. The reported two active metabolites were not detected in the plasma of any volunteer. Although there is no evidence that the major metabolite has pharmacological activity, the clinical importance of 2-pyridylacetic acid in humans should be reinvestigated.     

THE LACK EFFECT OF FOOD ON THE BIOAVAILABILITY OF NEFAZODONE TABLETS

The objective of this study was to assess the effect of food on the pharmacokinetics of nefazodone (NEF). A group of 24 healthy adult male volunteers received a single 200 mg dose of NEF under fasting conditions as well as 5 min after a high-fat breakfast. There was a 1 week washout between treatments. Serial blood samples were collected for 48 h after dosing and assayed by a validated HPLC method for NEF and the metabolites hydroxynefazodone (HO-NEF), m-chlorophenylpiperazine (mCPP), and triazoledione (dione). The mean (SD) peak concentration (C_max) for NEF was not affected by food and was 416 (220) ng mL⁻¹ and 446 (271) ng mL⁻¹ after the fed and fasted treatments, respectively. The median time to reach C_max (T_max ) was also unaffected by food and was 2 h for both treatments. However, the mean (SD) area under the curve (AUC) was significantly reduced by food from 1815 (1017) ng h mL⁻¹ to 1409 (695) ng h mL⁻¹. Although there was an 18% decrease in NEF AUC when administered with food, food had no effect on C_max and T_max values for NEF, HO-NEF, mCPP or dione or AUC values for HO-NEF, mCPP, or dione, indicating that NEF can be administered without regard to meals.     

Short-term air pollution exposure is associated with hospital length of stay and hospitalization costs among inpatients with type 2 diabetes: a hospital-based study

Air pollution is a risk factor for type 2 diabetes (T2D), exerting heavy economic burden on both individuals and societies. However, there is no apparent report regarding the influence of air pollutants such as particulate matter (PM_2.5 and PM₁₀), sulfur dioxide (SO₂), carbon monoxide (CO), nitrogen dioxide (NO₂), and ozone (O₃) on financial burden to individuals and societies suffering from T2D. This study aimed to determine whether short-term (no more than 16 d) air pollution exposure was associated with T2D-related length of stay (LOS) and hospitalization expenses incurred by patients. This investigation examined 2840 T2D patients hospitalized from December 17, 2013 to May 31, 2016 in China. Multiple linear regression analysis was applied to determine the association between short-term (no more than 16 d) ambient air pollution, LOS, and hospitalization expenses, controlling for age, gender, ethnicity, marital status, and weather conditions. Sulfur dioxide (SO₂) and carbon monoxide (CO) were significantly positively while nitrogen dioxide (NO₂) was negatively associated with presence of T2D, LOS, and expenses. A 10-μg/m³ rise in 16-d (lag 0–15) average concentrations of SO₂ and CO prior to hospitalization was correlated with a significant elevation in LOS and elevation in expenses in T2D patients. However, a 10-μg/m³ rise in 16-d average NO₂ was associated with marked negative alterations in LOS and hospital costs in T2D patients. Taken together, data demonstrate that exposure to air pollutants impacts differently on LOS and hospitalization costs for T2D patients. This is the first apparent report regarding the correlation between air pollution exposure and clinical costs of T2D in China. It is of interest that air pollutants affected T2D patients differently as evidenced by LOS and clinical expenses where SO₂ and CO exhibited a positive adverse relationship in contrast to NO₂.     

Direct effects of interleukin-8 on growth and functional activity of T lymphocytes

CD3⁺ T-lymphocytes were isolated from the normal donors by positive magnetic separation. Activation of the T cells with particles conjugated with antibodies to CD3, СD28 and СD2 molecules led to a marked increase in T-cell production of interleukine-8 (IL-8). We present evidence that IL-8 receptor α-chain (CXCR1, CD181) is expressed on the cell surface of 13.3% T cells. Activation of T-lymphocytes resulted in significant enhancement of CD181⁺ cells both in naive CD4⁺ T cell and terminally differentiated effector CD4⁺ T cell compartments with concomitant reduction of CD181⁺ cells in effector memory CD4⁺ T cell subset. The level of T cell activation was assessed judging from the surface expression of CD25 (IL-2 receptor α-chain). We demonstrate that IL-8 treatment (0.01–10.0 ng/ml concentration range) reduced the activation status of both CD4⁻ and CD4⁺ effector memory T cells, as well as terminally differentiated effector T cells, without significantly affecting the activation of naive T cells or central memory T cells. In addition, IL-8 up-regulated IL-2 and down-regulated IL-10 production by activated T cells, with no effect on interferon-gamma (IFN-γ) and IL-4 production. Data obtained suggests the importance of IL-8 in the direct regulation of adaptive T cell reactivity.