Contribution of Monoamine Oxidase(MAO) to the Binding of Tertiary Basic Drugs in Isolated Perfused Rat Lung

The effect of tertiary basic drugs on mitochondrial MAO activity and the effect of MAO inhibitors (MAOIs) on basic drug accumulation in the isolated perfused rat lung were studied to clarify the role of MAO in drug binding to lung tissue. In the perfused lung preparation, the inhibition of MAO by basic drugs correlated well with their lipid solubilities and followed competitive kinetics. The inhibitory rank order (imipramine diphenhydramine > quinine > metoclopramide > procainamide) also correlated with their accumulation in the perfused lung. Moreover, MAOI treatment decreased the accumulation of basic drugs in the lung, and the potency of MAOIs to inhibit drug accumulation in the lung correlated with their MAO inhibitory activity. These results indicate that lung MAO has specific binding sites for basic drugs and may function as a drug reservoir.     

郑州中华按蚊自然种群净增殖率和其他参数的研究

目的：获得中华按蚊自然净增殖率和其他种群动力学参数。方法：于1993年、1994年的7～8月份,在郑州郊区的水塘和稻田内,以实验种群动力学为基础,采用数学模型,计算出中华按蚊的净增殖率和其他种群参数值,并和实验种群参数值进行比较。结果：和实验种群动力学相比,除了平均世代周期长和12 d后成蚊存活百分比相近外,其余各项参数值明显偏低。结论：野外自然因素和天敌对中华按蚊所构成的环境阻力是很大的。计算出该蚊自然种群动力学的参数值对防蚊灭疟策略的制定具有重要意义。     

自然界郑州中华按蚊种群动力学参数

目的探讨自然界内郑州中华按蚊种群的繁衍动力学。方法采用自然调查和数学生态学的方法。结果求出自然界郑州中华按蚊1998年第6代的净增殖率Ro为3．522O,平均世代周期T为22．9420d,增长能力rc为O．0549,有限增殖速率λ为1．0564,种群增长1倍的时间t为12．6256d,雌蚊预期寿命ex为5．5加3d,瞬时出生率b为0．0620,瞬时死亡率d为0．0071,稳定年龄组配中未成熟期占98．2988％,成蚊占1．7012％。结论该研究为自然界中华按蚊种群的预测预报及防蚊灭疟策略的制订提供了可靠的科学依据。     

急性等容血液稀释在手术中的应用

目的 :探讨手术病人急性等容血液稀释自体输血对机体血流动力学、血液生化的影响。方法 :对 3 0例择期手术病人麻醉后放血 (8 0± 2 7)ml·kg-1,用等容量血定安 (gelofusine)进行血液稀释 ,观察急性等容血液稀释前后血流动力学、血液生化指标的变化。结果 :血液稀释后血红蛋白 (Hb)、血球压积 (Hct)和血小板计数 (Plc)下降幅度分别为 13 8% (P <0 .0 5 ) ,17 1% (P <0 .0 5 )和 7 1% (P >0 .0 5 ) ,但仍在临床正常范围内。血液稀释前后平均动脉压(MAP)、心率 (HR)、血氧饱和度 (SpO2 )、心电图 (ECG)均稳定 ,血Na+,K+,Cl-无明显变化。结论 :急性等容血液稀释是一种安全有效的自身输血方法 ,能有效减少或避免异体输血及由此所引起的输血相关疾病的发生 ,应积极推广应用。     

人工心脏圆盘泵的流动特性研究

人工心脏（血泵）一直存在泵体对血细胞剪切力过大和流速过快容易引起溶血的问题。为了研究人体正常血压情况下,血泵内部剪切力和速度场的分布情况,选择圆盘泵叶轮代替传统离心泵叶轮,对两种模型进行数值计算,分析不同叶轮内部剪切力和速度场的分布规律。研究表明传统离心泵内部流速高,叶片表面剪切力大,对血细胞的伤害大。圆盘泵相比传统离心泵,剪切力更小,流场速度分布均匀,流速更小。和传统离心泵相比,不同转速下圆盘泵能降低溶血的发生率。圆盘泵叶片数为6片时,抗溶血性能更好。研究结果为血泵的优化提供理论依据。     

Solubility Enhancement of Nucleosides and Structurally Related Compounds by Complex Formation

Water-soluble vitamins, amino acids, and nontoxic pharmaceutical excipients were studied as solubilizing agents for poorly water-soluble adenine (nucleic acid base), guanosine (nucleoside), and structurally related drugs (acyclovir and triamterene). The apparent solubility of the substrates (adenine, guanosine, acyclovir, or triamterene) was appreciably increased by forming complexes with the ligands (vitamins, amino acids, or other ligand). Apparent association constants (K _a ) values were measured at 25°C in pH 7 phosphate buffer using phase solubility analysis. The effect of combination ligands on substrate solubility was also studied. Additive solubility enhancement was obtained for several ligand pairs.     

Intrapulmonary gas mixing and dead space in artificially ventilated dogs

In this study we have investigated the effects of breath holding and of the physical properties of gases on four different respiratory dead spaces (V _D): the Fowler, the physiological, the washout and the inert gas dead space. The experiments were performed with dogs which were ventilated artifically with breathing patterns with different post-inspiratory breath holding times (t _a) of 0, 0.5, 1.0 and 2.0 s. Tracer amounts of acetone, ether and enflurane were infused continuously into a peripheral vein and a bolus of a mixture of krypton, Freon12 and SF₆ was introduced into the peritoneal cavity. After reaching steady state, samples of arterial blood, mixed venous blood and mixed expired air were taken simultaneously. From the partial pressures (P _a, P _¯V and P respectively) we determined the excretion (=P/P_¯V), retention (R=P_a/P_¯V) and the physiological dead space fraction (V _D,phys/V _T=(1 P/P_a) for each gas, where V _T is tidal volume. Further, we recorded the expirograms of the six tracer gases and of CO₂ from which the Fowler dead space fractions (V _D,Fowler/V _T) of the different gases were determined. Also the washout dead space fractions (V _D,washout/V _T) for He and SF₆ were determined as well as the inert gas dead space fraction (V _D,MIGET/V _T) with the use of the multiple inert gas elimination technique (MIGET).With the exception of V _D,phys/V _T for SF₆, all dead space fractions decreased with increasing t _a. V _D,phys/V _T for the poorly soluble gas SF₆ was considerably larger than V _D,phys/V _T for the remaining gases. For the highly soluble acetone V _Fowler/V _T was considerably smaller than V _D,Fowler/V _T for the other gases. V _{D,washout,SF6}/V _T was always larger than V _D,washout,He/V _T and V _D,Fowler,SF6/V _T. Further, V _D,phys/V _T was larger than V _D,Fowler/V _T for SF₆ and acetone. However, for gases with intermediate solubility in blood V _D,phys/V _T tended to be smaller than V _D,Fowler/V _T. We conclude that the respiratory dead spaces are affected by the breathing pattern and by the physical properties of gases, i.e. their diffusivity in alveolar gas and their solubility in blood or lung tissue.     

Furosemide dynamics in conscious rabbits: Modulation by angiotensin II

Summary The aim of this study was to investigate the effects of an infusion of angiotensin II (50 ng/kg/min) on furosemide pharmacodynamics and kinetics in the conscious rabbit. The protocol included a 90-minute phase to estimate the glomerular filtration rate and the renal plasma flow, followed by a 60-minute phase where 5 mg/kg (n=12) or 10 mg/kg (n=9) of furosemide were administered. During the pre-furosemide phase, compared to control rabbits, angiotensin II increased natriuresis and diuresis. In the presence of angiotensin II, the furosemide-induced natriuresis decreased, that is, it was 174±14 versus 95±25 µmol/min (p<0.05) and 187±17 versus 89±21 µmol/min (p<0.05) for the 5 and the 10 mg/kg doses, respectively. The infusion of angiotensin II decreased renal plasma flow without modifying the glomerular filtration rate, thus the filtration fraction was increased. Angiotensin II increased the area under the furosemide plasma concentrations as a function of time since it decreased its systemic clearance. However, furosemide urinary excretion rate was not altered and its renal clearance decreased slightly without reaching statistical significance. It is concluded that angiotensin II decreases the response to furosemide and the mechanism underlying this effect is related to the pharmacodynamics rather than the kinetics of the diuretic.     

Hydroxypropyl-β-Cyclodextrin Increases the Aqueous Solubility and Stability of Pilocarpine Prodrugs

Purpose. The effects of 2-hydroxypropyl--cyclodextrin (HP--CD) on the aqueous solubility and stability of two lipophilic bispilocarpine prodrugs were investigated at pH 7.4. Methods. The solubility of prodrugs was studied by phase-solubility method (0–72.5 mM HP--CD). The stability of one of the prodrugs was investigated as a function of temperature (40°C–70°C) and HP--CD concentration (0–72.5 mM). The apparent rate constants (k ₁, k ₂) for degradation of prodrug in 1:1 and 1:2 inclusion complexes and apparent stability constants (K _1:1, K _l:2) were calculated by the curve-fitting method. Results. The phase-solubility diagrams were classified as A_p-type and the apparent stability constants (K _l:l, K _l:2) for 1:1- and 1:2-inclusion complexes were calculated to be 143–815 M^–l and 29–825 M^–1, respectively. The stability of prodrug increased as a function of HP--CD concentration over the studied temperature range. The shelf-life (t _90%, calculated by the Arrhenius equation) of the prodrug in 72.5 mM HP--CD solution increased 5.1-fold and 6.1-fold at 25°C and 4°C, respectively. Conclusions. The solubility of the prodrugs was shown to increase markedly in phase-solubility studies. The degradation rate of prodrug in stability studies was shown to be slower in the l:2-complex than in the l:l-complex and the relative amounts of complex species were found to be dependent on CD concentration.     

Selective strategies in food webs

Food webs are described as control systems where the controlsare chosen according to given myopic strategies. In particular,strategies describing selective feeding and selective escapeare defined. The existence of optimal myopic solutions and theiruniqueness are discussed. Computer simulations modelling ‘switching’are given for a one-predator—two-prey system.