Capillary Gas Chromatography and Thermionic N-P-Specific Detection of 13-Bis(2-chloroethyl)-l-nitrosourea (BCNU) or l-(2-Chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) in Stability and Pharmacokinetic Studies

An expedient, rapid, and sensitive capillary gas chromatographic method for the analysis of l,3-bis(2-chloroethyl)-l-nitrosourea (BCNU) or l-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU) in plasma is described. Separation of the underivatized nitrosourea compounds was performed on a 0.33-mm-i.d., 25-m fused-silica, SE-30 capillary column, and detection was carried out using a thermionic N–P-specific detector. The compounds were extracted from plasma with benzene with a yield of >87%. The assay was linear in the ranges of 0.001 to 0.5 and 0.5 to 25 µg/ml for CCNU or 0.003 to 0.50 and 0.5 to 25 µg/ml for BCNU, with correlation coefficients from 0.9914 to 0.9999 and coefficients of variation (CV) of <3.3%. Other antineoplastic agents did not interfere in the assay. The method was employed to study the pharmacokinetics of BCNU in rabbits. The plasma concentration-time curves were fit to a two-compartment model with a mean (SE) , , and total-body clearance of 2.898 (0.913) hr^–1, 0.1228 (0.0179) hr^–1, and 7.211 (2.862) liters/hr · kg, respectively. Further, the stability of BCNU and CCNU in solution was examined at different temperatures. Both compounds were stable in benzene or acetone (4 to 37°C) but labile in plasma even if refrigerated. The apparent rate constants for degradation of BCNU and CCNU were 0.09921 and 0.02853 hr^–1 at 4°C and 5.998 and 2.553 hr^–1 at 37°C, respectively.     

Determination of tryptamine in rat brain by gas chromatography-mass spectrometry

Tryptamine (TA) occurs in trace levels in the brain, but its role in the central nervous system is not clear. However, there is evidence that TA may be a neuromodulator since it binds to specific binding sites in the brain. TA was measured as a diheptafluorobutyryl derivative in rat whole brain by capillary gas chromatography—mass spectrometry using negative chemical ionization (NCI) and single ion monitoring (SIM). d₄-TA was used as the internal standard. The ions m/z 532 and m/z 536 were monitored to identify TA and d₄-TA, respectively and to calculate the concentration of TA in rat whole brain which was found to be 0.19 ± 0.08 ng g⁻¹ (n = 8). The results confirm the earlier TA concentrations measured by GC—MS using positive electron impact ionization. However, NCI improved the signal/noise ratio of the method increasing its sensitivity for TA.     

A reevaluation of the status of cholesterol in erythrocytes infected by Plasmodium knowlesi and P. falciparum

The cholesterol synthesis of rhesus monkey erythrocytes parasitized by Plasmodium knowlesi and human erythrocytes infected by P. falciparum, as measured by incorporation of [1-¹⁴C]acetate and ³H₂O, was almost undetectable, concordant with very low levels of measurable 3-hydroxy-3-methyl glutaryl-CoA reductase activity. In addition, both types of infected cells exchanged cholesterol with the plasma at the same rate as uninfected cells. The data do not exclude the possibility of cholesterol transfer from uninfected to infected cells.     

Asymmetric and Axisymmetric Constant Curvature Liquid-Gas Interfaces in Pulmonary Airways

Airway closure and gas trapping can occur during lung deflation and inflation when fluid menisci form across the lumina of respiratory passageways. Previous analyses of the behavior of liquid in airways have assumed that the airway is completely wetted or that the contact angle of the liquid-gas interface with the airway wall is 0, and thus that the airway fluid forms an axisymmetric surface. However, some investigators have suggested that liquid in the airways is discontinuous and that contact angles can be as high as 67. In this study we consider the characteristics of constant curvature surfaces that could form a stable liquid-gas interface in a cylindrical airway. Our analysis suggests that, for small liquid volumes, asymmetric droplets are more likely to form than axisymmetric toroids. In addition, if the fluid contact angle is greater than 13, asymmetric droplets can sustain larger liquid volumes than axisymmetric toroids before collapsing to form menisci. These results suggest that (1) fluid formations other than axisymmetric toroids could occur in the airways; and (2) the analysis of the behavior of fluids and the development of liquid menisci within the lungs should include the potential role of asymmetric droplets.     

棘球蚴内容物导致肺损害的研究

目的 :观察棘球蚴囊内容物攻击兔所至肺功能和形态的损害。建立囊型包虫肺栓塞的动物模型。方法 :取囊型包虫内容物 ,分离出囊砂 ,与囊液配成 5 %的悬浊液。 2 1只家兔 ,分 3组 :Ⅰ :生理盐水组 ,Ⅱ :澄清囊液组 ,Ⅲ :囊砂悬浊液组。每只家兔都置入股动脉导管及股静脉导管。依照上述分组按 2mL/kg体重分别自静脉导管注射生理盐水、澄清囊液或含囊砂的悬浊液。于注射后 ( 5、30、6 0min)动态监测MAP、血气指标及血清血管活性物质(ET - 1、TXB2 、6 -keto -PGF1α)水平的变化。指标测定后 ,行肺部ECT检查。最后取出动物肺脏行光镜病检。结果 :Ⅲ组和Ⅱ组在注射后均出现MAP、血气指标的明显降低 (P <0 .0 5 )和血清TXB2 、6 -keto -PGF1α的升高 (P <0 .0 5 ) ,尤以Ⅲ组最明显 (P <0 .0 5 )。各组动物血清ET - 1水平在注射前后无明显变化 (P >0 .0 1)。ECT显示Ⅲ组动物肺部放射性缺损 ,Ⅱ组动物肺部放射性减弱。Ⅲ组肺脏病检见头节广泛栓塞于肺小动脉、微小动脉中 ,肺脏呈“急性呼吸窘迫综合症样”改变。Ⅱ组肺组织出现淤血、水肿及炎细胞浸润。结论 :Ⅲ组动物基本能够模拟出囊型包虫病肺栓塞的临床表现。囊液中有形成分在肺损害中起着重要的作用。TXB2 、6 -keto -PGF1α参与了肺损伤病理过程。     

Comparison of β-adrenoceptors mediating vasodilatation in canine subcutaneous adipose tissue and skeletal muscle

Blood flow changes in response to various drugs in simultaneously autoperfused canine subcutaneous adipose tissue and gracilis muscle were compared to study the vascular β-adrenoceptors. Compared to isoprenaline the β₂-selective agonist salbutamol was 4–6 times more potent as a vasodilator in the muscle than in adipose tissue. Furthermore two β₁-selective agonists (Tazolol and H80/62) caused vasodilatation in adipose tissue but not in the gracilis muscle. When given by close i.a. injection after β-adrenoceptor blockade, adrenaline was a more potent vasoconstrictor than noradrenaline in both tissues. Before β-blockade, however, noradrenaline was the more potent vasoconstrictor in the gracilis muscle whereas adrenaline was more potent in adipose tissue. Intravenous infusion of adrenaline in doses causing vasodilatation in the muscle caused vasoconstriction in adipose tissue whereas intravenous infusion of noradrenaline caused vasoconstriction in both tissues. The present findings suggest that the β-adrenoceptors mediating vasodilatation in skeletal muscle are mainly of the β₂-type, whereas β₁-adrenoceptors seem to predominate in subcutaneous adipose tissue. Since adrenaline is a much more potent β₂- than β₁-agonist, these differences point to different roles of intravascular adrenaline in the two sites. In skeletal muscle circulating adrenaline is mainly a vasodilator whereas in subcutaneous adipose tissue it mainly acts as a vasoconstrictor.     

Characteristics of\dot V_A /\dot Q distributions recovered from inert gas elimination datadistributions recovered from inert gas elimination data

The resolving powers of the enforced smoothing and log-normal parametric estimation techniques in recovering ventilation/perfusion ratio distributions were evaluated using noisy inert gas elimination data simulated from hypothetical distribution functions representing various degrees of heterogeneity. The resolving powers were assessed in terms of the statistical recoverabilities of the shunt, dead space, modality, and modal moments characterizing the perfusion distribution. For all distributions tested, both modal mean and shunt were estimated by either technique with sufficient accuracies. Modal dispersions (σ) were consistently overestimated by up to 0.15 decade for narrow distributions, but the mean errors became negligible for σ greater than 0.2 decade. As compared with the shunt, the dead space estimates were more variable and biased, probably due to their indirect estimation from the perfusion distribution, which was imperfectly recovered. Both broad unimodal and widely separated bimodal or trimodal distributions (σ>0.6 decade) were recovered as bimodal distributions of similar forms, so that detection of modality was difficult. The recoveries by both techniques were comparable in most cases studied, except that parametric estimation generally tended to be more sensitive to measurement errors and was computationally less efficient. These results provide a useful basis for the interpretation of distributions obtained from empirical inert gas data.     

Pump for accurate mixing of three gas components with predetermined fractions

A mixing pump that creates an accurate mixture of three gases at predetermined fractional ratios that can be set in steps of 10 ppm is described. A nearly continuous flow of each of the three component gases is produced by pistons driven by stepping motors; the gas mixture is forwarded by a fourth piston. The flow of each component gas is adjusted by the stepping frequency of the motor and a microcomputer system is used to adjust the three frequencies according to the desired fractional concentrations. The total flow of the gas mixture is adjustable between 0.1–500 ml/min and is nearly independent of the after-load. The accuracy of the pump was tested by mixing the respiratory gases, O₂ and CO₂, with various carrier gases (N, He or Ar) at various fractional ratios and total flow rates. The fractions of O₂ and CO₂ in the mixture were analysed with the Scholander technique. In the physiological range, the mixing error in the gas fractions was less than 4%. The pump is, thus, suited for producing calibration mixtures.     

Activity of the human carcinogen MeCCNU in the mouse bone marrow micronucleus assay

The nitrosourea mustard MeCCNU is the most recent organic chemical to be classified as a human carcinogen by IARC. MeCCNU gave a strong positive response when tested in the mouse bone marrow micronucleus assay. Activity was evident using either ip injection or oral gavage of the test chemical. These results further support the correlation between human carcinogens and their genotoxicity.     

O2 Uptake in hyperthyroidism during constant work rate and incremental exercise

Summary To investigate the effect of hyperthyroidism on the pattern and time course of O₂ uptake ( O₂) following the transition from rest to exercise, six patients and six healthy subjects performed cycle exercise at an average work rate (WR) of 18 and 20 W respectively. Cardiorespiratory variables were measured breath-by-breath. The patients also performed a progressively increasing WR test (1-min increments) to the limit of tolerance. Two patients repeated the studies when euthyroid. Resting and exercise steady-state (SS) O₂ (ml·kg^–1·min^–1) were higher in the patients than control (5.8, SD 0.9 vs 4.0, SD 0.3 and 12.1, SD 1.5 vs 10.2, SD 1.0 respectively). The increase in O₂ during the first 20 s exercise (phase I) was lower in the patients (mean 89 ml·min^–, SD 30) compared to the control (265 ml·min^–1, SD 90), while the difference in half time of the subsequent (phase 11) increase to the SS O₂ (patient 26 s, SD 8; controls 17 s, SD 8) were not significant (P = 0.06). The OZ cost per WR increment ( O₂/WR) in ml·min^–1·^–1, measured during the incremental period (mean 10.9; range 8.3–12.2), was always within two standard deviations of the normal value (10.3, SD 1). In the two patients who repeated the tests, both the increment of O₂ from rest to SS during constant WR exercise and the O₂/WRs during the progressive exercise were higher in the hyperthyroid state than during the euthyroid state. While both resting and exercise O₂ are increased in the hyperthyroid patients, the O₂ cost of a given increment of WR is within the normal range. However, a small reduction in the O₂ requirement to perform exercise following treatment of the hyperthyroid state suggests a subtle change O₂ cost of muscle work in this disease.