注射用伏立康唑前药在雌雄大鼠中代谢及毒性差异研究

目的：研究注射用伏立康唑前药（FLKZQY）在雌、雄大鼠中代谢及毒性差异,并观察SD大鼠体内性激素水平的变化对伏立康唑前药在大鼠体内代谢的影响,为其进一步临床应用提供依据。方法：选取5~6周龄SD大鼠,随机分成去势与伪手术组,雌、雄分开分组（雌、雄各半,每组8只）,手术后恢复3 d,然后连续7 d静脉注射120 mg·kg^-1·d^-1伏立康唑前药,于第7天进行眼眶采血。采用毒代动力学试验、酶联免疫吸附试验（ELISA）法,检测其代谢及毒性差异。结果：毒代动力学结果显示,伪手术雌鼠药时曲线下面积（AUC）、最大血药浓度（C_max）、半衰期（t_1/2）均高于伪手术雄鼠;去势雌鼠最大血药浓度（C_max）、半衰期（t_1/2）均较伪手术雌鼠显著性降低（P<0.05）,药时曲线下面积（AUC）极其显著性降低（P<0.01）;去势雄鼠受试物组与伪手术雄鼠受试物组相比药时曲线下面积（AUC）、半衰期（t_1/2）、最大血药浓度（C_max）则升高,其中AUC与C_max差异显著（P<0.05）;ELISA结果显示中,与伪手术雌鼠相比,去势雌鼠的肝脏细胞色素P450同工酶CYP2C19、CYP2C9以及CYP3A4含量均明显增加（P<0.05）,去势雄鼠与伪手术雄鼠相比P450同工酶含量降低,但未达到统计学差异。结论：在本试验条件下,注射用伏立康唑前药在雌、雄大鼠体内的代谢存在性别差异。而性激素水平可能通过调节伏立康唑相关代谢酶水平从而对伏立康唑代谢产生影响。     

毛细管电泳差异性检测尿液蛋白方法初探

Objective: To explore an optimized method for difference detection of urinary proteomics in patients with Bladder Cancer (BCs) by Capillary Electrophoresis separation technique coupled with diode array detector (CE-DAD). Methods: For detecting the difference in the contents of each urinary low-abundance proteins between the two groups, electrolytic additives were used to improve the buffer system, and the concentration of electro-osmotic flow was well controlled in this condition, in order to increase the separation efficiency. Results: The optimal conditions were established to detect the difference between the bladder cancer and the control group by CE-DAD, and the difference and correlation were also tested by the parallel experiment of ELISA method. Conclusion: This paper makes a preliminary exploration on the condition of difference detection by CE-DAD, and establishes the foundation for the institution of standardized experimental method in the future.     

A 2-year follow-up study on muscle size and dynamic strength in teenage tennis players

Growth trends in the cross-sectional area of the quadriceps femoris (CSA(QF)) and its dynamic strength in 12 teenage tennis players (six boys and six girls), aged from 10.7 to 13.2 years at the onset of the study, were investigated through a 2-year follow-up survey. CSA(QF) values at the three levels (proximal, mid, and distal to the knee joint) and dynamic torques during knee extensions at three pre-set velocities (1.05, 3.14, and 5.24 rad/s) were determined year by year, i.e., three times (T1, T2, and T3), using magnetic resonance imaging and an isokinetic dynamometer, respectively. In both genders, the CSA(QF) values at the three levels tended to increase across the measurement times, with greater gains in the boys than in the girls at the levels mid and distal to the knee joint. Among these changes, only the CSA(QF) at the level proximal to the knee joint significantly increased regardless of changes in both skeletal age and body height. The ratios of torque to the sum of CSA(QF) at the three levels (T/CSA) at 3.14 and 5.24 rad/s for the boys and at 5.24 rad/s for the girls were significantly higher in T2 and T3 than T1. Further, the relative increases in torque and T/CSA values at 3.14 and 5.24 rad/s were greater in the boys than the girls. The findings presented here indicate that young tennis players who are in the earlier stage of adolescence increase the CSA of the QF muscle beyond normally expected growth change at the level proximal to the knee joint and show a predominant development in torque generation capability during high-velocity knee extensions, with a greater gain in boys compared with girls.     

Progesterone receptors activation after acute cocaine administration

Cocaine modulates serum levels of progesterone in intact female and male rats, as well as in pregnant dams, and progesterone decreases or attenuates cocaine-induced behavioral and reward responses. It has been postulated that cocaine's modulation of serum progesterone levels may in turn alter progesterone receptor activity, thereby contributing to cocaine-induced alterations of neuronal functions and genomic regulations. To test this hypothesis, intact male rats received acute injections of saline or cocaine (15 or 30 mg/kg, dissolved in 0.9% saline, intraperitoneal). Progesterone serum levels, progesterone receptor (PR) protein levels, and PR-DNA binding complexes were measured in the striatum by radioimmunoassay, Western blot, and gel shift analyses, respectively. After injection of 15 mg/kg of cocaine, induction of progesterone serum levels was closely followed by an increase in receptor protein levels and DNA binding complexes. After injection of 30 mg/kg of cocaine, similar effects were observed along with an attenuation of receptor protein levels and DNA binding complexes at 60 min. Our results suggest that activation of progesterone receptors may be a mechanism by which cocaine mediates behavior through molecular alterations in the central nervous system.     

Long-lasting changes in behavioural and neuroendocrine indices in the rat following neonatal maternal separation: gender-dependent effects

Neonatal maternal separation (MS) has been used to model long-term changes in neurochemistry and behaviour associated with exposure to early-life stress. This study characterises changes in behavioural and neuroendocrine parameters following MS. On postnatal days (PND) 3-15, male and female Long-Evans rats underwent 3 h daily MS. Non-handled (NH) control offspring remained with the dams. Starting at PND 90, behaviour was assessed at weekly intervals in the elevated plus-maze, elevated T-maze, and locomotor activity boxes, and body weight monitored throughout. At the end of the study, adrenals were weighed and blood collected for analysis of plasma corticosterone and adrenocorticotropic hormone (ACTH) under basal conditions and following restraint stress. As adults, MS weighed more than NH animals. Activity on the open arms of the plus-maze was similar between MS and NH animals. In the T-maze, MS males had shorter emergence latencies than their NH counterparts. Spontaneous ambulation in a novel environment was significantly higher in MS than in NH animals, and males exhibited overall lower activity than females. Basal plasma corticosterone was lower in MS than in NH females, but no rearing condition difference was observed following restraint stress. Females had higher corticosterone and ACTH levels than males, whereas adrenal glands of MS animals weighed less than those of NH controls. The MS paradigm caused long-term gender dependent effects on behaviour and HPA axis status. The consistent gender differences confirm and expand existing results showing altered anxiety and stress reactivity in male and female rats.     

J‐difference editing of gamma‐aminobutyric acid (GABA): Simulated and experimental multiplet patterns

Purpose : To investigate factors that influence the multiplet pattern observed in J‐difference editing of gamma‐aminobutyric acid (GABA). Methods : Density matrix simulations were applied to investigate the shape of the 3 ppm GABA multiplet as a function of the editing sequence's slice‐selective refocusing pulse properties, in particular bandwidth, transition width, and flip angle. For comparison to the calculations, experimental measurements were also made at 3 T on a 10 mM GABA solution using the MEGA‐PRESS sequence at various refocusing pulse flip angles. Results : Good agreement was found between experiments and simulations. The edited multiplet consists of two outer lines of slightly unequal intensity due to strong coupling, and a smaller central line, the result of the unequal J‐couplings between the C4 and C3 protons. The size of the center peak increases with increasing slice‐selective refocusing pulse transition width, and deviation of the flip angle from 180°. Conclusion : The 3 ppm GABA multiplet pattern observed in the MEGA‐PRESS experiment depends quite strongly on the properties of the slice‐selective refocusing pulses used. Under some circumstance, the central peak can be quite large; this does not necessarily indicate inefficient editing, or a subtraction artifact, but should be recognized as a property of the pulse sequence itself. Magn Reson Med 70:1183–1191, 2013. © 2012 Wiley Periodicals, Inc.