Ultrasonic measurement of fetal femoral length in singleton and twin pregnancies

The fetal femoral length and biparietal diameter were measured by ultrasound on 1657 occasions in 1289 singleton pregnancies between 12 and 41 weeks' gestation. Mean values for fetal femoral length were significantly lower than those demonstrated in previous studies, with the difference becoming greater approaching term. Three hundred twenty-two measurements of fetal femoral length were made on 57 patients with twin pregnancies, with no significant difference noted between the means of these recordings and the means of the singleton pregnancies.     

Ocular fluorophotometry in the normal- and diabetic monkey

Normal- and diabetic rhesus monkeys without retinopathy demonstrable by ophthalmoscopy or fluorescein angiography were examined with ocular fluorophotometry to detect alterations in their blood-ocular barriers. All vitreous fluorophotometry values were corrected for fluorescence attributable to background levels and then normalized to a blood fluorescein level of 10 micrograms ml-1. Reproducibility studies demonstrated an average coefficient of variation of 0.17 for all animals combined. Insulin-dependent monkeys, both pancreatectomized and streptozotocin-treated, demonstrated significantly higher posterior vitreous fluorescence levels than either control animals or monkeys treated with streptozotocin that were not insulin-dependent. These results cannot be attributed to differences in fluorescein binding or to vitreous abnormalities. However, 14 out of 24 (58%) of the insulin-dependent animals exhibited posterior vitreous fluorescence values within two standard deviations of the control mean. No correlation was apparent between the vitreous values and age or duration of treatment. No difference in anterior chamber concentrations was found between groups after correction. Our results indicate that alterations in blood-retinal barrier can occur in insulin-dependent diabetic monkeys before development of retinopathy.     

Lack of effect of omeprazole,cimetidine, and ranitidine on the pharmacokinetics of ethanol in fasting male volunteers

Summary The effects of three gastric antisecretory drugs on the pharmacokinetics of ethanol have been studied in a randomized crossover experiment.Male medical students (n=12) took ethanol 0.8 g/kg body weight at 08.00 h after an overnight fast. On seven successive days before drinking ethanol they were given omeprazole 20 mg, cimetidine 800 mg, ranitidine 300 mg, or no drug, with a period of at least 7 days between treatments.The peak blood ethanol concentration of 21.9 to 22.8 mmol·l^–1 occurred at 64 to 70 min after the end of drinking.The rate of disappearance of ethanol from the blood ranged from 3.0 to 3.3 mmol·l^–1·h^–1 and the rate of removal from the whole body ranged from 8.0 to 8.5 g·h^–1.The apparent volume of distribution of ethanol was almost the same for all four treatments: mean 0.68 l·kg^–1, corresponding to a mean total body water of 441 (59% body weight). Mean areas under the concentration-time profiles of ethanol ranged from 83 to 87 mmol·l^–1·h for the four treatments.It is concluded that omeprazole, cimetidine and ranitidine do not alter the kinetics of a moderate dose of ethanol.     

L-454,560, a potent and selective PDE4 inhibitor with in vivo efficacy in animal models of asthma and cognition

Type 4 phosphodiesterases (PDE4) inhibitors are emerging therapeutics in the treatment of a number of chronic disorders including asthma, chronic obstructive pulmonary disease (COPD) and cognitive disorders. This study delineates the preclinical profile of L-454,560, which is a potent, competitive and preferential inhibitor of PDE4A, 4B, and 4D with IC50 values of 1.6, 0.5 and 1.2 nM, respectively. In contrast to the exclusive binding of cilomilast and the preferential binding of roflumilast to the PDE4 holoenzyme state (Mg2+-bound form), L-454,560 binds to both the apo-(Mg2+-free) and holoenzyme states of PDE4. The intrinsic enzyme potency for PDE4 inhibition by L-454,560 also results in an effective blockade of LPS-induced TNFalpha formation in whole blood (IC50 = 161 nM) and is comparable to the human whole blood potency of roflumilast. The cytokine profile of inhibition of L-454,560 is mainly a Th1 profile with significant inhibition of IFNgamma and no detectable inhibition of IL-13 formation up to 1 microM. L-454,560 was also found to be efficacious in two models of airway hyper-reactivity, the ovalbumin (OVA) sensitized and challenged guinea pig and the ascaris sensitized sheep model. Furthermore, L-454560 was also effective in improving performance in the delayed matching to position (DMTP) version of the Morris watermaze, at a dose removed from that associated with potential emesis. Therefore, L-454,560 is a novel PDE4 inhibitor with an overall in vivo efficacy profile at least comparable to roflumilast and clearly superior to cilomilast.     

Evaluation of the clearance characteristics of bioadhesive systems in humans

This paper describes the characterisation, radiolabelling and clearance characteristics of three bioadhesive nasal delivery systems; starch microspheres, chitosan microspheres and chitosan solution. The time taken for 50% of these bioadhesive materials and a control to be cleared from the nasal cavity, after nasal administration to human volunteers, was evaluated using gamma scintigraphy. The data show that the control was cleared rapidly, with a half life of 21 min, whereas the bioadhesive delivery systems had much longer half lives. The clearance of the chitosan solution almost doubled to 41 min, whilst the half life of clearance for the starch microspheres more than tripled to 68 min and for the chitosan microspheres the half life of clearance quadrupled to 84 min. From the results reported in this study it is possible to determine that both chitosan systems and the starch microspheres have good bioadhesive characteristics. The results have supported the hypothesis that chitosan delivery systems can reduce the rate of clearance from the nasal cavity, thereby increasing the contact time of the delivery system with the nasal mucosa, providing the potential for increasing the bioavailability of drugs incorporated into these systems.     

单克隆抗体博来霉素A6偶联物对白血病细胞特异性结合与内化

抗CCT2单克隆抗体博来霉素A6偶联物可吸附胶体金颗粒(McAb-A6-Au)。电镜观察表明,在4℃,1h,表面有McAb-A6-Au颗粒的CEM细胞最高达78%;在37℃,4h,内化McAb-A6-Au颗粒的CEM细胞高达72%。而抗原性无关的U937细胞仅为14%。并且McAb-A6-Au颗粒能直接穿过细胞膜、核膜进入细胞浆和细胞核。37℃,1h已有10～18%的CEM细胞核内有McAb-A 6-Au颗粒。实验结果提示了单抗与博来霉素A6的偶联物与选择性地结合靶细胞,而且进入细胞速度快、穿透力强,有可能成为治疗白血病药物。