In vitro P-glycoprotein-mediated transport of (R)-, (S)-, (R,S)-methadone, LAAM and their main metabolites

Methadone and L-alpha-acetylmethadol (LAAM) are used as treatment for opiate addiction. Using a cellular model, we aimed to determine if methadone, LAAM and their main metabolites are substrates of the human P-glycoprotein transporter (P-gp), which is encoded by the ABCB1 gene, and whether methadone transport exhibits stereoselectivity. Pig kidney epithelial cells (control) and human ABCB1-transfected cells were incubated with methadone, LAAM and their metabolites, and their intra- and extracellular concentrations were measured. The intra- to extracellular ratios of methadone, LAAM and their metabolites were all decreased in ABCB1-transfected cells compared to controls (p < 0.05), thus indicating that they are substrates of P-gp. A weak stereoselectivity in methadone transport was observed towards the (S)-enantiomer. P-gp may therefore affect the pharmacokinetics and pharmacodynamics of methadone and LAAM.     

急性冠脉综合征血清C-反应蛋白的变化

目的观察C-反应蛋白在冠心病急性冠脉综合征（ACS）时的变化,以了解ACS与炎症之间的关系。方法测定ACS组45例急性心肌梗塞（AMI）、56例不稳定型心绞痛（UA）病人血清CRP含量,与50例稳定型心绞痛（SA）对照。结果ACS中CRP增高,AMI升高最为明显,AMI与UA、AMI与SA、UA与SA之间比较,结果均有显著差异（P〈0．01）。病人近期心脏主要事件的发生比AMI组与UA组与SA比较,均有显著差异（P〈0．01）。结论血清CRP（C-反应蛋白）是预测ACS心肌损伤程度以及近期预后的有效指标。     

An investigation of Luria's hypothesis on prompting in aphasic naming disturbances

This study investigated Luria's hypothesis that aphasic subgroups would respond differentially to phonemic prompts. Responsiveness to initial-sound cues was examined in 40 aphasics—10 Broca's, conduction, Wernicke's, and anomic aphasics who had naming difficulties. Results, with the exception of the anomic aphasic group, supported Luria's predictions. Broca's aphasics were responsive to phonemic cueing, while Wernicke's aphasics were not. Conduction aphasics tended to respond in a fashion similar to the Wernicke's group. The relationship of cueing responsiveness to underlying naming mechanisms is discussed.     

Legal and ethical issues in the international transaction of donor sperm and eggs

Pertinent ethical and legal issues in the international transaction of donor sperm and eggs are discussed. Firstly, there may be legislative and ethical “contradiction” by the local health authority in permitting import of donor gametes, due to varying policies on donor reimbursement in different countries. This is particularly significant in countries where the underlying principle of gamete donation is altruistic motivation, and where reimbursement is given only for direct “out-of-pocket” expenses i.e. traveling costs. Secondly, there is a lack of clear and coherent internationally-binding legislation and regulatory guidelines overseeing the exchange of donor gametes across international borders. In particular, provisions should be made for donor traceability if gametes are sourced from abroad. Thirdly, in the case of “frozen-egg donation” from abroad, patients must rightfully be informed that current cryopreservation technology is still sub-optimal, and all studies have consistently shown that the chances of conception are always lower with “frozen-eggs” compared to freshly-retrieved eggs. Finally, regulatory safeguards should be put in place to prevent fertility clinics and medical professionals from “re-selling” imported donor gametes at a profit to the patient, since it would be thoroughly unprofessional for them to earn a profit simply through the ‘brokerage’ of donated human material.     

Is it ethically justifiable to cryopreserve oocytes and ovarian tissues of healthy women not facing premature ovarian failure, but seeking to extend their biological clocks?

Recent advances in oocyte and ovarian tissue cryopreservation technology have not only brought hope to women facing premature loss of ovarian function; it can also be utilized for healthy women seeking to extend their biological clocks. This is a major issue of contention in healthcare ethics. Proponents of this new technology argue that this enables women to fully pursue educational and career goals in their youth, whilst upon reaching middle age they would have more financial resources for their offspring. Nevertheless, this argument is flawed by the reality that even if the cryopreservation of oocytes and ovarian tissue were optimized, this would in no way be a guaranteed route for women to have biological children later in life. Moreover, because only a limited amount of autologous reproductive material can be cryopreserved and stored for a single healthy woman, there is a risk of material depletion before reproductive success is attained. Another prime consideration is the increased morbidity and mortality associated with clinical assisted reproduction in older women. Hence, it is suggested that the cryopreservation and storage of oocytes and ovarian tissues be restricted only to women facing the prospect of premature ovarian failure.