NMDA receptor-mediated processes in the Parabrachial/Kölliker fuse complex influence respiratory responses directly and indirectly via changes in cortical activation state

We tested the hypothesis that glutamate, acting via NMDA-type receptors (NMDAr) in the Parabrachial/K?lliker fuse (PBrKF) nucleus of the pons, is involved both directly and indirectly (via changes in cortical activation state) in modulating breathing and ventilatory responses to hypoxia. To this end we examined the effects of MK-801, injected either systemically or directly into the PBrKF, on the breathing patterns of urethane-anaesthetized rats breathing air or an hypoxic gas mixture as electroencephalographic (EEG) activity alternated between State I (awake-like) and State III (NREM sleep-like) EEG patterns. Regardless of EEG state, systemic MK-801 reduced ventilation primarily by reducing tidal volume while microinjection of MK-801 into the PBrKF reduced ventilation by reducing breathing frequency. With both injections, EEG pattern changed from State I to III mimicking the change from wakefulness to NREM sleep that occurs in unanaesthetized rats given MK-801 systemically. Systemic injection of MK-801 delayed and reduced the response to hypoxia while microinjection of MK-801 into the PBrKF did not reduce the HVR but sustained the hypoxic increase in tidal volume well into the post-hypoxic recovery period. Thus, while NMDAr in the PBrKF complex of the pons play a role in modulating sleep/wake-like states as well as changes in breathing pattern associated with changes in cortical activation state, they are neither involved in the hypoxic ventilatory response nor in the change in hypoxic sensitivity associated with the changes in cortical activation state.     

Specific intracellular adhesion molecule-grabbing nonintegrin R1 is not involved in the murine antibody response to pneumococcal polysaccharides

Streptococcus pneumoniae is a microorganism that frequently causes serious infections in children, the elderly, and immunocompromised patients. We studied whether the specific intracellular adhesion molecule-grabbing nonintegrin R1 (Sign-R1) receptor, involved in the uptake of capsular polysaccharides (caps-PS) by antigen-presenting cells, is necessary for the antibody response to pneumococcal caps-PS and phosphorylcholine (PC). The antibody response to caps-PS and PC was evaluated after vaccination with soluble caps-PS (Pneumovax) and after vaccination with heat-killed S. pneumoniae. The role of Sign-R1 was investigated by using Sign-R1 knockout mice and anti-Sign-R1 monoclonal antibodies. The immunoglobulin M (IgM) and IgG antibody response to PC and caps-PS (serotypes 3 and 14) was not affected by anti-Sign-R1 monoclonal antibodies. The IgM antibody response in Sign-R1 knockout mice was comparable to the antibody response in wild-type mice. The IgG antibody response to serotype 3, but not to serotype 14, tended to be lower in Sign-R1 knockout mice compared to wild-type mice. In conclusion, we found that Sign-R1 is not involved in the IgM antibody production to PC and caps-PS serotype 3 or 14 and the IgG immune response to PC and caps-PS serotype 14. There is no direct relation between capture and uptake of caps-PS serotype 14 by Sign-R1 and the initiation of the anti-caps-PS antibody production in mice.     

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.