Amantadine hydrochloride specifically blocks the release of virus particles from H7 influenza virus infected cells. This appears to be the direct consequence of an amantadine induced change in the haemagglutinin (HA) to its low pH conformation. The effect is indirect and mediated via interaction of the drug with the M2 protein since mutants altered in this component alone are insensitive to amantadine. The tining of drug action, some 15-20 min after synthesis, and its coincidence with proteolytic cleavage indicates that the modifications to HA occur late during transport but prior to insertion into the plasma membrane. Reversal by mM concentrations of amines and 0.1 /M monensin indicates that amantadine action causes a reduction in intravesicular pH which triggers the conformational change in HA. We conclude, therefore, that the function of MN inhibited by amantadine is involved in counteracting the acidity of vesicular compartments of the exocytic pathway in infected cells and is important in protecting the structural integrity of the acid-sensitive glycoprotein.
Gonadotoxic treatment results in a significant reduction in sperm quality. The type of cancer or disease, and the pre-treatment sperm concentrations were found to be the most significant factors governing post-treatment semen quality and recovery of spermatogenesis. All categories of patients displayed varying degrees of azoospermia and oligozoospermia, and recovery of gonadal function from these states was not significant. This highlights the importance of ensuring sperm banking before treatment, including for patients with benign conditions. Several factors and associations are discussed further in order to give an insight into the pre- and post-gonadotoxic treatment effects.
The complex moral, ethical and legal concerns that have arisen as a result of posthumous assisted reproduction (PAR) are examined in this report. Difficult questions such as what constitutes informed consent, and whether it is ethical to retrieve spermatozoa from patients who are in a coma, are considered. Legal issues, such as whether gametes can be considered as property and the need to clarify the legal definition of paternity in cases of children born in such circumstances, are also discussed, while other points regarding the advisability of PAR, respecting the wishes of the deceased donor and the need to protect the interests of the unborn child, are outlined. The motives of the gestating women, viewing their desire for PAR perhaps as part of the grieving process, and the effects on the children concerned are examined; it is concluded that there appears to be no adverse effect, but this finding might be premature. The report also asserts the need for responsible accounting on the part of fertility clinics, and calls for fairness, transparency and patience to help the bereaved reach an unbiased yet informed decision. This may be achieved by offering ample time for informed and support counselling. Finally, consideration should be expressed for the welfare of unborn child, in a balanced, pragmatic and sensible manner.
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