the metabolism. A reduction in hydroxylamine pro- hydrogen peroxide in the metabolism. Hydroxylam- duction could be controlled by intravenous injection ine forms hydroxylamine phosphate with monophos- of hydroxylamine solution. No data is available for phate ion [(NH3OH)3PO4]. Similar linkage is possible the effects of the injection of dilute aqueous solu- for sulphite ions through thiophosphoric acids, tions of pure hydroxylamine. The salts of this com- monothiophosphoric acid (H3PSO3) and dithiophos- phoric acid (H3PS2O2) and trithiophosphoric acid moderately toxic (mouse, lethal dose 408 mg/kg (H3PS3O). It is proposed that proteins and enzymes of body weight). Enhanced metabolic production can be modified to form complexes containing poly- of hydroxylamine is possible using sildenafil. How- phosphoric acid along with hydrogen peroxide, hyd- ever, the muscle stimulant action of this compound roxylamine or sulphite groups which can be used to could be counterproductive in some instances transfer the required active compounds into the where cardiac function is affected and in addition granular cells of the brain with the possibility of giv- the compound contains the benzene nucleus. Alter- ing relief from the effects of Alzheimer’s disease.
native sulphite and nitrite carriers without thebenzene nucleus are preferred. Deficiencies in gly-coaldehyde and methanol are controllable by direct Compounds for treatment of the condition by [1] Robertson DS. The percussion reactions involved in brain transfer into the metabolism through the digestive function. Med Hypotheses 2002;59(6):682–95.
system must survive the chemical conditions in this [2] Genovesi G, Paolini P, Marcellini L, Vernillo E, Salvati G, organ. Proteins and enzymes are frequently linked Polidori G et al. Relationship between autoimmune thyroid to polyphosphoric acids (phosphoproteins, casein, disease and AlzheimerÕs disease. Panminerva Med 1996;38(1):61–4. Oliver.
vitellin, chymosin), as are phosphatides (lecithin).
[3] Robertson DS. Percussion chemistry and muscle function.
Enzymes like chymosin are stable in the stomach.
A mode of transfer of the active compounds into [4] Cantab TH, Murphy BC. D,V Influenzal pneumonia: the the metabolism is the use of enzyme or protein car- intravenous injection of hydrogen peroxide. Lancet 1920; riers in place of benzene nucleus carriers. Polyphos- [5] Finney JW, Jay BE, Race GJ. Removal of cholesterol and other phoric acids react with hydrogen peroxide to give lipids from experimental animals and human atheromatous peroxymonophosphoric acid (H3PO5) and peroxydi- arteries by dilute hydrogen peroxide. Angiology 1966;17: phosphoric acid (H4P2O8). These two acids convert 223–8. peroxide. Circ. 1965. 31 (Suppl) pp. 207–210.
from one to the other in aqueous solution accordingto the pH of the solution. Peroxymonophosphoric acid predominates in acid solution and peroxydi- 205 Pickersleigh Road, Malvern, Worcestershire phosphoric acid predominates in alkaline solution.
These compounds are possible sources of enhanced Immunomodulation, allohormones and fertility substances discussed in the above mentioned paperfall within a class referred to as allohormones [2,3].
Bazar et al. [1] reported that catecholamines present Secondly, by combining their results with findings in the semen influence female immune response, and from fundamental biological research the authors may represent a strategy to increase sperm survival.
provide essential insight into fertility problems faced In relation to this idea, there are two issues that I in reproductive medicine. In the following, I will want to address here. Firstly, the type of bioactive briefly elaborate on both these issues.
As Bazar et al. [1] rightly stated, it is not uncom- [4]) that have an allohormonal function within mon for substances that are transferred into the the female reproductive tract. Additionally, link- mating partner (via semen or otherwise) to influ- ing knowledge of fundamental and applied re- ence the outcome of fertilization [4]. As a matter search clearly benefits the issue of fertility, of fact, the biological literature focusing on sexual which is relevant for animal breeding programs selection is riddled with such examples [5], some of as well as human reproduction. And, the overlap which are quite extreme [6]. Obviously, sexual between the different fields illustrates that for a selection favours the transfer of bioactive sub- full understanding of reproductive processes, fun- stances that enhance the chances of the sperm fer- damental research is as important as applied tilizing the partnerÕs eggs. This selective force is particularly strong in species where semen (spermand seminal fluid) is costly to produce and spermcompetition is fierce, because in such cases fertili-zation is not assured [7].
Bioactive substances that influence the fate of sperm after transfer can help to ensure paternity.
Because such substances are transferred between [1] Bazar KA, Yun AJ, Lee PY. Immunomodulatory function of individuals of the same species, and act directly seminal catecholamines may be an adaptation for repro- on the physiology or behaviour without the involve- duction. Med Hypotheses 2004;63:168–71.
ment of sensory organs, they have been defined as [2] Koene JM, Ter Maat A. Allohormones: a class of bioactive substances favoured by sexual selection. J Comp Physiol A allohormones [2,3]. Given their immunomodulatory effect in the female, catecholamines that are [3] Koene JM, Ter Maat A. The distinction between phero- transferred via the semen should also be seen as mones and allohormones. J Comp Physiol A 2002;188: Fertility in humans, and especially lack thereof, [4] Kelly RW. Prostaglandins in primate semen: biasing the immune system to benefit spermatozoa and virus. Prostag is a recurring problem in reproductive medicine.
Leukotr Ess Fatty Acids 1997;57:113–8.
However, such problems may become much more [5] Chapman T, Arnqvist G, Bangham J, Rowe L. Sexual conflict.
understandable when they are put into a broader scientific framework, as has been brought forward [6] Snook RR. Sexual selection: conflict, kindness and chican- by several researchers [1,4,8]. Although the [7] Birkhead TR, Møller AP. Sperm competition and sexual necessity of immunomodulation of the human fe- selection. New York: Academic Press Ltd.; 1998.
male reproductive tract may seem puzzling, in [8] Gangestad SW. Sexually antagonistic coevolution: theory, evolutionary terms this makes perfect sense. As evidence, and implications for patterns of human mating already alluded to in the above, males of promis- and fertility. In: Offspring: human fertility behavior in cuous species are usually interested in maximizing their paternity, while females want to optimize [9] Kelly RW, Critchley HOD. Immunomodulation by human the quality of their offspring. Evidently, these seminal plasma: a benefit for spermatozoon and pathogen.
two interests will often not coincide, resulting in sexual conflict [5,8]. Especially in the case of low-ered immune response in the female, the cost for the female is high due to the increased risk of infection [9]. Hence, such a conflict may lead to counter-adaptation by the female, which can then result in an arms race between immunomodulat- ing seminal products and hostile female reproduc- In conclusion, catecholamines could be one of many seminal products (such as prostaglandins



PharmacoEconomics - Italian Research Articles 2008; 10 (2): 99-111 © 2008 Adis Data Information BV. Tutti i diritti riservati. Una panoramica delle metodologie per la valutazione delle cure informali negli studi di economia sanitaria* Marc A. Koopmanschap, 1,2 Job N.A. van Exel, 1,2 Bernard van den Berg 3 e Werner B.F. Brouwer 1,2 1 Department of Health Policy and Management (iBMG), Eras

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