Experimental jetlag disrupts circadian clock genes but improves performance in racehorses after light-dependent rapid resetting of neuroendocrine systems and the rest-activity cycle.

Abrupt alterations in the 24-h light : dark cycle, such as those resulting from transmeridian air travel, disrupt circadian biological rhythms in humans with detrimental consequences on cognitive and physical performance. In the present study, a jetlag-simulated phase shift in photoperiod temporally impaired circadian peaks of peripheral clock gene expression in racehorses but acutely enhanced athletic performance without causing stress. Indices of aerobic and anaerobic capacities were significantly increased by a phase-advance, enabling prolonged physical activity before fatigue occurred. This was accompanied by rapid re-entrainment of the molecular clockwork and the circadian pattern of melatonin, with no disturbance of the adrenal cortical axis, but a timely rise in prolactin, which is a hormone known to target organs critical for physical performance. Subsequent studies showed that, unlike the circadian pattern of melatonin, and in contrast to other species, the daily rhythm of locomotor activity was completely eliminated under constant darkness, but it was restored immediately upon the reintroduction of a light : dark cycle. Resetting of the rhythm of locomotion was remarkably fast, revealing a rapid mechanism of adaptation and a species dependency on light exposure for the expression of daily diurnal activity. These results show that horses are exquisitely sensitive to sudden changes in photoperiod and that, unlike humans, can benefit from them; this appears to arise from powerful effects of light underlying a fast and advantageous process of adjustment to the phase shift.

Population growth and global warming.

When I was born in 1930, the human population of the world was a mere 2 billion. Today, it has already reached 6.8 billion, and is projected to reach 9.1 billion by 2050. That is unsustainable. It is slowly beginning to dawn on us that Global Warming is the result of increasing human CO2 emissions, and the more people there are in the world, the worse it will become. Ultimately, it is the sky that will prove to be the limit to our numbers. The developed countries of the world are the most affluent, and also the most effluent, so we must lead by example and contain our own population growth and per capita emissions. We also have a big debt to repay to former colonial territories in Africa, Asia and South America, who desperately need our help to contain their excessive rates of population growth. Belgian and Dutch obstetricians and gynaecologists can play a critical role in this endeavour. After all, we already have a pill that will stop global warming - the oral contraceptive pill.

New ways of preventing HIV infection: thinking simply, simply thinking.

HIV infection is the greatest health crisis in human history. It continues to spread unchecked among the poor in the developing world because we have failed to design simple preventative methods that are available and affordable to those living on under Dollars 2 a day. Five new methods are discussed. (i) A natural microbicide. Intravaginal lime or lemon juice has been used for centuries as a traditional contraceptive. The juice can also kill HIV in the laboratory, but clinical trials are needed to see if vaginal application is acceptable, safe and effective. (ii) Intravaginal oestrogen. Monkeys can be protected from Simian immunodeficiency virus (SIV) infection by keratinizing the vagina with topical oestrogen. If women take the oral contraceptive pill vaginally it retains its contraceptive efficacy, and the oestrogen it contains should thicken the vagina and protect against HIV infection. Clinical trials are needed. (iii) Male circumcision. Removal of the inner foreskin removes the main site of HIV entry into the penis, resulting in a sevenfold reduction in susceptibility to infection. The practice needs to be promoted. (iv) Post-coital penile hygiene. Wiping the penis immediately after intercourse with lime or lemon juice or vinegar should kill the virus before it has had a chance to infect. A clinical trial of efficacy is needed. (v) PhotoVoice. Asking schoolchildren in developing countries to photograph their impressions of HIV/AIDS is a powerful way of getting them to discuss the subject openly, and develop their own preventative strategies.

The HIV/AIDS pandemic: new ways of preventing infection in men.

Nelson Mandela has recently said that HIV/AIDS is the greatest health crisis in human history. At the end of 2001, UNAIDS estimated that there were 40 million people living with the infection, with 5 million new cases, and 3 million deaths per year. About half the infected individuals are men, and heterosexual intercourse is the commonest route of infection. Although condoms remain the first line of defence, they are unpopular in parts of Africa, where the pandemic is worst, so an alternative is needed. Post-coital penile hygiene has received little attention. Wiping the glans penis and inner foreskin immediately after intercourse with an acidic solution like lemon or lime juice, or even vinegar, should immediately kill the virus and might prevent infection; clinical trials are urgently needed. Several studies in Africa and India have now conclusively demonstrated a 2-7-fold protective effect of male circumcision against HIV infection. Circumcision removes the inner foreskin and the frenulum, which are the prime sites of HIV entry into the penis. Since male circumcision also protects men from human papilloma virus infection, and their wives from cervical carcinoma, the procedure should be encouraged in developed and developing countries.

Functional analysis of the cooled rat testis.

Direct cooling of the testis results in the depletion of most germ cells in vivo. Germ cell-depleted testes are now commonly used to investigate spermatogenic regeneration and can serve as recipients for germ cell transplantation. The present study explored the effects of cooling rat testes on the depletion of endogenous germ cells, spermatogenic regeneration, and Sertoli cell function. Adult rat testes were cooled with iced Ringer's solution for 60 minutes, which results in the initiation of apoptotic germ cell loss within 8 hours. Pachytene spermatocytes at stages XII-I were the cells most sensitive to cooling. In 46%-67% of seminiferous tubule cross-sections, only Sertoli cells remained in the cooled testes 3-10 weeks after treatment. Germ cell loss was accompanied by a significant decrease in circulating inhibin B and an increase in follicle-stimulating hormone concentrations, which indicated a change in Sertoli cell function. Quantitative analysis of mRNA expression associated with apoptotic signals showed no significant uniform changes among the cooled testes, although some individuals had a distinct up-regulation of FAS mRNA at 24 hours. Attempts to use the cooled testes as recipient testes for mouse-to-rat germ cell transplantation were undertaken, but none of the mouse germ cells transplanted into the testes 15-34 days after cooling appeared to have undergone spermatogenesis 64-92 days after transplantation. These data suggest that modifications to Sertoli cell function resulting from testicular cooling create an environment that is unable to support spermatogenesis by donor germ cells.

Long-term fertility control in the kangaroo and the wallaby using levonorgestrel implants.

Non-lethal management techniques are needed for overabundant captive and wild populations of macropodid marsupials for which lethal techniques are considered inappropriate and may be hazardous. The tammar wallaby, Macropus eugenii, was used as a model species to investigate the effect of s.c. levonorgestrel implants on reproduction during breeding and non-breeding seasons. Implants were tested on captive and wild populations of eastern grey kangaroos, Macropus giganteus. In both species, levonorgestrel successfully stopped reproduction by inhibiting oestrus. However, levonorgestrel did not affect the reactivation and subsequent development of blastocysts in diapause that had been conceived before treatment and it did not impair lactation, as young were reared to weaning in both species. The contraceptive effects of the implant were reversible, as removal of the implants from tammar wallabies was followed by a rapid return of fertility. Levonorgestrel implants had no apparent adverse effects on body condition in either species, although in the wild kangaroos a small increase in body condition did occur. Levonorgestrel implants are long-acting and so far have provided 48 months of contraception in the tammar wallaby and 27 months of contraception in the kangaroo, although the implants should provide contraception for more than 5 years in the kangaroo. Thus, levonorgestrel implants provide a safe, highly effective and long-term method of fertility control for macropodid marsupials and should be applicable for the management of overabundant captive and selected wild populations.

Control of red fox (Vulpes vulpes) fertility with cabergoline: dose response and timing of intervention.

Cabergoline, a potent dopamine agonist and inhibitor of prolactin secretion, was investigated as a potential fertility control agent in the red fox ( Vulpes vulpes). Sixty silver fox vixens were selected randomly and artificially inseminated. Cabergoline was fed to groups of 12 vixens in a minced beef ration either as a single dose of 25, 50 or 100 microg kg(-1), or a dose of 50 microg kg(-1) that was repeated 2 days later (2 x 50 microg kg(-1)). Four foxes from each group of 12 were given cabergoline at day 28, day 35 or day 48 after artificial insemination, and a control group of four foxes was used as a comparison for each dose day. In a separate trial, two groups of five foxes were selected randomly from the farm population and fed 100 microg kg(-1) of either cabergoline or a placebo each day from day 42 to day 46 of pregnancy. Foxes that received single doses of cabergoline of 100 microg kg(-1) or 2 x 50 microg kg(-1) aborted at day 28, but the same doses did not result in abortions when administered on days 35 and 48. Although lactation was not terminated in groups that received a single or double dose of cabergoline, increased post-natal cub mortality was associated with cabergoline administration. Growth of cubs between 4 and 8 weeks of age was not inhibited in vixens that received cabergoline. Doses of 100 microg cabergoline kg(-1) administered each day from day 42 to day 46 resulted in abortions and terminated lactation. The capacity of single doses of cabergoline to cause abortions in the red fox during mid- rather than late pregnancy is contrary to reported observations for the domestic dog. This finding indicates that luteotrophic support of the corpus luteum by prolactin may be more important at mid-pregnancy in the red fox. The results of this study support previous field observations that cabergoline delivered in bait affects the reproductive success of vixens and may be a practical adjunct to the lethal control of wild red foxes in Australia.

Assisted reproductive techniques for hybridization of camelids.

The camelid family comprises the Old World camelids (or dromedary and Bactrian camels) and the New World camelids (namely the llamas, alpacas, guanacos and vicunas). Although the species within each group can hybridize among themselves to produce fertile offspring, it is only recently that a hybrid between New and Old World camelids has been reported. To create this hybrid, semen was collected from male camels by artificial vagina (AV) and inseminated into female guanacos (n = 9) and llamas (n = 3) at the appropriate stage of their follicular wave cycle. Similarly, guanaco and llama semen was collected, also by AV, and inseminated into female camels (n = 42). Although several conceptions occurred, only one hybrid (camel sire x guanaco dam) continued to term and was born alive after 328 days of gestation, and another is pregnant at the time of writing (camel sire x llama dam). Further studies are presently being carried out using extraspecific embryo transfer to try and improve the success rate of live offspring being born. Female guanacos (n = 4) are treated with hormones to stimulate their ovaries to produce several follicles before being inseminated with camel semen. Of the 12 camel recipients that have to date received hybrid embryos (camel sire x guanaco dam), 10 conceived, but 9 of these subsequently aborted between 30 and 365 days and only one recipient was still pregnant at the time of writing.

The future fertility of mankind: effects on world population growth and migration.

The world's population, currently just over 6 billion, is projected to increase to 9-10 billion by the year 2050. Most of this growth will occur in the developing countries of Asia, where there is an enormous unmet demand for contraception, while an increasing number of developed countries will have declining populations. The human immunodeficiency virus (HIV) pandemic will target developing countries, with India destined to become its new epicenter. By 2050, there may be 1 billion HIV-infected people in the world. The significant protective effect of male circumcision may spare Islamic countries, such as Pakistan, Bangladesh, Iran and Indonesia, from the worst effects of the pandemic. Australia will be increasingly threatened by the high rates of population growth of her Asian neighbours. This, coupled with political instability and sea-level rises as a consequence of global warming, will turn the present trickle of refugees from a variety of Asian countries seeking safe haven on our sparsely populated northern coastline into a veritable flood. There will come a time when we have neither the manpower, nor the means, nor even the moral right to intercept, detain or repatriate the thousands who will come in peace, in search of a better life. However, if Australia is to stabilize its future population at around 23 million, which seems highly desirable on ecological grounds, then the net immigration rate must be limited to approximately 50000 people per year. Because the final point of departure for all these refugees is Indonesia, it is essential that Australia maintains good relations with Indonesia, so that together we can attempt to manage the refugee problem. However, Indonesia's own population is destined to increase by 100 million in the next 50 years, which will only exacerbate the situation. Australia would be well advised to make a major increase in its paltry financial assistance to Indonesia's excellent family planning programmes, which are currently starved of funds. Helping Indonesia to contain its population growth is Australia's best long-term investment for its own future.

Contraceptive effects of levonorgestrel implants in a marsupial.

The effect of subcutaneous levonorgestrel implants on reproduction in female tammar wallabies was investigated during the breeding and non-breeding season. Female tammars were given either a control or a levonorgestrel implant and their pouch young were removed to terminate embryonic diapause. Both the control and the levonorgestrel-implant animals treated during the months of May and June gave birth, demonstrating that levonorgestrel does not prevent the reactivation of the diapausing blastocyst or its subsequent development when given at these times. However, none of the levonorgestrel-treated animals mated post partum, whereas all of the control females that gave birth had a post partum oestrus and mated. Control animals gave birth again when the neonate was removed, and continued to breed normally during the following 36 months of the investigation. None of the levonorgestrel-treated animals gave birth again or mated during the next 36 months. Animals given control implants during December did not reactivate or give birth until the normal start of the breeding season in late January. Animals treated with levonorgestrel implants during December did not reactivate with the control animals at the beginning of the breeding season and did not give birth during the next 36 months. There were no effects of levonorgestrel treatment on early lactation. Levonorgestrel implants were removed from six females and four of these animals resumed reproductive activity, confirming that the contraceptive effect of the implants is reversible. Levonorgestrel implants therefore provide a highly effective, reversible and long-term method of contraception for tammar wallabies. This contraceptive system appears to offer a method of population control for the management of overabundant captive and selected wild populations of macropodid marsupials.

Sexual differentiation of oestradiol-LH positive feedback in a marsupial.

The surge of LH that induces ovulation in mammals showing spontaneous ovulation is precipitated by the positive feedback of increasing oestrogens from the developing follicles in the ovary. In eutherians, exogenous oestrogens can mimic this effect by eliciting an LH surge in females, but not usually in males. The absence of a positive LH response to eutherian males is either due to an acute suppression by the secretory products of the testes during adulthood or the permanent disabling of the system by testosterone during early development. This phenomenon is examined in tammar wallabies, Macropus eugenii. The results show that the oestradiol-LH positive feedback response is sexually dimorphic in this marsupial. A surge in plasma LH occurred between 15 and 28 h after injection of 2.5 micrograms oestradiol benzoate kg-1 in 13 of 16 intact females and 4 of 4 ovariectomized females, but in none of 11 intact males. Five females each implanted with a 100 mg testosterone pellet 3 months earlier failed to produce an LH surge. Four males castrated in adulthood and three adult males castrated before puberty also failed to show an LH surge. However, three males castrated 24-26 days after birth showed an unambiguous LH surge when challenged with oestradiol benzoate during adulthood. Thus, in tammar wallabies, the ability to generate an LH surge to oestradiol is a sexually dimorphic response that is suppressed in the male by the organizational effects of the testes in early life and presumably supplemented by an inhibitory effect of circulating testosterone in adulthood.

Hybridizing Old and New World camelids: Camelus dromedarius x Lama guanicoe.

Thirty female dromedary camels were inseminated on a total of 50 occasions with 2-4 ml of fresh guanaco semen diluted with an equal volume of commercially available camel semen extender. Similarly, nine female guanacos were inseminated on 34 occasions with 4-6 ml of fresh, diluted camel semen. Only two of the dromedary females conceived; one aborted a female foetus on day 260 of gestation and the other gave birth to a stillborn female calf on day 365. Six conceptions occurred in the female guanacos. Two of these conceptuses, diagnosed by ultrasound, were resorbed between days 25 and 40 of gestation, one female foetus was aborted on day 291, another female foetus was aborted on day 302, and one female calf was stillborn on day 365 of gestation. The sixth foetus, a male, was born prematurely but alive after a 328-day gestation. It had a phenotypic appearance intermediate between that of a camel and a guanaco and its hybrid parentage was confirmed by the DNA fingerprinting of eight llama microsatellites. To our knowledge, this is the first viable hybrid ever to be produced between Old World and New World camelids, which have been reproductively isolated from one another for at least 11 million years. The preponderance of female hybrids is in accordance with Haldane's law. Histological examination of their ovaries revealed a failure of meiosis, with only an occasional abnormal oocyte surrounded by follicle cells. Although the diploid chromosone number of camels and guanacos is the same (2n = 74), sufficient genetic change has taken place to make the pairing of homologous chromosomes no longer possible.