Artemisinin and partner-drug resistance in Plasmodium falciparum are major threats to malaria control and elimination. Triple artemisinin-based combination therapies (TACTs), which combine existing co-formulated ACTs with a second partner drug that is slowly eliminated, might provide effective treatment and delay emergence of antimalarial drug resistance.
Thyrotrophin-releasing hormone (TRH) is known to be inactivated by enzymes present in the rat hypothalamus. To make a further study of the enzymes' action on the tripeptide, synthetic TRH was incubated with two hypothalamic subcellular fractions. By using a direct radioimmunoassay for TRH, the tripeptide was shown to be rapidly degraded by both supernatant and particulate fractions, with higher enzyme activity in the particulate fraction. Of several biologically-active peptides tested, only luteinizing hormone-releasing hormone was found to inhibit TRH inactivation; bacitracin, a polypeptide antibiotic, was also effective in inhibiting inactivation. Enzyme activity was highest in the middle hypothalamic area and lowest in the posterior hypothalamic area. Thin layer chromatography of the products of enzyme cleavage revealed the formation of only deamidated TRH in the supernatant fraction and the constitutent amino acids (pyroGlu, His, ProNH2) and histidylproline-diketopiperazine by the particular fraction, suggesting the presence of an amidase in the supernatant and two peptidases in the particulate fractions. These properties of the enzymes inactivating TRH may indicate that the enzymes could be of importance in regulating the endocrine and other functions attributed to this hypothalamic regulatory hormone.
Plasma concentrations of glucose and insulin were measured in ten patients during the Jarisch-Herxheimer reaction of tetracycline-treated louse-borne relapsing fever. Plasma glucose fell significantly in eight of the ten patients associated with the peak of the reaction, but plasma insulin remained low. Glucoregulation by insulin was therefore normal. This evidence questions the role of macrophage mediator-induced pancreatic insulin release in causing hypoglycaemia in borreliosis or bacterial endotoxicosis.
No abstract is provided for this article.
In most cooperatively breeding vertebrates, dominant breeders have higher reproductive success and live longer than subordinate helpers, and subordinates might consequently be expected to challenge the dominants in their group for status. However, in contrast to noncooperative species, challenges for dominance are rare. This could be because subordinates are unable to displace dominants or because the risk of attempting to do so is prohibitively high. Alternatively, because subordinates are commonly the offspring of dominants and more established breeders tend to produce more young, subordinates may maximize their inclusive fitness by allowing related dominants to maintain their position and helping them to raise future offspring. Here, we use more than 13 years of data from a wild population of Kalahari meerkats Suricata suricatta to investigate whether subordinate females would be likely to gain higher inclusive fitness by displacing their dominant mothers than by remaining as helpers. We first show that the breeding success of dominant females increases during the first 2–3 years of their tenure and then declines. Combining estimates of breeding success in each year of tenure with age-specific survival probabilities, we then calculate the reproductive value of successful challengers and nonchallengers. Our results show that, in any year, subordinate females would achieve higher inclusive fitness by displacing their dominant mother than by remaining as helpers. We conclude that the low frequency with which displacement occurs probably reflects the potential costs associated with challenging for status and the low probability of success.
