Arm-in-cage testing of natural human-derived mosquito repellents

BACKGROUND: Individual human subjects are differentially attractive to mosquitoes and other biting insects. Previous investigations have demonstrated that this can be attributed partly to enhanced production of natural repellent chemicals by those individuals that attract few mosquitoes in the laboratory. The most important compounds in this respect include three aldehydes, octanal, nonanal and decanal, and two ketones, 6-methyl-5-hepten-2-one and geranylacetone [(E)-6,10-dimethylundeca-5,9-dien-2-one]. In olfactometer trials, these compounds interfered with attraction of mosquitoes to a host and consequently show promise as novel mosquito repellents. METHODS: To test whether these chemicals could provide protection against mosquitoes, laboratory repellency trials were carried out to test the chemicals individually at different concentrations and in different mixtures and ratios with three major disease vectors: Anopheles gambiae, Culex quinquefasciatus and Aedes aegypti. RESULTS: Up to 100% repellency was achieved depending on the type of repellent compound tested, the concentration and the relative composition of the mixture. The greatest effect was observed by mixing together two compounds, 6-methyl-5-hepten-2-one and geranylacetone in a 1:1 ratio. This mixture exceeded the repellency of DEET when presented at low concentrations. The repellent effect of this mixture was maintained over several hours. Altering the ratio of these compounds significantly affected the behavioural response of the mosquitoes, providing evidence for the ability of mosquitoes to detect and respond to specific mixtures and ratios of natural repellent compounds that are associated with host location. CONCLUSION: The optimum mixture of 6-methyl-5-hepten-2-one and geranylacetone was a 1:1 ratio and this provided the most effective protection against all species of mosquito tested. With further improvements in formulation, selected blends of these compounds have the potential to be exploited and developed as human-derived novel repellents for personal protection

Vitamin D depletion does not affect key aspects of the preeclamptic phenotype in a transgenic rodent model for preeclampsia

Maternal vitamin D deficiency is proposed as a risk factor for preeclampsia in humans. We tested the hypothesis that vitamin D depletion aggravates and high supplementation ameliorates the preeclampsia phenotype in an established transgenic rat model of human renin-angiotensin system-mediated preeclampsia. Adult rat dams, transgenic for human angiotensinogen (hAGT) and mated with male rats transgenic for human renin (hREN), were fed either vitamin D-depleted chow (VDd) or enriched chow (VDh) 2 weeks before mating and during pregnancy. Mean blood pressure was recorded by tail-cuff, and 24-hour urine samples were collected in metabolic cages at days 6 and 18 of gestation. Rats were sacrificed at day 21 of gestation. Depleted dams (VDd) had negligible serum 25-hydroxyvitamin D2+3 levels (mean ± SEM; 2.95 +/- 0.45 nmol/l vs. VDh 26.20 +/- 2.88 nmol/l, P = .01), but in both groups, levels of 1,25(OH)2D3 remained below detection level of 25 pmol/l. Dietary vitamin D depletion did not aggravate hypertension (mean +/- SEM BP, day 20 of gestation: 151.38 +/- 5.65 mmHg VDd vs. 152.00 +/- 4.10 mmHg VDh) or proteinuria. Fetal anthropometrics were similar between the groups, whereas VDd displayed lower placental:fetal weight ratios (0.15 vs. 0.16 g/g, P = .01) and increased sFlt-1/PlGF ratio. Expression of hREN was lower in placenta of VDd dams (0.82 +/- 0.44 AU vs. 1.52 +/- 0.15 AU, P = .04). Expression of key vitamin D metabolizing enzymes was unchanged. Dietary vitamin D intervention did not alter key aspects of the preeclampsia phenotype using the transgenic rodent model of human renin-angiotensin system-mediated pre-eclampsia, plausibly due to altered vitamin D metabolism or excretion in the transgenic rats

Monitoring of Selected Skin-Borne Volatile Markers of Entrapped Humans by Selective Reagent Ionization Time of Flight Mass Spectrometry in NO +

[Image: see text] Selective reagent ionization time-of-flight mass spectrometry with NO(+) as the reagent ion (SRI-TOF-MS (NO(+))) was applied for near real-time monitoring of selected skin-borne constituents which are potential markers of human presence. The experimental protocol involved a group of 10 healthy volunteers enclosed in a body plethysmography chamber mimicking the entrapment environment. A total of 12 preselected omnipresent in human scent volatiles were quantitatively monitored. Among them there were six aldehydes (n-propanal, n-hexanal, n-heptanal, n-octanal, n-nonanal, and 2 methyl 2-propenal), four ketones (acetone, 2-butanone, 3-buten-2-one, and 6-methyl-5-hepten-2-one), one hydrocarbon (2-methyl 2-pentene), and one terpene (DL-limonene). The observed median emission rates ranged from 0.28 to 44.8 nmol × person(–1) × min(–1) (16–1530 fmol × cm(–2) × min(–1)). Within the compounds under study, ketones in general and acetone in particular exhibited the highest abundances. The findings of this study provide invaluable information about formation and evolution of a human-specific chemical fingerprint, which could be used for the early location of entrapped victims during urban search and rescue operations (USaR)