Long-acting intramuscular injections of ELQ-331, an antimalarial agent.

The overarching premise of this investigation is that injectable, long-acting antimalarial medication would encourage adherence to a dosage regimen for populations at risk of contracting the disease. To advance support for this goal, we have developed oil-based formulations of ELQ-331 (a prodrug of ELQ-300) that perform as long-acting, injectable chemoprophylactics with drug loading as high as 160 mg/ml of ELQ-331. In a pharmacokinetic study performed with rats, a single intramuscular injection of 12.14 mg/kg maintained higher plasma levels than the previously established minimum fully protective plasma concentration (33.25 ng/ml) of ELQ-300 for more than 4 weeks. The formulations were well tolerated by the rats and the tested dose produced no adverse reactions. We believe that by extending the length of time between subsequent injections, these injectable oil-based solutions of ELQ-331 can offer a more accessible, low-cost option for long-acting disease prevention and reduced transmission in malaria-endemic regions and may also be of use to travelers.

The impact of Spodoptera exigua herbivory on Meloidogyne incognita-induced root responses depends on the nematodes' life cycle stages.

Induced responses to above-ground and below-ground herbivores may interact via systemic signalling in plants. We investigated whether the impact of above-ground herbivory on root-knot nematode-induced responses depends on the nematode's life cycle stages. Tomato plants were infected with the nematode (Meloidogyne incognita) for 5, 15 or 30 days before receiving Spodoptera exigua caterpillars above-ground. We collected root materials after 24 h of caterpillar feeding. We investigated phytohormones and α-tomatine levels, and the expression of defence and glycoalkaloid metabolism (GAME) marker genes in tomato roots. Nematode infection alone increased the endogenous root levels of jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), α-tomatine and the expression of the GLYCOALKALOID METABOLISM 1 (GAME1) gene mostly at 30 days post-nematode inoculation. Caterpillar feeding alone upregulated Lipoxygenase D and downregulated Basic-ß-1-glucanase and GAME1 expression in roots. On nematode-infected plants, caterpillar feeding decreased JA levels, but it increased the expression of Leucine aminopeptidase A. The induction patterns of ABA and SA suggest that caterpillars cause cross-talk between the JA-signalling pathway and the SA and ABA pathways. Our results show that caterpillar feeding attenuated the induction of the JA pathway triggered by nematodes, mostly in the nematodes' reproduction stage. These results generate a better understanding of the molecular and chemical mechanisms underlying frequent nematode-plant-caterpillar interactions in natural and agricultural ecosystems.