Anti-ACE monoclonal antibody, clone 4D6

Routine monitoring of occurrence, levels and mechanisms of insecticide resistance informs effective management strategies, and should be used to assess the effect of new tools on resistance. As part of a cluster randomised controlled trial evaluating a novel insecticide-based intervention in central Cote d'Ivoire, we assessed resistance and its underlying mechanisms in Anopheles gambiae populations from a subset of trial villages. Resistance to multiple insecticides in An. gambiae s.s. and An. coluzzii was detected across villages, with dose-response assays demonstrating extremely high resistance intensity to the pyrethroid deltamethrin (>1,500-fold), and mortality following exposure to pyrethroid-treated bednets was low (<30% mortality in cone bioassays). The 1014F kdr mutation was almost fixed (90%) in all villages but the 1575Y kdr-amplifying mutation was relatively rare (<15%). The carbamate and organophosphate resistance-associated Ace-1 G119S mutation was also detected at moderate frequencies (22-43%). Transcriptome analysis identified overexpression of P450 genes known to confer pyrethroid resistance (Cyp9K1, Cyp6P3, and Cyp6M2), and also a carboxylesterase (COEAE1F) as major candidates. Cyp6P3 expression was high but variable (up to 33-fold) and correlated positively with deltamethrin resistance intensity across villages (r(2)=0.78, P=0.02). Tools and strategies to mitigate the extreme and multiple resistance provided by these mechanisms are required in this area to avoid future control failures.

Hypertension is considered one of the most serious long-term medical conditions. Angiotensin I-converting enzyme (ACE), as one of the most important targets for hypertension drugs. It converts angiotensin I to vasopressor angiotensin II through a catalytic hydrolysis process. ACE has been found in higher amounts in the brain cells of Alzheimer disease patients. Brain-penetrating ACE inhibitors (ACEI) decreased the impact of Alzheimer disease in elderly hypertensive patients. It is expected that the inclusion of ACEI-rich foods has a potential to eliminate these health issues. Therefore, this study explored the occurrence of ACEI in food extracts combining an ACE inhibition assay with LC/ESIMS quantification analysis, showing that naturally occurring nicotianamine (NA), ubiquitously present in higher plants, is an important constituent in ACEI active foods. Furthermore, oral administration of NA and NA-rich food extracts improved spatial learning and memory functions in rats, in addition to hypertensive relief. Thus, NA is suggested to be a brain-penetrating ACEI, while the inclusion of NA rich foods will contribute to the "quality of life" of patients with Alzheimer disease by relieving hypertension and dementia.