Archives: Projekti

IMI projekti

Diabetes mellitus Type 2 in the Croatian Population after Chronic Exposure to Arsenic

Croatian-German Research projects within the Programme of Encouraging Joint Participant Exchange in projects established between the Ministry of Science, Education, and Sports and the German Academic Exchange Service (DAAD) for 2015-2016

The main aim of this project is to assess the effect of As exposure on Diabetes Mellitus Type 2 (DMT2) risk in a representative sample of the Croatian population. The proposed study is preliminary in character and designed as a case-control study.

Design of Novel Centrally Active Cholinesterase Reactivators

Croatian-French cooperation programme “Cogito” of the Hubert Curien Partnership

Duration: 2015-2016

Our collaboration and investigation focused on the synthesis of effective reactivators of organophosphorus (OP) compound-inhibited cholinesterases (French group) along with a determination of interaction of cholinesterases with reactivators (Croatian group), all with the goal of developing new antidotes for intoxication with highly-toxic OP compounds. In order to achieve this goal, our
partners from Rouen synthesized seven new oximes while our research included:

  • determination of in silico interactions (molecular modelling) in order to obtain an insight of oxime accommodation in the active site of the enzyme and further structure optimization for effective reactivators in acetylcholinesterase (AChE) inhibited by tabun and VX determination of IC50 values, i.e. reversible inhibition constants for interaction of AChE and butyrylcholinesterase (BChE) with oximes;
  • determination of parameters and reactivation constants for tabun and VX-inhibited AChE and BChE with oximes.

From seven new oximes, three were shown to be exceedingly effective reactivators and we will continue to investigate their efficiency through ex vivo and in vivo testing. The results were presented at two international scientific meetings as two posters and one oral presentation.

BChE Reactivators for Nerve Agent and Pesticide OP Detoxification in Human Tissue

NIH CounterACT Exploratory/Developmental Projects in Translational Research (R21)

2013-2016

This project focused on the detoxification of nerve agent and pesticide organophosphates (OPs) directly in the tissue of OP-exposed individuals as a means of protecting them from both acute and chronic consequences of OP intoxication. It was based on two premises:

  • An oxime reactivator antidote, when combined with human butyrylcholinesterase (BChE), can degrade nerve agent and pesticide OP toxicants in vivo by converting BChE from a stoichiometric to a catalytic OP bioscavenger.
  • If adequate turnover is achieved through the administered oxime, the amounts of endogenous BChE naturally present in human tissue, primarily in plasma, lungs and intestines, should be sufficient to establish, in combination with an exogenously administered oxime, an efficient catalytic OP bioscavenger without supplemental administration of purified human BChE.