AAD Group Research Articles

Pharmacological receptors of nematoda as target points for action of antiparasitic drugs

Cholinergic receptors of parasitic nematodes are one of the most important possible sites of action of antiparasitic drugs. This paper presents some of our own results of electrophysiological and pharamcological examinations of nicotinic and muscarinic receptors of nematodes, as well as data from literature on a new class of anthelmintics that act precisely on cholinergic receptors. The nicotinic acetylcholine receptor (nAChR) is located on somatic muscle cells of nematodes and it is responsible for the coordination of parasite movement. Cholinomimetic anthelmintics act on this receptor, as well as acetylcholine, an endogenic neurotransmitter, but they are not sensitive to enzyme acetylcholineesterase which dissolves acetylcholine. As opposed to the nicotinic receptor of vertebra, whose structure has been examined thoroughly, the stoichiometry of the nicotinic receptor of nematodes is not completely known. However, on the grounds of knowledge acquired so far, a model has been constructed recently of the potential composition of a type of nematodes nicotinic receptor, as the site of action of anthelmintics. Based on earlier investigations, it is supposed that a conventional muscarinic receptor exists in nematodes as well, so that it can also be a new pharamocological target for the development of antinematode drugs. The latest class of synthesized anthelmintics, named aminoacetonitriles (AAD), act via the nicotinic receptor. Monepantel is the first drug from the AAD group as a most significant candidate for registration in veterinary medicine. Even though several groups of cholinomimetic anthelmintics (imiodazothiazoles, tetrahydropyrimidines, organophosphat anthelmintics) have been in use in veterinary practice for many years now, it is evident that cholinergic receptors of nematodes still present an attractive place in the examinations and development of new antinematode drugs. .

Endovascular stent-grafts for acute and chronic type B aortic dissection: comparison of clinical outcomes

Endovascular stent-graft treatment has emerged as an alternative for patients with type B aortic dissection (AD), either at acute or chronic phase, in selected patients. This study aimed to investigate the results of endovascular stent-graft repair for acute and chronic type B AD. From May 2002 to July 2007, 67 patients with type B AD were treated by endovascular stent-graft placement. There were 32 patients in the acute phase (AAD group) and 35 patients in the chronic phase (CAD group). The patients were followed up from 1 to 65 months (average, 17 +/- 16 months). The immediate and follow-up clinical outcomes were documented and compared between the 2 groups. Placement of endovascular stent-grafts across the primary entry tears was technically successful in all 67 patients. Compared with patients in the CAD group, those in the AAD group had higher percentages of pleural effusion (15.6% vs 0, P = 0.02) and visceral/leg ischemia (21.9% vs 2.9%, P = 0.02). Procedure related complications, including endoleak and post-implantation syndrome occurred more frequently in AAD group than in CAD group (21.9% vs 2.9% and 31.3% vs 8.6%, respectively; P = 0.02 and P = 0.02). Kaplan-Meier analysis showed no significant difference in survival rate at 4 years between the 2 groups (86.4% vs 92.3%, P = 0.42 by Log-rank test). But the 4-year event-free survival rate was higher in patients with chronic dissection than in patients with acute dissection (96.2% vs 73.9%; P = 0.02 by Log-rank test). Endovascular repair with stent-graft was safe and effective for the treatment of both acute and chronic type B AD. However, both immediate and long term major complications occurred more frequently in patients with acute dissection than in those with chronic dissection.