RESUMO
The ability of venom-derived peptides to disrupt physiological processes in mammals provides an exciting source for pharmacological development. Our research group has identified a new class of neuroactive peptides from the venom of a Brazilian social wasp, Polybia occidentalis, with the potential pharmacological profile to treat epilepsies. The study was divided into five phases: Phase 1 concerned the extraction, isolation and purification of Occidentalin-1202(n) from the crude venom, followed by the synthesis of an identical analogue peptide, named Occidentalin-1202(s). In Phase 2, we described the effects of both peptides in two acute models of epilepsy-kainic acid and pentylenetetrazole-induced model of seizures-and measured estimated ED50 and therapeutic index values, electroencephalographic studies and C-fos evaluation. Phase 3 was a compilation of advanced tests performed with Occidentalin-1202(s) only, reporting histopathological features and its performance in the pilocarpine-induced status epilepticus. After the determination of the antiepileptic activity of Occidentalin-1202(s), Phase 4 consisted of evaluating its potential adverse effects, after chronic administration, on motor coordination (Rotarod) and cognitive impairment (Morris water maze) tests. Finally, in Phase 5, we proposed a mechanism of action using computational models with kainate receptors. The new peptide was able to cross the blood-brain barrier and showed potent antiseizure effects in acute (kainic acid and pentylenetetrazole) and chronic (temporal lobe epilepsy model induced by pilocarpine) models. Motor and cognitive behaviour were not adversely affected, and a potential neuroprotective effect was observed. Occidentalin-1202 can be a potent blocker of the kainate receptor, as assessed by computational analysis, preventing glutamate and kainic acid from binding to the receptor's active site. Occidentalin-1202 is a peptide with promising applicability to treat epilepsy and can be considered an interesting drug model for the development of new medicines.
RESUMO
Objetivos: A alergia a veneno de himenópteros pode condicionar a vida da criança de forma significativa. Pretende-se, com a exposição de dois casos clínicos e uma breve revisão do tema, salientar a importância da referenciação dessas crianças a consultas especializadas, para início de dessensibilização.Descrição dos casos: Duas crianças, aos três e aos seis anos, tiveram anafilaxia a picada de vespa e abelha, respectivamente. Em ambas, após a determinação de IgE específica e confirmação alergológica, iniciou-se dessen-sibilização com veneno de himenópteros em esquema ultra-rush, sem intercorrências relevantes, apenas edema no local da injeção. Após doze meses de injeções a cada quatro semanas, recebem agora manutenção com injeções a cada seis semanas. No primeiro caso, a criança foi picada por vespa aos dez meses de imunoterapia, desencadeando apenas reação local diminuta.Conclusões: Em ambos os casos, a imunoterapia específica subcutânea com veneno em esquema ultra-rush foisegura e eficaz, oferecendo o conforto de um menor número de injeções e de deslocamentos ao hospital na fasede indução. A manutenção da terapêutica já demonstrou efeito protetor na reexposição ao veneno em uma dascrianças.
clinical cases and a brief review on the topic, emphasizing the importance of referral of these children to specialized care for early desensitization.Cases description: Two children, at three and six years, had anaphylactic reaction to wasp and bee stings, respectively. In both cases, after the determination of specific IgE and allergologic confirmation, desensitization with hymenoptera venom in ultra-rush regimen was done, without relevant side effect apart from swelling at the injection site. After twelve months of injections every four weeks, the children are now receiving maintenance injections every six weeks. In the first case, the child was stung by wasp at ten months of immunotherapy, triggering only small localreaction.Conclusions: In both cases, the subcutaneous venom immunotherapy with ultra-rush regimen was safe and effective, providing the comfort of a smaller number of injections and hospital visits during the induction phase. Maintenance therapy has demonstrated a protective effect on re-exposure to the poison in one child.