Occurrence of pyrethroid resistance mutation in Cydia pomonella (Lepidoptera: Tortricidae) throughout Argentina.

Pyrethroid insecticides were intensively used against Cydia pomonella in the Río Negro and Neuquén valley, main production area of pome fruits in Argentina. Therefore, the first objective was to evaluate lambda-cyhalothrin resistance levels in C. pomonella larvae from orchards in this area that are currently under pyrethroids treatments. The second objective was to evaluate the frequency of kdr mutation in C. pomonella across Argentina. High levels of resistance to lambda-cyhalothrin (resistance ratios > 30) were determined in all the populations evaluated. The L1014F (kdr) mutation was evaluated in 355 diapausing larvae collected in 12 orchards from San Juan to Santa Cruz provinces (1690 km away from each other). The highest frequency of kdr mutation was determined in larvae from the Río Negro and Neuquén valley (0.61), followed by those from Mendoza (0.36). The kdr allele was absent or present at very low frequencies in orchards subjected to low pyrethroid pressure. The frequency of detection of kdr mutation in C. pomonella from Argentina is related to the use of pyrethroids against this pest in different areas. Target-site insensitivity is, at least, one of the mechanisms involved in resistance to lambda-cyhalothrin in codling moth from the Río Negro and Neuquén valley.

In vitro activity of N-benzenesulfonylbenzotriazole on Trypanosoma cruzi epimastigote and trypomastigote forms.

Chagas disease is still an important health problem in Central and South America. However, the only drugs currently available for specific treatment of this disease may induce toxic side effects in the host. The aim of this work was to determine the activity of N-benzenesulfonylbenzotriazole (BSBZT) against the protozoan parasite Trypanosoma cruzi. The effects of BSBZT and benzotriazole (BZT) were compared to those of benznidazole (BZL) on epimastigote and trypomastigote forms. BSBZT was found to have an in vitro growth inhibitory dose-dependent activity against epimastigotes, with flow cytometry analysis confirming that the treated parasites presented size reduction. BSBZT showed an IC(50) of 21.56 µg/mL (81.07 µM) against epimastigotes at 72 h of incubation, whereas BZT did not affect the growth of this parasite form. Furthermore, the toxic effect of BSBZT, was stronger and appeared earlier (at 24h) in trypomastigotes than in epimastigotes, with the LC(50) of this compound being 28.40 µg/mL (106.79 µM) against trypomastigotes. The concentrations of BSBZT used in this study presented low hemolytic activity and cytotoxicity. Consequently, at concentrations near IC(50) and LC(50) (25µg/mL), BSBZT caused only 2.4% hemolysis and 15% of RAW 264.7 cell cytotoxicity. These results reveal the potential of BSBZT as a prototype in drug design for developing new anti-T. cruzi compounds.

Cruzipaína, la principal cisteín proteasa de trypanosoma cruzi en la interrelación huésped-parásito / Cruzipain, a major Trypanosoma cruzi cystein protease in the host-parasite interplay

La enfermedad de Chagas, causada por el parásito protozoarioTrypanosoma cruzi, es endémica en América Central y Sudaméricay representa la miocarditis más frecuente a nivel mundial.El establecimiento de la infección crónica conduce a una patologíacardíaca debilitante por la cual mueren más de 50,000 personascada año. No existe consenso sobre si la causa del daño tisulares ocasionada por el parásito o está exacerbada por una respuestaautoinmune. En ambos escenarios, ha sido sugerido quecruzipaína- la principal cisteín proteasa del T. cruzi- cumple unrol importante en la progresión de la enfermedad.Cruzipaína, miembro de la superfamilia de las papaínas, seexpresa como una mezcla compleja de isoformas en los diferentesestadíos de desarrollo de todas las cepas del parásito. Esta glicoproteínaparticipa en la internalización del T. cruzi en las célulasmamíferas, lo que ha sido demostrado con inhibidores específicosde la enzima que interfieren en la invasión celular y la replicacióndel parásito. Además, cruzipaína genera una fuerte respuestaimmune en individuos infectados. Estas característicashacen de cruzipaína un potencial blanco de drogas terapéuticas.La presente revisión resume el conocimiento actual sobre elrol de cruzipaína en la patogénesis de la enfermedad, su compromisoen la invasión de células del huésped así como su participaciónen la activación y evasión de la respuesta inmune enmodelos experimentales y en pacientes chagásicos. El avance enesta área de investigación, proveerá nuevas estrategias terapéuticastendientes a incrementar la respuesta inmunoprotectiva yprevenir la respuesta deletérea producida por el parásito

The protozoan parasite Trypanosoma cruzi, etiological agentof Chagas disease, is endemic in Central and South America andproduces the most common myocarditis worldwide.Parasite persistence eventually leads to a debilitating heartdisease that kills more than 50,000 people every year. There is noconsensus as to whether tissue damage is caused entirely by theparasite or is exacerbated by an autoimmune response. In bothmodels of disease progression, cruzipain- the major cysteine proteinaseof T. cruzi- has been suggested to play an important role.Cruzipain is a member of the papain superfamily, and it isexpressed as a complex mixture of isoforms by different strains ofthe parasite, as well as in all its developmental stages. This parasiteglycoprotein plays a role in the process of T. cruzi internalizationinto mammalian cells, as proved by specific enzyme inhibitors, whichinterfere with cell invasion and inhibit parasite replication.In addition, cruzipain not only is essential for parasite survivalbut also generates a strong immune response in infected individuals.These characteristics point to cruzipain as a potential targetfor drug therapy and for the generation of immune responses.This review analyses our present knowledge of the role ofcruzipain in the disease pathogenesis, its involvement in host cellinvasion, immune activation and evasion by T. cruzi in experimentalmodels and human infection. Ongoing studies in this researcharea may provide novel therapeutic strategies that couldenhance the immunoprotective response while preventing thedeleterious parasite elicited responses observed during Chagasdisease