Advances in the pharmacology of lGICs auxiliary subunits.

Ligand-gated ion channels (LGICs) are cell surface integral proteins that mediate the fast neurotransmission in the nervous system. LGICs require auxiliary subunits for their trafficking, assembly and pharmacological modulation. Auxiliary subunits do not form functional homomeric receptors, but are reported to assemble with the principal subunits in order to modulate their pharmacological profiles. For example, nACh receptors are built at least by co-assemble of α and ß subunits, and the neuronal auxiliary subunits ß3 and α5 and muscle type ß, δ, γ, and ϵ determine the agonist affinity of these receptors. Serotonergic 5-HT3B, 5-HT3C, 5-HT3D and 5-HT3E are reported to assemble with the 5-HT3A subunit to modulate its pharmacological profile. Functional studies evaluating the role of γ2 and δ auxiliary subunits of GABAA receptors have made important advances in the understanding of the action of benzodiazepines, ethanol and neurosteroids. Glycine receptors are composed principally by α1-3 subunits and the auxiliary subunit ß determines their synaptic location and their pharmacological response to propofol and ethanol. NMDA receptors appear to be functional as heterotetrameric channels. So far, the existence of NMDA auxiliary subunits is controversial. On the other hand, Kainate receptors are modulated by NETO 1 and 2. AMPA receptors are modulated by TARPs, Shisa 9, CKAMP44, CNIH2-3 auxiliary proteins reported that controls their trafficking, conductance and gating of channels. P2X receptors are able to associate with auxiliary Pannexin-1 protein to modulate P2X7 receptors. Considering the pharmacological relevance of different LGICs auxiliary subunits in the present work we will highlight the therapeutic potential of these modulator proteins.

Aspectos parasitológicos y epidemiológicos de los donantes de sangre seropositivos para Trypanosoma cruzi, en un hospital universitario / Parasitological and epidemiological aspects of Trypanosoma cruzi seropositive blood donors

Background: After the interruption of the transmission of Chagas disease via vector insects in Chile, there is little available epidemiological information about this parasitosis in blood banks. Aim To update the rates of T cruzi positive blood donors. To measure parasitological and epidemiological parameters in blood donors with anti T cruzi antibodies. Material and Methods: An ELISA-T cruzi test was carried out in 30,309 blood donors between 2000 and 2004. In 75 blood donors with an ELISA-T cruzi positive test and 79 donors with negative ELISA (controls), a survey about personal or parental history of biting by a kissing bug (Triatomine), was performed. A blood sample was also obtained to perform Polymerase Chain Reaction (PCR) for T cruzi and a xenodiagnostic test. Results: Annual frequency of positive ELISA for T cruzi serum antibodies in blood donors varied from 0.31 percent to 0.45 percent. Twenty eight percent of subjects with positive and 6 percent of subjects with negative specific antibodies answered the survey about biting. PCR and xenodiagnostic test were positive in 52 (69 percent) and 16 (21 percent) of positive ELISA-T cruzi test blood donors, respectively. Xenodiagnostic was also positive in 5 individuals who had a negative PCR. Conclusions: Seroprevalence of T cruzi antibodies decreased from 3 percent in 1968 to 0.3 percent in 2004.

[Parasitological and epidemiological aspects of Trypanosoma cruzi seropositive blood donors]. / Aspectos parasitológicos y epidemiológicos de los donantes de sangre seropositivos para Trypanosoma cruzi,en un hospital universitario.

BACKGROUND: After the interruption of the transmission of Chagas disease via vector insects in Chile, there is little available epidemiological information about this parasitosis in blood banks. AIM: To update the rates of T cruzi positive blood donors. To measure parasitological and epidemiological parameters in blood donors with anti T cruzi antibodies. MATERIAL AND METHODS: An ELISA-T cruzi test was carried out in 30,309 blood donors between 2000 and 2004. In 75 blood donors with an ELISA-T cruzi positive test and 79 donors with negative ELISA (controls), a survey about personal or parental history of biting by a kissing bug (Triatomine), was performed. A blood sample was also obtained to perform Polymerase Chain Reaction (PCR) for T cruzi and a xenodiagnostic test. RESULTS: Annual frequency of positive ELISA for T cruzi serum antibodies in blood donors varied from 0.31% to 0.45%. Twenty eight percent of subjects with positive and 6% of subjects with negative specific antibodies answered the survey about biting. PCR and xenodiagnostic test were positive in 52 (69%) and 16 (21%) of positive ELISA-T cruzi test blood donors, respectively. Xenodiagnostic was also positive in 5 individuals who had a negative PCR. CONCLUSIONS: Seroprevalence of T cruzi antibodies decreased from 3% in 1968 to 0.3% in 2004.