A number of new Au(I) and Au(III) complexes of chloroquine (CQ) have been prepared, characterized, and evaluated in vitro against several strains of Plasmodium falciparum. [(CQ)Au(PPh(3))][NO(3)] (2) was synthesized by reaction of AuCl(PPh(3)) with AgNO(3) followed by treatment with CQ. Similar reactions of AuCl(PR(3)) (R = Me, Et) with KPF(6) and CQ yielded [(CQ)Au(PMe(3))][PF(6)] (3), and [(CQ)Au(PEt(3))][PF(6)] (4), respectively. KAuCl(4) reacted with CQ to produce the Au(III) complex [(CQ)(2)Au(Cl)(2)]Cl (5), which in turn formed [(CQ)Au(Cl)(SR)(Et(2)O)]Cl (6) by reaction with 1-thio-beta-d-glucose-2,3,4,6-tetraacetate (SRH). The new compounds were characterized by a combination of elemental analysis, fast atom bombardment mass spectrometry (FAB-MS), and NMR spectroscopy. All the complexes display in vitro activity against CQ-sensitive and CQ-resistant strains of Plasmodium falciparum. The highest activity for this series was obtained for complex 4, which is 5 times more active than chloroquine diphosphate (CQDP) against the CQ-resistant strain FcB1. On preincubation of noninfected red blood cells with complexes 1, 5, and 6, protection against subsequent infection was observed in some cases. No clear structure-activity correlations could be established for this series of compounds.
Antimalarial drugs such as chloroquine are beneficial agents in systemic lupus and rheumatoid arthritis. In this work, two new chloroquine diphosphate (CQDP) complexes containing Zn(II) and Au(III) of formula Zn(CQDP)(NO 3 ) 2 (1) and Au(CQDP)Cl 3 (2), respectively, were synthesized and characterized by physico-chemical and spectroscopic methods. To examine their possible antiinflammatory properties, the new derivatives were tested in the range from 1 to 100 lM on the respiratory burst of isolated human neutrophils (PMNs) as well as in whole blood. In isolated PMNs, complex 1 inhibited the isoluminol-enhanced chemiluminescence (IL-CL) only at the highest concentration tested, whereas in the whole blood assay, 10 lM of this complex was sufficient to significantly inhibit the luminolenhanced chemiluminescence (L-CL). On the contrary, complex 2 dose-dependently inhibited the IL-CL but affected the L-CL only at 100 lM. In conclusion, both complexes are more active than CQDP and may be useful for future treatment of diseases resulting from exacerbated neutrophil functions.
The effects of gold-chloroquine derivatives with the formula [Au(PR3)(CQ)]PF6 (where R = Ph (1), Et or Me) on the superoxide anion production by human neutrophils (PMNs, polymorphonuclear cells) were investigated. When these complexes (0.1-3 mumol/l) were added to PMNs prior to the activators formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA), they inhibited isoluminol-horseradish peroxidase-dependent chemiluminescence (CLisol). The inhibition was a direct result of effects on PMNs since chemiluminescence in the cell-free system (horseradish peroxidase-hydrogen peroxidase-isoluminol) was not affected. The above mentioned concentrations of the complexes did not show in vitro toxicity on the cells. On the other hand, when 1 mumol/l of complex 1 was added to cells after stimulation, the chemiluminescence of PMNs stimulated by PMA was inhibited, but not the chemiluminescence stimulated by fMLP. The gold-chloroquine binding was essential for the referred activity as chemiluminescence was not influenced by the precursors chloroquine (CAS 54-05-7) and AuCl(PPh3). Furthermore, the extent of inhibition of chemiluminescence in PMNs activated by PMA did not increase with the duration of preincubation in presence of 1 mumol/l of 1. Extensive washing of cells after preincubation with 1 mumol/l of 1 reversed the aforementioned inhibition. All these results show that the gold-chloroquine binding can lead to compounds with specific properties that could make them useful in the treatment of some inflammatory diseases.
RESUMENEl objetivo del presente estudio fue determinar la eficacia de la rehabilitación logopédica en la inserción escolar en niños con autismo. Se realizó estudio analítico en niños menores de 15 años atendidos por autismo en Neuropediatría del Hospital Belén de Trujillo, entre enero 2010 a diciembre del 2013. Las edades de los niños con autismo tuvieron en promedio 76,0 ±41,7 meses, la proporción de varones/mujeres fue 2,6. Rehabilitación logopédica recibieron 23(28,75%) niños (casos), el 57(71,25%) no recibieron rehabilitación y fueron los controles. El 82,6% de niños que recibieron rehabilitación logopédica acudieron a la escuela, el 26,3% que no recibieron rehabilitación acudieron a un centro educacional. La influencia de la rehabilitación logopédica sobre la socialización no fue significativa, fue favorable para la mejoría del lenguaje y del rendimiento escolar. Se concluye que rehabilitación logopédica es eficaz en la inserción escolar, favorece la educación institucional, mejora del lenguaje y del rendimiento escolar (p<0.05) y es poco accesible a niños con autismo.Palabras clave: Autismo infantil; rehabilitación logopédica; inserción escolar; trastornos del lenguaje; intervención psicopedagógica. ABSTRACTThe objetives were to determine the effectiveness of speech rehabilitation on school integration. Analytical study was performed in children under 15 years old treated for autism in Neuropediatrics at the Belen Hospital of Trujillo from january 2010 to december 2013. The sample was 80 children with autism, 23 of them received speech rehabilitation (cases) and 57 did not receive rehabilitation(controls). The ages of the children with autism had an average of 76.0 ± 41.7 months, the proportion of male/female was 2.6. Rehabilitation speech therapy receibed 23(28.75%) children (cases), 57 (71.25%) were not receiving rehabilitation were controls. 82.6% of children who received speech rehabilitation atended school, 26.3% who did not receive rehabilitation atended an educational center. The influence of socialization on speech rehabilitation was not significant was favorable for the improvement of lenguage and school perfomance. It is concluded that speech rehabilitation is effective in school integration, promotes institutional education, language and improving school perfomance (p<0.05) and is very accessible to children with autism.
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