Leishmaniasis Tegumentaria Americana: factores de riesgo para las fallas terapéuticas con antimoniato de meglumina / American Tegumentary Leishmaniasis: risk factors for therapeutic failure with meglumine antimoniate

INTRODUCCIÓN Salta presenta la mayor endemicidad de leishmaniasis tegumentaria en Argentina. La quimioterapia es la mayor estrategia de control, y el antimoniato de meglumina constituye el tratamiento de primera línea. Hay reportes acerca de distintos rangos de eficacia de los antimoniales y la influencia de factores clínicos y epidemiológicos en la respuesta al tratamiento, pero existen escasos datos acerca de este tema en pacientes de Argentina. OBJETIVOS Describir las características del tratamiento con antimoniato de meglumina recibido por pacientes con leishmaniasis tegumentaria diagnosticados en Salta. Realizar una caracterización epidemiológica y clínica de estos pacientes, e identificar factores involucrados en la respuesta al tratamiento. OBJETIVOS Describir las características del tratamiento con antimoniato de meglumina recibido por pacientes con leishmaniasis tegumentaria diagnosticados en Salta. Realizar una caracterización epidemiológica y clínica de estos pacientes, e identificar factores involucrados en la respuesta al tratamiento. MÉTODOS Se realizó un estudio observacional de casos y controles, recabando datos filiatorios, demográficos, epidemiológicos, de la clínica y del tratamiento. RESULTADOS De 129 pacientes diagnosticados entre 2000 y 2014, se obtuvieron datos de tratamiento y seguimiento de 43; 19 (44,2%) presentaron buena respuesta y 24 (55,8%) tuvieron falla terapéutica. Se observó un predominio de la forma mucosa (17/24, 70,8%) sobre la forma cutánea (7/24, 29,2%) en los tratamientos fallidos, y todos los pacientes con lesiones mucosas y cutáneas concomitantes (5/17) presentaron falla en el tratamiento. El análisis bivariado mostró asociación estadísticamente significativa entre las interrupciones en el tratamiento y las fallas terapéuticas (p=0,02, test de Fisher), y todos los tratamientos de duración menor fallaron (3/20). El análisis multivariado no pudo establecer asociación significativa de ninguna de las variables como factores de riesgo en la ocurrencia de fallas en el tratamiento. DISCUSIÓN Se demostró una asociación significativa entre las interrupciones en el tratamiento y las fallas terapéuticas. El número de pacientes no permitió establecer asociaciones mediante análisis multivariado.

Biological characterization of Trypanosoma cruzi strains.

Biological parameters of five Trypanosoma cruzi strains from different sources were determined in order to know the laboratory behaviour of natural populations. The parameters evaluated were growth kinetics of epimastigotes, differentiation into metacyclic forms, infectivity in mammalian cells grown in vitro and parasite susceptibility to nifurtimox, benznidazole and gentian violet. Differences in transformation to metacyclic, in the percentage of infected cells as well as in the number of amastigotes per cell were observed among the strains. Regarding to pharmacological assays, Y strain was the most sensitive to the three assayed compounds. These data demonstrate the heterogeneity of natural populations of T. cruzi, the only responsible of infection in humans.

Relationship between biological behaviour and randomly amplified polymorphic DNA profiles of Trypanosoma cruzi strains.

Once known some biological characteristics of six Trypanosoma cruzi strains, randomly amplified polymorphic DNA (RAPD) analysis was made. Cluster analysis by UPGMA (unweighted pair group method analysis) was then applied both to biological parameters and RAPD profiles. Inspection of the UPGMA phenograms indicates identical clusters, so supporting that usefulness of biological parameters to characterization of T. cruzi strains still remains.

Synthesis and antichagasic properties of new 1,2,6-thiadiazin-3,5-dione 1,1-dioxides and related compounds.

In a search for antichagasic drugs, 14 new 4-(nitroarylidene)-1,2,6-thiadiazin-3,5-dione 1,1-dioxide derivatives were synthesized and tested in vitro against the epimastigote form of Trypanosoma cruzi and some of them showed important antiprotozoan activity. Attempts to synthesize new 4-(nitroarylidene)-3,5-diamino-1,2,6-thiadiazine 1,1-dioxides were unsuccessful. The antichagasic properties of nitroarylidene-malononitrile and nitroarylidene-cyanoacetamide derivatives, thus obtained, were also tested. The cytotoxic properties against Vero cells of compounds which showed remarkable in vitro antichagasic activity were evaluated. All compounds tested exhibited high toxicity percentages at 100 micrograms/ml. However, compound 3c showed in vitro antichagasic and cytotoxic properties such as nifurtimox at the dose of 10 micrograms/ml.

[Prevalence and seasonal variation of Pediculosis capitis in children and the young population of the health region, Buenos Aires, Argentina]. / Prevalencia y estacionalidad de la Pediculosis capitis en la población infanto-juvenil de la region sanitaria, Buenos Aires, Argentina.

The prevalence of the parasitic disease Pediculosis capitis was studied over a period of one year from 1-8-1992 to 31-7-1993, in Sanitary Region XI of the Buenos Aires province, Argentina which is composed of 15 districts located on the ENE, and in other areas under the influence of the Hospital Interzonal de Agudos, Especialidad Pediatría "Sup. Sor María Ludovica" de Plata, center of this Sanitary Region. A total number of 552 individuals of from medium to medium low social level of the child population of from 0 to 16 years of age were sampled at random over 52 consecutive weeks. All individuals who actually had the parasite at the time of examination were considered as positive for this disease. The results are expressed in terms of prevalence and its monthly and seasonal variations analyzed. Prevalence showed high values during all months, the lowest being in February (12%) and the highest in August (56.8%), the annual mean being of 38.04% (+/- 4.05%). Seasonally, its lowest value occurred in the summer (16.8%), the values for the remaining seasons being very similar to one another, but always higher than 38%.

Research for new antichagasic drugs.

A series of ten 1-[(5-nitrothenylidene)amino]azoles has been synthesized by the reaction of 5-nitrothiophene-2-carbaldehyde with 1-aminopyrazole, 1-aminoimidazole, 1- and 4- amino-1,2,4-triazoles, 1-aminoindole, 1- and 2-aminoindazoles, 1-aminobenzimidazole and 1- and 2-aminobenzotriazoles. Physical data, spectroscopic characteristics and biological properties of all the derivatives have been examined. The antiprotozoal activity has been tested against Trypanosoma cruzi, comparative to Nifurtimox (Lampit).

Ca2+-dependence of 3H-catecholamines release evoked by black widow spider venom gland extract in rat hypothalamus, occipital cortex and caudate nucleus.

The release of 3H-catecholamines evoked by Black Widow spider venom gland extract (BW-GE) has been studied in the isolated rat hypothalamus (HT), occipital cortex (OC), preloaded with 3H-noradrenaline, and isolated caudate nucleus (CN) preloaded with 3H-dopamine. The BWGE at a concentration of 0.04 gland/ml increased significantly 3H-output in isolated slices of rat HT, OC and CN. This effect was markedly depressed when control calcium concentration in the medium (1.68 mM) was reduced (0-0.56 mM) or enhanced (3 mM), as well as in the presence of an organic Ca2+ antagonist, verapamil (10 microM), or ionophore A 23187 (40 microM), a substance that increases the influx of calcium into the cell. Morphine (up to 0.4 mM) evoked no effect upon 3H-noradrenaline release induced by BWGE. Morphine (10 microM), but not ionophore A 23187 or high Ca2+ (3 mM), reduced 3H-noradrenaline release induced by 20 mM K+. Low Ca2+ and verapamil produced similar effects than those observed for BWGE. Our results demonstrate differences between BWGE and potassium stimuli, and indicate that BWGE releases 3H-catecholamines by a calcium dependent process.

Ca2+-dependence of 3H-catecholamines release evoked by black widow spider venom gland extract in rat hypothalamus, occipital cortex and caudate nucleus.

The release of 3H-catecholamines evoked by Black Widow spider venom gland extract (BW-GE) has been studied in the isolated rat hypothalamus (HT), occipital cortex (OC), preloaded with 3H-noradrenaline, and isolated caudate nucleus (CN) preloaded with 3H-dopamine. The BWGE at a concentration of 0.04 gland/ml increased significantly 3H-output in isolated slices of rat HT, OC and CN. This effect was markedly depressed when control calcium concentration in the medium (1.68 mM) was reduced (0-0.56 mM) or enhanced (3 mM), as well as in the presence of an organic Ca2+ antagonist, verapamil (10 microM), or ionophore A 23187 (40 microM), a substance that increases the influx of calcium into the cell. Morphine (up to 0.4 mM) evoked no effect upon 3H-noradrenaline release induced by BWGE. Morphine (10 microM), but not ionophore A 23187 or high Ca2+ (3 mM), reduced 3H-noradrenaline release induced by 20 mM K+. Low Ca2+ and verapamil produced similar effects than those observed for BWGE. Our results demonstrate differences between BWGE and potassium stimuli, and indicate that BWGE releases 3H-catecholamines by a calcium dependent process.