Microsatellite markers reveal a spectrum of population structures in the malaria parasite Plasmodium falciparum.

Multilocus genotyping of microbial pathogens has revealed a range of population structures, with some bacteria showing extensive recombination and others showing almost complete clonality. The population structure of the protozoan parasite Plasmodium falciparum has been harder to evaluate, since most studies have used a limited number of antigen-encoding loci that are known to be under strong selection. We describe length variation at 12 microsatellite loci in 465 infections collected from 9 locations worldwide. These data reveal dramatic differences in parasite population structure in different locations. Strong linkage disequilibrium (LD) was observed in six of nine populations. Significant LD occurred in all locations with prevalence <1% and in only two of five of the populations from regions with higher transmission intensities. Where present, LD results largely from the presence of identical multilocus genotypes within populations, suggesting high levels of self-fertilization in populations with low levels of transmission. We also observed dramatic variation in diversity and geographical differentiation in different regions. Mean heterozygosities in South American countries (0.3-0.4) were less than half those observed in African locations (0. 76-0.8), with intermediate heterozygosities in the Southeast Asia/Pacific samples (0.51-0.65). Furthermore, variation was distributed among locations in South America (F:(ST) = 0.364) and within locations in Africa (F:(ST) = 0.007). The intraspecific patterns of diversity and genetic differentiation observed in P. falciparum are strikingly similar to those seen in interspecific comparisons of plants and animals with differing levels of outcrossing, suggesting that similar processes may be involved. The differences observed may also reflect the recent colonization of non-African populations from an African source, and the relative influences of epidemiology and population history are difficult to disentangle. These data reveal a range of population structures within a single pathogen species and suggest intimate links between patterns of epidemiology and genetic structure in this organism.

Angiogénesis inducida por colágena polivinilpirrolidona y heparina en el músculo isquémico / Angiogenesis induced by polivinilpirrolidone collagen and heparin in the ischemic muscle

Estudio de investigación experimental, prospectivo y comparativo, con el objeto de evaluar los efectos de la aplicación exógena de colágena tipo I, Polivinilpirrolidona (PVP) y heparina, en túneles musculares fibrocolágenos, en la extremidad isquémica de la rata, para inducir neovascularización o angiogénesis. Se usó un modelo de isquemia en la extremidad posterior derecha de 40 ratas Wistar en dos tiempos. 1º Ligadura de la arteria iliaca común vía abdominal y colocación de una protesis de silasticpoliéster en el músculo gracilis para la generación de un túnel fibrocolágeno. 2º Ocho semanas después, exposición del paquete vascular femoral, ligadura de esta arteria, localización y extracción de la prótesis, perforación y lavado del túnel fibrocolágeno y aplicación de sustancias. En el grupo I se aplicó solución fisiológica, en el grupo II colágena tipo I con PVP, en el grupo III heparina sódica y grupo IV colágena tipo I con (PVP) y heparina sódica. Para la valoración se llevó a cabo angiografía de las extremidades tratadas, cuantificando el número de intersecciones en una superficie milimétrica de 50 x 50 mm. El mayor número de intersecciones se obtuvo en el grupo IV con una medida de 20.22 contra una media de 13.5 intersecciones en el grupo I (control con sol. fisiológica) = p de 0.14 mediante el análisis de varianza para comparar dos grupos (ANOVA). El estudio demuestra mayor angiogénesis en el músculo isquemico de la rata, si se aplica colágena tipo I con (PVP) y heparina

Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance.

To assess the relationship between mutations in Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) and clinical pyrimethamine-sulfadoxine resistance, polymerase chain reaction surveys and analyses for new mutations were conducted in four countries with increasing levels of pyrimethamine-sulfadoxine resistance: Mali, Kenya, Malawi, and Bolivia. Prevalence of mutations at DHFR codon 108 and a new mutation at DHPS 540 correlated with increased pyrimethamine-sulfadoxine resistance (P < .05). Mutations at DHFR 51, DHFR 59, and DHPS 437 correlated with resistance without achieving statistical significance. Mutations at DHFR 164 and DHPS 581 were common in Bolivia, where pyrimethamine-sulfadoxine resistance is widespread, but absent in African sites. Two new DHFR mutations, a point mutation at codon 50 and an insert at codon 30, were found only in Bolivia. DHFR and DHPS mutations occur in a progressive, stepwise fashion. Identification of specific sets of mutations causing in vivo drug failure may lead to the development of molecular surveillance methods for pyrimethamine-sulfadoxine resistance.