Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection.</p> <p>Methods/design</p> <p>Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals.</p> <p>Discussion</p> <p>Preliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these findings warrant further evaluation to determine if long-term administration of statins may benefit the virological and immunological evolution in HIV-1-infected individuals before the use of antiretroviral therapy is required.</p> <p>Trial registration</p> <p>Registration number NCT00721305.</p

Spatial avoidance of invading pastoral cattle by wild ungulates: insights from using point process statistics

Traditional rangelands in many developing countries are currently being encroached by cultivation, driving some herders to illegally use protected areas for grazing their cattle. Since cattle are an exotic species in these ecosystems, they might have an impact on the local wild herbivore communities, notably through competition. We used point pattern statistics to characterise the spatial relationships between wild ungulate species and cattle herds within a protected area in west Africa undergoing seasonal intrusions by cattle. We predicted that the wild ungulate species that are ecologically and morphologically similar to cattle, in terms of body mass and diet, would be more sensitive to grass depletion by cattle and would be separated from cattle to a larger extent. The spatial distribution of browsing and mixed-feeding antelopes did not seem to be affected much by cattle presence, whereas most grazing species showed spatial separation from cattle. Interestingly, elephants also showed significant separation from cattle herds. We discuss the likely processes that may have contributed to the observed spatial patterns. Thespatial displacement of certain wild species, including megaherbivores, affects the whole community structure and, thus, other components of the ecosystem

Phylogeny of the Neotropical sages (Salvia subg. Calosphace; Lamiaceae) and insights into pollinator and area shifts

Salvia subg. Calosphace (Lamiaceae, Lamiales) is a highly diverse clade endemic to the New World. The phylogenetic relationships of Calosphace have been previously investigated using DNA sequences of nuclear ITS region and plastid psbA–trnH intergenic spacer, but the resulting trees lack resolution and support for many clades. The present paper reassesses the phylogenetic relationships of subgenus Calosphace, including a broader taxon sampling, with a special focus on representing previously unsampled sections, and using an additional plastid marker (trnL–trnF region). Our results show increased resolution and overall patterns of support, recovering ten main clades. Within core Calosphace, the most inclusive of these main clades, 17 new subclades were identified. Of the 42 sections for which more than one species was analysed, only 12 are monophyletic. Our biogeographical analysis identified at least twelve migrations to South America from Mexican and Central American lineages, in agreement with previous suggestions of multiple origins of South American Calosphace diversity. This analysis also confirmed a colonization of the Antilles by Andean lineages. The reconstruction of ancestral states of pollination syndromes showed multiple shifts to ornithophily from melittophily and one reversal to the latter.Fil: Fragoso-Martínez, Itzi. Universidad Nacional Autónoma de México; MéxicoFil: Martínez-Gordillo, Martha. Universidad Nacional Autónoma de México; MéxicoFil: Salazar, Gerardo A.. Universidad Nacional Autónoma de México; MéxicoFil: Sazatornil, Federico David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Jenks, Aaron A.. Berkeley University; Estados UnidosFil: García Peña, María del Rosario. Universidad Nacional Autónoma de México; MéxicoFil: Barrera-Aveleida, Giovanna. Universidad Nacional Autónoma de México; MéxicoFil: Benitez Vieyra, Santiago Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Magallón, Susana. Universidad Nacional Autónoma de México; MéxicoFil: Cornejo-Tenorio, Guadalupe. Universidad Nacional Autónoma de México; MéxicoFil: Granados Mendoza, Carolina. Universidad Nacional Autónoma de México; Méxic