Toll receptors type-2 and CR3 expression of canine monocytes and its correlation with immunohistochemistry and xenodiagnosis in visceral leishmaniasis

The aim of the present study was to investigate TLR2 expression in peripheral blood monocytes from dogs naturally infected with Leishmania (Leishmania) infantum to determine whether it correlates with CD11b/CD18 (CR3) expression, and to evaluate the potential of dogs as sources of infection using phlebotomine xenodiagnosis. Forty eight dogs were serologically diagnosed with L. infantum infection by indirect immunofluorescence antibody test (IFAT) and enzyme linked immunosorbent assay (ELISA). Parasitological exams from bone-marrow aspirates were positive by PCR analysis. All dogs were clinical defined as symptomatic. Ear skin tissue samples were obtained for immunohistochemistry (IHQ) analysis. The potential of these dogs as a source of infection using phlebotomine xenodiagnosis (XENO) was evaluated. Flow cytometry was carried out on peripheral blood mononuclear cells using superficial receptors including CD14, CD11b, TLR2 and MHCII. IHQ ear skin tissue parasite load and XENO where done where we found a strict correlation (r = 0.5373). Dogs with higher expression of MFI of CD11b inside CD14 monocytes were represented by dogs without parasite ear tissue load that were unable to infect phlebotomines (IHQ⁻/XENO⁻). Dogs with lower expression of MFI of CD11b inside CD14 monocytes were represented by dogs with parasite ear tissue load and able to infect phlebotomines (IHQ⁺/XENO⁺) (p = 0,0032). Comparable results were obtained for MFI of MHCII (p = 0.0054). In addition, considering the population frequency of CD11b⁺TLR2⁺ and CD11b⁺MHCII⁺, higher values were obtained from dogs with IHQ⁻/XENO⁻ than dogs with IHQ⁺/XENO⁺ (p = 0.01; p = 0.0048, respectively). These data, together with the TLR2 and NO assays results (CD11b⁺TLR2⁺ and NO with higher values for dogs with IHQ⁻/XENO⁻ than dogs with IHQ⁺/XENO⁺), led to the conclusion that IHQ⁻/XENO⁻ dogs are more resistant or could modulate the cellular immune response essential for Leishmania tissue clearance.     

Study of Liquid Dimethyl Sulfoxide by Computer Simulation

The paper reports Monte Carlo and molecular dynamicsresults for pure liquid dimethyl sulfoxide (DMSO) at298 K and 1 atm. The classical 6–12 Lennard–Jones plusCoulomb pairwise potential was used to calculateintermolecular interaction energy. Potentialparameters for the liquid were optimized in this work.Some thermodynamic and dynamical properties obtained,such as heat of vaporization, density and diffusioncoefficient, are in good agreement with theexperimental values. The present model is comparedwith other models for DMSO reported previously. It isshown to be an improvement over earlier potentials.The structure factors and the radial distributionfunctions (rdf), are compared with experimentalresults for the liquid. The analysis shows that thestructure of DMSO is not completely understood yet anddeserves deeper investigation. The geometry of thedimer that corresponds to the rdf plots obtained, isreported. The results suggest that the dipole momentof this dimer plays an important role in the structureof the liquid.     

Falcipain-2 inhibition by suramin and suramin analogues

Falcipain-2 is a cysteine protease of the malaria parasite Plasmodium falciparum that plays a key role in the hydrolysis of hemoglobin, a process that is required by intraerythrocytic parasites to obtain amino acids. In this work we show that the polysulfonated napthylurea suramin is capable of binding to falcipain-2, inhibiting its catalytic activity at nanomolar concentrations against both synthetic substrates and the natural substrate hemoglobin. Kinetic measurements suggest that the inhibition occurs through an noncompetitive allosteric mechanism, eliciting substrate inhibition. Smaller suramin analogues and those with substituted methyl groups also showed inhibition within the nanomolar range. Our results identify the suramin family as a potential starting point for the design of falcipain-2 inhibitor antimalarials that act through a novel inhibition mechanism.     

Circaseptan Rhythms of Semen Characteristics of a Brazilian Breed (“Mangalarga”) Stallion

We describe the semen characteristics of a 21-year old “mangalarga” stallion living under natural temperature and photoperiod conditions in São José do Rio Pardo, São Paulo, Brazil (latitude 21°36' S; longitude 46°53' W). The horse fed on natural pasture and a nutritionally balanced feed twice a day (11:00 and 17:00 h). Water and a mineral supplement were available “ad libitum”. Semen was collected for over 36 months (Oct 89-Dec 92) almost daily between 08:00 and 10:00 h by an artificial vagina and evaluated for volume of ejaculate, spermatozoa motility and concentration by standard procedures. Analysis of data from a total of 128-days was performed according to the Fast Fourier Transform Technique (FFT). Statistically significant periods of 7-day were demonstrated for volume, motility, and spermatozoa concentration. Circaseptan rhythms and, particularly, the circannual rhythm (already described in a previous publication) are probably related to ecological diversity and reproductive strategies.     

New Developments and Applications of the MP2RAGE Sequence - Focusing the Contrast and High Spatial Resolution R1 Mapping

MR structural T1-weighted imaging using high field systems (>3T) is severely hampered by the existing large transmit field inhomogeneities. New sequences have been developed to better cope with such nuisances. In this work we show the potential of a recently proposed sequence, the MP2RAGE, to obtain improved grey white matter contrast with respect to conventional T1-w protocols, allowing for a better visualization of thalamic nuclei and different white matter bundles in the brain stem. Furthermore, the possibility to obtain high spatial resolution (0.65 mm isotropic) R₁ maps fully independent of the transmit field inhomogeneities in clinical acceptable time is demonstrated. In this high resolution R₁ maps it was possible to clearly observe varying properties of cortical grey matter throughout the cortex and observe different hippocampus fields with variations of intensity that correlate with known myelin concentration variations.     

Selenium and mercury levels in rat liver slices co-treated with diphenyl diselenide and methylmercury

Organoseleno-compounds have been investigated for its beneficial effects against methylmercury toxicity. In this way, diphenyl diselenide (PhSe)₂ was demonstrated to decrease Hg accumulation in mice, protect against MeHg-induced mitochondrial dysfunction, and protect against the overall toxicity of this metal. In the present study we aimed to investigate if co-treatment with (PhSe)₂ and MeHg could decrease accumulation of Hg in liver slices of rats. Rat liver slices were co-treated with (PhSe)₂ (0.5; 5 µM) and/or MeHg (25 µM) for 30 min at 37 °C and Se and Hg levels were measured by inductively coupled plasma mass spectrometry (ICP-MS) in the slices homogenate, P1 fraction, mitochondria and incubation medium. Co-treatment with (PhSe)₂ and MeHg did not significantly alter Se levels in any of the samples when compared with compounds alone. In addition, co-treatment with (PhSe)₂ and MeHg did not decrease Hg levels in any of the samples tested, although, co-incubation significantly increased Hg levels in homogenate. We suggest here that (PhSe)₂ could exert its previously demonstrated protective effects not by reducing MeHg levels, but forming a complex with MeHg avoiding it to bind to critical molecules in cell.