High levels of T lymphocyte activation in Leishmania-HIV-1 co-infected individuals despite low HIV viral load

Background: Concomitant infections may influence HIV progression by causing chronic activation leading to decline in T-cell function. In the Americas, visceral (AVL) and tegumentary leishmaniasis (ATL) have emerged as important opportunistic infections in HIV-AIDS patients and both of those diseases have been implicated as potentially important co-factors in disease progression. We investigated whether leishmaniasis increases lymphocyte activation in HIV-1 co-infected patients. This might contribute to impaired cellular immune function. Methods: To address this issue we analyzed CD4(+) T absolute counts and the proportion of CD8(+) T cells expressing CD38 in Leishmania/HIV co-infected patients that recovered after anti-leishmanial therapy. Results: We found that, despite clinical remission of leishmaniasis, AVL co-infected patients presented a more severe immunossupression as suggested by CD4(+) T cell counts under 200 cells/mm(3), differing from ATL/HIV-AIDS cases that tends to show higher lymphocytes levels (over 350 cells/mm(3)). Furthermore, five out of nine, AVL/HIV-AIDS presented low CD4(+) T cell counts in spite of low or undetectable viral load. Expression of CD38 on CD8(+) T lymphocytes was significantly higher in AVL or ATL/HIV-AIDS cases compared to HIV/AIDS patients without leishmaniasis or healthy subjects. Conclusions: Leishmania infection can increase the degree of immune system activation in individuals concomitantly infected with HIV. In addition, AVL/HIV-AIDS patients can present low CD4(+) T cell counts and higher proportion of activated T lymphocytes even when HIV viral load is suppressed under HAART. This fact can cause a misinterpretation of these laboratorial markers in co-infected patients.

Incidence and risk factors of aplastic anemia in Latin American countries: the LATIN case-control study

Background Associations between aplastic anemia and numerous drugs, pesticides and chemicals have been reported. However, at least 50% of the etiology of aplastic anemia remains unexplained. Design and Methods This was a case-control, multicenter, multinational study, designed to identify risk factors for agranulocytosis and aplastic anemia. The cases were patients with diagnosis of aplastic anemia confirmed through biopsy or bone marrow aspiration, selected through an active search of clinical laboratories, hematology clinics and medical records. The controls did not have either aplastic anemia or chronic diseases. A total of 224 patients with aplastic anemia were included in the study, each case was paired with four controls, according to sex, age group, and hospital where the case was first seen. Information was collected on demographic data, medical history, laboratory tests, medications, and other potential risk factors prior to diagnosis. Results The incidence of aplastic anemia was 1.6 cases per million per year. Higher rates of benzene exposure (>= 30 exposures per year) were associated with a greater risk of aplastic anemia (odds ratio, OR: 4.2; 95% confidence interval, CI: 1.82-9.82). Individuals exposed to chloramphenicol in the previous year had an adjusted OR for aplastic anemia of 8.7 (CI: 0.87-87.93) and those exposed to azithromycin had an adjusted OR of 11.02 (CI 1.14-108.02). Conclusions The incidence of aplastic anemia in Latin America countries is low. Although the research study centers had a high coverage of health services, the underreporting of cases of aplastic anemia in selected regions can be discussed. Frequent exposure to benzene-based products increases the risk for aplastic anemia. Few associations with specific drugs were found, and it is likely that some of these were due to chance alone.

Near full-length genome analysis of low prevalent human immunodeficiency virus type 1 subclade F1 in Sao Paulo, Brazil

Background: The genetic diversity of the human immunodeficiency virus type 1 (HIV-1) is critical to lay the groundwork for the design of successful drugs or vaccine. In this study we aimed to characterize and define the molecular prevalence of HIV-1 subclade F1 currently circulating in Sao Paulo, Brazil. Methods: A total of 36 samples were selected from 888 adult patients residing in Sao Paulo who had previously been diagnosed in two independent studies in our laboratory as being infected with subclade F1 based on pol subgenomic fragment sequencing. Proviral DNA was amplified from the purified genomic DNA of all 36 blood samples by 5 fragments overlapping PCR followed by direct sequencing. Sequence data were obtained from the 5 fragments of pure subclade F1 and phylogenetic trees were constructed and compared with previously published sequences. Subclades F1 that exhibited mosaic structure with other subtypes were omitted from any further analysis Results: Our methods of fragment amplification and sequencing confirmed that only 5 sequences inferred from pol region as subclade F1 also holds true for the genome as a whole and, thus, estimated the true prevalence at 0.56%. The results also showed a single phylogenetic cluster of the Brazilian subclade F1 along with non-Brazilian South American isolates in both subgenomic and the full-length genomes analysis with an overall intrasubtype nucleotide divergence of 6.9%. The nucleotide differences within the South American and Central African F1 strains, in the C2-C3 env, were 8.5% and 12.3%, respectively. Conclusion: All together, our findings showed a surprisingly low prevalence rate of subclade F1 in Brazil and suggest that these isolates originated in Central Africa and subsequently introduced to South America.

IL-17 Produced during Trypanosoma cruzi Infection Plays a Central Role in Regulating Parasite-Induced Myocarditis

Background: Chagas disease is a neglected disease caused by the intracellular parasite Trypanosoma cruzi. Around 30% of the infected patients develop chronic cardiomyopathy or megasyndromes, which are high-cost morbid conditions. Immune response against myocardial self-antigens and exacerbated Th1 cytokine production has been associated with the pathogenesis of the disease. As IL-17 is involved in the pathogenesis of several autoimmune, inflammatory and infectious diseases, we investigated its role during the infection with T. cruzi. Methodology/Principal Findings: First, we detected significant amounts of CD4, CD8 and NK cells producing IL-17 after incubating live parasites with spleen cells from normal BALB/c mice. IL-17 is also produced in vivo by CD4(+), CD8(+) and NK cells from BALB/c mice on the early acute phase of infection. Treatment of infected mice with anti-mouse IL-17 mAb resulted in increased myocarditis, premature mortality, and decreased parasite load in the heart. IL-17 neutralization resulted in increased production of IL-12, IFN-gamma and TNF-alpha and enhanced specific type 1 chemokine and chemokine receptors expression. Moreover, the results showed that IL-17 regulates T-bet, ROR gamma t and STAT-3 expression in the heart, showing that IL-17 controls the differentiation of Th1 cells in infected mice. Conclusion/Significance: These results show that IL-17 controls the resistance to T. cruzi infection in mice regulating the Th1 cells differentiation, cytokine and chemokine production and control parasite-induced myocarditis, regulating the influx of inflammatory cells to the heart tissue. Correlations between the levels of IL-17, the extent of myocardial destruction, and the evolution of cardiac disease could identify a clinical marker of disease progression and may help in the design of alternative therapies for the control of chronic morbidity of chagasic patients.

Hantavirus Pulmonary Syndrome, Central Plateau, Southeastern, and Southern Brazil

Hantavirus pulmonary syndrome (HPS) is an increasing health problem in Brazil because of encroachment of sprawling urban, agricultural, and cattle-raising areas into habitats of subfamily Sigmodontinae rodents, which serve as hantavirus reservoirs. From 1993 through June 2007, a total of 884 cases of HIPS were reported in Brazil (case-fatality rate 39%). To better understand this emerging disease, we collected 89 human serum samples and 68 rodent lung samples containing antibodies to hantavirus from a 2,500-km-wide area in Brazil. RNA was isolated from human samples and rodent lung tissues and subjected to reverse transcription-PCR. Partial sequences of nucleocapsid protein and glycoprotein genes from 22 human and 16 rodent sources indicated only Araraquara virus and Juquitiba virus lineages. The case-fatality rate of HPS was higher in the area with Araraquara virus. This virus, which may be the most virulent hantavirus in Brazil, was associated with areas that have had greater anthropogenic changes.

Central nitrergic system regulation of neuroendocrine secretion, fluid intake and blood pressure induced by angiotensin-II

Background: Nitric oxide (NO) synthesis has been described in several circumventricular and hypothalamic structures in the central nervous system that are implicated in mediating central angiotensin-II (ANG-II) actions during water deprivation and hypovolemia. Neuroendocrine and cardiovascular responses, drinking behavior, and urinary excretions were examined following central angiotensinergic stimulation in awake freely-moving rats pretreated with intracerebroventricular injections of N omega-nitro-L-arginine methyl ester (L-NAME, 40 mu g), an inhibitor of NO synthase, and L-arginine (20 ug), a precursor of NO. Results: Injections of L-NAME or ANG-II produced an increase in plasma vasopressin (VP), oxytocin (OT) and atrial natriuretic peptide (ANP) levels, an increase in water and sodium intake, mean arterial blood pressure and sodium excretion, and a reduction of urinary volume. L-NAME pretreatment enhanced the ANG-II response, while L-arginine attenuated VP and OT release, thirst, appetite for sodium, antidiuresis, and natriuresis, as well as pressor responses induced by ANG-II. Discussion and conclusion: Thus, the central nitrergic system participates in the angiotensinergic responses evoked by water deprivation and hypovolemia to refrain neurohypophysial secretion, hydromineral balance, and blood pressure homeostasis.

Size at birth and lipoprotein concentrations in adulthood: two prospective studies in Latin American cities

Background The relationship between birth weight and plasma lipoproteins is inconsistent. Aims To assess the association between birth weight and (1) body mass index (BMI) at birth and (2) lipoproteins in young adults, and also to explore the possible effect of current obesity as a possible effect modifier. Methods Two prospective studies based on representative samples of subjects born in the 1970s were carried out in Ribeirao Preto, Brazil (n = 2063) and Limache, Chile (n = 999). The surveys were carried out between 2001 and 2004. Results Mean birth weights were 3267 g and 3177 g and mean adult BMIs were 24.3 kg/m(2) and 25.8 kg/m(2) in the Brazilian and Chilean samples, respectively. Total adult cholesterol was 4.57 mmol/l in Chileans, 0.26 mmol/l higher than in Brazilians (p < 0.001). The main finding was an interaction between adult obesity (BMI 30 or over) and birth weight and also BMI at birth and low-density lipoprotein (LDL) and total cholesterol. A birth-weight increment of 1 kg was associated with a decrease in total cholesterol (-0.374 mmol/l, 95% CI -0.567 to -0.181) and LDL (-0.304 mmol/l (-0.479 to -0.129) in obese participants only. These associations persisted after allowing for gestational age in a smaller sample. This finding was consistent in separate analyses in the Brazilian and Chilean samples. No associations were found in relation to high-density lipoprotein and triglyceride concentrations. Conclusion The results suggest that those who were of low birth weight and are obese are more likely to have high cholesterol and LDL concentrations. Thus preventing obesity may be especially rewarding in subjects with a low birth weight.

First Report of the Isolation and Molecular Characterization of Rickettsia amblyommii and Rickettsia felis in Central America

During 2010, 15 adult ticks, identified as Amblyomma cajennense, were collected from horses in Cahuita and Turrialba districts, whereas 7 fleas, identified as Ctenocephalides felis, were collected from a dog in San Jose city, Costa Rica. In the laboratory, three A. cajennense specimens, two from Cahuita and one from Turrialba, were individually processed for rickettsial isolation in cell culture, as was a pool of seven fleas. Rickettsiae were successfully isolated and established in Vero cell culture from the three ticks and from a pool of seven fleas in C6/36 cell culture. The three tick isolates were genotypically identified as Rickettsia amblyommii, and the flea isolate was identified as Rickettsia felis through DNA sequencing of portions of the rickettsial genes gltA, ompA, and ompB of each isolate. In addition, other seven ticks were shown to contain rickettsial DNA. Polymerase chain reaction products of at least two of these ticks were sequenced and also showed to correspond to R. amblyommii. Overall, 66.7% (10/15) of the A. cajennense adult ticks were found to be infected with rickettsiae. This is the first report of a successful isolation in cell culture of R. amblyommii and R. felis from Central America.

Allopatric speciation in ticks: genetic and reproductive divergence between geographic strains of Rhipicephalus (Boophilus) microplus

Background: The cattle tick, Rhipicephalus (Boophilus) microplus, economically impact cattle industry in tropical and subtropical regions of the world. The morphological and genetic differences among R. microplus strains have been documented in the literature, suggesting that biogeographical and ecological separation may have resulted in boophilid ticks from America/Africa and those from Australia being different species. To test the hypothesis of the presence of different boophilid species, herein we performed a series of experiments to characterize the reproductive performance of crosses between R. microplus from Australia, Africa and America and the genetic diversity of strains from Australia, Asia, Africa and America. Results: The results showed that the crosses between Australian and Argentinean or Mozambican strains of boophilid ticks are infertile while crosses between Argentinean and Mozambican strains are fertile. These results showed that tick strains from Africa (Mozambique) and America (Argentina) are the same species, while ticks from Australia may actually represent a separate species. The genetic analysis of mitochondrial 12S and 16S rDNA and microsatellite loci were not conclusive when taken separately, but provided evidence that Australian tick strains were genetically different from Asian, African and American strains. Conclusion: The results reported herein support the hypothesis that at least two different species share the name R. microplus. These species could be redefined as R. microplus (Canestrini, 1887) (for American and African strains) and probably the old R. australis Fuller, 1899 (for Australian strains), which needs to be redescribed. However, experiments with a larger number of tick strains from different geographic locations are needed to corroborate these results.

Molecular and geographic analyses of vampire bat-transmitted cattle rabies in central Brazil

Background: Vampire bats are important rabies virus vectors, causing critical problems in both the livestock industry and public health sector in Latin America. In order to assess the epidemiological characteristics of vampire bat-transmitted rabies, the authors conducted phylogenetic and geographical analyses using sequence data of a large number of cattle rabies isolates collected from a wide geographical area in Brazil. Methods: Partial nucleoprotein genes of rabies viruses isolated from 666 cattle and 18 vampire bats between 1987 and 2006 were sequenced and used for phylogenetic analysis. The genetic variants were plotted on topographical maps of Brazil. Results: In this study, 593 samples consisting of 24 genetic variants were analyzed. Regional localization of variants was observed, with the distribution of several variants found to be delimited by mountain ranges which served as geographic boundaries. The geographical distributions of vampire-bat and cattle isolates that were classified as the identical phylogenetic group were found to overlap with high certainty. Most of the samples analyzed in this study were isolated from adjacent areas linked by rivers. Conclusion: This study revealed the existence of several dozen regional variants associated with vampire bats in Brazil, with the distribution patterns of these variants found to be affected by mountain ranges and rivers. These results suggest that epidemiological characteristics of vampire bat-related rabies appear to be associated with the topographical and geographical characteristics of areas where cattle are maintained, and the factors affecting vampire bat ecology.

Tooth Movement Activates the Central Amygdala and the Lateral Hypothalamus by the Magnitude of the Force Applied

Objective: To determine if the magnitude of the force used to induce incisor tooth movement promotes distinct activation in cells in the central amygdala (CEA) and lateral hypothalamus (LH) of rats. Also, the effect of morphine on Fos immunoreactivity (Fos-IR) was investigated in these nuclei. Materials and Methods: Adult male rats were anesthetized and divided into six groups: only anesthetized (control), without orthodontic appliance (OA), OA but without force, OA activated with 30g or 70g, OA with 70g in animals pretreated with morphine (2 mg/kg, intraperitoneal). Three hours after the onset of the experiment the rats were reanesthetized and perfused with 4% paraformaldehyde. The brains were removed and fixed, and sections containing CEA and LH were processed for Fos protein immunohistochemistry. Results: The results show that in the control group, the intramuscular injection of a ketamine/xylazine mixture did not induce Fos-IR cells in the CEA or in the LH. Again, the without force group showed a little Fos-IR. However, in the 70g group the Fos-IR was the biggest observed (P < .05, Tukey) in the CEA and LH compared with the other groups. In the 30g group, the Fos-IR did not differ from the control group, the without OA group, and the without force group. Furthermore, pretreatment with morphine in the 70g group reduced Fos-IR in these regions. Conclusions: Tooth movement promotes Fos-IR in the CEA and LH according to the magnitude of the force applied. (Angle Orthod. 2010;80:111-115.)

Placentation in Sigmodontinae: a rodent taxon native to South America

Background: Sigmodontinae, known as ""New World rats and mice,"" is a large subfamily of Cricetidae for which we herein provide the first comprehensive investigation of the placenta. Methods: Placentas of various gestational ages ranging from early pregnancy to near term were obtained for five genera, i.e. Necromys, Euryoryzomys, Cerradomys, Hylaeamys, and Oligoryzomys. They were investigated by means of histology, immunohistochemistry, a proliferation marker, DBA-lectin staining and transmission electron microscopy. Results: The chorioallantoic placenta was organized in a labyrinthine zone, spongy zone and decidua and an inverted yolk sac persisted until term. The chorioallantoic placenta was hemotrichorial. The interhemal barrier comprised fetal capillary endothelium and three layers of trophoblast, an outermost, cellular layer and two syncytial ones, with interspersed trophoblast giant cells (TGC). In addition, accumulations of TGC occurred below Reichert's membrane. The junctional zone contained syncytial trophoblast, proliferative cellular trophoblast, glycogen cells and TGC that were situated near to the maternal blood channels. In three of the genera, TGC were also accumulated in distinct areas at the placental periphery. PAS-positive glycogen cells derived from the junctional zone invaded the decidua. Abundant maternal uNK cells with positive response to PAS, vimentin and DBA-lectin were found in the decidua. The visceral yolk sac was completely inverted and villous. Conclusion: The general aspect of the fetal membranes in Sigmodontinae resembled that found in other cricetid rodents. Compared to murid rodents there were larger numbers of giant cells and in some genera these were seen to congregate at the periphery of the placental disk. Glycogen cells were found to invade the decidua but we did not identify trophoblast in the walls of the deeper decidual arteries. In contrast these vessels were surrounded by large numbers of uNK cells. This survey of wild-trapped specimens from five genera is a useful starting point for the study of placentation in an important subfamily of South American rodents. We note, however, that some of these rodents can be captive bred and recommend that future studies focus on the study of time dated pregnancies.

The role of the observed tropical convection in the generation of frost events in the southern cone of South America

Based on previous results obtained from observations and linear wave theory analysis, the hypothesis that large-scale patterns can generate extreme cold events in southeast South America through the propagation of remotely excited Rossby waves was already suggested. This work will confirm these findings and extend their analysis through a series of numerical experiments using a primitive equation model where waves are excited by a thermal forcing situated in positions chosen according to observed convection anomalies over the equatorial region. The basic state used for these experiments is a composite of austral winters with maximum and minimum frequency of occurrence of generalized frosts that can affect a large area known as the Wet Pampas located in the central and eastern part of Argentina. The results suggest that stationary Rossby waves may be one important mechanism linking anomalous tropical convection with the extreme cold events in the Wet Pampas. The combination of tropical convection and a specific basic state can generate the right environment to guide the Rossby waves trigged by the tropical forcing towards South America. Depending on the phase of the waves entering the South American continent, they can favour the advection of anomalous wind at low levels from the south carrying cold and dry air over the whole southern extreme of the continent, producing a generalized frost in the Wet Pampa region. On the other hand, when a basic state based on the composites of minimum frosts is used, an anomalous anticyclone over the southern part of the continent generates a circulation with a south-southeast wind which brings maritime air and therefore humidity over the Wet Pampas region, creating negative temperature anomalies only over the northeastern part of the region. Under these conditions even if frosts occur they would not be generalized, as observed for the other basic state with maximum frequency of occurrence of generalized frosts.

Fossil groups in the Millennium Simulation Evolution of the brightest galaxies

Aims. We create a catalogue of simulated fossil groups and study their properties, in particular the merging histories of their first-ranked galaxies. We compare the simulated fossil group properties with those of both simulated non-fossil and observed fossil groups. Methods. Using simulations and a mock galaxy catalogue, we searched for massive (>5 x 10(13) h(-1) M-circle dot) fossil groups in the Millennium Simulation Galaxy Catalogue. In addition, we attempted to identify observed fossil groups in the Sloan Digital Sky Survey Data Release 6 using identical selection criteria. Results. Our predictions on the basis of the simulation data are: (a) fossil groups comprise about 5.5% of the total population of groups/clusters with masses larger than 5 x 10(13) h(-1) M-circle dot. This fraction is consistent with the fraction of fossil groups identified in the SDSS, after all observational biases have been taken into account; (b) about 88% of the dominant central objects in fossil groups are elliptical galaxies that have a median R-band absolute magnitude of similar to-23.5-5 log h, which is typical of the observed fossil groups known in the literature; (c) first-ranked galaxies of systems with M > 5 x 10(13) h(-1) M-circle dot, regardless of whether they are either fossil or non-fossil, are mainly formed by gas-poor mergers; (d) although fossil groups, in general, assembled most of their virial masses at higher redshifts in comparison with non-fossil groups, first-ranked galaxies in fossil groups merged later, i.e. at lower redshifts, compared with their non-fossil-group counterparts. Conclusions. We therefore expect to observe a number of luminous galaxies in the centres of fossil groups that show signs of a recent major merger.

Age distribution of the central stars of galactic disk planetary nebulae

Context. Determination of the ages of central stars of planetary nebulae (CSPN) is a complex problem, and there is presently no single method that can be generally applied. We have developed several methods of estimating the ages of CSPN, based on both the observed nebular properties and some properties of the stars themselves. Aims. Our aim is to estimate the ages and the age distribution of CSPN and to compare the derived results with mass and age determinations of CSPN and white dwarfs based on empirical determinations of these quantities. Methods. We considered a sample of planetary nebulae in the galactic disk, most of which (similar to 69%) are located in the solar neighbourhood, within 3 kpc from the Sun. We discuss several methods of deriving the age distribution of CSPN, namely; (i) the use of an age-metallicity relation that also depends on the galactocentric distance; (ii) the use of an age-metallicity relation obtained for the galactic disk; and (iii) the determination of ages from the central star masses obtained from the observed nitrogen abundances. Results. We estimated the age distribution of CSPN with average uncertainties of 1-2 Gyr, and compared our results with the expected distribution based both on the observed mass distribution of white dwarfs and on the age distribution derived from available mass distributions of CSPN. Based on our derived age distributions, we conclude that most CSPN in the galactic disk have ages under 6 Gyr, and that the age distribution is peaked around 2-4 Gyr.