Duality of the murine CD8 compartment.

CD8αβ plays crucial roles in the thymic selection, differentiation, and activation of some, but not all, CD8(+) T cells, whereas CD8αα does not. To investigate these roles, we produced mice that expressed transgene P14 T-cell receptor β (TCRβ) chain and CD8β or did not (WT and KO mice, respectively). The primary CD8(+) T-cell response to acute lymphocytic choriomeningitis virus (LCMV) infection was predominantly D(b)/GP33 specific and CD8 independent in KO mice and was mostly CD8 dependent in WT mice. Cytotoxic T lymphocytes (CTL) from KO mice failed to mobilize intracellular Ca(2+) and to kill via perforin/granzyme. Their strong Fas/FasL-mediated cytotoxicity and IFN-γ response were signaled via a Ca(2+)-independent, PI3K-dependent pathway. This was also true for 15-20% of CD8-independent CTL found in WT mice. Conversely, the perforin/granzyme-mediated killing and IFN-γ response of CD8-dependent CTL were signaled via a Ca(2+), p56(lck), and nuclear factor of activated T cells-dependent pathway. Deep sequencing of millions of TCRα chain transcripts revealed that the TCR repertoires of preimmune CD8(+) T cells were highly diverse, but those of LCMV D(b)/GP33-specific CTL, especially from KO mice, were narrow. The immune repertoires exhibited biased use of Vα segments that encoded different complementary-determining region 1α (CDR1α) and CDR2α sequences. We suggest that TCR from WT CD8-independent T cells may engage MHC-peptide complexes in a manner unfavorable for efficient CD8 engagement and Ca(2+) signaling but permissive for Ca(2+)-independent, PI3K-dependent signaling. This duality of the CD8 compartment may provide organisms with broader protective immunity.

Infectious diseases not immune to genome-wide association.

Two genome-wide association studies for meningococcal disease and tuberculosis identify new loci associated with susceptibility to these infectious diseases. They highlight a role for the acquired and innate immune systems in host control of several human pathogens and demonstrate that denser genotyping platforms and population-specific reference panels are necessary for genetic studies in African populations.

Immune response to the mumps component of the MMR vaccine in the routine of immunisation services in the Brazilian National Immunisation Program

A non-controlled longitudinal study was conducted to evaluate the combined vaccine against measles, mumps and rubella (MMR) immunogenicity in 150 children vaccinated in the routine of three health units in the city of Rio de Janeiro, Brazil, 2008-2009, without other vaccines administered during the period from 30 days before to 30 days after vaccination. A previous study conducted in Brazil in 2007, in 1,769 children ranging from 12-15 months of age vaccinated against yellow fever and MMR simultaneously or at intervals of 30 days or more between doses, had shown low seroconversion for mumps regardless of the interval between administration of the two vaccines. The current study showed 89.5% (95% confidence interval: 83.3; 94.0) seroconversion rate for mumps. All children seroconverted for measles and rubella. After revaccination, high antibody titres and seroconversion rates were achieved against mumps. The results of this study and others suggest that two MMR doses confer optimal immunoresponses for all three antigens and the possible need for additional doses should be studied taking into account not only serological, but also epidemiological data, as there is no serological correlate of protection for mumps.

Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil

Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of partners greater than three (p = 0.002), CD4+ lymphocyte count < 200/mm3 (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%), low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.

Molecular characterization of signalling complexes involved in G-protein coupled receptor-induced cardiac hypertrophy

In response to pathological stresses, the heart undergoes a remodelling process associated with cardiac hypertrophy. Since sustained hypertrophy can progress to heart failure, there is an intense investigation about the intracellular signalling pathways that control cardiomyocyte growth. Accumulating evidence has demonstrated that most stimuli known to initiate pathological changes associated with the development of cardiac hypertrophy activate G protein-coupled receptors (GPCRs) including the αl-adrenergic- (αl-AR), Angiotensin II- (AT-R) and endothelin-1- (ET-R) receptors. In this context, we have previously identified a cardiac scaffolding protein, called AKAP-Lbc (Α-kinase anchoring protein), with an intrinsic Rho specific guanine nucleotide exchange factor activity, that plays a key role in integrating and transducing hypertrophic signals initiated by these GPCRs (Appert-Collin, Cotecchia et al. 2007). Activated RhoA controls the transcriptional activation of genes involved in cardiomyocyte hypertrophy through signalling pathways that remain to be characterized. Here, we identified the nuclear factor-Kappa Β (NF-κΒ) activating kinase ΙΚΚβ as a novel AKAP-Lbc interacting protein. This raises the hypothesis that AKAP-Lbc might promote cardiomyocyte growth by maintaining a signalling complex that promotes the activation of the pro-hypertrophic transcription factor NF-κΒ. In fact, the activation of NF- κΒ-dependent transcription has been detected in numerous disease contexts, including hypertrophy, ischemia/reperfusion injury, myocardial infarction, allograft rejection, myocarditis, apoptosis, and more (Hall, Hasday et al. 2006). While it is known by more than a decade that NF-κΒ is a critical mediator of cardiac hypertrophy, it is currently poorly understood how pro-hypertrophic signals controlling NF-κΒ transcriptional activity are integrated and coordinated within cardiomyocytes. In this study, we show that AKAP-Lbc and ΙΚΚβ form a transduction complex in cardiomyocytes that couples activation of αl-ARs to NF-κB-mediated transcriptional reprogramming events associated with cardiomyocyte hypertrophy. In particular, we can show that activation of ΙΚΚβ within the AKAP-Lbc complex promotes NF-κB-dependent production of interleukine-6 (IL-6), which, in turn, enhances foetal gene expression. These findings indicate that the AKAP-Lbc/ΙΚΚβ complex is critical for selectively directing catecholamine signals to the induction of cardiomyocyte hypertrophy.

A dynamic view of hepatitis C virus replication complexes.

Hepatitis C virus (HCV) replicates its genome in a membrane-associated replication complex (RC). Specific membrane alterations, designated membranous webs, represent predominant sites of HCV RNA replication. The principles governing HCV RC and membranous web formation are poorly understood. Here, we used replicons harboring a green fluorescent protein (GFP) insertion in nonstructural protein 5A (NS5A) to study HCV RCs in live cells. Two distinct patterns of NS5A-GFP were observed. (i) Large structures, representing membranous webs, showed restricted motility, were stable over many hours, were partitioned among daughter cells during cell division, and displayed a static internal architecture without detectable exchange of NS5A-GFP. (ii) In contrast, small structures, presumably representing small RCs, showed fast, saltatory movements over long distances. Both populations were associated with endoplasmic reticulum (ER) tubules, but only small RCs showed ER-independent, microtubule (MT)-dependent transport. We suggest that this MT-dependent transport sustains two distinct RC populations, which are both required during the HCV life cycle.

Jasmonate signaling pathway.

Jasmonates in plants are cyclic fatty acid-derived regulators structurally similar to prostaglandins in metazoans. These chemicals mediate many of plants' transcriptional responses to wounding and pathogenesis by acting as potent regulators for the expression of numerous frontline immune response genes, including those for defensins and antifungal proteins. Additionally, the pathway is critical for fertility. Ongoing genetic screens and protein-protein interaction assays are identifying components of the canonical jasmonate signaling pathway. A massive molecular machine, based on two multiprotein complexes, SCF(COI1) and the COP9 signalosome (CNS), plays a central role in jasmonate signaling. This machine functions in vivo as a ubiquitin ligase complex, probably targeting regulatory proteins, some of which are expected to be transcriptional repressors. Some defense-related mediators, notably salicylic acid, antagonize jasmonates in controlling the expression of many genes. In Arabidopsis, NONEXPRESSOR OF PR GENES (NPR1) mediates part of this interaction, with another layer of control provided further downstream by the mitogen-activated protein kinase (MAPK) homolog MPK4. Numerous other interpathway connections influence the jasmonate pathway. Insights from Arabidopsis have shown that an allele of the auxin signaling gene AXR1, for example, reduces the sensitivity of plants to jasmonate. APETALA2 (AP2)-domain transcription factors, such as ETHYLENE RESPONSE FACTOR 1 (ERF1), link the jasmonate pathway to the ethylene signaling pathway. As progress in characterizing several new mutants (some of which are hypersensitive to jasmonic acid) augments our understanding of jasmonate signaling, the Connections Map will be updated to include this new information.

The TcI and TcII Trypanosoma cruzi experimental infections induce distinct immune responses and cardiac fibrosis in dogs

Trypanosoma cruzi infection may be caused by different strains with distinct discrete typing units (DTUs) that can result in variable clinical forms of chronic Chagas disease. The present study evaluates the immune response and cardiac lesions in dogs experimentally infected with different T. cruzi strains with distinct DTUs, namely, the Colombian (Col) and Y strains of TcI and TcII DTU, respectively. During infection with the Col strain, increased levels of alanine aminotransferase, erythrocytes, haematocrit and haemoglobin were observed. In addition, CD8+ T-lymphocytes isolated from the peripheral blood produced higher levels of interleukin (IL)-4. The latter suggests that during the acute phase, infection with the Col strain may remain unnoticed by circulating mononuclear cells. In the chronic phase, a significant increase in the number of inflammatory cells was detected in the right atrium. Conversely, infection with the Y strain led to leucopoenia, thrombopoenia, inversion of the ratio of CD4+/CD8+ T-lymphocytes and alterations in monocyte number. The Y strain stimulated the production of interferon-γ by CD4+ and CD8+ T-lymphocytes and IL-4 by CD8+ T-cells. In the chronic phase, significant heart inflammation and fibrosis were observed, demonstrating that strains of different DTUs interact differently with the host.

Genetic variability in G2 and F2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure

Human respiratory syncytial virus (HRSV) is an important respiratory pathogens among children between zero-five years old. Host immunity and viral genetic variability are important factors that can make vaccine production difficult. In this work, differences between biological clones of HRSV were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. Viral clones were selected by plaque assay in the absence and presence of serum and nucleotide sequences of the G2 and F2 genes of HRSV biological clones were compared. One non-synonymous mutation was found in the F gene (Ile5Asn) in one clone of an HRSV-B sample and one non-synonymous mutation was found in the G gene (Ser291Pro) in four clones of the same HRSV-B sample. Only one of these clones was obtained after treatment with the child's serum. In addition, some synonymous mutations were determined in two clones of the HRSV-A samples. In conclusion, it is possible that minor sequences could be selected by host antibodies contributing to the HRSV evolutionary process, hampering the development of an effective vaccine, since we verify the same codon alteration in absence and presence of human sera in individual clones of BR-85 sample.

Strength and cost of an induced immune response are associated with a heritable melanin-based colour trait in female tawny owls.

1. Melanin pigments provide the most widespread source of coloration in vertebrates, but the adaptive function of such traits remains poorly known. 2. In a wild population of tawny owls (Strix aluco), we investigated the relationships between plumage coloration, which varies continuously from dark to pale reddish, and the strength and cost of an induced immune response. 3. The degree of reddishness in tawny owl feather colour was positively correlated with the concentration of phaeomelanin and eumelanin pigments, and plumage coloration was highly heritable (h(2) = 0.93). No carotenoids were detected in the feathers. 4. In mothers, the degree of melanin-based coloration was associated with antibody production against a vaccine, with dark reddish females maintaining a stronger level of antibody for a longer period of time compared to pale reddish females, but at a cost in terms of greater loss of body mass. 5. A cross-fostering experiment showed that, independent of maternal coloration, foster chicks reared by vaccinated mothers were lighter than those reared by nonvaccinated mothers. Hence, even though dark reddish mothers suffered a stronger immune cost than pale reddish mothers, this asymmetric cost was not translated to offspring growth. 6. Our study suggests that different heritable melanin-based colorations are associated with alternative strategies to resist parasite attacks, with dark reddish individuals investing more resources towards the humoral immune response than lightly reddish conspecifics.

Fab antibodies capable of blocking T cells by competitive binding have the identical specificity but a higher affinity to the MHC-peptide-complex than the T cell receptor.

In transplant rejection, graft versus host or autoimmune diseases T cells are mediating the pathophysiological processes. Compared to unspecific pharmacological immune suppression specific inhibition of those T cells, that are involved in the disease, would be an alternative and attractive approach. T cells are activated after their T cell receptor (TCR) recognizes an antigenic peptide displayed by the Major Histocompatibility Complex (MHC). Molecules that interact with MHC-peptide-complexes in a specific fashion should block T cells with identical specificity. Using the model of the SSX2 (103-111)/HLA-A*0201 complex we investigated a panel of MHC-peptide-specific Fab antibodies for their capacity blocking specific T cell clones. Like TCRs all Fab antibodies reacted with the MHC complex only when the SSX2 (103-111) peptide was displayed. By introducing single amino acid mutations in the HLA-A*0201 heavy chain we identified the K66 residue as the most critical binding similar to that of TCRs. However, some Fab antibodies did not inhibit the reactivity of a specific T cell clone against peptide pulsed, artificial targets, nor cells displaying the peptide after endogenous processing. Measurements of binding kinetics revealed that only those Fab antibodies were capable of blocking T cells that interacted with an affinity in the nanomolar range. Fab antibodies binding like TCRs with affinities on the lower micromolar range did not inhibit T cell reactivity. These results indicate that molecules that block T cells by competitive binding with the TCR must have the same specificity but higher affinity for the MHC-peptide-complex than the TCR.

The role of nonhematopoietic MHC class II expression in immune responses and tolerance

Si les rôles fonctionnels de diverses cellules immunitaires infiltrant des tissus enflammés sont assez bien compris, par contre, étonnamment, on connaît bien moins la capacité des cellules non hématopoïétiques résidant dans des tissus, à moduler l'activité biologique des cellules immunitaires immigrantes, et donc le résultat de la réponse immunitaire. La présentation des antigènes, dans le contexte des molécules du CMH de classe II (CMHII) à la surface des cellules présentatrices d'antigènes (CPA) professionnelles à une sous- population de lymphocytes T, est cruciale pour le développement des réponses immunitaires protectives spécifiques de l'antigène. En général, l'expression de CMHII est réservée aux CPAs. Toutefois, au cours des pathologies inflammatoires spécifiques d'organe, telles que l'auto-immunité ou la maladie inflammatoire de l'intestin, l'expression de CMHII est également induite par la cytokine interféron (IFN)-y sur des cellules non hématopoïétiques qui résident dans des tissus enflammés. Les conséquences de ce phénomène sont encore peu comprises. Dans cette étude, nous avons utilisé une souche de souris génétiquement modifiées, qui n'a pas la capacité d'induire l'expression de CMHII sur les cellules non hématopoïétiques, mais a maintenu la régulation normale d'expression de CMHII sur les cellules hématopoïétiques. Nous avons appliqué ces souris à différents modèles d'inflammation intestinale et à un modèle de maladie qui imite la maladie auto-immune de l'inflammation du muscle cardiaque (myocardite) chez l'homme. Nous avons pu montrer que, au cours de l'inflammation intestinale, l'expression du CMHII nonhématopoïétique, ou encore l'expression du CMHII par les cellules épithéliales de l'intestin, confère une protection contre la maladie, en réduisant les cellules immunitaires inflammatoires et en augmentant les cellules Τ régulatrices anti-inflammatoires. Ces résultats pourraient expliquer l'échec des traitements d'anti-IFN-γ dans les maladies intestinales inflammatoires chez l'homme. En revanche, dans la myocardite auto-immune, nos résultats indiquent que la présentation d'antigènes par les cellules non hématopoïétiques du coeur est nécessaire pour l'apparition de la pathologie cardiaque, comme nos souris sont résistantes à la maladie. Toutefois, cela n'est pas dû à un défaut d'activation des lymphocytes T, car les lymphocytes Τ des souris mutantes sont parfaitement capables de promouvoir la maladie après le transfert adoptif dans des animaux de type naturel. Nos résultats suggèrent que, durant les maladies inflammatoires spécifiques d'organe, la présentation d'antigène par des cellules non hématopoïétiques module et contribue au résultat de la réponse immunitaire d'une manière opposée, conférant soit la protection contre la maladie ou sa promotion. Nos résultats pourraient ouvrir la voie à des thérapies qui prennent en compte la contribution de la présentation d'antigènes par les cellules non hématopoïétiques, au cours des maladies inflammatoires spécifiques d'organe. - Les molécules du CMH de classe II (CMHII) sont fondamentales pour la présentation des antigènes aux lymphocytes Τ CD4+, car elles permettent le développement des réponses immunitaires spécifiques de l'antigène. Il est largement admis que l'expression de CMHII est réservée aux cellules présentatrices d'antigènes (CPA). Cependant, dans des conditions inflammatoires, l'expression de CMHII est en principe également induite par l'interféron (IFN)-y sur les cellules non hématopoïétiques, telles que les cellules épithéliales et les cardiomyocytes. Une controverse existe jusqu'à présent au sujet de la fonction de cette présentation d'antigènes non professionnelle, pour savoir si elle favorise la tolérance ou l'immunité dépendante des lymphocytes Τ in vivo. Pour répondre à cette question, nous avons testé des souris qui ne sont pas capables d'induire l'expression du CMHII sur les cellules non hématopoïétiques (souris PIV-/- K14 CIITA Tg) parmi différents modèles murins de pathologies inflammatoires, à savoir les modèles de vaccination pour induire des réponses spécifiques d'antigènes des lymphocytes B, plusieurs modèles de colite et un modèle de myocardite auto-immune expérimental (EAM). Pour cela, nous avons administré à ces souris un modèle de colite atténuée, induite par une infection chronique à Helicobacter hepaticus et par l'administration d'anticorps monoclonaux bloquant le récepteur de l'interleukine (IL)-10 (anti-IL-10R). Dans ce système, nous avons pu observer que l'expression abrogée de CMHII a aggravé la colite bactérienne, soit par les cellules non hématopoïétiques, soit exclusivement par les cellules épithéliales intestinales (CEI) dans un autre modèle murin (souris plV_fl/fl vil-Cre Tg). Ce phénotype du côlon a été associé à une augmentation des fréquences de cellules immunitaires innées, de lymphocytes Th1 CD4+, et d'expression des cytokines et de chimiokines pro-inflammatoires, y compris l'IFN-γ. Notamment, l'expression défectueuse de CMHII non hématopoïétique a également réduit les cellules Τ régulatrices (Treg) Forkhead box P3 (FoxP3)+, sans influencer les fréquences des cellules innées lymphoïdes et des cellules Th17. Ces résultats suggèrent un rôle tolérogène de CEIs CMHII+ qui contribue à l'homéostasie immunitaire intestinale. En revanche, dans le modèle d'EAM, les souris ayant subi une ablation de CMHII non hématopoïétique étaient résistantes à l'induction de la maladie, alors que la progression de la pathologie cardiaque, dans les souris de type naturel ou hétérozygotes, a été accompagnée par une régulation positive de l'expression de CMHII du myocarde. Cependant, l'inflammation cardiaque pourrait être transférée de manière adoptive depuis des souris amorcées PIV-/- K14 CIITA Tg vers des souris de type naturel, indiquant l'absence de défaut intrinsèque d'amorçage des cellules T CD4+ dans notre modèle de souris. Ces observations impliquent un rôle à jouer pour des cellules CMHII+ non hématopoïétiques résidentes du coeur, dans la promotion active de ΙΈΑΜ. En conclusion, nos résultats, provenant de diverses pathologies inflammatoires spécifiques d'organes, suggèrent un rôle complexe et divergent, soit tolérogène, soit immunogène/ pathologique, pour l'expression de CMHII non hématopoïétique au cours des pathologies inflammatoires. L'expression non professionnelle de CMHII semble influencer le résultat des réponses immunitaires en fonction de différents facteurs, tels que le tissu cible, le(s) type(s) de cellule(s) non hématopoïétique(s) participante(s) et l'origine de l'inflammation. Nos résultats pourraient potentiellement ouvrir la voie à des applications thérapeutiques, qui tiennent compte de la contribution de la présentation d'antigènes par des CPAs non professionnelles, au cours de l'inflammation spécifique d'organe. - MHC class II (MHCII) molecules are fundamental for the presentation of antigens to CD4+ Τ cells, allowing the development of antigen-specific immune responses. It is widely accepted that MHCII expression is restricted to antigen-presenting cells (APC). However, under inflammatory conditions, MHCII expression is typically also induced by interferon (IFN)-y on nonhematopoietic cells such as epithelial cells and cardiomyocytes. So far, it remains controversial whether this nonprofessional antigen-presentation function promotes CD4+ Τ cell-dependent tolerance or immunity in vivo. To address this issue, we utilised mice which lack inducible MHCII expression on nonhematopoietic cells (pIV-/- K14 CIITA Tg mice) in different mouse models of inflammatory pathologies, namely immunisation models to induce antigen-specific Β cell responses, various colitis models and a model of experimental autoimmune myocarditis (EAM). In an attenuated model of colitis induced by chronic Helicobacter hepaticus infection and treatment with anti-interleukin (IL)-10 receptor (anti-IL-10R) monoclonal blocking antibody, we observed that abrogated MHCII expression by nonhematopoietic cells or, in an alternative tamoxifen-inducible mouse model (plV_fl/fl vil-Cre Tg mice), exclusively by intestinal epithelial cells (IEC), exacerbated bacterial-driven colitis, which was associated with increased colonic frequencies of innate immune cells, CD4+ Th1 cells and expression of proinflammatory cytokines and chemokines, including IFN-γ. Notably, defective nonhematopoietic MHCII expression also resulted in reduced Forkhead box P3 (FoxP3)+ regulatory Τ (Treg) cells without influencing innate lymphoid cell (ILC) and Th17 cell frequencies. These findings suggest a tolerogenic role of MHClT lECs to contribute to intestinal immune homeostasis. In contrast, in the EAM model, mice ablated of nonhematopoietic MHCII were resistant to disease induction, whereas progression of cardiac pathology in WT and heterozygous control mice was accompanied by upregulation of myocardial MHCII expression. However, cardiac inflammation could be adoptively transferred from primed pIV-/- K14 CIITA Tg mice into WT mice, indicating no intrinsic defect of CD4+ Τ activation in our mouse model. These observations imply a role for MHCIT heart-resident nonhematopoietic cells in actively promoting EAM. In conclusion, our findings from different organ-specific inflammatory pathologies suggest a complex and diverging role - either tolerogenic or immunogenic/ pathologic - for nonhematopoietic MHCII expression during inflammatory pathologies: Nonprofessional MHCII expression appears to influence the outcome of immune responses depending on 7 factors such as the target tissue, participating non hematopoietic cell type(s) and the origin of inflammation. Our findings may potentially open the way to therapeutic applications taking into account the contribution of antigen presentation by nonprofessional, tissue-resident APCs during organ-specific inflammation.

Levels of immune cells in transcendental meditation practitioners.

CONTEXT Relationships between mind and body have gradually become accepted. Yogic practices cause modulation of the immune system. Transcendental meditation (TM) is a specific form of mantra meditation. We reported previously different plasma levels of catecholamines and pituitary hormones in TM practitioners comparing with a control group, and patterns of the daytime secretion of these hormones different from those normally described. AIMS The aim of the following study is to evaluate the immune system in these meditation practitioners, by determining leukocytes and lymphocytes subsets. METHODS TM group consisted of 19 subjects who regularly practice either TM or the more advanced Sidhi-TM technique. A control group consisted of 16 healthy subjects who had not previously used any relaxation technique. Total leukocytes, granulocytes, lymphocytes and monocytes were counted by an automated quantitative hematology analyzer, whereas lymphocytes subsets were determined by flow cytometry. Samples were taken from each subject at 0900 h after an overnight fast. RESULTS The results indicated that the TM group had higher values than the control group in CD3+CD4-CD8+ lymphocytes (P < 0.05), B lymphocytes (P < 0.01) and natural killer cells (P < 0.01), whereas CD3+CD4+CD8- lymphocytes showed low levels in meditation practitioners (P < 0.001). No significant differences were observed in total leukocytes, granulocytes, monocytes, total lymphocytes or CD3+ lymphocytes comparing both groups. CONCLUSIONS The technique of meditation studied seems to have a significant effect on immune cells, manifesting in the different circulating levels of lymphocyte subsets analyzed. The significant effect of TM on the neuroendocrine axis and its relationship with the immune system may partly explain our results.

The effect of colostrum source (goat vs. sheep) and timing of the first colostrum feeding (2h vs. 14h after birth) on body weight and immune status of artificially reared newborn lambs.

Several factors can affect lamb body weight (BW) and immune status during the first days of life, including colostrum source and timing of the first colostrum feeding. The aim of this study was to evaluate the effects of colostrum source (goat or sheep) and timing of the first colostrum feeding (2 or 14h after birth) on lamb BW and immune status. In this study, 40 lambs were removed from their dams at birth and randomly assigned into 4 groups of 10 lambs each. Lambs were subsequently fed at 2 or 14h after birth with goat or sheep colostrum. Blood samples and BW recording were performed before feeding. Blood plasma was used to measure the immunoglobulin concentration (IgG and IgM), chitotriosidase activity, and complement system activity (total and alternative pathways). In general, no differences in any of the measured variables were observed among the 4 groups, indicating that neither colostrum source nor timing of the first colostrum feeding had an effect on these variables. These findings may improve management on lamb farms that raise animals under artificial conditions, because our results indicate that it is not necessary to feed colostrum to lambs immediately after birth and that goat colostrum may be used to feed newborn lambs.

Antiplasmodial activity of iron(II) and ruthenium(II) organometallic complexes against Plasmodium falciparum blood parasites

This work reports the in vitro activity against Plasmodium falciparumblood forms (W2 clone, chloroquine-resistant) of tamoxifen-based compounds and their ferrocenyl (ferrocifens) and ruthenocenyl (ruthenocifens) derivatives, as well as their cytotoxicity against HepG2 human hepatoma cells. Surprisingly with these series, results indicate that the biological activity of ruthenocifens is better than that of ferrocifens and other tamoxifen-like compounds. The synthesis of a new metal-based compound is also described. It was shown, for the first time, that ruthenocifens are good antiplasmodial prototypes. Further studies will be conducted aiming at a better understanding of their mechanism of action and at obtaining new compounds with better therapeutic profile.