Immunomodulatory effects of zinc and DHEA on the Th-1 immune response in rats infected with Trypanosoma cruzi

Chagas` disease is considered the sixth most important neglected tropical disease worldwide. Considerable knowledge has been accumulated concerning the role of zinc on cellular immunity. The steroid hormone dehydroepiandrosterone (DHEA) is also known to modulate the immune system. The aims of this paper were to investigate a possible synchronization of their effects on cytokines and NO production and the resistance to Trypanosoma cruzi during the acute phase of infection. It was found that zinc, DHEA or zinc and DHEA supplementation enhanced the immune response, as evidenced by a significant reduction in parasitemia levels. Zinc and DHEA supplementation exerted additive effects on the immune response by elevation of macrophage counts, and by increasing concentrations of IFN-gamma and NO. (C) 2009 Elsevier GmbH. All rights reserved.

Innate immune lectins kill bacteria expressing blood group antigen

The expression of ABO(H) blood group antigens causes deletion of cells that generate self-specific antibodies to these antigens but this deletion limits adaptive immunity toward pathogens bearing cognate blood group antigens. To explore potential defense mechanisms against such pathogens, given these limitations in adaptive immunity, we screened for innate proteins that could recognize human blood group antigens. Here we report that two innate immune lectins, galectin-4 (Gal-4) and Gal-8, which are expressed in the intestinal tract, recognize and kill human blood group antigen-expressing Escherichia coli while failing to alter the viability of other E. coli strains or other Gram-negative or Gram-positive organisms both in vitro and in vivo. The killing activity of both Gal-4 and Gal-8 is mediated by their C-terminal domains, occurs rapidly and independently of complement and is accompanied by disruption of membrane integrity. These results demonstrate that innate defense lectins can provide immunity against pathogens that express blood group-like antigens on their surface.

The Ruthenium Complex cis-(Dichloro) Tetraammineruthenium(III) Chloride Presents Immune Stimulatory Activity on Human Peripheral Blood Mononuclear Cells

Ruthenium compounds in general are well suited for medicinal applications. They have been investigated as immunosuppressants, nitric oxide scavengers, antimicrobial agents, and antimalarials. The aim of this study is to evaluate the immunomodulatory activity of cis-(dichloro) tetraammineruthenium(III) chloride (cis-[RuCl(2)(NH(3))(4)]Cl) on human peripheral blood mononuclear cells (PBMC). The cytotoxic studies performed here revealed that the ruthenium( III) complex presents a cytotoxic activity towards normal human PBMC, only at very high concentration. Results also showed that cis-[ RuCl(2)(NH(3))(4)] Cl presents a dual role on PBMC stimulating proliferation and interleukin-2 (IL-2) production at low concentration and inducing cytotoxicity, inability to proliferate, and inhibiting IL-2 production at high concentration. The noncytotoxic activity of cis-[RuCl(2)(NH(3))(4)] Cl at low concentration towards PBMC, which correlates with the small number of annexin V positive cells and also the absence of DNA fragmentation, suggest that this compound does not induce apoptosis on PBMC. For the first time, we show that, at low concentration (10-100 mu g L(-1)), the cis-[ RuCl(2)(NH(3))(4)] Cl compound induces peripheral blood lymphocytes proliferation and also stimulates them to IL-2 production. These results open a new potential applicability of ruthenium(III) complexes as a possible immune regulatory compound acting as immune suppressor at high concentration and as immune stimulator at low concentration.

Trypanosoma cruzi: Do different sylvatic strains trigger distinct immune responses?

Strains of Trypanosoma cruzi are multiclonal populations that can be classified in groups or genotypes, differing in pathogenicity, virulence, and histotropism. In this experiment the distinct behavior of two strains of T. cruzi, MORC-1 and MORC-2, was documented. Blood parasitemia, spleen proliferation, nitric oxide, histopathology of the spleen and heart were used as tools to evaluate parasite persistence. Groups of male mice were separated and divided in three groups: Control (C), Infected (IM-1) and Infected (IM-2). The peak of parasitemia occurred on 10 days post infection for both strains. LPS stimulated animals, infected MORC-2 group displayed significant higher concentrations of NO when compared to infected MORC-1 group (P < 0.05). For ConA stimulated lymphoproliferation, infected MORC-1 group displayed higher proliferation index as compared to infected MORC-2 group. An opposite behavior for IL-4 and TNF-alpha was observed according to the strain. For MORC-1 enhanced concentrations of IL-4 were present with concomitant reduced levels of TNF-alpha, while for MORC-2 enhanced concentrations of TNF-alpha and reduced levels of IL-4 were found. The histopathology of heart and spleen showed important differences in which MORC-1 displayed statistically enhanced number of amastigote in the heart and spleen as compared to MORC-2. Concluding, each strain triggered a distinct immune response with enhanced cytokine TH-1 profile for MORC-2 and TH-2 for MORC-1. (C) 2009 Elsevier Inc. All rights reserved.

Trypanosoma cruzi: Dehydroepiandrosterone (DHEA) and immune response during the chronic phase of the experimental Chagas` disease

Dehydroepiandrosterone (DHEA) has long been considered as a precursor for many steroid hormones. It also enhances the immune responses against a wide range of viral, bacterial, and parasitic pathogens. The aims of this work were to evaluate the influences of exogenous DHEA treatment on Wistar rats infected with the Y strain of Trypanosoma cruzi during the acute and its influence on the chronic phase of infection. Animals were subcutaneous treated with 40 mg/kg body weight/day of DHEA. DHEA treatment promoted increased lymphoproliferative responses as well as enhanced concentrations of NO and IL-12. So, we point in the direction that our results validate the utility of the use of DHEA as an alternative therapy candidate against T cruzi. (C) 2009 Published by Elsevier B.V.

A randomized and controlled trial of a participative ergonomics intervention to reduce injuries associated with manual tasks: physical risk and legislative

A participative ergonomics approach to reducing injuries associated with manual tasks is widely promoted; however only limited evidence from uncontrolled trials has been available to support the efficacy of such an approach. This paper reports on a randomized and controlled trial of PErforM, a participative ergonomics intervention designed to reduce the risks of injury associated with manual tasks. One hundred and seventeen small to medium sized food, construction, and health workplaces were audited by government inspectors using a manual tasks risk assessment tool (ManTRA). Forty-eight volunteer workplaces were then randomly assigned to Experimental and Control groups with the Experimental group receiving the PErforM program. Inspectors audited the workplaces again, 9 months following the intervention. The results showed a significant decrease in estimates of manual task risk and suggested better legal compliance in the Experimental group.

Prevention of child behavior problems through universal implementation of a group behavioral family intervention.

The aim of this mental health promotion initiative was to evaluate the effectiveness of a universally delivered group behavioral family intervention (BFI) in preventing behavior problems in children. This study investigates the transferability of an efficacious clinical program to a universal prevention intervention delivered through child and community health services targeting parents of preschoolers within a metropolitan health region. A quasiexperimental two-group (BFI, n=804 vs. Comparison group, n=806) longitudinal design followed preschool aged children and their parents over a 2-year period. BFI was associated with significant reductions in parent-reported levels of dysfunctional parenting and parent-reported levels of child behavior problems. Effect sizes on child behavior problems ranged from large (.83) to moderate (.47). Positive and significant effects were also observed in parent mental health, marital adjustment, and levels of child rearing conflict. Findings are discussed with respect to their implication for significant population reductions in child behavior problems as well as the pragmatic challenges for prevention science in encouraging both the evaluation and uptake of preventive initiatives in real world settings.

The management of elderly patients with femoral fractures - A randomised controlled trial of early intervention versus standard care

Objective: To determine the effect of an early intervention program in an acute care setting on the length of stay in hospital of elderly patients with proximal femoral fractures. Setting: Acute orthopaedic ward of a large teaching hospital. Design and Participants: A randomised controlled trial comparing 38 intervention patients with 33 Standard Care patients. Intervention: Early surgery, minimal narcotic analgesia, intense daily therapy and close monitoring of patient needs via a multidisciplinary approach versus routine hospital management. Main outcome measures: Length of stay (LOS); deaths; level of independent functioning. Results: Mean LOS was shorter in the Intervention group than in the Standard Care group (21 days v. 32.5 days; P<0.01). After adjusting for other factors that could affect LOS (e.g. age, sex, pre-trauma functional levels, pre-trauma comorbidity and postsurgical complications), the Intervention program was significantly predictive of shorter LOS (P=0.01). The Intervention group did not experience greater numbers of deaths, deterioration in function or need for social support than the Standard Care group. Conclusion: This early intervention program in an acute care setting results in significantly shorter length of hospital stay for elderly patients with femoral fractures.

Reducing coronary heart disease in the Australian Coalfields: evaluation of a 10-year community intervention

Coronary heart disease is a leading cause of death in Australia with the Coalfields district of New South Wales having one of the country's highest rates. Identification of the Coalfields epidemic in the 1970's led to the formation of a community awareness program in the late 1980's (the healthy heart support group) followed by a more intense community action program in 1990, the Coalfields Healthy Heartbeat (CHHB). CHHB is a coalition of community members, local government officers, health workers and University researchers. We evaluate the CHHB program, examining both the nature and sustainability of heart health activities undertaken, as well as trends in risk factor levels and rates of coronary events in the Coalfields in comparison with nearby local government areas. Process data reveal difficulties mobilising the community as a whole; activities had to be selected for interested subgroups such as families of heart disease patients, school children, retired people and women concerned with family nutrition and body maintenance. Outcome data show a significantly larger reduction in case fatality for Coalfields men (although nonfatal heart attacks did not decline) while changes in risk factors levels were comparable with surrounding areas. We explain positive responses to the CHHB by schools, heart attack survivors and women interested in body maintenance in terms of the meaning these subgroups find in health promotion discourses based on their embodied experiences. When faced with a threat to one's identity, health discourse suddenly becomes meaningful along with the regimens for health improvement. General public disinterest in heart health promotion is examined in the context of historical patterns of outsiders criticising the lifestyle of miners, an orientation toward communal lather than individual responsibility for health (i.e, community 'owned' emergency services and hospitals) and anger about risks from environmental hazards imposed by industrialists. (C) 1999 Elsevier Science Ltd. All rights reserved.

Human and murine cytomegalovirus evasion of cytotoxic T lymphocyte and natural killer cell-mediated immune responses

Herpesviruses, such as human and murine cytomegalovirus, possess an impressive array of genes believed to assist in virus survival against the host immune response. In this review, we cover the rapidly growing area of cytomegalovirus evasion of cellular immunity, specifically cytotoxic T lymphocytes and natural killer cells. The proposed mechanisms of action of viral proteins involved in blocking peptide presentation to CD8(+) T cells, namely, interference with peptide generation, inhibition of peptide assembly with class I MHC and retention/destabilization of class I MHC complexes, are described. In addition, recent evidence implicating the viral class I MHC-like proteins as inhibitors of natural killer cell-mediated clearance is reviewed, (C) 1998 Academic Press.

Dendritic cells: the driving force behind autoimmunity in rheumatoid arthritis?

Dendritic cells (DC) are likely to play a significant role in immune-mediated diseases such as autoimmunity and allergy. To date there are few treatments capable of inducing permanent remission in rheumatoid arthritis (RA) and elucidation of the role of DC may provide specific strategies for disease intervention. Dendritic cells have proven to be powerful tools for immunotherapy and investigations are under way to determine their clinical efficacy in transplantation and viral and tumour immunotherapy. The present review will focus on the current view of DC and their role in autoimmunity, in particular RA. Two possible roles for DC in the pathogenesis of RA will be proposed, based on recent advances in the field.

Immune responses induced by BCG recombinant for human papillomavirus L1 and E7 proteins

Recombinant bacille Calmette-Guerin (BCG) based vaccine delivery systems could potentially share the safety and effectiveness of BCG. We therefore prepared recombinant BCG vaccines which expressed the L1 late protein of the human papillomavirus (HPV) 6b or the E7 early protein of the HPV 16. The two recombinants were evaluated as immunogens in C57BL/6J and BALB/c mice, and compared with a conventional protein/adjuvant system using E7 or L1 mixed with Quil-A adjuvant. rBCG6bL1 and rBCG16E7 primed specific immune responses, represented by DTH, T-proliferation and antibody, and rBCG16E7 induced cytotoxic immune response to E7 protein. The magnitude of the observed responses were less than those elicited by protein/adjuvant vaccine. As recombinant BCG vaccines expressing HPV6bL1 or HPV16E7 persist at low levels in the immunised host, they may be beneficial to prime or retain memory responses to antigens, but are unlikely to be useful as a single component vaccine strategy. (C) 2000 Elsevier science Ltd. All rights reserved.