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Regulatory T cells (Tregs) are essential for maintaining immune homeostasis by serving as negative regulators of adaptive immune system effector cell responses. Reduced production or function of Tregs has been implicated in several human autoimmune diseases. The cytokine interleukin 2 plays a central role in promoting Treg differentiation, survival, and function in vivo and may therefore have therapeutic benefits for autoimmune diseases. mRNA‐6231 is an investigational, lipid nanoparticle‐encapsulated, mRNA‐based therapy that encodes a modified human interleukin 2 mutein fused to human serum albumin (HSA‐IL2m). Herein, we report the development of a semi‐mechanistic kinetic‐pharmacodynamic model to quantify the relationship between subcutaneous dose(s) of mRNA‐6231, HSA‐IL2m protein expression, and Treg expansion in nonhuman primates. The nonclinical kinetic‐pharmacodynamic model was extrapolated to humans using allometric scaling principles and the physiological basis of pharmacological mechanisms to predict the clinical response to therapy a priori. Model‐based simulations were used to inform the dose selection and design of the first‐in‐human clinical study (NCT04916431). The modeling approach used to predict human responses was validated when data became available from the phase I clinical study. This validation indicates that the approach is valuable in informing clinical decision‐making. [ABSTRACT FROM AUTHOR]

Despite being some of the most anecdotally well‐known roads to pathogenesis, the mechanisms governing autoimmune rheumatic diseases are not yet fully understood. The overactivation of the cellular immune system and the characteristic development of autoantibodies have been linked to oxidative stress. Typical clinical manifestations, such as joint swelling and deformities and inflammation of the skin and internal organs, have also been connected directly or indirectly to redox mechanisms. The differences in generation and restraint of oxidative stress provide compelling evidence for the broad variety in pathology among rheumatic diseases and explain some of the common triggers and discordant manifestations in these diseases. Growing evidence of redox mechanisms in pathogenesis has provided a broad array of new potential therapeutic targets. Here, we explore the mechanisms by which oxidative stress is generated, explore its roles in autoimmunity and end‐organ damage, and discuss how individual rheumatic diseases exhibit unique features that offer targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]

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Summary: Plants have evolved a multi‐layered immune system to fight off pathogens. However, immune activation is costly and is often associated with growth and development penalty. In crops, yield is the main breeding target and is usually affected by high disease resistance. Therefore, proper balance between growth and defence is critical for achieving efficient crop improvement. This review highlights recent advances in attempts designed to alleviate the trade‐offs between growth and disease resistance in crops mediated by resistance (R) genes, susceptibility (S) genes and pleiotropic genes. We also provide an update on strategies for optimizing the growth–defence trade‐offs to breed future crops with desirable disease resistance and high yield. [ABSTRACT FROM AUTHOR]

Some biological phenomena offer clues to solving real-life, complex problems. Researchers have been studying techniques such as neural networks and genetic algorithms for computational intelligence and their applications to such complex problems. The problem of security management is one of the major concerns in the development of eBusiness services and networks. Recent incidents have shown that the perpetrators of cybercrimes are using increasingly sophisticated methods. Hence, it is necessary to investigate non-traditional mechanisms, such as biological techniques, to manage the security of evolving eBusiness networks and services. Towards this end, this paper investigates the use of an Artificial Immune System (AIS). The AIS emulates the mechanism of human immune systems that save human bodies from complex natural biological attacks. The paper discusses the use of AIS on one aspect of security management, viz. the detection of credit card fraud. The solution is illustrated with a case study on the management of frauds in credit card transactions, although this technique may be used in a range of security management applications in eBusiness. [ABSTRACT FROM AUTHOR]

Asthma is a complex heterogeneous and mutifactorial disease occurring at the interface of multiple genes that interact with various environmental stimuli insulting the immune system at different levels and different times of disease susceptibility. The present paper is a review of the current status of the genetics of asthma. Sequence variants in hundreds of genes have been associated with asthma using both family-based and case control screening methods. As the number of genes known to be associated with asthma risk is rapidly growing, it is essential to begin integrating epidemiologic, genetic and genomic strategies to unravel the relationships between genotype and phenotype, and elucidate the pathogenesis of asthma with the goal to make clinical use of these discoveries. Please cite this paper as: Halapi E and Bjornsdottir US. Overview on the current status of asthma genetics. The Clinical Respiratory Journal 2009; 3: 2-7. [ABSTRACT FROM AUTHOR]

The nocturnal surge of melatonin is the endocrine expression of the circadian system and is essential for organizing the timing of various endogenous processes. Previous works suggest that, in the beginning of a defense response, the increase in circulating tumor necrosis factor-α (TNF-α) leads to a transient block of nocturnal melatonin production and promotes a disruption of internal time organization. In the present paper, the concentration of melatonin and cytokines [TNF-α, interferon-γ (IFN-γ), interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12] in the colostrum (postdelivery day 3) and in the milk (postdelivery days 10, 15, 20 and 30) obtained at midday and midnight from mothers who gave birth by vaginal or cesarean section were compared. The nocturnal melatonin surge observed 3 days after vaginal delivery was absent after cesarean section. IL-12 presented no daily variation in either case, while daily variations in IFN-γ, IL-10, IL-4 and IL-5 were observed after vaginal delivery and cesarean section. On the other hand, the increase in TNF-α after cesarean section resulted in suppression of the nocturnal melatonin surge. Daily variation of IL-2 was only observed after recovery of the nocturnal melatonin surge, 30 days after cesarean section. The present paper supports the hypothesis of a cross-talk between the pineal gland and the immune system, which could represent a putative immune–pineal axis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to a paper by J. Hoyle and SM Yentis regarding trends in the assessment of neuraxial blockade especially with regards to the number of different motor blockade scores ascribed to Bromage.

This paper looks at the dynamic interface between disease, environmental degradation, and human behaviour. It is argued that the role of the ecosystem in maintaining health on a planetary scale can be likened to an organism's immune system. However, humanity's mental and emotional disconnection from these autopoietic processes is a form of ecological autism which is detrimental to the health of humans and ecosystems alike. This ecological autism is resulting in human systems acting like an autoimmune disorder; so that GAIA is living with AIDS. It is suggested that employing metaphors of the immune system to aid understanding and empathy might ameliorate this by helping humanity to realize its embeddedness within nature and to recognize the consequences of its actions. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Current treatments for ischemic cardiomyopathy are aimed toward minimizing the deleterious consequences of damaged myocardium. The possibility of treating heart failure by generating new myocardium and vascular structures has provided major impetus for recent stem cell research. Mesenchymal stem cells (MSCs), also referred to as marrow stromal cells, differentiate into a wide variety of lineages, including myocardial smooth muscle and possibly endothelial cells. The multilineage potential of MSCs, their ability to elude detection by the host's immune system, and their relative ease of expansion in culture make MSCs a very promising source of stem cells for transplantation. This paper reviews animal and human trials studying the role of MSCs in cardiomyogenesis and vasculogenesis in postinfarct myocardium, factors that stimulate MSC differentiation, routes of MSC delivery, and methods of detecting MSC engraftment. [ABSTRACT FROM AUTHOR]

This paper reviews the social and behavioral factors acting on thebrain that influence health, illness, and death. Using data from several areas ofresearch, a new paradigm is proposed for understanding health and illness.This paradigm, psychoendoneuroimmunology (PENI), provides both the conceptsand the mechanisms for studying and explaining mind-body relationships.The brain is the body's first line of defense against illness, and the mindis the functioning of the brain. PENI incorporates ideas, belief systems, hopes,and desires as well as biochemistry, physiology, and anatomy. As we change ourthoughts, we are changing our brain and thus our biology and our body. Beliefsystems set a baseline for the brain upon which other variables will act andhave their effects. [ABSTRACT FROM AUTHOR]

Summary In this paper we investigate the relationship between the chronic burden of mid-gut parasites (eugregarine trophozooites) and the effect of an acute haemolymph challenge (a nylon insert) on two important insect immune effector systems (phenol oxidase (PO) and the encapsulation response) in a field-population of damselflies. PO levels in the haemolymph, and the magnitude of the encapsulation response were maintained, regardless of chronic and subsequent acute experimental immune challenges. The maintenance of these effector systems is therefore probably an important life-history requirement in these damselflies. Investment in mid-gut PO levels was significantly negatively related to the animal's chronic parasite burden after an acute experimental challenge in the haemolymph, suggesting that maintaining PO levels across two physiological compartments (haemolymph and mid-gut) is costly. The results suggest that the immune effector system activity in different physiological compartments in an insect's body is affected by chronic parasite burdens in the face of the demands imposed by an acute immune insult. [ABSTRACT FROM AUTHOR]

Protein interactions (PI) underlie complex biological processes. Protein interaction partners include DNA, RNA, ions, small chemical compounds, and proteins (protein-protein interactions; PPI). Analysis of sequence variants within regions corresponding to experimentally validated PI sites presents novel opportunities for understanding of complex diseases. Such information has not been systematically collected due to the fact that datasets are dispersed throughout databases and publications. Sequence variants and PI regions were obtained from the UniProt database. The location of the variants was compared to start and end positions of each PPI. Associations of sequence variants with phenotype were obtained from databases including COSMIC, GAD, PharmGKB, and dbSNP. We developed a catalogue of 603 sequence variants located within regions corresponding to experimentally validated PI sites, mostly PPI regions. These sequence variants were previously associated with risk for cancer, reproduction, ageing, renal, and immune system diseases. The developed catalogue connects information from different research papers and databases, represents a new layer of information and enables designing new hypotheses. It provides a baseline for prioritization of sequence variants, which may affect protein function and binding sites. The study contributes to the development of the proteogenomics field and provides new insights for understanding molecular mechanisms underlying disease development. [ABSTRACT FROM AUTHOR]

Ad-hoc social networks (ASNETs) explore social properties of nodes in communications. The usage of various social applications in a resource-scarce environment and the dynamic nature of the network create unnecessary congestion that might degrade the quality of service dramatically. Traditional approaches use drop-tail or random-early discard techniques to drop data packets from the intermediate node queue. Nonetheless, because of the unavailability of the social properties, these techniques are not suitable for ASNETs. In this paper, we propose a Bio-inspired packet dropping (BPD) algorithm for ASNETS. BPD imitates the matching procedure of receptors and epitopes in immune systems to detect congestions. The drop probability settings depend on the selection of data packets, which is based on node popularity level. BPD selects the most prioritized node through social properties, which is inspired by the B-cell stimulation in immune systems. To fairly prioritize data packets, two social properties are used: (1) similarity and (2) closeness centrality between nodes. Extensive simulations are carried out to evaluate and compare BPD to other existing schemes in terms of mean goodput, mean loss rate, throughput, delay, attained bandwidth, and overhead ratio. The results show that the proposed scheme outperforms these existing schemes. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This problem (proposed for the 4th International Symposium on Applied Stochastic Models and Data Analysis) concerns an exploratory study related to the presently accepted hypothesis that temporal curves of the forced pulse luminescence of specialized blood cells, granulocytes, may indicate the level of effectiveness of the immunological system. This paper presents a new set of empirical data and an analysis of its structure. [ABSTRACT FROM AUTHOR]

This review is the companion to the foregoing paper critically reviewing research on the biological, psychological and social aspects of the etiology of cervical cancer. The immune system mediates some (but not all) of the effects of these factors. Factors with relevant immunological associations fro cervical oncogenesis are examined here. A critical review of research presented in both papers is offered at eth conclusion of each aspects. This is followed by a tabular summary of the immunological studies relevant to the biological, psychological and social aspects of cervical cancer. Estimated likelihoods of association for the immunological factors selected within each aspects are given based upon both the number and quality of studies conducted, and are followed by selected comments. The paper concludes with a theoretical integration of the entire model (represented in both reviews) and the promulgation of a set of integrative hypotheses across domains (including their immunological aspects) for the purpose of illustrating the potential utility of this model in addressing future research questions. [ABSTRACT FROM AUTHOR]

Presents a table of contents for the Volume 22 of the "Scandinavian Journal of Immunology." Murine Metabolic Enzymes in Lymphocytes; Cathepsin B Activity in Human Blood Monocytes during Differentiation in Vitro; Induction of Immunoglobulin Secretion by Protein A from Staphylococcus aureus in Human Blood and Bone Marrow B Cells.

X-irradiated (250 rad), cyclophosphamide-treated or Atx A mice injected with syngeneic trinitrophenylated spleen cells (TNP-SC) and footpad challenged with syngeneic lymphoblasts generated delayed-type hypersensitivity (DTH) responses 24, 48 and 72 h after challenge. The syngeneic-DTH (syn-DTH) response was mediated by Lyt-1+ cells and suppressed with Lyt-1+2+3+, I-Jk+ cells. The suppressor cells were obtained from spleens or thymuses of normal syngeneic mice. Suppressor factor (SF) was extracted or released from Lyt-1+2+3+, I-Jk+ cells obtained from normal A mice (but not from X-irradiated A mice). The factor blocked the DTH responses of X-irradiated mice injected with syngeneic TNP-SC and challenged with syngeneic lymphoblasts when injected into the mice both at the induction phase and the elicitation phase of the DTH. The factor failed to abrogate allogeneic and xenogeneic DTH. However, allogeneic factor (derived from C57BL/6 mice) abolished the syn-DTH response of mice injected with syngeneic TNP-SC and challenged with syngeneic lymphoblasts. The SF was produced by Lyt-1+2+3+, I-Jk+ T cells or by thymocytes. The combined extracted product of Lyt-1+ and Lyt-2+ cells did not abrogate the syn-DTH response. Normal spleen cells depleted of phagocytes by a magnetic procedure also produced the SF. These findings indicate, therefore, that suppressive factor (or factors; see Discussion of the accompanying paper, Ref.17) controls the immunological autoreactivity against syngeneic TNP-SC. [ABSTRACT FROM AUTHOR]

The primary objective of this meta‐analysis was to provide the comprehensive understanding of the intricate correlation that existed between immune senescence and its effects on the advancement of lung cancer as well as recovery of cutaneous wounds. By conducting this systematic review of six rigorous studies utilizing databases such as PubMed and Web of Science, this research examined the multitude of facets pertaining to immune aging and consequences it bear on the health outcomes. The incorporated studies encompassed wide range of geographical and methodological viewpoints, with the specific emphasis on non‐small‐cell lung cancer and diverse scenarios related to wound recovery. This analysis synthesized discoveries regarding therapeutic responses, cellular and molecular mechanisms and impact of lifestyle factors on immune senescence. The findings suggested that immune senescence has substantial impact on the effectiveness of treatments for lung cancer and cutaneous wounds healing process; therefore, targeted therapies and holistic approaches may be able to mitigate these effects. By following the revised PRISMA guidelines, this meta‐analysis guarantee thorough and ethically sound methodology for amalgamating pre‐existing literature. The study concluded by emphasizing the critical nature of comprehending immune senescence in the context of clinical practice and proposed avenues for further investigation to enhance health results among the elderly. [ABSTRACT FROM AUTHOR]

The concept of ' locus minoris resistentiae' ( lmr) is an old but still effective way of thinking in Medicine. In Dermatology, there are many reports of privileged localization of cutaneous diseases on injured skin, which therefore represents a typical condition of lmr. Lately the innovative concept of immunocompromised cutaneous district ( ICD) has been introduced to explain why a previously injured cutaneous site may become in time a privileged location for the outbreak of opportunistic infections, tumors, and immune reactions. An ample documentation of multifarious disorders (infectious, neoplastic, immune) appearing in ICDs was delineated by Ruocco et al. in 2009. These cases were grouped according to the clinical settings responsible for the local immune imbalance: regional chronic lymphedema; herpes-infected sites, which feature the well-known Wolf's isotopic response; and otherwise damaged areas, comprising sites of vaccination, ionizing or UV radiation, thermal burns, and traumas. In the following five years, what was a 'novel' pathogenic concept has been extended to an enlarging variety of clinical conditions. This paper focuses on ICD and the expanding spectrum of this now established pathogenic concept. [ABSTRACT FROM AUTHOR]

Many of the reviews include discussion of diffusible molecules involved in cell-cell communication during the evolution of innate and adaptive responses (eg, interferons) and how these mediators influence the outcome of the dynamic processes visualized by optical methods. New data on tissue-resident T cells also fall in this category, as do recent observations of perivascular co-localization of effector lymphocytes and presenting cells at sites of effector function within tissues. Technologies are now emerging that will permit combining the protein and cell-based optical imaging methods used to date with recent advances in nucleic acid/genomic methods, especially single-cell sequencing. [Extracted from the article]

This paper reviews the physicochemical properties and nutritional significance of inulin fructans (oligofructose and inulin). These compounds are naturally present in a large number of food crops and serve in our diet as dietary fiber. Inulin fructans can be isolated and purified from the chicory root and used as ingredients in a large range of foods to improve structure and/or taste and to increase the intake of dietary fiber. Inulin fructans have a low caloric value, are safe, and generally well tolerated up to a level of 20 g/d. They exert a range of effects, which can be differentiated into direct effects on the gut and the intestinal flora and indirect systemic effects. Direct effects on the gut include prebiotic (bifidogenic) effects, improvement of bowel habits and bowel function in constipated subjects, increased colonic absorption of minerals (Ca and Mg), and secretion of satiety hormones. Indirect effects are on blood lipids, bone mineral content, the immune system, and energy homeostasis. These issues are discussed and it is argued that promising avenues for research are particularly in the areas of energy homeostasis and systemic low-grade inflammation in relation to changes in the composition of the intestinal microbiota. [ABSTRACT FROM AUTHOR]

A relationship between COVID-19 infection and an increasing incidence of atrial fibrillation has been observed. However, the underlying pathophysiology as a precipitant to AF has not been reviewed. This paper will consider the possible pathological and immunological AF mechanisms as a result, of COVID-19 infection. We discuss the role myocardial microvascular pericytes expressing the ACE-2 receptor and their potential for an organ-specific cardiac involvement with COVID-19. Dysfunctional microvascular support by pericytes or endothelial cells may increase the propensity for AF via increased myocardial inflammation, fibrosis, increased tissue edema, and interstitial hydrostatic pressure. All of these factors can lead to electrical perturbances at the tissue and cellular level. We also consider the contribution of Angiotensin, pulmonary hypertension, and regulatory T cells as additional contributors to AF during COVID-19 infection. Finally, reference is given to two common drugs, corticosteroids and metformin, in COVID-19 and how they might influence AF incidence. [ABSTRACT FROM AUTHOR]

Aim: The study aims to provide a selective review of the literature pertaining to the hypothalamic-pituitary-adrenal (HPA) axis and immune abnormalities as informative biological indicators of vulnerability in bipolar disorder (BD)., Method: We summarize key findings relating to HPA axis and immunological abnormalities in bipolar patients and their high-risk offspring. Findings derive from a review of selected original papers published in the literature, and supplemented by papers identified through bibliography review. Neurobiological findings are discussed in the context of emergent BD in those at genetic risk and synthesized into a neurodevelopmental model of illness onset and progression., Results: BD is associated with a number of genetic and possibly epigenetic abnormalities associated with neurotransmitter, hormonal and immunologically mediated neurobiological pathways. Data from clinical and high-risk studies implicate HPA axis and immune system abnormalities, which may represent inherited vulnerabilities important for the transition to illness onset. Post-mortem and clinical studies implicate intracellular signal transduction processes and disturbance in energy metabolism associated with established BD. Specifically, long-standing maladaptive alterations such as changes in neuronal systems may be mediated through changes in intracellular signalling pathways, oxidative stress, cellular energy metabolism and apoptosis associated with substantial burden of illness., Conclusions: Prospective longitudinal studies of endophenotypes and biomarkers such as HPA axis and immune abnormalities in high-risk offspring will be helpful to understand genetically mediated biological pathways associated with illness onset and progression. A clinical staging model describing emergent illness in those at genetic risk should facilitate this line of investigation., (© 2011 Blackwell Publishing Asia Pty Ltd.)

Clinical pharmaceutical trials aimed at modulating the immune system in Alzheimer's Disease have largely focused on either dampening down central proinflammatory innate immunity or have manipulated adaptive immunity to facilitate the removal of centrally deposited beta amyloid. To date, these trials have had mixed clinical therapeutic effects. However, a number of clinical studies have demonstrated disturbances of both systemic and central innate immunity in Alzheimer's Disease and attention has been drawn to the close communication pathways between central and systemic immunity. This paper highlights the need to take into account the potential systemic effects of drugs aimed at modulating central immunity and the possibility of developing novel therapeutic approaches based on the manipulation of systemic immunity and its communication with the central nervous system., (© 2011 Blackwell Publishing Ltd.)

Innate immune adaptor proteins are critical components of the innate immune system that propagate pro‐inflammatory responses from their upstream receptors, and lead to pathogen clearance from the host. Bacterial pathogens have developed strategies to survive inside host cells without triggering the innate immune surveillance in ways that are still not fully understood. Here, it is reported that Pseudomonas aeruginosa induces its quorum sensing mechanism after macrophage engulfment. Further investigation of its secretome identified a quorum sensing regulated product, LasB, is responsible for innate immune suppression depending on the MyD88‐mediated signaling. Moreover, it is showed that this specific type of pathogen‐mediated innate immune suppression is due to the enzymatic digestion of the death domains of the innate immune adaptors, mainly MyD88, and attributed to LasB's large substrate binding groove. Lastly, it is demonstrated that the secretion of LasB from P. aeruginosa directly contributed to MyD88 degradation within macrophages. Hence, it is discovered an example of bacterial quorum sensing‐regulated cellular innate immune suppression by direct cleavage of immune adaptors. [ABSTRACT FROM AUTHOR]

We are frequently exposed to potentially harmful microbes of various types on a daily basis. Our immune system is an amazing collection of unique organs and cells that defends us from hazardous germs as well as certain diseases. It plays a crucial role in protecting the body against external invaders, including bacteria, viruses, and parasites. Maintaining a healthy immune system requires consuming a balanced diet that provides a variety of macro‐ and micronutrients. By consuming sufficient amounts of water, minerals such as zinc and magnesium, micronutrients, herbs, and foods rich in vitamins C, D, and E, and adopting a healthy lifestyle, one can enhance their health and immunity, and prevent infections. This article provides a comprehensive review of the scientific literature on common foods known for their potential to boost human immunity. The review begins by discussing the various components of the immune system and their functions. It then delves into the current understanding of how nutrition can influence immune response, highlighting the importance of a well‐balanced diet in supporting optimal immune function. The article presents an extensive analysis of a range of common foods that have been studied for their immune‐boosting properties. These foods include fruits, vegetables, whole grains, and animal‐based foods. Each food category is explored in terms of its specific nutrients and bioactive compounds that contribute to immune support. Foods such as milk, eggs, fruits, leafy greens, and spices like onion, garlic, and turmeric contain beneficial compounds that can enhance the immune system's function, activate and inhibit immune cells, and interfere with multiple pathways that eventually lead to improved immune responses and defense. The available literature on the issue was accessed via online resources and evaluated thoroughly as a methodology for preparing this manuscript. [ABSTRACT FROM AUTHOR]

Intestinal flora is very important for improving the development of the immune system in newborns. Maternal diet during pregnancy and lactation is one of the key factors affecting the growth and development of offspring. The objective of the present study was to examine whether supplementation of maternal diet with milk oligosaccharides and Bifidobacterium could influence the development of the intestinal flora and immune system of neonatal mice. In total, 30 pregnant Institute of Cancer Research (ICR) mice were randomly divided into six groups: a control group (basal diet) and five intervention groups (basal diet supplemented with different doses of 2′‐fucosyllactose [2′‐FL] and Bifidobacterium Bb12) during the pregnancy period. All female mice were monitored for physical health during gavage. After delivery, the number of mice in each litter, any deformity, and the development of the offspring were recorded. The spleen, blood, and fecal samples of six groups of 10–12 day‐old offspring were collected. The results demonstrated that maternal milk oligosaccharides and probiotics conferred protective effects against lipopolysaccharide (LPS)‐induced immunosuppression in mice offspring by significantly enhancing the immune organ indexes, splenocyte proliferation, immunoglobulin (immunoglobulin G, A, M) production as well as improving the macrophage phagocytosis (p <.05). The abundance of Lactobacilli and Bifidobacteria in the feces of offspring mice in the intervention groups was significantly higher than that of the offspring mice in the control group (p <.05). These findings suggest that the combination of 2′‐FL and Bifidobacterium Bb12 displayed synergistic interactions between the two components that could promote the development of the immune system of the offsprings and improve their microbiota through maternal ingestion. [ABSTRACT FROM AUTHOR]

Lipopolysaccharide ( LPS)-binding protein ( LBP) functions as an acute phase protein and plays a key role in the innate immune response to bacterial challenge. It is a potential acute-phase biomarker in monitoring the progress of severe sepsis, infectious endocarditis and cardiovascular disease. LBP is mainly synthesized in hepatocytes and generates binding of bacteria and/or their products such as LPS to cell surface receptors, thereby initiating an innate host response. Interestingly, LBP has a dual role depending on its relatively low or high concentrations, and augments or downregulates the innate host defense accordingly. Emerging evidence indicates that LBP can be produced by non-hepatocytes, including respiratory type II epithelial cells, intestinal epithelial cells and human gingival epithelia. These findings suggest that LBP formation at extrahepatic cells may be crucial in containing microbial in situ challenge constantly, critically contributing to tissue homeostasis. This review provides an update on the characteristics and novel functions of LBP as well as its gene polymorphisms and potential use as a biomarker in assessing common infectious and inflammatory diseases such as periodontal disease. This paper highlights the expression profiles of LBP in human oral/gingival cells, how its expression could be modulated by periodontopathogens such as Porphyromonas gingivalis, as well as the relevant regulation mechanisms and signaling pathways involved. The critical roles of LBP in periodontal homeostasis and perspectives for its clinical application are discussed. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases ( MMPs) are critical factors in maintaining the integrity of mucosa and mediating normal biological processes. An imbalance between tissue levels of these mediators and their natural inhibitors is believed to underlie the pathophysiology of many diseases, including those affect the gastrointestinal and oral mucosae. The ongoing development of synthetic inhibitors of these mediators may provide opportunities to develop treatment modalities for patients suffering from these diseases. Understanding the role of MMPs in the pathophysiology of many diseases, however, is far from complete, and the improvement of pharmaceutical management strategies can only be achieved if the underlying process of these diseases is completely comprehended. This paper reviews the functions of matrix metalloproteinases and addresses their role in mediating mucosal pathologies with emphasis on oral mucosa. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • P2X7 receptors are involved in the production of pro-inflammatory cytokines, such as Il-1β, by central and peripheral immune cells. Il-1β has been implicated as an important mediator of inflammation. Therefore, the P2X7 receptor is an attractive therapeutic target for inflammatory diseases. WHAT THIS STUDY ADDS • Findings in pharmacokinetics, pharmacodynamics, safety and tolerability of a P2X7 receptor modulator, GSK1482160, from the first human study for the molecule are described. A pharmacokinetic/pharmacodynamic model for LPS-stimulated ATP-induced Il-1β production in blood allowed the integration of all relevant data and provided in vivo evidence of the nature of the drug-receptor interaction. The model has the potential to be used to simulate future trials. AIMS This paper describes findings from the first-in-human study for GSK1482160, an orally available allosteric P2X7 receptor modulator. The study aimed to assess the pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of the compound in healthy subjects. METHODS Escalating single doses of up to 1 g were administered to healthy subjects in a single-blind and placebo-controlled fashion. Safety, tolerability, blood drug concentrations and ex vivo Il-1β production in blood were evaluated. RESULTS Drug concentration peaked within 3.5 h of dosing under fasting conditions and declined thereafter with a relatively short half-life of less than 4.5 h. Exposure was proportional to dose with between subject variability of less than 60%. A PK/PD model quantified Il-1β as a function of drug exposure. The model allowed simulation of in vivo pharmacology for various untested dose levels and regimens. Furthermore, the mechanistic model supported the hypothesis that the compound reduces the efficacy of ATP at the P2X7 receptor without affecting its affinity. No major safety or tolerability concerns were identified in this small study ( n= 29), except for one case of asymptomatic accelerated idioventricular rhythm at the top dose. CONCLUSION The model-based approach maximized analysis power by integrating all biomarker data and revealed mechanistic insight into the pharmacology of P2X7 modulation by GSK1482160. Simulations by this model ultimately led to the discontinuation of the development of this compound. The therapeutic relevance of the P2X7 receptor remains to be tested in patients. The mechanistic-model-based approach can be applied widely to drug development. [ABSTRACT FROM AUTHOR]

Within anthropology and human biology, there is growing interest in immune function and its importance to the ecology of human health and development. Biomedical research currently dominates our understanding of immunology, and this paper seeks to highlight the potential contribution of a population-based, ecological approach to the study of human immune function. Concepts from life-history theory are applied to highlight the major challenges and demands that are likely to shape immune function in a range of ecological contexts. Immune function is a major component of maintenance effort, and since resources are limited, trade-offs are expected between investment in maintenance and other critical life-history functions involving growth and reproduction. An adaptationist, life-history perspective helps make sense of the unusual developmental trajectory of immune tissues, and emphasizes that this complex system is designed to incorporate information from the surrounding ecology to guide its development. As a result, there is substantial population variation in immune development and function that is not considered by current biomedical approaches. In an attempt to construct a framework for understanding this variation, immune development is considered in relation to the competing life-history demands that define gestation, infancy, childhood, adolescence, and adulthood. Each life stage poses a unique set of adaptive challenges, and a series of hypotheses is proposed regarding their implications for immune development and function. Research in human ecological immunology is in its earliest stages, but this is a promising area of exploration, and one in which anthropology is well-positioned to make important contributions., (Copyright 2003 Wiley-Liss, Inc.)

Please cite this paper as: Squires et al. (2012) Influenza research database: an integrated bioinformatics resource for influenza research and surveillance. Influenza and Other Respiratory Viruses 6(6), 404-416. Background The recent emergence of the 2009 pandemic influenza A/H1N1 virus has highlighted the value of free and open access to influenza virus genome sequence data integrated with information about other important virus characteristics. Design The Influenza Research Database (IRD, http://www.fludb.org) is a free, open, publicly-accessible resource funded by the U.S. National Institute of Allergy and Infectious Diseases through the Bioinformatics Resource Centers program. IRD provides a comprehensive, integrated database and analysis resource for influenza sequence, surveillance, and research data, including user-friendly interfaces for data retrieval, visualization and comparative genomics analysis, together with personal log in-protected 'workbench' spaces for saving data sets and analysis results. IRD integrates genomic, proteomic, immune epitope, and surveillance data from a variety of sources, including public databases, computational algorithms, external research groups, and the scientific literature. Results To demonstrate the utility of the data and analysis tools available in IRD, two scientific use cases are presented. A comparison of hemagglutinin sequence conservation and epitope coverage information revealed highly conserved protein regions that can be recognized by the human adaptive immune system as possible targets for inducing cross-protective immunity. Phylogenetic and geospatial analysis of sequences from wild bird surveillance samples revealed a possible evolutionary connection between influenza virus from Delaware Bay shorebirds and Alberta ducks. Conclusions The IRD provides a wealth of integrated data and information about influenza virus to support research of the genetic determinants dictating virus pathogenicity, host range restriction and transmission, and to facilitate development of vaccines, diagnostics, and therapeutics. [ABSTRACT FROM AUTHOR]

When a woman becomes pregnant, there is a vast series of physiological, vascular, and psychological changes. Among the most commonly reported changes are those involving sleep. Pregnant women report that their ability to maintain sleep and acquire continuous refreshing sleep is impaired during the perinatal period as compared to the non‐pregnant period. A growing literature supports the hypothesis that disturbed sleep (which comes in many forms) during the perinatal period is associated with an increased risk of adverse maternal, delivery, and infant outcomes. Among the suggested biological pathways linking sleep and adverse outcomes are disturbances in the immune and hormonal systems. The following paper will discuss (a) the various sleep processes that are commonly disturbed during the perinatal period and the methods used to collect sleep data; (b) the evidence linking sleep to adverse outcomes; and (c) how one specific biological pathway, the immune system, likely mediates these associations. The goal of this paper is to clarify the role that sleep disturbance has during pregnancy. [ABSTRACT FROM AUTHOR]

This paper highlights the multiple putative thymic and extrathymic points of intersection and interaction between glucocorticoids (GCs) and catecholamines (CAs)-the end-point mediators of the major routes of communication between the brain and the immune system-in the context of intricate thymic T cell-developmental tuning. More specifically, we discuss in detail findings indicating that adrenal GCs can influence thymopoiesis by adjusting directly and/or indirectly (through modulation of pituitary and local ACTH synthesis) not only thymic GC synthesis, in a cell type-specific manner, but also thymic CA bioavailability (via altering CA outflow from sympathetic nerve endings and local CA synthesis), β and α1-adrenoceptor (AR) expression, and/or AR-mediated intracellular signal transduction in thymic cells. In addition, this short review points to GC- and CA-sensitive stages along the multistep T cell-developmental journey and the possible effects of altered GC, and consequently CA signaling, on thymopoietic efficiency. [ABSTRACT FROM AUTHOR]

Immunological dysfunction has been proposed to explain the etiology of recurrent pregnancy loss (RPL). The immunological environment differs between the decidua basalis and decidua parietalis, and also between RPL cases with normal fetal chromosomes and those with abnormal fetal chromosomes. The problem with analyzing decidual tissues from spontaneous abortions is that cause versus effect phenomena are difficult to distinguish. Recent data show that the immune system in a late-stage miscarriage is completely different from that in an early-stage miscarriage. If immunocompetent cells can cause RPL, the immunological environment may be a causative factor, especially in an early-stage miscarriage, at the decidua basalis, and/or in cases of RPL with a normal embryo. Careful examination of the immune system at the decidua basalis in an early-stage miscarriage in RPL cases with normal fetal chromosomes may reveal useful information. This paper aimed at finding a cause of RPL by analyzing the balance of the immune system between T cells and NK cells in an early-stage miscarriage. [ABSTRACT FROM AUTHOR]

Primary immunodeficiencies (PIDs) are genetic disorders of the immune system comprising many different phenotypes. Although previously considered rare, recent advances in their clinical, epidemiological, and molecular definitions are revealing how much we still need to learn about them. For example, geographical and ethnic variations as well as the impact of certain practices influence their frequency and presentation, making it necessary to consider their study in terms of regions. The Latin American Society for Immunodeficiencies was established as an organization dedicated to provide scientific support for basic and clinical research and to develop tools and educational resources to promote awareness in the medical community. Initiatives such as these are positively influencing the way PIDs are tackled in these countries, as shown by recent reports and publications. This paper provides a historical compilation and a current view of the many issues faced by scientists studying these diseases in these countries, highlighting the diverse scientific contributions and offering a promising perspective for the further developments in this field in Latin America. [ABSTRACT FROM AUTHOR]

Major challenges in periodontology include understanding the pathophysiology, the interplay between various components of the host response, parallels with other diseases and identifying biomarkers of the disease. Four reviews were compiled with the aim of better understanding: (1) the role of polymorphic nuclear leucocytes (PMNs), i.e. neutrophils; (2) the function of cytokine networks in the host response; (3) whether parallels exist with rheumatoid arthritis (RA); and (4) whether useful biomarkers currently exist to help in the management of periodontal disease. Based on the focused questions, electronic and manual searches were conducted for human, animal and cellular studies on the above topics. Papers fulfilling the inclusion criteria were selected and reviews were written and reviewed and corrected before the academy meeting to produce consensus statements. The following consensus statements were produced. PMNs are important in the pathophysiology of periodontal disease but there is limited evidence on their much quoted destructive potential. Cytokine networks are enormously complex and we are really at the beginning of understanding their role in the disease process. RA has both similarities and marked differences to periodontal disease although the existing utilization of anti-cytokine therapies and other molecules in its treatment may have importance in periodontal disease therapy. Biomarkers for periodontal disease have yet to be completely defined but the ratio of receptor activator of NF- κB ligand to osteoprotegerin appears to be a biomarker test with utility for detecting bone destruction. [ABSTRACT FROM AUTHOR]

Jespers V, Francis SC, van de Wijgert J, Crucitti T. Methodological issues in sampling the local immune system of the female genital tract in the context of HIV prevention trials. Am J Reprod Immunol 2011; 65: 368-376 The spread of HIV continues unabated in the most vulnerable populations of the world. HIV prevention methods, such as a vaginal microbicide, a mucosal vaccine, pre-exposure prophylaxis or a vaccine, are urgently needed in the fight against new infections. We must make a commitment to supporting innovative research and product design, so that one or more of these products provide a halt to the spread of HIV. Above all, these products should be proven to be safe and not negatively disturb the local immune system in a way that facilitates or enhances heterosexual transmission of HIV. HIV specific and non specific cellular and humoral local vaginal immunity must be assessed in clinical trials when testing prevention products for safety or efficacy. A proven, well-documented and standardized sampling strategy will provide high quality data to be able to assess both safety and local immune responses. In this paper, we will discuss methods for vaginal immunology sampling in the context of clinical trials. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Genc M, Onderdonk A. Endogenous bacterial flora in pregnant women and the influence of maternal genetic variation. BJOG 2011;118:154-163. Preterm labour, premature prelabour rupture of membranes and low birth weight have all been associated with either specific maternal genital tract infections or an altered vaginal microflora during pregnancy. Factors that influence the variation in microbial-host interaction play an important role in individual susceptibility to adverse pregnancy outcomes. The innate immune responses at mucosal surfaces play a crucial role against microbial invasion. Multiple genes are responsible for the regulation of the innate immune system. Genetic polymorphisms that disrupt innate immune recognition or the responses to infectious microorganisms could explain the alterations in microflora and individual susceptibility to pregnancy complications. [ABSTRACT FROM AUTHOR]

The clinical manifestations of human Chagas disease are associated with distinct and complex host-parasite interactions that directly involve the host's immune system. In this study, we analysed the relationship between the production of intracytoplasmic cytokines after in vitro stimulation with the recombinant antigens CRA (cytoplasmatic repetitive antigen) or FRA (flagellar repetitive antigen) from Trypanosoma cruzi and the chronic cardiac or indeterminate clinical forms of Chagas disease. The chagasic patient groups consisted of 39 individuals, selected at the Chagas Disease Unit of the Oswaldo Cruz University Hospital, whom presented either a cardiac form without cardiac dilatation (CARD 1), cardiac form with cardiac dilatation (CARD 2) or indeterminate form (IND). Blood samples were obtained from these patients and cultured in the presence of CRA or FRA. The cytokines produced by lymphocytes and monocytes after antigen stimulation were analysed by flow cytometry. Our results showed that the IFN-γ and TNF-α, produced by CD8+ T lymphocytes after in vitro stimulation with CRA, differed among chagasic patients with CARD 1, CARD 2 or IND. We propose that these cytokines could be utilized as immunological markers for clinical cardiac forms of Chagas disease. In a prospective study of patients presenting IND and CARD 1, the assay performed in this paper could serve as a tool to monitor therapeutic interventions, thus improving the patient's quality of life. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Souza-Smith, Kurtz, Molina and Breslin (2010). Adaptation of Mesenteric Collecting Lymphatic Pump Function Following Acute Alcohol Intoxication. Microcirculation 17(7), 514-524. Abstract Objective: Acute alcohol intoxication increases intestinal lymph flow by unknown mechanisms, potentially impacting mucosal immunity. We tested the hypothesis that enhanced intrinsic pump function of mesenteric lymphatics contributes to increased intestinal lymph flow during alcohol intoxication. Methods: Acute alcohol intoxication was produced by intragastric administration of 30% alcohol to conscious, unrestrained rats through surgically implanted catheters. Time-matched controls received either no bolus, vehicle, or isocaloric dextrose. Thirty minutes after alcohol administration, rats were anesthetized and mesenteric collecting lymphatics were isolated and cannulated to study intrinsic pumping parameters. In separate experiments, mesenteric lymphatics were isolated to examine direct effects of alcohol on intrinsic pump activity. Results: Lymphatics isolated from alcohol-intoxicated animals displayed significantly decreased CF compared to the dextrose group, elevated SVI versus all other groups, and decreased myogenic responsiveness compared to sham. Elevating pressure from 2 to 4 cm H2O increased the volume flow index 2.4-fold in the alcohol group versus 1.4-fold for shams. Isolated lymphatics exposed to 20 mM alcohol had reduced myogenic tone, without changes in CF or SVI. Conclusions: Alcohol intoxication enhances intrinsic pumping by mesenteric collecting lymphatics. Alcohol directly decreases lymphatic myogenic tone, but effects on phasic contractions occur by an unidentified mechanism. [ABSTRACT FROM AUTHOR]

The airway mucosal surfaces are constantly exposed to inhaled particles that can be potentially toxic, infectious or allergenic and should elicit inflammatory changes. The proximal and distal air spaces, however, are normally infection and inflammation free due to a specialized interplay between cellular and molecular components of the pulmonary innate immune system. Surfactant protein D (SP-D) is an epithelial-cell-derived immune modulator that belongs to the small family of structurally related Ca2+-dependent C-type collagen-like lectins. While collectins can be detected in mucosal surfaces of various organs, SP-A and SP-D (the ‘lung collectins’) are constitutively expressed in the lung at high concentrations. Both proteins are considered important players of the pulmonary immune responses. Under normal conditions however, SP-A-/- mice display no pathological features in the lung. SP-D-/- mice, on the other hand, show chronic inflammatory alterations indicating a special importance of this molecule in regulating immune homeostasis and the function of the innate immune cells. Recent studies in our laboratory and others implied significant associations between changes in SP-D levels and the presence of airway inflammation both in animal models and patients raising a potential usefulness of this molecule as a disease biomarker. Research on wild-type and mutant recombinant molecules in vivo and in vitro showed that SP-D binds carbohydrates, lipids and nucleic acids with a broad spectrum specificity and initiates phagocytosis of inhaled pathogens as well as apoptotic cells. Investigations on gene-deficient and conditional over expressor mice in addition, provided evidence that SP-D directly modulates macrophage and dendritic cell function as well as T cell-dependent inflammatory events. Thus, SP-D has a unique, dual functional capacity to induce pathogen elimination on the one hand and control of pro-inflammatory mechanisms on the other, suggesting a potential suitability for therapeutic prevention and treatment of chronic airway inflammation without compromising the host defence function of the airways. This paper will review recent findings on the mechanisms of immune-protective function of SP-D in the lung. Cite this as: L. R. Forbes and A. Haczku, Clinical & Experimental Allergy, 2010 (40) 547–562. [ABSTRACT FROM AUTHOR]

Corticosteroids, such as prednisone and dexamethasone, are commonly prescribed medications that suppress the immune system and decrease inflammation. Common side effects of long-term treatment with corticosteroids include weight gain, osteoporosis, and diabetes mellitus. This paper reviews the literature on psychiatric and cognitive changes during corticosteroid therapy and potential treatment options. Hypomania and mania are the most common mood changes during acute corticosteroid therapy, although depression has also been reported. However, depression is reported to be more common than mania during long-term treatment with corticosteroids. A decline in declarative and working memory is also reported during corticosteroid therapy. Corticosteroids are associated with changes in the temporal lobe, detected by structural, functional, and spectroscopic imaging. The mood and cognitive symptoms are dose dependent and frequently occur during the first few weeks of therapy. Other risk factors are not well characterized. Controlled trials suggest that lithium and phenytoin can prevent mood symptoms associated with corticosteroids. Lamotrigine and memantine also have been shown to reverse, at least partially, the declarative memory effects of corticosteroids. Uncontrolled trials suggest that antipsychotics, anti-seizure medications, and perhaps some antidepressants can also be useful for normalizing mood changes associated with corticosteroids. Thus, both the symptoms and treatment response are similar to those of bipolar disorder. Moreover, corticosteroid-induced mood and cognitive alterations have been shown to be reversible with dose reduction or discontinuation of treatment. [ABSTRACT FROM AUTHOR]

Neuroimmunomodulation describes the field focused on understanding the mechanisms by which the central nervous system interacts with the immune system, potentially leading to changes in animal behavior. Nonetheless, not many articles dealing with neuroimmunomodulation employ behavior as an analytical endpoint. Even fewer papers deal with social status as a possible modifier of neuroimmune phenomena. In the described sets of experiments, we tackle both, using a paradigm of social dominance and subordination. We first review data on the effects of different ranks within a stable hierarchical relationship. Submissive mice in this condition display more anxiety-like behaviors, have decreased innate immunity, and show a decreased resistance to implantation and development of melanoma metastases in their lungs. This suggests that even in a stable, social, hierarchical rank, submissive animals may be subjected to higher levels of stress, with putative biological relevance to host susceptibility to disease. Second, we review data on how dominant and submissive mice respond differentially to lipopolysaccharide (LPS), employing a motivational perspective to sickness behavior. Dominant animals display decreased number and frequency in several aspects of behavior, particularly agonistic social interaction, that is, directed toward the submissive cage mate. This was not observed in submissive mice that maintained the required behavior expected by its dominant mate. Expression of sickness behavior relies on motivational reorganization of priorities, which are different along different social ranks, leading to diverse outcomes. We suggest that in vitro assessment of neuroimmune phenomena can only be understood based on the behavioral context in which they occur. [ABSTRACT FROM AUTHOR]

Ablation of liver tissue produces in situ tumoural antigens and elicits specific immune responses. The aim of this review is to examine the available data about the local and systemic responses produced and to compare differences between the methods available. A literature search was undertaken for all papers focusing on immune responses following ablative therapy of the liver, including experimental and clinical studies. Following ablative procedures, the cellular response is elicited by the presentation of antigens by dendritic cells to specific CD4+ T cells, which in turn stimulate natural killer or CD8+ cytotoxic cells. The local release of intracellular debris activates Kupffer cells to produce cytokines, which, in the immediate vicinity, activate monocytes/macrophages or specific T cells that respond and produce systemic reactions such as fever, thrombocytopaenia or shock. The immune responses elicited by cryotherapy, both cellular and cytokine, seem far greater than those produced by radiofrequency or microwave ablation, probably as a consequence of the peculiar mechanism of cell death of the former (disruptive necrosis). This mechanism is considered central to the pathogenesis of cryoshock. Ablative techniques stimulate the immune system and provide an easy way to achieve in vivo vaccination against tumoural antigens. Immunomodulatory approaches have the potential to augment the initial immune stimulation and this combined approach could pave the way to a more selective and specific method of treating liver tumours. [ABSTRACT FROM AUTHOR]

Control of the acute phase of Trypanosoma cruzi infection is critically dependent on cytokine-mediated macrophage activation to intracellular killing, natural killer (NK) cells, CD4+ T cells, CD8+ T cells and B cells. Cell-mediated immunity in T. cruzi infection is also modulated by cytokines, but in addition to parasite-specific responses, autoimmunity can be also triggered. Importantly, cytokines may also play a role in the cell-mediated immunity of infected subjects. Here we studied the role of cytokines in the regulation of innate and adaptive immunity during the acute phase of T. cruzi infection in Wistar rats. Melatonin is an effective regulator of the immune system. Macrophages and T lymphocytes, which have melatonin receptors, are target cells for the immunomodulatory function of melatonin. In this paper melatonin was orally given via two protocols: prior to and concomitant with infection. Both treatments were highly effective against T. cruzi with enhanced action for the concomitant treatment. The data suggest an up-regulation of the TH-1 immune response as all analyzed parameters, interleukin (IL)-4, IL-10, transforming growth factor-β1 and splenocyte proliferation, displayed reduced levels as compared with the untreated counterparts. However, the direct effects of melatonin on immune cells have not been fully investigated during T. cruzi infection. We conclude that in light of the current results, melatonin exerted important therapeutic benefits through its immune regulatory effects. [ABSTRACT FROM AUTHOR]

This paper reveals that a discontinuous in vitro induction, namely, the periodic presence and absence of foreign induction factors, might be, under a certain condition, more effective to stimulate stem cells' differentiation than a continuous induction. Bone marrow stem cells (BMSCs) derived from Sprague Dawley rats were employed to examine the effects of discontinuous additions of osteogenic supplements with a series of alternate frequency in contrast to those with continuous induction or no induction. The results demonstrated that a suitable discontinuous induction was more able to achieve osteogenesis than not only no induction but also the associated continuous induction. Additionally, the osteogenic supplements were confirmed to enhance cell differentiation but suppress cell proliferation. So, the combination of differentiation extent per cell and cell number accounts for the “unexpected” good osteogenic effect of the discontinuous induction. The induction effect was found to be dependent upon alternate frequency, and the optimum alternate period in our experimental systems was determined to be around 4 days. Since it is very common to change culture medium every 2−4 days, such a strategy of discontinuous induction does not bring any extra manual work but reduces the consumption of foreign induction factors and significantly enhances the global differentiation efficacy. Our work thus affords a convenient and practical approach to achieve differentiation of BMSCs, which might be useful for potential large-scale culture and differentiation of stem cells. Meanwhile, the existence of optimum frequency implies some unknown inherent rhythms of cell proliferation and differentiation. [ABSTRACT FROM AUTHOR]

Selenium (Se) is an essential micronutrient that, through its incorporation into selenoproteins, plays a pivotal role in maintaining optimal health. Insufficient intake of Se enhances predisposition to diseases associated with oxidative stress to cells and tissues while supplementation above the recommended levels has been shown to confer health benefits such as enhanced immune competence and resistance to viral infections and in animal models and human studies. Recent studies have also shown that different sources of Se differ in their bioavailability and bioactivity and that Se-enriched milk may be a superior source of Se. In this paper, we briefly describe the nature of selenoproteins, sources of Se in diets and the known mechanisms by which Se/selenoproteins regulate redox balance, augment immune function and mediate resistance to viral infections. [ABSTRACT FROM AUTHOR]

The hygiene hypothesis suggests that the absence of infectious exposure at a critical point in immune system development leads to a greater risk for the later development of atopic disease. As a result, it may be possible to devise strategies that can block the onset of atopic diseases such as asthma. This paper outlines the rationale, background and design for the Trial of Infant Probiotic Supplementation study, which is designed to test the effectiveness of a daily infant probiotic supplement in the first 6 months of life in preventing the development of early markers of asthma. [ABSTRACT FROM AUTHOR]