Relation between the fatty acid composition of peripheral blood mononuclear cells and measures of immune cell function in health free-living subjects aged 25-72 y

Background: There is little information about the relation between the fatty acid composition of human immune cells and the function of those cells over the habitual range of fatty acid intakes. Objective: The objective of the study was to determine the relation between the fatty acid composition of human peripheral blood mononuclear cell (PBMC) phospholipids and the functions of human immune cells. Design: One hundred fifty healthy adult subjects provided a fasting blood sample. The phagocytic and oxidative burst activities of monocytes and neutrophils were measured in whole blood. PBMCs were isolated and used to measure lymphocyte proliferation in response to the T cell mitogen concanavalin A and the production of cytokines in response to concanavalin A or bacterial lipopolysaccharide. The fatty acid composition of plasma and PBMC phospholipids was determined. Results: Wide variations in fatty acid composition of PBMC phospholipids and immune cell functions were identified among the subjects. The proportions of total Polyunsaturated fatty acids (PUFAs), of total n-6 and n-3 PUFAs, and of several individual PUFAs in PBMC phospholipids were positively correlated with phagocytosis by neutrophils and monocytes, neutrophil oxidative burst, lymphocyte proliferation, and interferon gamma production. The ratios of saturated fatty acids to PUFAs and of n-6 to n-3 PUFAs were negatively correlated with these same immune functions. The relation of PBMC fatty acid composition to monocyte oxidative burst was the reverse of its relation to monocyte phagocytosis and neutrophil oxidative burst. Conclusion: Variations in the fatty acid composition of PBMC phospholipids account for some of the variability in immune cell functions among healthy adults.

PASSCLAIM - gut health and immunity

Background The gut and immune system form a complex integrated structure that has evolved to provide effective digestion and defence against ingested toxins and pathogenic bacteria. However, great variation exists in what is considered normal healthy gut and immune function. Thus, whilst it is possible to measure many aspects of digestion and immunity, it is more difficult to interpret the benefits to individuals of variation within what is considered to be a normal range. Nevertheless, it is important to set standards for optimal function for use both by the consumer, industry and those concerned with the public health. The digestive tract is most frequently the object of functional and health claims and a large market already exists for gut-functional foods worldwide. Aim To define normal function of the gut and immune system and describe available methods of measuring it. Results We have defined normal bowel habit and transit time, identified their role as risk factors for disease and how they may be measured. Similarly, we have tried to define what is a healthy gut flora in terms of the dominant genera and their metabolism and listed the many, varied and novel methods for determining these parameters. It has proved less easy to provide boundaries for what constitutes optimal or improved gastric emptying, gut motility, nutrient and water absorption and the function of organs such as the liver, gallbladder and pancreas. The many tests of these functions are described. We have discussed gastrointestinal well being. Sensations arising from the gut can be both pleasant and unpleasant. However, the characteristics of well being are ill defined and merge imperceptibly from acceptable to unacceptable, a state that is subjective. Nevertheless, we feel this is an important area for future work and method development. The immune system is even more difficult to make quantitative judgements about. When it is defective, then clinical problems ensure, but this is an uncommon state. The innate and adaptive immune systems work synergistically together and comprise many cellular and humoral factors. The adaptive system is extremely sophisticated and between the two arms of immunity there is great redundancy, which provides robust defences. New aspects of immune function are discovered regularly. It is not clear whether immune function can be "improved". Measuring aspects of immune function is possible but there is no one test that will define either the status or functional capacity of the immune system. Human studies are often limited by the ability to sample only blood or secretions such as saliva but it should be remembered that only 2% of lymphocytes circulate at any given time, which limits interpretation of data. We recommend assessing the functional capacity of the immune system by: measuring specific cell functions ex vivo, measuring in vivo responses to challenge, e. g. change in antibody in blood or response to antigens, determining the incidence and severity of infection in target populations during naturally occurring episodes or in response to attenuated pathogens.

Estimating the direct aerosol radiative perturbation: impact of ocean surface representation and aerosol non-sphericity

Atmospheric aerosols are now actively studied, in particular because of their radiative and climate impacts. Estimations of the direct aerosol radiative perturbation, caused by extinction of incident solar radiation, usually rely on radiative transfer codes and involve simplifying hypotheses. This paper addresses two approximations which are widely used for the sake of simplicity and limiting the computational cost of the calculations. Firstly, it is shown that using a Lambertian albedo instead of the more rigorous bidirectional reflectance distribution function (BRDF) to model the ocean surface radiative properties leads to large relative errors in the instantaneous aerosol radiative perturbation. When averaging over the day, these errors cancel out to acceptable levels of less than 3% (except in the northern hemisphere winter). The other scope of this study is to address aerosol non-sphericity effects. Comparing an experimental phase function with an equivalent Mie-calculated phase function, we found acceptable relative errors if the aerosol radiative perturbation calculated for a given optical thickness is daily averaged. However, retrieval of the optical thickness of non-spherical aerosols assuming spherical particles can lead to significant errors. This is due to significant differences between the spherical and non-spherical phase functions. Discrepancies in aerosol radiative perturbation between the spherical and non-spherical cases are sometimes reduced and sometimes enhanced if the aerosol optical thickness for the spherical case is adjusted to fit the simulated radiance of the non-spherical case.

Allogeneic apoptotic thymocyte-stimulated dendritic cells expand functional regulatory T cells

P>Dendritic cells (DCs) play an important role in the clearance of apoptotic cells. The removal of apoptotic cells leads to peripheral tolerance, although their role is still not clear. We show that the uptake of apoptotic thymocytes by DCs converts these cells into tolerogenic DCs resistant to maturation by lipopolysaccharide, modulating the production of interleukin-12 and up-regulating the expression of transforming growth factor-beta(1) latency associated peptide. We also observed that DCs pulsed with apoptotic cells in the allogeneic context were more efficient in the expansion of regulatory T cells (Tregs), and that this expansion requires contact between DCs and the T cell. The Tregs sorted from in vitro culture suppressed the proliferation of splenocytes in vitro in a specific and non-specific manner. In the in vivo model, the transfer of CD4+ CD25- cells to Nude mice induced autoimmunity, with cell infiltrate found in the stomach, colon, liver and kidneys. The co-transfer of CD4+ CD25- and CD4+ CD25+ prevented the presence of cell infiltrates in several organs and increased the total cell count in lymph nodes. Our data indicate that apoptotic cells have an important role in peripheral tolerance via induction of tolerogenic DCs and CD4+ CD25+ Foxp3+ cells that present regulatory functions.

Peritrophic membrane role in enhancing digestive efficiency Theoretical and experimental models

The pentrophic membrane (PM) is an anatomical structure surrounding the food bolus in most insects. Rejecting the idea that PM has evolved from coating mucus to play the same protective role as it, novel functions were proposed and experimentally tested. The theoretical principles underlying the digestive enzyme recycling mechanism were described and used to develop an algorithm to calculate enzyme distributions along the midgut and to infer secretory and absorptive sites. The activity of a Spodoptera frugiperda microvillar aminopeptidase decreases by 50% if placed in the presence of midgut contents. S. frugiperda trypsin preparations placed into dialysis bags in stirred and unstirred media have activities of 210 and 160%, respectively, over the activities of samples in a test tube. The ectoperitrophic fluid (EF) present in the midgut caeca of Rhynchosciara americana may be collected. If the enzymes restricted to this fluid are assayed in the presence of PM contents (PMC) their activities decrease by at least 58%. The lack of PM caused by calcofluor feeding impairs growth due to an increase in the metabolic cost associated with the conversion of food into body mass. This probably results from an increase in digestive enzyme excretion and useless homeostatic attempt to reestablish destroyed midgut gradients. The experimental models support the view that PM enhances digestive efficiency by: (a) prevention of non-specific binding of undigested material onto cell Surface; (b) prevention of excretion by allowing enzyme recycling powered by an ectoperitrophic counterflux of fluid; (c) removal from inside PM of the oligomeric molecules that may inhibit the enzymes involved in initial digestion; (d) restriction of oligomer hydrolases to ectoperitrophic space (ECS) to avoid probable partial inhibition by non-dispersed undigested food. Finally,PM functions are discussed regarding insects feeding on any diet. (C) 2008 Elsevier Ltd. All rights reserved.

Pure strategy equilibria of multidimensional and non-monotonic auctions

We give necessary and sufficient conditions for the existence of symmetric equilibrium without ties in interdependent values auctions, with multidimensional independent types and no monotonic assumptions. In this case, non-monotonic equilibria might happen. When the necessary and sufficient conditions are not satisfied, there are ties with positive probability. In such case, we are still able to prove the existence of pure strategy equilibrium with an all-pay auction tie-breaking rule. As a direct implication of these results, we obtain a generalization of the Revenue Equivalence Theorem. From the robustness of equilibrium existence for all-pay auctions in multidimensional setting, an interpretation of our results can give a new justification to the use of tournaments in practice.

Hematological parameters in two neotropical freshwater teleost, Leporinus macrocephalus (Anostomidae) and Prochilodus lineatus (Prochilodontidae)

Leporinus macrocephalus is a non-migratory omnivore fish which occurs in waters with a relatively high oxygen rate. Prochilodus lineatus is a migratory fish that inhabits deoxygenated hypolimnion and feeds on detritus material. Red blood cell, thrombocytes and white blood cell counts, hematocrit and hemoglobin, serum electrolytes (sodium, potassium, calcium, magnesium and chloride), metabolic products (total serum protein and plasma glucose) and blood cells major axis length for L. macrocephalus and P. lineatus were compared. White blood cell counts for both species indicated a similar activity of the immune functions. The concentration of total protein, sodium, calcium, magnesium and chloride, MCV, as well as red blood cells, monocytes, and thrombocytes size in L. macrocephalus were higher than in P. lineatus. However, P. lineatus had higher red blood cell counts, hematocrit and hemoglobin, which reflects a considerable adaptation to survive in an environment with low levels of oxygen.

Imunidade inata da glândula mamária bovina: resposta à infecção

A imunidade na glândula mamária pode ser classificada, assim como em outros sistemas, em inata ou inespecífica e adaptativa ou específica. A imunidade inata é a defesa predominante durante os estágios iniciais da infecção. As respostas inespecíficas estão presentes no local da infecção ou são ativadas rapidamente por numerosos estímulos e não aumentam pela exposição repetida ao mesmo agente etiológico. O primeiro obstáculo enfrentado por um patógeno para adentrar o úbere é composto pela barreira formada pelo esfíncter do teto e pelo tampão de queratina formado pelo epitélio queratinizado. Uma vez que o microrganismo tenha atravessado o canal do teto e alcançado a cisterna mamária, passam a atuar diversos fatores solúveis e celulares. Dentre os fatores solúveis, estão presentes: lactoperoxidase, sistema complemento, citocinas, lactoferrina, lisozima e NAGase. As defesas celulares inespecíficas na glândula mamária são representadas pelos neutrófilos, pelos macrófagos e pelas células natural killer. Na medida em que esses mecanismos funcionam adequadamente, a maioria dos patógenos será rapidamente eliminada antes que o sistema imune específico seja ativado, sem resultar em alterações na quantidade ou qualidade do leite produzido. Uma melhor compreensão sobre os mecanismos de defesa da glândula mamária e suas alterações durante os períodos críticos da infecção é imprescindível para o desenvolvimento de métodos mais eficazes de profilaxia e controle da mastite, a principal doença dos ruminantes leiteiros. O presente estudo revisou os principais aspectos responsáveis pelo desenvolvimento da imunidade inata na glândula mamária bovina.

Immunization with pVAXhsp65 Decreases Inflammation and Modulates Immune Response in Experimental Encephalomyelitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluating and classifying contaminated areas based on loss functions using annealing simulations

This paper presents a methodology based on geostatistical theory for quantifying the risks associated with heavy-metal contamination in the harbor area of Santana, Amapa State, Northern Brazil. In this area there were activities related to the commercialization of manganese ore from Serra do Navio. Manganese and arsenic concentrations at unsampled sites were estimated by postprocessing results from stochastic annealing simulations; the simulations were used to test different criteria for optimization, including average, median, and quantiles. For classifying areas as contaminated or uncontaminated, estimated quantiles based on functions of asymmetric loss showed better results than did estimates based on symmetric loss, such as the average or the median. The use of specific loss functions in the decision-making process can reduce the costs of remediation and health maintenance. The highest global health costs were observed for manganese. (c) 2008 Elsevier B.V. All rights reserved

Imbalance of IL-2, IFN-gamma and IL-10 secretion in the immunosuppression associated with human paracoccidioidomycosis

Patients with paracoccidioidomycosis (PCM) display a certain degree of immunecompromise characterized by lymphocyte hyporesponsiveness to the main Paracoccidioides brasiliensis antigen (gp43). To determine whether cytokines are involved in this state, we evaluated the secretion of IL-2, IL-10 and IFN-gamma by peripheral blood mononuclear cells (PBMC) from patients with the acute (AF) and chronic (CF) forms of PCM and from healthy, P. brasiliensis-sensitized subjects. gp43-stimulated PBMC from healthy subjects produced substantial amounts of IL-2, IFN-gamma and IL-10, whereas PBMC from AF and CF patients produced low levels of IL-2 and IFN-gamma but substantial amounts of IL-10, Phytohaemagglutinin-induced cytokine secretion was comparable among AF and CF patients and healthy subjects, suggesting integrity of non-specific cellular immune mechanisms in PCM. gp43-pulsed adherent cells, but not non-adherent cells, mere the main source of IL-10, Moreover, IL-2 and IFN-gamma secretion correlated inversely with the amount of specific antibodies produced by patients and healthy subjects. Our results suggest that the imbalance in cytokine production of patients with PCM plays a role in the gp43-hyporesponsiveness and the marked (non-protective) antibody production of these patients. (C) 2001 Academic Press.

Correlation between cell-mediated immunity and clinical forms of paracoccidioidomycosis

Cellular immune response to specific and non-specific stimulants was investigated, both in vivo and in vitro, in 29 healthy controls and in 53 previously untreated patients with the chronic isolated organic form (CIOF), the chronic mixed form (CMF) and the acute progressive form (APF) of paracoccidioidomycosis. The study included skin tests to Paracoccidioides brasiliensis antigen (PbAg) and phytohaemagglutinin (PHA), DNCB sensitization, determination of T lymphocytes and complement rosette-forming cells, lymphocyte transformation and leucocyte migration inhibition tests using PbAg and PHA. Patients displayed staggered cutaneous response to PHA and to PbAg, with marked decrease in intensity in the APF group. DNCB sensitization test and proliferative response of lymphocytes to PHA and PbAg were severely depressed in most of the patients. Leucocyte migration inhibition indices to PbAg were highly positive, while response to PHA was slightly decreased regardless of the clinical form. The number of T lymphocytes was reduced in most of patients and in them the number of complement-rosette forming cells was normal. The distribution of patients according to a suppression index, based in the results of the tests employed, revealed a tendency towards an increased degree of cellular immunosuppression from the least severe (CIOF) to the most severe (APF) clinical form of the disease. On the whole, the present study demonstrated a gamut of immunological reactivity in paracoccidioidomycosis. © 1985.

Patologia do Coração na AIDS. Estudo de 73 Necropsias Consecutivas

Purpose - To study the incidence and the etiology of the cardiac lesions in AIDS patients. Methods - The autopsy protocols and the filled slides of the heart from 73 consecutive AIDS patients were reviewed. There were, at least, 2 slides of each heart stained by haematoxylin-eosin; when indicated, Ziehl-Nielsen, Gram and Gomori Grocott stains were used. Results - No cause of death was assigned to the heart. There was involvement of the heart in 66 (90%) cases. Marked atrophy of cardiac fibers with or without lipomatosis was observed in 38 patients. Interstitial infiltrates of myocardium were present in 38 necropsies and in 13 of these cases a probable pathogen was demonstrated: cryptococcus neoforms in three cases and mycobacteria tuberculosis, atypical mycobacteria, toxoplasma gondii, trypanosoma cruzi and cytomegalovirus in two cases each. Bacterial endocarditis was found in 4 autopsies and Kaposi sarcome in one. The pericardium was involved in 22 cases; in 12 there was only non specific mononuclear infiltration. Conclusion - Autopsy examination of the heart from AIDS patients revealed frequent pathologic involvement.

The deep mycoses in HIV infection

The deep mycoses are uncommon infections, usually acquired from the inhalation or ingestion of fungal spores, sometimes from the soil in areas of endemicity, such as in the Americas and south-east Asia, or from decaying vegetable matter. They are also seen in immunocompromised persons and, increasingly, in HIV-infected persons. Respiratory involvement is frequent, with granuloma formation, and mucocutaneous involvement may be seen. Oral lesions of the deep mycoses are typically chronic but non-specific, though nodular or ulcerative appearances are common. Person-to-person transmission is rare. In HIV disease, the most common orofacial involvement of deep mycoses has been in histoplasmosis, cryptococcosis, aspergillosis and zygomycosis. Diagnosis is usually confirmed by lesional biopsy although culture may also be valuable. Treatment is with amphotericin or an azole.

Chitosan nanoparticles for non-viral gene therapy

The cationic polysaccharide chitosan has been widely used for non-viral transfection in vitro and in vivo and has many advantages over other polycations. Chitosan is biocompatible and biodegradable and protects DNA against DNase degradation. However following administration the ChitosanDNA polyplexes must overcome a series of barriers before DNA is delivered to the cell nucleus. This paper describes the most important parameters involved in the chitosan-DNA interaction and their effects of on the condensation, shape, size and protection of DNA. Strategies developed for chitosanDNA polyplexes to avoid non-specific interaction with blood components and to overcome intracellular obstacles as the crossing of die cell membrane, endosomal escape and nuclear import are presented. © 2006 American Chemical Society.