Carlos Eduardo Tosta

The effects of anesthesia with thiopental on T lymphocyte responses to antigen and mitogens in vivo and in vitro.

In this study we show that antigen-specific lymphocyte proliferation and interleukin (IL)-2 production by peripheral blood lymphocytes from patients under thiopental anesthesia are significantly depressed. In contrast, mitogen-induced lymphocyte proliferation and IL-2 secretion are not depressed. We have also shown that tetanus toxoid (TT) specific CD4+ T cell clones, with a known cytokine production profile, were sensitive to the inhibitory effects of thiopental and exhibited decreased proliferation to TT as well as decreased secretion of IL-2. We observed no difference regarding IL-4 production by these clones. The data suggest that the immunosuppressive effect of thiopental is confined to antigen-specific responses. In addition, we have shown that whereas IL-2 and interferon-gamma production is dramatically impaired by the drug, IL-4 production is not significantly altered. This last finding has important implications regarding the type of immune response that is most affected by this anesthetic agent. In spite of the transient decrease in antigen-driven IL-2 synthesis, no clinical evidence of infection was noted in any healthy patient.

Novel Microtechnique for Assessment of Postnatal Maturation of the Phagocytic Function of Neutrophils and Monocytes

ABSTRACT We describe a simple test for the evaluation of phagocytosis and provide a chart of reference values to evaluate normal phagocytosis by age. We assessed the postnatal maturation of phagocytic function of neutrophils and monocytes. Phagocytosis was evaluated in newborn children delivered vaginally or by cesarean section, infants, preschool children, schoolchildren, and adult subjects. Two drops of blood were placed on a microscope slide and incubated with Saccharomyces cerevisiae yeasts, and phagocytosis was evaluated by microscopy. Our technique showed results comparable to or better than those obtained by other usual techniques. The neutrophils of newborn children delivered by cesarean section showed a phagocytic capacity 45% higher than those of neonates delivered vaginally, whereas neutrophils from children in the latter group showed the lowest phagocytic capacity of all age groups. Phagocytosis by neutrophils reached the levels seen in adults at about the first year of life, while there were no important variations in phagocytosis by monocytes in the different age groups. The technique described is reliable and fast, uses only a few drops of blood, and allows better preservation of cell function due to the minimal manipulation to which the cells are submitted. The delayed maturation of the phagocytic function by neutrophils may account for the high levels of susceptibility of newborn and infant children to bacterial infections. This practical method of assessment of phagocytosis may allow the diagnosis of primary or secondary phagocytic deficiencies to be made more easily and may allow better monitoring and treatment of those with dysfunctions of these cells.

Inhibition of nitric oxide production by macrophages in chromoblastomycosis: a role for Fonsecaea pedrosoi melanin.

Chromoblastomycosis is a chronic and progressive deep mycosis that is usually found in tropical and subtropical areas. Fonsecaea pedrosoi is considered its most frequent etiologic agent and causes a typical granulomatous inflammatory response, whose degree reflects the immune status of the host. Since macrophages play a fundamental role in the control of the infection, this study aimed at investigating the production of oxygen reactive specimens, the phagocytic capacity and the production of nitric oxide (NO) by macrophages employing in vitro assays and an in vivo model of chromoblastomycosis. Our results demonstrated that, during the infection, peritoneal macrophages show an increased phagocytic capacity and H2O2 production, but also a reduced ability to produce NO. Moreover, F. pedrosoi stimulated H2O2 production in vitro but not the synthesis of NO. The incubation of IFNγ and LPS-stimulated macrophages with melanin, obtained from the fungus, inhibited NO production. Examination of the liver and spleen of infected animals, at day 30 or 60 following inoculation, showed a progressive increase in the number and size of granulomas, indicating that macrophages are properly mobilized and activated. Our data suggest that the inability of the host to clear F. pedrosoi, leading to a chronic disease, is due, at least in part, to the inhibition of NO synthesis by macrophages by fungus-produced melanin.

Soroprevalência da infecção pelo vírus da hepatite B e pelo plasmódio em Lábrea, Amazonas: estimativa da ocorrência de prováveis coinfecções

The Amazon region is known for the high occurrence of hepatitis B virus (HBV) infection, and accounts for more than 98% of malaria cases in Brazil. Despite the controversy, it has been proposed that when associated they may lead to important effects in the natural history of both infections. This study estimates the prevalence of coinfection within general population of an endemic region of HBV and malaria in the Brazilian Amazon. The prevalence of HBsAg was 3.3% (95% CI 2.1%-5.1%,) and total anti-HBc 49.9% (95% CI 45.9%-53.8%). The prevalence of antibodies against Plasmodium vivax and Plasmodium falciparum antigens was 51.4% (311/605) (95% CI 47.3%-55.4%). Related to the simultaneous presence of malaria antibodies and HBV serological markers, in 1.8% (11/605), (95% CI 1.0%-3.3%), the presence of HBsAg was also demonstrated, mean age 26 years (p <0.001). This study points to similarities in the distribution of these diseases, such as the occurrence mainly among young adults. The events may occur in different times. Also shown differences such as the low risk of malaria in the group up to fifteen years, where HBV circulates with moderate intensity. The prevalence of HBV and malaria coinfection is in fact less than the rates of HBsAg carriage, showing a heterogeneous pattern related to the clinical spectrum of HBV infection.

Antibody response to Salmonella typhi in human schistosomiasis mansoni.

Antibody response to Salmonella typhi O and H antigens was evaluated in 24 individuals with either hepatointestinal or hepatosplenic schistosomiasis mansoni before and after typhoid vaccination, and compared with that of non-infected controls. Before vaccination, Schistosoma-infected patients showed a higher frequency of positive antibody to O antigen and the same frequency to H antigen when compared with that of healthy individuals. However, those with hepatosplenic schistosomiasis showed higher titres of antibody to H antigen than those with hepatointestinal disease or healthy individuals. Infected subjects, particularly those with hepatointestinal disease, showed a decreased response after typhoid vaccine. This diminished ability to mount an immune response towards typhoid antigens during schistosomiasis may interfere with the clearance of the bacteria from blood stream and, therefore, play a role in the prolonged survival of salmonella as observed in some patients with chronic salmonellosis associated with schistosomiasis.

T cell-dependent immunodepression in vivo in Schistosoma mansoni infected patients

T-cell function was evaluated in 29 patients with either hepatointestinal or hepatosplenic schistosomiasis by intradermal tests to recall antigens. Immunodepression was detected in 26% of the subjects with hepatointestinal schistosomiasis and in 50% of those with the hepatosplenic form. Cellular immunodepression was related to worm load and spleen size. This non specific T-cell immunodepression may represent a serious constraint to the elimination of intracellular pathogens both in hepatosplenic or hepatointestinal schistosomiasis.

Effects of lethal and non-lethal malaria on the mononuclear phagocyte system.

Estudou-se o efeito da infeccao causada por especie letal (Plasmodium berghei) e nao- letal (P. yoelii) de plasmodio sobre o sistema de fagocitos mononucleares de camundongo BALB/c. O P. yoelii causou maior e mais prolongada expansao e ativacao do sistema de macrofagos. As duas mais importantes populacoes de fagocitos esplenicos - macrofagos de polpa vermelha e da zona marginal - exibiam maior aumento do numero de celulas nesta infeccao. Durante a evolucao da malaria por P. berghei, o baco foi progressivamente ocupado por tecido hematopoietico e, na fase terminal da infeccao, observou-se significativa deplecao dos linfocitos e macrofagos esplenicos. Os dados apresentados indicam que a evolucao da malaria depende do tipo de interacao entre o plasmodio e o sistema de fagocitos mononucleares.

Coevolutionary networks: a novel approach to understanding the relationships of humans with the infectious agents.

Human organism is interpenetrated by the world of microorganisms, from the conception until the death. This interpenetration involves different levels of interactions between the partners including trophic exchanges, bi-directional cell signaling and gene activation, besides genetic and epigenetic phenomena, and tends towards mutual adaptation and coevolution. Since these processes are critical for the survival of individuals and species, they rely on the existence of a complex organization of adaptive systems aiming at two apparently conflicting purposes: the maintenance of the internal coherence of each partner, and a mutually advantageous coexistence and progressive adaptation between them. Humans possess three adaptive systems: the nervous, the endocrine and the immune system, each internally organized into subsystems functionally connected by intraconnections, to maintain the internal coherence of the system. The three adaptive systems aim at the maintenance of the internal coherence of the organism and are functionally linked by interconnections, in such way that what happens to one is immediately sensed by the others. The different communities of infectious agents that live within the organism are also organized into functional networks. The members of each community are linked by intraconnections, represented by the mutual trophic, metabolic and other influences, while the different infectious communities affect each other through interconnections. Furthermore, by means of its adaptive systems, the organism influences and is influenced by the microbial communities through the existence of transconnections. It is proposed that these highly complex and dynamic networks, involving gene exchange and epigenetic phenomena, represent major coevolutionary forces for humans and microorganisms.

Ação de mosquiteiros impregnados com deltametrina sobre a morbidade da malária em uma área da Amazônia Brasileira

In 1992 an investigation regarding the value of insecticide impregnated mosquito nets was conducted in the municipality of Costa Marques, Rondonia. Impregnated mosquito nets gave similar protection to those not impregnated, without modifying the incidence of infection during the season of low transmission. The multivariate analysis for age and antibody titre showed a significant protection of impregnated nets against the risk of infection only in the season of high transmission, when bed nets were used more correctly. There was no difference in the effect of both kinds of bed nets in the prevention of high parasitaemia. At the end of the study, there was a reduction of the prevalence of splenomegaly in both groups but hematocrit values rose to normal in the below 15 year olds using impregnated nets.In 1992 an investigation regarding the value of insecticide impregnated mosquito nets was conducted in the municipality of Costa Marques, Rondonia. Impregnated mosquito nets gave similar protection to those not impregnated, without modifying the incidence of infection during the season of low transmission. The multivariate analysis for age and antibody titre showed a significant protection of impregnated nets against the risk of infection only in the season of high transmission, when bed nets were used more correctly. There was no difference in the effect of both kinds of bed nets in the prevention of high parasitaemia. At the end of the study, there was a reduction of the prevalence of splenomegaly in both groups but hematocrit values rose to normal in the below 15 year olds using impregnated nets.

Co-infecção humana pelo plasmódio e o vírus da hepatite B: aspectos clínicos, sorológicos e imunológicos

The Amazon region is known for a high prevalence of hepatitis B infection, and accounts for more than 90% of malaria cases in Brazil. It has been suggested that the occurrence of coinfections may be important, and may influence the natural history of both diseases. This study evaluated 545 patients with acute malaria, in Coari, Western Brazilian Amazon. 333 (61.1%) presented Plasmodium vivax malaria, 193 (35.4%) Plasmodium falciparumand 19 (3.5%) mixed infections. The HBsAg prevalence was 4.2% and total anti-HBc 49.7%. Patients with HBV serological markers presented no clinical differences than those with malaria only, nor showed any association with classic signs of hepatic disorder. Although showing no statistical significance, HBsAg reactive subjects presented lower parasitic load and higher antibody titers, suggesting the possibility that the immune response in a coinfected individual is differentiated and leads to a variation in the parasite load and antibody production.