Rosana Maria Feio Libonati

Estradiol, but Not Dehydroepiandrosterone, Decreases Parasitemia and Increases the Incidence of Cerebral Malaria and the Mortality in Plasmodium berghei ANKA-Infected CBA Mice

Objective: The effect of castration and subsequent replacement of dehydroepiandrosterone (DHEA) or estradiol on parasitemia, mortality and incidence of cerebral malaria (CM) was evaluated in CBA mice infected with Plasmodium berghei ANKA. Methods: Female mice were castrated, and groups of 12–15 animals received daily injections of DHEA, estradiol or saline. Four days after the start of treatment, mice were inoculated with 1 × 106P. berghei ANKA-parasitized erythrocytes. DHEA treatment was continued during the 5 days after infection, and estradiol was administered during the follow-up. Parasitemia was evaluated daily in Giemsa-stained blood smears. Signs of CM were determined by the manifestation of coma, limb paralysis and/or convulsions. Plasma TNF-α levels were evaluated by sandwich ELISA. Nitric oxide synthase (NOS) activity in the brain of moribund mice was measured by the method of Bredt and Snyder. Results: In non-castrated infected mice, the incidence of CM was 50%, and plasma TNF-α increased and brain NOS activity decreased compared to non-infected controls. Castration had no major effect on the parameters analyzed (parasitemia, mortality, CM incidence, TNF-α levels or NOS activity). Estradiol replacement caused a decrease in parasitemia but resulted in higher CM incidence and faster mortality, with an increase in NOS activity. Conclusions: Estradiol modulated the immune response of P. berghei ANKA-infected CBA mice, decreasing parasitemia and increasing NOS activity, and impacted negatively on survival and CM incidence, showing that neuroimmunoendocrine interactions are important in the physiopathogenesis of malaria infections.

Abordagem metabólica e nutricional da lipodistrofia em uso da terapia anti-retroviral

A terapia anti-retroviral altamente ativa, usada contra o Virus da Imunodeficiencia Humana, vem possibilitando a melhora do quadro clinico-laboratorial de portadores da Sindrome da Imunodeficiencia Adquirida. Contudo, alteracoes metabolicas e complicacoes morfologicas, associadas ao uso da terapia, vem sendo investigadas. A utilizacao prolongada desta terapia tem um impacto importante sobre o estado nutricional dos pacientes. Antes da sua utilizacao, a perda de peso e a desnutricao, consequencias das infeccoes oportunistas, eram os maiores problemas nutricionais. Atualmente, o foco principal das discussoes tem sido as complicacoes metabolicas e morfologicas, dentre elas a lipodistrofia, com a dislipidemia, a resistencia a insulina, a osteopenia, e a distribuicao alterada da gordura corporal, aumentando assim os riscos de doencas cardiovasculares. A nutricao desempenha um papel fundamental no suporte da saude desses pacientes, integrando as equipes multiprofissionais, promovendo a melhora da adesao a terapia anti-retroviral e do prognostico da doenca. No entanto, para que se tenha mais conhecimento sobre a terapia, as proporcoes de seus efeitos adversos, e o perfil nutricional desses pacientes, a curto e a longo prazos, e de suma importância que se estude mais sobre este assunto, a fim de permitir perspectivas de um regime terapeutico mais seguro dentro de seus alcances metodologicos, proporcionando uma melhor qualidade de vida aos pacientes.

Immunohistochemical evaluation of macrophage activity and its relationship with apoptotic cell death in the polar forms of leprosy

The objective of the present study was to investigate the correlation between macrophage activity and apoptosis in the polar forms of leprosy because the immunopathological phenomena involved in these forms are still poorly understood. For this purpose, 29 skin biopsy samples obtained from patients with the polar forms of leprosy were analyzed. Macrophage activity and apoptosis were evaluated by immunohistochemistry using lysozyme, CD68, iNOS and caspase 3 as markers. The nonparametric Mann-Whitney test and Spearmans linear correlation test were used for statistical analysis. The results suggest that the apoptosis rate is under the direct influence of macrophage activity in lesions of patients with the tuberculoid form. In contrast, in lepromatous lesions other factors seem to induce programmed cell death, possibly TGF-beta. Further studies are necessary to identify additional factors involved in the immunopathogenesis of leprosy.

Immunohistochemical analysis of the expression of TNF-alpha, TGF-beta, and caspase-3 in subcutaneous tissue of patients with HIV Lipodystrophy Syndrome

INTRODUCTION HIV Lipodystrophy Syndrome (HIVLS) is a multifactorial clinical expression that presents alterations in the metabolism and distribution pattern of body fat via immunological changes capable of disrupting homeostasis. This study aimed to analyze the degree of inflammatory, anti-inflammatory, and apoptosis activity in the subcutaneous tissue of patients, based on the expression of Tumor Necrosis Factor-α (TNF-α), Transforming Growth Factor-β (TGF-β), and caspase-3, respectively, and correlate them with clinical data and with each other. METHODS This is a cross-analytical study. The biopsy of subcutaneous cellular tissue was performed on the right thigh of 19 patients with HIVLS who were attended to at a university hospital, and four people without HIV and lipodystrophy, for comparison. The type of lipodystrophy and the estimation of body fat were obtained during the consultation or obtained from medical charts. The cytokine expression was observed in the adipose tissue through the streptavidin-biotin peroxidase method, and analyzed by optical microscopy. RESULTS Despite the mixed clinical form having been prevalent in both genders, men were more lipoatrophic and women were more lipohypertrophic. Men showed higher expression of TNF-α and caspase-3 than women. Patients with lipodystrophy had higher expression of TNF-α and caspase-3 and lower TGF-β, compared to the control group. The percentage of body fat was negatively correlated with the expression of TNF-α and caspase-3. Longer durations of infection and use of antiretroviral therapy (ARVT) were positively associated with the levels of TNF-α. The expression of caspase-3 and TGF-β was associated with higher levels of TNF-α. CONCLUSION Regardless of the clinical form, HIVLS is characterized by a chronic inflammatory process associated with the male gender, the percentage of body fat, and lipoatrophy manifestations. There is increased apoptotic activity in more inflamed tissues and there is correlation between TNF-α and TGF-β, which suggests a possible negative feedback mechanism between the inflammatory and anti-inflammatory activity.

Environmental impact and seroepidemiology of HTLV in two communities in the eastern Brazilian amazon.

The objective of this study was to detect antibodies for human T lymphotropic virus (HTLV) in subjects residing in two communities located in the eastern Brazilian Amazon and on the shores of the Tucuruí hydroelectric power plant. A total of 657 serum samples were analysed using an enzyme‐linked immunosorbent assay with an anti‐HTLV antibody (Symbiosis™, São Paulo, Brazil), demonstrating a virus prevalence of 4.7%. Most individuals with HTLV were aged over 30 years (P = 0.013), were unmarried (P = 0.019), resided in the area for more than 10 years (P = 0.001), had a low level of education (P = 0.015), and had a family income of up to

Avaliação do consumo alimentar em pacientes HIV positivos com lipodistrofia

305 (100%). In contrast, there was no significant association between infection and sex, city of birth, haemotransfusion, or previous surgery. The prevalence observed in these communities suggests that the residents should be concerned about HTLV infection, and that some areas may become endemic for HTLV. J. Med. Virol. 85:1585–1590, 2013.

CLINICAL AND IMMUNOLOGICAL PROFILES OF ANAEMIA IN CHILDREN AND ADOLESCENTS WITH PLASMODIUM VIVAX MALARIA IN THE PARÁ STATE, BRAZILIAN AMAZON

Objective: To identify the dietary intake profile of HIV positive patients with lipodystrophy. Materials and Methods: This is a cross-sectional, descriptive study, conducted in 2010 with HIV-infected patients with lipodystrophy using antiretroviral therapy. Patients were recruited in a reference Hospital of Northern Brazil, in BelemPara. We have collected socio-demographic and food intake related data. To evaluate the food consumption, we have used a 24 hour recordatory method, applied in two week days and one day in the weekend. Results: We have evaluated 39 patients. Diet composition analysis in relation to macronutrients showed an adequate intake of calories and fat, but with high levels of protein (> 15%) and insufficient carbohydrate ( 52 mg). The dietary cholesterol was excessive (>200 mg) in both genders. Conclusion: The diet consumed by lipodystrophy patients presented inadequate profile in relation to macronutrients and micronutrients, indicating the need for nutritional counseling.

An analysis of the influence of sex hormones on Balb/c mice infected with Plasmodium berghei.

Children and adolescents are at great risk for developing iron deficiency anaemia worldwide. In the tropical areas, malaria and intestinal parasites may also play an important role in anaemia pathogenesis. This study aimed at evaluating clinical and immunological aspects of anaemia in children and adolescents with Plasmodium vivax malaria, in the Pará State, Brazil. A longitudinal study was performed in two Reference Centers for malaria diagnosis in the Brazilian Amazon in children and adolescents with malaria (n = 81), as compared to a control group (n = 40). Patients had blood drawn three times [before treatment (D0), after treatment (D7) and at the first cure control (D30)] and hemogram, autoantibody analysis (anticardiolipin, antibodies against normal RBC membrane components) and cytokine studies (TNF and IL-10) were performed. Stool samples were collected for a parasitological examination. Malaria patients had a 2.7-fold greater chance of anaemia than the control group. At D0, 66.1% of the patients had mild anaemia, 30.5% had moderate and 3.5% had severe anaemia. Positivity to intestinal helminths and/or protozoa at stool examinations had no influence on anaemia. Patients had significantly lower levels of plasmatic TNF than control individuals at D0. Low TNF levels were more prevalent among patients with moderate/severe anaemia than in those with mild anaemia and among anaemic patients than in anaemic controls. TNF levels were positively correlated with the haemoglobin rates and negatively correlated with the interval time elapsed between the onset of symptoms and diagnosis. Both plasma TNF levels and haemoglobin rates increased during the follow-up period. The IL-10 levels were lower in patients than in the controls at day 0 and decreased thereafter up to the end of treatment. Only the anti-anticardiolipin autoantibodies were associated with moderate/severe anaemia and, possibly by reacting with the parasite glycosylphosphatidylinositol (a powerful stimulator of TNF production), may have indirectly contributed to decrease the TNF levels, which could be involved in the malarial vivax anaemia of these children and adolescents. More studies addressing this issue are necessary to confirm these findings and to add more information on the multifactorial pathogenesis of the malarial anaemia.

Myocarditis associated with Plasmodium vivax malaria: a case report

Sex steroids can determine several responses in the clinical evolution of malaria. Seventy Balb-c mice were randomly distributed into 7 groups (10 mice per group): G1 to G6 corresponding to castrated females, castrated females that received estradiol cypionate, uncastrated females, castrated males, castrated males that received intramuscular testosterone decanoate and uncastrated males infected with Plasmodium berghei, and G7, the control group. The mice were evaluated with regard to survival, parasitemia, temperature, body weight, hemoglobin level (anemia) and splenic index. Castrated infected females had lower rates of survival. In the castrated male, the administration of testosterone had a negative influence on survival. There was a progressive increase in parasitemia without repercussions for survival. Castration had a significant influence on weight gain in females. Weight loss was observed in all mice, except those in groups G2 and G5, although this bore no direct relation to parasitemia. A significant and progressive decline in temperature and hemoglobin levels occurred in mice over the course of their infection, which differed from the G7 group. The weight of the spleen in relation to total body weight did not differ among the groups of infected mice, but was significantly higher than it was for the control group.

Dyslipidemia in Patients with Lipodystrophy in the Use of Antiretroviral Therapy

Malaria remains a major public health problem in Brazil where Plasmodium vivax is the predominant species, responsible for 82% of registered cases in 2013. Though benign, P. vivax infection may sometimes evolve with complications and a fatal outcome. Here, we report a severe case of P. vivax malaria in a 35-year-old Brazilian man from a malaria endemic area, who presented with reversible myocarditis.