Queto T.,Laboratorio Of Fisiopatologia Humana |
Xavier-Elsas P.,Federal University of Rio de Janeiro |
Gardel M.A.,Laboratorio Of Fisiopatologia Humana |
De Luca B.,Laboratorio Of Fisiopatologia Humana |
And 7 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2010
Rationale: The mechanism of action of diethylcarbamazine (DEC), an antifilarial drug effective against tropical pulmonary eosinophilia, remains controversial. DEC effects on microfilariae depend on inducible NO synthase (iNOS). In eosinophilic pulmonary inflammation, its therapeutic mechanism has not been established. We previously described the rapid up-regulation of bone marrow eosinophilopoiesis in ovalbumin (OVA)-sensitized mice by airway allergen challenge, and further evidenced the down-regulation of eosinophilopoiesis by iNOS- and CD95L-dependent mechanisms. Objectives:We investigated whether: (1) DEC can prevent the effects of airway challenge of sensitized mice on lungs and bone marrow, and (2) its effectiveness depends on iNOS/CD95L. Methods: OVA-sensitized BALB/c mice were intranasally challenged for 3 consecutive days, withDECadministered over a 12-, 3-, or 2-day period, ending at the day of the last challenge. We evaluated: (1) airway resistance, cytokine (IFN-γ, IL-4, IL-5, and eotaxin) production, and pulmonary eosinophil accumulation; and (2) bone marrow eosinophil numbers in vivo and eosinophil differentiation ex vivo. Measurements and Main Results: DEC effectively prevented the effects of subsequent challenges on: (1) airway resistance, Th1/Th2 cytokine production, and pulmonary eosinophil accumulation; and (2) eosinophilopoiesis in vivo and ex vivo. Recovery from unprotected challenges included full responses to DEC during renewed challenges. DEC directly suppressed IL-5-dependent eosinophilopoiesis in naive bone marrow. DEC was ineffective in CD95L-deficient gld mice and in mice lacking iNOS activity because of gene targeting or pharmacological blockade. Conclusions: DEC has a strong impact on pulmonary eosinophilic inflammation in allergic mice, as well as on the underlying hemopoietic response, suppressing the eosinophil lineage by an iNOS/ CD95L-dependent mechanism. Source
Falcao M.C.B.A.,Federal University of Pernambuco |
Zirpoli J.C.,Federal University of Pernambuco |
de Albuquerque V.M.,University of Pernambuco |
Filho B.M.,Federal University of Pernambuco |
And 9 more authors.
Arquivos Brasileiros de Cardiologia | Year: 2012
Background: The massive use of Highly-Active Antiretroviral Therapy (HAART) in individuals with human immunodeficiency virus (HIV) coincided with an increase in cardiovascular disease, a major cause of morbidity and mortality in this group. Objective: To determine the frequency of carotid atherosclerosis and the association between biomarker levels and carotid intimal-medial thickening in HIV-positive individuals treated for HIV at referral centers in Pernambuco. Methods: This was a cross-sectional study of 122 HIV-positive patients. Subclinical carotid atherosclerosis was considered with the presence of increased intimal-medial thickness of the common carotid artery > 0.8 mm or plaques in the carotid ultrasound. The following inflammatory biomarkers were analyzed: IL6, IL1-β, TNF-α, high-sensitivity CRP, sVCAM-1 and sICAM-1. Results: Of the 122 patients analyzed, most were men (60.7%) aged > 40 years (57.4%) receiving HAART (81.1%). The prevalence of atherosclerosis was 42.6% (52 cases). Patients older than 40 years and intermediate or high Framingham score were more likely to develop atherosclerosis at the univariate analysis. Age older than 40 years (OR = 6.57, 95%CI: 2.66 to 16.2, p = 0.000), male gender (OR = 2.76, 95%CI: 1.12 to 6.79, p = 0.027) and presence of syndrome metabolic (OR = 2.27, 95%CI: 0.94 to 5.50, p = 0.070) were associated with atherosclerosis at the multivariate analysis. Elevated levels of inflammatory cytokines and adhesion molecules were not associated with the presence of atherosclerosis. Conclusion: There was no association between inflammatory biomarkers, adhesion molecules and presence of carotid atherosclerosis. However, a higher chance of subclinical atherosclerosis was observed in men, those older than 40 years, with intermediate / high Framingham score or metabolic syndrome. Source
Monteiro V.S.,University of Pernambuco |
Monteiro V.S.,Institute Medicina Integral Professor Fernando Figueira IMIP |
Lacerda H.R.,University of Pernambuco |
Lacerda H.R.,Federal University of Pernambuco |
And 8 more authors.
Arquivos Brasileiros de Cardiologia | Year: 2011
Background: Antiretroviral therapy has dramatically increased life expectancy in patients with HIV/AIDS although atherosclerosis has been associated with long-standing therapy. Objective: To investigate the prevalence of atherosclerosis in patients with AIDS undergoing antiretroviral therapy and the influence of different schemes and duration of treatment. Methods: HIV/AIDS patients were approached during routine consultations. Those who had been on antiretroviral therapy for at least two years had their blood collected for analysis of lipid profile and fasting glycemia and underwent cardiac CT for quantification of calcium score within six days at the most. Atherosclerosis was defined as calcium score greater than zero (CAC>0). Traditional risk factors, metabolic syndrome and Framingham score were analyzed. Results: Fifty-three patients performed cardiac CT. Twenty-seven (50.94%) were male, mean age 43.4 years; 20.00% had hypertension, 3.77% diabetes, 67.92% hypercholesterolemia, 37.74% hypertriglyceridemia and 47.17% low HDL. Thirteen (24.53%) met criteria for metabolic syndrome and 96.23% were classified in Framingham score as "low risk." Ten patients (18.87%) were smokers. Mean duration of antiretroviral treatment was 58.98 months. Coronary atherosclerosis occurred in 11 (20.75%) patients. Duration of antiretroviral therapy was not related to atherosclerosis (p = 0.41) and there were no significant differences between different antiretroviral regimens (p = 0.71). Among traditional risk factors, smoking (OR = 27.20; p = 0.023) and age (OR = 20.59; p = 0.033) were significant in the presence of atherosclerosis. There was a trend towards a positive association of atherosclerosis with hypercholesterolemia (OR = 8.30; p = 0.0668). Conclusion: Factors associated with atherosclerosis were age, smoking and hypercholesterolemia. Duration and type of antiretroviral therapy had no influence on the prevalence of atherosclerosis. Source
Ribeiro E.L.,Federal University of Pernambuco |
Ribeiro E.L.,Instituto Aggeu Magalhaes |
Barbosa K.P.D.S.,Federal University of Pernambuco |
Fragoso I.T.,Federal University of Pernambuco |
And 7 more authors.
Mediators of Inflammation | Year: 2014
Diethylcarbamazine (DEC) is an antifilarial drug with potent anti-inflammatory properties as a result of its interference with the metabolism of arachidonic acid. The aim of the present study was to evaluate the anti-inflammatory activity of DEC in a mouse model of acute inflammation (carrageenan-induced pleurisy). The injection of carrageenan into the pleural cavity induced the accumulation of fluid containing a large number of polymorphonuclear cells (PMNs) as well as infiltration of PMNs in lung tissues and increased production of nitrite and tumor necrosis factor-α and increased expression of interleukin-1β, cyclooxygenase (COX-2), and inducible nitric oxide synthase. Carrageenan also induced the expression of nuclear factor-B. The oral administration of DEC (50 mg/Kg) three days prior to the carrageenan challenge led to a significant reduction in all inflammation markers. The present findings demonstrate that DEC is a potential drug for the treatment of acute lung inflammation. © 2014 Edlene Lima Ribeiro et al. Source
Donato M.A.M.,Instituto Aggeu Magalhaes |
Ribeiro E.L.,Instituto Aggeu Magalhaes |
de Oliveira Cipriano Torres D.,Instituto Aggeu Magalhaes |
Soares e Silva A.K.,Instituto Aggeu Magalhaes |
And 4 more authors.
Tissue and Cell | Year: 2015
Sildenafil is an important phosphodiesterase inhibitor used to treat a range of diseases, including cardiovascular disease, prostatic hyperplasia and pulmonary hypertension. Its main mechanism of action is the inhibition of phosphodiesterase 5, leading to increased intracellular cyclic guanosine 3',5'-monophosphate. This second messenger plays an interesting role in the reproductive tract. The aim of the present study was to evaluate the effect of Sildenafil on folliculogenesis and fertility in mice. To do so, C57BL/6 wild-type mice and inducible nitric oxide synthase knockout (iNOS-/-) mice were treated with Sildenafil, and reproductive variables were evaluated. The treated and control animals underwent estrous cycle and fertility assay. Lipid profile, serum nitric oxide levels and the expression of endothelial nitric oxide synthase, inducible nitric oxide synthase and guanylate cyclase were evaluated. Additionally, ovaries were submitted to histological and morphological analysis. The findings demonstrated that chronic treatment with Sildenafil had no effect on folliculogenesis or fertility in C57BL/6 mice, suggesting that this drug can be safely used by women of childbearing age. © 2015 Elsevier Ltd. Source