RESUMO
Consumption of different types of oil may have different effects on cardiovascular risk. The exact role of maize oil, cod liver oil, soya oil and extra virgin olive oil on endothelial function, oxidative stress and inflammation is unknown. We evaluated the effect of acute consumption of these types of oil on endothelial function, oxidative stress and inflammation in healthy adults. Thirty-seven healthy volunteers were randomised to receive an oral amount of each type of oil or water. Endothelial function was evaluated by gauge-strain plethysmography at baseline and 1, 2 and 3 h after consumption. Oxidative stress status was determined by total lipid peroxides (PEROX), while inflammatory process was estimated by measuring the soluble form of vascular adhesion molecule 1. Serum levels of the two previous markers were measured at baseline and 3 h after oil consumption. Reactive hyperaemia (RH) was significantly decreased after maize oil consumption compared with controls (P < 0.05). However, the consumption of cod liver oil and soya oil induced a significant improvement of RH after 1 h, compared with controls (P < 0.05). There was no significant effect of any type of oil consumption on endothelium-independent dilatation, total lipid PEROX and vascular adhesion molecule 1 serum levels. Consumption of maize oil leads to impaired endothelial function, while soya oil and cod liver oil slightly improve endothelial function. However, all types of oils did not affect inflammatory process and systemic oxidative stress, suggesting that their effect on endothelial function may not be mediated by free radicals bioavailability.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Óleo de Fígado de Bacalhau/farmacologia , Óleo de Milho/farmacologia , Endotélio Vascular/fisiologia , Ácidos Graxos/farmacologia , Antebraço/irrigação sanguínea , Inflamação/sangue , Óleos/farmacologia , Óleos de Plantas/farmacologia , Adulto , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Óleo de Milho/efeitos adversos , Gorduras Insaturadas na Dieta/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Humanos , Inflamação/prevenção & controle , Azeite de Oliva , Estresse Oxidativo/efeitos dos fármacosRESUMO
Tumor necrosis factor alpha (TNF-alpha) is a cytokine, implicated in the pathogenesis of many inflammatory diseases, as well as in the immune-mediated response to infection, especially against intracellular pathogens. TNF-alpha antagonists have represented a revolution in the management of connective tissue diseases, such as rheumatoid arthritis. However, the use of these agents has been implicated with the emergence of a growing number of opportunistic infections. Here we report the case of a visceral Leishmaniasis in a 77-year-old woman who had been previously treated for rheumatoid arthritis with infliximab. The atypical presentation of this patient, previously treated with an anti-TNF-alpha biologic agent, where no splenomegaly or hepatomegaly was identified, is emphasized.
Assuntos
Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Hospedeiro Imunocomprometido , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/imunologia , Idoso , Exame de Medula Óssea , Feminino , Humanos , Infliximab , Leucopenia/etiologiaRESUMO
BACKGROUND: Studies indicate that myeloperoxidase (MPO) is associated with disease progression and severity in heart failure (HF), while it may provide a mechanistic link between inflammation and adverse cardiac remodeling. The mechanisms that regulate MPO are unclear, while it is unknown whether specific treatments such as HMG-CoA reductase inhibitors and xanthine oxidase inhibitors may modify MPO. Therefore in the present study we examined the effects of rosuvastatin and allopurinol on MPO levels in patients HF. METHODS: Sixty clinically stable patients with systolic HF were randomized to receive rosuvastatin 10mg/day, allopurinol 300mg/day or placebo and followed up for 1 month. Plasma levels of MPO and serum levels of soluble CD40 ligand, interleukin-6, and oxidized LDL were determined using ELISA. All measurements were made before and after 1-month treatment. RESULTS: Rosuvastatin significantly reduced plasma levels of MPO (p=0.003), which remained unchanged in the other groups. Furthermore, the change of MPO levels in the rosuvastatin-treated group was significantly different compared with the other groups (p<0.05). Rosuvastatin administration also led to a significant decrease in oxidized LDL (p=0.009), while the other inflammatory markers remained unchanged in all groups. In the total population, a significant correlation was observed between the baseline levels of MPO and hsCRP (r=0.275, p=0.027), fibrinogen (r=0.278, p=0.025), and sCD40L (r=0.288, p=0.021). CONCLUSIONS: Short-term treatment with rosuvastatin regulates inflammatory process in patients with heart failure by significantly reducing plasma levels of MPO. This finding reveals a novel pleiotropic effect of statins in patients with heart failure, and provides further insights into the pathophysiological mechanisms of MPO in heart failure.
Assuntos
Fluorbenzenos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Peroxidase/sangue , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Idoso , Alopurinol/farmacologia , Alopurinol/uso terapêutico , Biomarcadores/sangue , Colesterol/sangue , LDL-Colesterol/sangue , Doença Crônica , Feminino , Fluorbenzenos/uso terapêutico , Insuficiência Cardíaca/sangue , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inflamação/tratamento farmacológico , Masculino , Pirimidinas/uso terapêutico , Rosuvastatina Cálcica , Sulfonamidas/uso terapêutico , Triglicerídeos/sangueRESUMO
INTRODUCTION: Congestive heart failure (HF) is characterised by increased proinflammatory stimulation and impaired endothelial function. Statin treatment exerts a beneficial effect on endothelial function and inflammatory process in patients with atherosclerosis. However, its effect in patients with HF is not well studied. Therefore, in the present study we compared the effect of short-term treatment with rosuvastatin or ezetimibe on endothelial function in patients with HF. METHODS: In this double-blind, placebo controlled, cross-over trial, 22 patients with HF were randomised to receive ezetimibe 20 mg/d or rosuvastatin 10 mg/d for 4 weeks, with 4 weeks wash-out period between the two interventions. Endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery at the beginning and at the end of each treatment period. RESULTS: There was no change in the baseline brachial diameter after treatment with either ezetimibe (p=NS) or rosuvastatin (p=NS). However, there was a significant improvement of FMD in the rosuvastatin group (p<0.05) but not in the ezetimibe group (p=NS). The changes in lipid levels were similar between groups (p=NS). The change in FMD was not significantly correlated with the decrease of serum LDL in either the ezetimibe or rosuvastatin treated groups. CONCLUSIONS: Rosuvastatin improves endothelial function in patients with congestive heart failure, by mechanisms independent of lipid-lowering. On the contrary, lipid-lowering treatment achieved by ezetimibe is unable to affect endothelial function in these patients. These findings indicate a direct beneficial effect of statins in patients with congestive heart failure, further to lipid-lowering.
Assuntos
Azetidinas/uso terapêutico , Endotélio Vascular/fisiologia , Fluorbenzenos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Lipídeos/sangue , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Azetidinas/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Endotélio Vascular/efeitos dos fármacos , Ezetimiba , Feminino , Fluorbenzenos/farmacologia , Insuficiência Cardíaca/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Pirimidinas/farmacologia , Rosuvastatina Cálcica , Sulfonamidas/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologiaRESUMO
BACKGROUND: Patients with chronic heart failure (HF) are characterized by alterations in matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) levels. However, the impact of hypolipidemic and antioxidant treatment in MMPs and TIMPs is unknown. In the present study, we sought to compare the effects of statins and xanthine oxidase inhibitors on circulating levels of MMPs and TIMPs in patients with chronic HF. METHODS: Forty-two clinically stable patients with mild to moderate HF were randomized to receive rosuvastatin 10 mg or allopurinol 300 mg daily and followed up for 1 month. Serum levels of MMP-2, -9, TIMP-1, and -2 were measured before and after treatment. RESULTS: Levels of MMP-2 and -9 were significantly decreased in the rosuvastatin group (from 251±52 ng/ml and 400±206 ng/ml to 215±47 ng/ml and 309±166 ng/ml, p<0.001 and p<0.05 respectively), but not in the allopurinol group. In the rosuvastatin group, TIMP-2 levels were significantly increased (from 85±17 ng/ml to 93±16 ng/ml, p<0.05), while TIMP-1 remained unchanged. In the allopurinol group, no significant changes were observed regarding the levels of TIMPs. CONCLUSIONS: Short-term rosuvastatin but not allopurinol administration decreases MMP-2 and -9 and increases TIMP-2 levels.
Assuntos
Alopurinol/administração & dosagem , Biomarcadores/sangue , Fluorbenzenos/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Idoso , Doença Crônica , Quimioterapia Combinada , Matriz Extracelular/metabolismo , Feminino , Sequestradores de Radicais Livres/administração & dosagem , Insuficiência Cardíaca/imunologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Rosuvastatina Cálcica , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismoRESUMO
BACKGROUND: Depression has been associated with increased inflammatory process. Although anti-depressive medication has anti-inflammatory effect in major depression, its role in patients with heart failure (HF) is unknown. In the present study we evaluated the impact of antidepressive medication on the expression of proinflammatory cytokines and acute phase response proteins, in patients with HF and major depression. METHODS: The study population consisted of 250 patients with HF (154 suffering from major depression). Patients with major depression were under selective serotonin reuptake inhibitors (SSRIs, n=120) or tricyclic antidepressants (TCA) and/or serotonin/norepinephrine reuptake inhibitors (SNRIs) (n=34), for at least 6 months. RESULTS: Levels of TNF-alpha, IL-6, CRP and fibrinogen were not significantly different between HF patients with depression under treatment and those without depression (p=NS for all). However, TNF-alpha and CRP levels were significantly lower in patients receiving TCA/SNRI compared to patients receiving SSRIs or those without depression (p<0.05 for all). Similarly, patients under TCA/SNRI had significantly lower heart rate compared to those treated with SSRIs or those without depression. In multivariate analysis, treatment with SNRI/TCA was an independent predictor for log(TNF-alpha) (beta=0.036(SE:0.016) and log(CRP) (beta=0.099(SE:0.048), p=0.041). CONCLUSIONS: In the present study we demonstrate for the first time that treatment of patients with HF and major depression with TCAs/SNRIs, is associated with lower levels of TNF-alpha and CRP, suggesting that the type of antidepressive treatment may have a significant effect on the underlying inflammatory process.