Activation of monocytes and cytokine production in patients with peripheral atherosclerosis obliterans

BACKGROUND: Arterial peripheral disease is a condition caused by the blocked blood flow resulting from arterial cholesterol deposits within the arms, legs and aorta. Studies have shown that macrophages in atherosclerotic plaque are highly activated, which makes these cells important antigen-presenting cells that develop a specific immune response, in which LDLox is the inducing antigen. As functional changes of cells which participate in the atherogenesis process may occur in the peripheral blood, the objectives of the present study were to evaluate plasma levels of anti-inflammatory and inflammatory cytokines including TNF-α, IFN-γ, interleukin-6 (IL-6), IL-10 and TGF-β in patients with peripheral arteriosclerosis obliterans, to assess the monocyte activation level in peripheral blood through the ability of these cells to release hydrogen peroxide (H(2)O(2)) and to develop fungicidal activity against Candida albicans (C. albicans) in vitro. METHODS: TNF-α, IFN-γ, IL-6, IL-10 and TGF-β from plasma of patients were detected by ELISA. Monocyte cultures activated in vitro with TNF-alpha and IFN-gamma were evaluated by fungicidal activity against C. albicans by culture plating and Colony Forming Unit (CFU) recovery, and by H(2)O(2 )production. RESULTS: Plasma levels of all cytokines were significantly higher in patients compared to those detected in control subjects. Control group monocytes did not release substantial levels of H(2)O(2 )in vitro, but these levels were significantly increased after activation with IFN-γ and TNF-α. Monocytes of patients, before and after activation, responded less than those of control subjects. Similar results were found when fungicidal activity was evaluated. The results seen in patients were always significantly smaller than among control subjects. Conclusions: The results revealed an unresponsiveness of patient monocytes in vitro probably due to the high activation process occurring in vivo as corroborated by high plasma cytokine levels

Prophylaxis of deep-vein thrombosis after lower extremity amputation: Comparison of low molecular weight heparin with unfractionated heparin

OBJETIVO: Comparar a eficácia e segurança da profilaxia com heparina de baixo peso molecular (enoxaparina) versus heparina não fracionada (HNF). MÉTODOS: Setenta e cinco pacientes (59 homens e 16 mulheres ), submetidos a amputação maior dos membros inferiores (30 acima do joelho e 45 abaixo do joelho ), foram tratados ao acaso com HNF subcutânea (5,000 IU -2x/dia ) ou enoxaparina subcutânea (40mg/dia ) durante a hospitalização . A profilaxia teve início 12 horas antes da cirurgia ou , em casos emergenciais , no primeiro dia de pós-operatório. RESULTADOS: Os dois grupos de tratamento foram comparáveis em termos de características gerais . A avaliação da TVP foi feita por meio de exame clínico diário e pelo mapeamento dúplex antes e 5-8 dias após a cirurgia . A TVP foi documentada no lado operado em 9,75% dos pacientes tratados com enoxaparina e em 11,76% dos pacientes tratados com HNF (p=0,92) e houve um caso de TVP bilateral em cada grupo . Sangramentos não foram verificados nos 2 grupos . CONCLUSÃO: A enoxaparina e HNF foram igualmente eficientes e seguras para a profilaxia da TVP em pacientes submetidos à amputação de membros inferiores .PURPOSE: To compare the efficacy and safety of a low molecular weight heparin (enoxaparin) with unfractionated heparin (UH) in this prophylaxis. METHODS: Seventy five patients (59 men and 16 women), undergoing major lower extremity amputation (30 above-knee and 45 below-knee), were randomized to be treated with subcutaneous UH (5,000 IU t.i.d.) or enoxaparin (40mg/day) during hospitalization. Prophylaxis was started 12 hours before surgery or, in emergency cases, in the first postoperative day. RESULTS: The two groups were comparable with regard to baseline characteristics. Evaluation of DVT was performed by daily clinical examination and by duplex scanning before and 5 to 8 days after surgery. DVT was documented in the operated limb in 9.75% in patients treated with enoxaparin and in 11.76% in patients treated with UH (p=0.92) and there was one bilateral thrombosis in each group . Bleeding complications were not observed in both groups. CONCLUSION: Enoxaparin and UH were both efficient and safe for the prophylaxis of DVT in patients submitted to lower extremity amputation