As a by-product of heme catabolism by the heme oxygenase system, carbon monoxide (CO) has been neglected for many years, and only recently has its role as an essential signaling molecule been appreciated. In the past decade, the use of CO gas in pre-clinical experimental models of disease has produced some remarkable data indicating that its therapeutic delivery to mammals could alleviate inflammatory processes and cardiovascular disorders. However, the inherent toxic nature of CO cannot be ignored, knowing that inhalation of uncontrolled amounts of this gas can ultimately lead to serious systemic complications and neuronal derangements. From a clinical perspective, a key question is whether a safe and therapeutically effective threshold of CO can be reached locally in organs and tissues without delivering potentially toxic amounts through the lung. The advent of CO-releasing molecules (CO-RMs), a group of compounds capable of carrying and liberating controlled quantities of CO in cellular systems, appears a plausible alternative in the attempt to overcome the limitations of CO gas. Although in its infancy and far from being used for clinical applications, the CO-RMs technology is supported by very encouraging biological results and reflected by the chemical versatility of these compounds and their endless potential to be transformed into CO-based pharmaceuticals.

Carbon monoxide-releasing molecules are emerging as a new class of pharmacological agents that regulate important cellular function by liberating CO in biological systems. Here, we examined the role of carbon monoxide-releasing molecule 3 (CORM-3) in modulating neuroinflammatory responses in BV-2 microglial cells, considering its practical application as a novel therapeutic alternative in the treatment of stroke. BV-2 microglia cells were incubated for 24 h in normoxic conditions with thrombin alone or in combination with interferon-␥ to simulate the inflammatory response. Cells were also subjected to 12 h of hypoxia and reoxygenated for 24 h in the presence of thrombin and interferon-␥. In both set of experiments, the anti-inflammatory action of CORM-3 was evaluated by assessing its effect on nitric oxide production (nitrite levels) and tumor necrosis factor (TNF)-␣ release. CORM-3 (75 M) did not show any cytotoxicity and markedly attenuated the inflammatory response to thrombin and interferon-␥ in normoxia and to a lesser extent in hypoxia as evidenced by a reduction in nitrite levels and TNF-␣ production. Inactive CORM-3, which does not liberate CO and is used as a negative control, failed to prevent the increase in inflammatory mediators. Blockade of endogenous CO production by tin protoporphyrin-IX did not change the anti-inflammatory activity of CORM-3, suggesting that CO liberated from the compound is responsible for the observed effects. In addition, inhibition of the mitogen-activated protein kinases phosphatidyl inositol 3 kinase and extracellular signal-regulated kinase amplified the anti-inflammatory effect of CORM-3. These results suggest that the anti-inflammatory activity of CORM-3 could be exploited to mitigate microglia activity in stroke and other neuroinflammatory diseases.Stroke is the major cause of disabilities in adults, leaving more than half of the survivors dependent on others for everyday activities (Wolfe et al., 2000). It is also a major cause of dementia, depression, epilepsy, and falls (Rothwell et al., 2004). This pathological event is characterized by blockade of blood supply to the brain and consequently oxygen and glucose deprivation, which lead to necrotic cell death and tissue infarct. Rescuing the surrounding partially ischemic penumbra depends on the severity of brain edema, subsequent neuroinflammation, and production of free radicals.Microglia are the main inflammatory-reacting cells in the brain after ischemia (Suk, 2004). They act through redoxsensitive inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and NAD(P)H oxidase, which produce NO, superoxide, peroxynitrite, and other reactive oxygen species (ROS) that mediate their phagocytic ability. Free radicals generated during the inflammatory process can directly damage neurons by interacting with their lipid-rich membranes or by increasing ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor susceptibility to the toxic effects of glutamate (Zhao et al., 2004).Another important ...

Infected popliteal aneurysm is a rare high-risk condition that can present as an emergency with acute rupture and sepsis. Management of acute ischemia in the presence of local and systemic sepsis is challenging. Open surgery is not always possible and carries a high risk of morbidity and death. An endovascular approach has been advocated in infected aneurysms elsewhere in the body, with good short-term and medium-term outcomes encouraging such approach in the popliteal artery. We report a case of successful endovascular treatment of an infected ruptured popliteal aneurysm with favorable outcome after 2-year follow-up and a related review of the literature.

There is a wide variation in the reported incidence of DVT in arterial surgery (2%-24%). This is mostly due to the diversity of screening methods used and the inclusion or exclusion of below knee DVT. There is insufficient evidence to make a valid conclusion regarding the routine use of anticoagulants prophylaxis in arterial surgery. However, until such evidence becomes available, DVT prophylaxis in patients undergoing arterial surgery will continue to be guided by evidence gained from studies of general surgical patients.