Selective arterialization of a cardiac vein in a model of cardiac microangiopathy and macroangiopathy in sheep

ObjectiveSome patients with significant arteriosclerosis of the heart are not amenable to revascularization of a coronary artery because they have a combination of microangiopathy and significant macroangiopathy. We investigated the benefit of arterialization of a cardiac vein under these circumstances in an acute animal model.MethodsIn the hearts of 8 sheep, microspheres were injected into the left coronary artery; 60 minutes later, a stenosis of the left anterior descending artery was performed. After 45 minutes, retrograde venous revascularization was performed by sewing the left internal thoracic artery to the concomitant vein of the left anterior descending artery in a beating-heart technique. For flow reversal, the vein was ligated proximally to the anastomosis. The efficiency of the bypass graft was evaluated by coronary angiography and flow measurement. Cardiac output, electrocardiography, and mean arterial blood pressure were assessed in each phase of the experiment.ResultsThe ischemic state of the myocardium was confirmed by a significant decrease of cardiac output, stroke volume, and mean arterial blood pressure, and a significant elevation of the ST segment in the electrocardiography. After retrograde venous revascularization was established, cardiac output and stroke volume increased and ST elevations decreased. The grafts showed adequate flow (26.15 ± 2.08 mL/min), and reversed blood flow in the grafted vein was proved by coronary angiography.ConclusionRetrograde venous revascularization is possible and improves cardiac function in a state of acute ischemia caused by a combination of microangiopathy and macroangiopathy

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1.

Ferroptosis is associated with lipid hydroperoxides generated by the oxidation of polyunsaturated acyl chains. Lipid hydroperoxides are reduced by glutathione peroxidase 4 (GPX4) and GPX4 inhibitors induce ferroptosis. However, the therapeutic potential of triggering ferroptosis in cancer cells with polyunsaturated fatty acids is unknown. Here, we identify conjugated linoleates including α-eleostearic acid (αESA) as ferroptosis inducers. αESA does not alter GPX4 activity but is incorporated into cellular lipids and promotes lipid peroxidation and cell death in diverse cancer cell types. αESA-triggered death is mediated by acyl-CoA synthetase long-chain isoform 1, which promotes αESA incorporation into neutral lipids including triacylglycerols. Interfering with triacylglycerol biosynthesis suppresses ferroptosis triggered by αESA but not by GPX4 inhibition. Oral administration of tung oil, naturally rich in αESA, to mice limits tumor growth and metastasis with transcriptional changes consistent with ferroptosis. Overall, these findings illuminate a potential approach to ferroptosis, complementary to GPX4 inhibition

Wound infection after excision and primary midline closure for pilonidal disease: risk factor analysis to improve patient selection.

BACKGROUND: Excision and primary midline closure for pilonidal disease (PD) is a simple procedure; however, it is frequently complicated by infection and prolonged healing. The aim of this study was to analyze risk factors for surgical site infection (SSI) in this context. METHODS: All consecutive patients undergoing excision and primary closure for PD from January 2002 through October 2008 were retrospectively assessed. The end points were SSI, as defined by the Center for Disease Control, and time to healing. Univariable and multivariable risk factor analyses were performed. RESULTS: One hundred thirty-one patients were included [97 men (74%), median age = 24 (range 15-66) years]. SSI occurred in 41 (31%) patients. Median time to healing was 20 days (range 12-76) in patients without SSI and 62 days (range 20-176) in patients with SSI (P < 0.0001). In univariable and multivariable analyses, smoking [OR = 2.6 (95% CI 1.02, 6.8), P = 0.046] and lack of antibiotic prophylaxis [OR = 5.6 (95% CI 2.5, 14.3), P = 0.001] were significant predictors for SSI. Adjusted for SSI, age over 25 was a significant predictor of prolonged healing. CONCLUSION: This study suggests that the rate of SSI after excision and primary closure of PD is higher in smokers and could be reduced by antibiotic prophylaxis. SSI significantly prolongs healing time, particularly in patients over 25 years

Stardust Interstellar Preliminary Examination X: Impact speeds and directions of interstellar grains on the Stardust dust collector

On the basis of an interstellar dust model compatible with Ulysses and Galileo observations, we calculate and predict the trajectories of interstellar dust (ISD) in the solar system and the distribution of the impact speeds, directions, and flux of ISD particles on the Stardust Interstellar Dust Collector during the two collection periods of the mission. We find that the expected impact velocities are generally low ( 1, and that some of the particles will impact on the cometary side of the collector. If we assume astronomical silicates for particle material and a density of 2 g cm?3, and use the Ulysses measurements and the ISD trajectory simulations, we conclude that the total number of (detectable) captured ISD particles may be on the order of 50. In companion papers in this volume, we report the discovery of three interstellar dust candidates in the Stardust aerogel tiles. The impact directions and speeds of these candidates are consistent with those calculated from our ISD propagation model, within the uncertainties of the model and of the observations