Glycerophospholipids represent a common class of lipids critically important for integrity of cellular membranes. Oxidation of esterified unsaturated fatty acids dramatically changes biological activities of phospholipids. Apart from impairment of their structural function, oxidation makes oxidized phospholipids (OxPLs) markers of “modified-self” type that are recognized by soluble and cell-associated receptors of innate immunity, including scavenger receptors, natural (germ line-encoded) antibodies, and C-reactive protein, thus directing removal of senescent and apoptotic cells or oxidized lipoproteins. In addition, OxPLs acquire novel biological activities not characteristic of their unoxidized precursors, including the ability to regulate innate and adaptive immune responses. Effects of OxPLs described in vitro and in vivo suggest their potential relevance in different pathologies, including atherosclerosis, acute inflammation, lung injury, and many other conditions. This review summarizes cur...

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Generation and Biological Activities of Oxidized Phospholipids

Chemistry of phospholipid oxidation

Free radicals derived primarily from molecular oxygen have been implicated in a variety of human disorders including atherosclerosis, cancer, neurodegenerative diseases, and aging.1 Damage to tissue biomolecules, including lipids, proteins, and DNA, by free radicals is postulated to contribute importantly to the pathophysiology of oxidative stress. Lipids are readily attacked by free radicals resulting in the formation of a number of peroxidation products.2 The isoprostanes (IsoPs) are a unique series of prostaglandin-like compounds formed in vivo via the non-enzymatic free radical-initiated peroxidation of arachidonic acid, a ubiquitous polyunsaturated fatty acid (PUFA). Since discovery of these molecules over twenty years ago by Morrow and Roberts, one class of IsoPs, the F2-IsoPs, have become the biomarker of choice for assessing endogenous oxidative stress because these molecules are chemically stability and have been detected in all biological fluids and tissues analyzed.3-5 In addition to F2-IsoPs, a variety of IsoPs with different ring structures have been identified. Several of these compounds possess potent biological activities that could account for some of the pathophysiological effects of oxidative injury. Further, IsoP-like molecules are also generated from a number of different PUFAs including α-linolenic acid, eicosapentaenoic acid (EPA), adrenic acid, and docosahexaenoic acid (DHA) (Figure 1). There are many excellent reviews in the literature describing not only the quantification of F2-IsoPs in human health and disease but also the biological activities of these molecules.6-9 Thus, this review seeks to give readers a comprehensive, up-to-date overview of our current knowledge regarding IsoPs including the chemistry and biochemistry of their formation and metabolism, the utility of measuring these compounds as markers of in vivo oxidant stress, and their biological properties.




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Figure 1


Structures of polyunsaturated fatty acids that have been shown to generate isoprostane-like compounds.

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Isoprostane Generation and Function

A comparison of five lipid extraction solvent systems for lipidomic studies of human LDL

Background— We sought to perform a systematic lipid analysis of atherosclerotic plaques using emerging mass spectrometry techniques.

Methods and Results— A chip-based robotic nanoelectrospray platform interfaced to a triple quadrupole mass spectrometer was adapted to analyze lipids in tissue sections and extracts from human endarterectomy specimens by shotgun lipidomics. Eighteen scans for different lipid classes plus additional scans for fatty acids resulted in the detection of 150 lipid species from 9 different classes of which 24 were detected in endarterectomies only. Further analyses focused on plaques from symptomatic and asymptomatic patients and stable versus unstable regions within the same lesion. Polyunsaturated cholesteryl esters with long-chain fatty acids and certain sphingomyelin species showed the greatest relative enrichment in plaques compared to plasma and formed part of a lipid signature for vulnerable and stable plaque areas in a systems-wide network analysis. In principal component analyses, the combination of lipid species across different classes provided a better separation of stable and unstable areas than individual lipid classes.

Conclusions— This comprehensive analysis of plaque lipids demonstrates the potential of lipidomics for unraveling the lipid heterogeneity within atherosclerotic lesions.

Comparative Lipidomics Profiling of Human Atherosclerotic Plaques

We identified and quantified the hydroperoxides, hydroxides, epoxides, isoprostanes, and core aldehydes of the major phospholipids as the main components of the oxophospholipids (a total of 5–25 pmol/μmol phosphatidylcholine) in a comparative study of human atheroma from selected stages of lesion development. The developmental stages examined included fatty streak, fibrous plaque, necrotic core, and calcified tissue. The lipid analyses were performed by normal-phase HPLC with on-line electrospray MS using conventional total lipid extracts. There was great variability in the proportions of the various oxidation products and a lack of a general trend. Specifically, the early oxidation products (hydroperoxides and epoxides) of the glycerophosphocholines were found at the advanced stages of the plaques in nearly the same relative abundance as the more advanced oxidation products (core aldehydes and acids). The anticipated linear accumulation of the more stable oxidation products with progressive development of the atherosclerotic plaque was not apparent. It is therefore suggested that lipid infiltration and/or local peroxidation is a continuous process characterized by the formation and destruction of both early and advanced products of lipid oxidation at all times. The process of lipid deposition appears to have been subject to both enzymatic and chemical modification of the normal tissue lipids. Clearly, the appearance of new and disproportionate old lipid species excludes randomness in any accumulation of oxidized LDL lipids in atheroma.

Phospholipids and oxophospholipids in atherosclerotic plaques at different stages of plaque development

An electrosurgical device and methods are disclosed for creating a channel through a region of tissue. The device comprises an elongate member for receiving the energy from an electrical energy source. An electrical insulation layer surrounds the elongate member along the device proximal region. An electrode tip is coupled to the distal end of the elongate member for delivering the energy, the electrode tip being configured and sized for delivering the energy in a manner such that electrical arcing is generated in the region of tissue in order to create a channel through at least a portion of the region of tissue. An electrically insulative thermal shield is disposed between the electrode tip and the device proximal region for preventing arcing therebetween during the delivery of the energy and for thermally protecting the device proximal region from heat produced by the delivery of the energy through the electrode tip.

Electrosurgical device for creating a channel through a region of tissue and methods of use thereof

Perforating radiofrequency (PRF) energy has been used to obtain percutaneous transseptal left heart access. Contrary to ablative radiofrequency (RF), myocardial tissue responses to PRF thermal injury are incompletely defined. In this study, a newly developed RF catheter system for transseptal left atrial entry was compared with conventional needle puncture. Of 15 piglets having transfemoral cardiac catheterization, 12 had transseptal procedures. Needle punctures (NP) and PRF were followed by acute (1 hr; 3 NP, 3 PRF) and chronic necropsy (1 month; 3 NP, 3 PRF). The remaining three piglets had intentional RF aortic perforation through the atrial roof with necropsy at 1 month. Gross and histopathological effects were examined. Acutely, the gross RF lesion was similar to needle puncture. Histologically, the RF lesions had minimal mural thrombus, an inner zone of thermal injury characterized by grayish cytoplasmic staining (elastic trichrome), and a bubbly transformation of the cytoplasm in innermost cardiomyocytes, partial persistence of cross-striations, and an acute inflammatory reaction. The outer extent of the lesion (< 1 mm) was defined by a halo of contraction band necrosis similar to needle puncture. Acute NP injury showed comparable depth and extent of myocyte necrosis (principally contraction bands) with adjacent tissue hemorrhage and edema. At 1 month, a well-developed densely collagenous scar was present in both aortic and transseptal PRF lesions. The extent of acute RF injury is similar to that seen in conventional NP, but the characteristics of tissue insult are different. Both show well-developed healing at 1 month.

Radiofrequency perforation and conventional needle percutaneous transseptal left heart access: pathological features.

A method for creating a channel through an occlusion located in a substantially elongated body vessel of a patient, The method uses a channel creating apparatus defining an apparatus distal end portion insertable into the body vessel, the channel creating apparatus including an energy delivery component operatively coupled to the apparatus distal end portion for delivering energy substantially adjacent the apparatus distal end portion. The method includes: inserting the apparatus distal end portion into the body vessel; creating a channel first portion through the occlusion harder section using, at least in part, a delivery of energy into the occlusion harder portion; and creating a channel second portion through the occlusion softer portion by pushing the apparatus distal end portion through at least a portion of the occlusion softer portion substantially without delivering energy into the occlusion softer portion.

Method for creating a channel through an occlusion and apparatus therefor

Purpose This paper reviews an area of interdisciplinary collaboration in the design of healthcare facilities that attempts to optimize hospital space-planning using automated statistical techniques from the discipline of Operations Research (OR). This review articulates Facility Layout Problems (FLPs) as a general class of OR problems. Furthermore, the review highlights limitations of these techniques, which necessitate an ethical and participatory engagement with computerized processes of healthcare architecture. Design/methodology/approach An in-depth critical review was carried out, which revealed a number of common themes, collectively theorized as metamodeling processes, or models of models, through which various FLP modelling techniques can be challenged and debated in terms of their architectural viability, and ethical ramifications. Findings This review provides a methodological basis for the further evaluation of computational models. It was found that most of the reviewed studies are functionally focused on flow efficiency and, in general, do not consider broader contextual, relational, social, or salutogenic design values. Originality/value This review is the first on the subject written from an architectural perspective. It can be used by a broad range of readers as its critical review of past and present hospital layout modelling techniques discusses their capabilities and limitations. As such, it also enables them to consider ethical values while critiquing the epistemology of computational processes hidden beneath algorithmic outputs.

Ramsey Leung

Papers

Phospholipids and oxophospholipids in atherosclerotic plaques at different stages of plaque development

Electrosurgical device for creating a channel through a region of tissue and methods of use thereof

Radiofrequency perforation and conventional needle percutaneous transseptal left heart access: pathological features.

Method for creating a channel through an occlusion and apparatus therefor

A review of computerized hospital layout modelling techniques and their ethical implications