The Pathogenesis of Atherosclerosis: Atherogenesis and Inflammation

Background— The formation of reactive oxygen species is a critical event in atherosclerosis because it promotes cell proliferation, hypertrophy, growth arrest, and/or apoptosis and oxidation of LDL. In the present study, we investigated whether reactive oxygen species-induced oxidative damage to DNA occurs in human atherosclerotic plaques and whether this is accompanied by the upregulation of DNA repair mechanisms. Methods and Results— We observed increased immunoreactivity against the oxidative DNA damage marker 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxo-dG) in plaques of the carotid artery compared with the adjacent inner media and nonatherosclerotic mammary arteries. Strong 8-oxo-dG immunoreactivity was found in all cell types of the plaque including macrophages, smooth muscle cells, and endothelial cells. As shown by competitive ELISA, carotid plaques contained 160±29 8-oxo-dG residues/105 dG versus 3±1 8-oxo-dG residues/105 dG in mammary arteries. Single-cell gel electrophoresis showed elevated level...

Elevated Levels of Oxidative DNA Damage and DNA Repair Enzymes in Human Atherosclerotic Plaques

https://rapm.bmj.com/content/rapm/43/7/756.full.pdf

Erector Spinae Plane Block Versus Retrolaminar Block: A Magnetic Resonance Imaging and Anatomical Study.

Oxidative DNA damage: assessment of the role in carcinogenesis, atherosclerosis, and acquired immunodeficiency syndrome.

a,b,d Abstract: Arterial smooth muscle cell (SMC) migration and proliferation are central features in atherogenesis. Altered gene expression and cell proliferation in atherosclerotic lesions have some similar characteristics with certain solid tumors and thus might have similar mechanisms that lead to SMC proliferation. Among cancer cells common features are genome-wide hypo- methylation which correlates with transformation and tumor progression, and coincident over- expression of methyltransferase (MTase). The purpose of the present study was to analyze whether alterations in DNA methylation and MTase expression are present in atherosclerotic lesions. A signie cant reduction in genomic 5-methylcytosine content was detected in advanced human atherosclerotic lesions and in lesions of ApoE knock-out mice. SMC were shown to develop hypomethylation in vitro during transformation from a contractile to synthetic pheno- type. Balloon denudation of New Zealand White rabbit aorta caused proliferation of intimal SMC with concomitant genomic hypomethylation in the thickened intima. By using in situ hybridization the overall transcriptional activity was found to be increased in clusters of lesion SMC. Marked heterogeneity was seen in MTase mRNA expression in various types of atheros- clerotic lesions among intimal and medial SMC. These e ndings show that (1) genomic hypomethylation occurs during atherogenesis in human, mouse and rabbit lesions and that it correlates with increased transcriptional activity; (2) MTase is expressed in atherosclerotic lesions; and (3) hypomethylation is present in advanced lesions at the same level as in malignant tumors and may affect cellular proliferation and gene expression in atherosclerotic lesions.

https://journals.sagepub.com/doi/pdf/10.1191/1358863x02vm418oa

DNA hypomethylation and methyltransferase expression in atherosclerotic lesions

BACKGROUND:The benefits of thoracic paravertebral block (TPVB) have been demonstrated for patients undergoing surgery for breast cancer. However, pleural puncture resulting in pneumothorax is a serious complication associated with traditional approaches using guidance from anatomic landmarks and ner

Ultrasound-Guided Thoracic Paravertebral Blockade: A Retrospective Study of the Incidence of Complications.

The monoclonal hypothesis equates atherosclerotic plaques with benign smooth muscle cell tumors and proposes that plaques can arise via mutational or viral events. Here, we provide direct evidence that molecular events, heretofore associated only with tumor cells, are common to plaque cells as well. Three distinct groups of human coronary artery plaque (hCAP) DNA samples transfected into NIH 3T3 cells gave rise to transformed foci. DNA samples from a panel of normal noncancerous human tissues, including coronary artery, were negative in the assay. Southern-blotted focus DNA yielded positive signals when hybridized to the 32P-labeled nick-translated repetitive human "Alu" DNA sequence. The DNA from cloned foci was used successfully in a second round of transfection. Focus DNA hybridized to nick-translated v-Ki-ras, v-Ha-ras, or N-ras probes failed to detect human fragments of these genes. Primary focus cells from each of five clones elicited tumors after injection into nude mice (6/42). Several distinct high molecular weight (greater than 6.6 kilobases) bands were detected after BamHI-digested tumor DNA was hybridized to Alu. Preliminary characterization of these hCAP DNA-associated tumors indicates that they are similar to the fibrosarcomas that arise after injection of ras-transformed cells into nude mice. We propose that transforming genes in plaque cells behave in a manner analogous to the way in which oncogenes behave in cancer cells.

Transforming gene in human atherosclerotic plaque DNA.

BACKGROUND:Communication failures are a significant cause of preventable medical errors, and poor-quality handoffs are associated with adverse events. We developed and implemented a simple checklist to improve communication during intraoperative transfer of patient care.METHODS:A prospective observa

An electronic checklist improves transfer and retention of critical information at intraoperative handoff of care.

nesthesiologists routinely use peripheral nerve blocks as an alternative or an adjunct to general anesthesia in addition to postoperative analgesia for a wide variety of procedures. More recently, emergency physicians have also begun using regional techniques in lieu of procedural sedation for a wide variety of extremity procedures such as reduction of shoulder dislocation.1 The goal of a peripheral nerve block is to apply a local anesthetic directly onto a peripheral nerve or nerve plexus to completely anesthetize the surgical site. Historically, anesthesiologists have performed peripheral nerve blocks using the paresthesia technique, in which the needle is inserted at a point determined by standard anatomic landmarks and then advanced until the patient feels paresthesia in the relevant sensory distribution.2 In the 1970s and 1980s, anesthesiologists began using a nerve stimulator to improve needle localization.3 Essentially, a nerve stimulator is a device that sends current through the block needle to elicit contraction of relevant muscle groups when in close proximity to the nerve of interest. These techniques are effective and are still in use, although they have many drawbacks. Over the past decade, ultrasound has gained popularity for peripheral nerve blockade because it allows the anesthesiologist to directly visualize the nerves of interest, the needle tip itself, and the spread of the local anesthetic in the desired location. In addition, the ultrasound image reliably depicts other structures such as blood vessels and lungs that the anesthesiologist wants to avoid. For these reasons, ultrasound guidance has increasingly become the standard technique for regional anesthesia.4 Brachial plexus blockade has long been used for upper extremity surgery, and there are several standard techniques. The interscalene block is especially useful for shoulder surgery. In this article, we will describe the technique of an ultrasound-guided interscalene block and then discuss its advantages over the traditional landmark technique.

https://www.aium.org/misc/soundJudgment8.pdf

Ultrasound-guided interscalene blocks.

A randomized clinical trial of burst vs. spaced physical therapy for Parkinsons disease.

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