Natriuretic peptide receptor-C is up-regulated in the intima of advanced carotid artery atherosclerosis

OBJECTIVE: Natriuretic peptide receptor-C (NPR-C/NPR-3) is a cell surface protein involved in vascular remodelling that is up-regulated in atherosclerosis. NPR-C expression has not been well characterized in human carotid artery occlusive lesions. We hypothesized that NPR-C expression correlates with intimal features of vulnerable atherosclerotic carotid artery plaque. METHODS: To test this hypothesis, we evaluated NPR-C expression by immunohistochemistry (IHC) in carotid endarterectomy (CEA) specimens isolated from 18 patients. The grade, location, and co-localization of NPR-C in CEA specimens were evaluated using two tissue analysis techniques. RESULTS: Relative to minimally diseased CEA specimens, we observed avid NPR-C tissue staining in the intima of maximally diseased CEA specimens (65%; p=0.06). Specifically, maximally diseased CEA specimens demonstrated increased NPR-C expression in the superficial intima (61%, p=0.17), and deep intima (138% increase; p=0.05). In the superficial intima, NPR-C expression significantly co-localized with vascular smooth muscle cells (VSMCs) and macrophages. The intensity of NPR-C expression was also higher in the superficial intima plaque shoulder and cap regions, and significantly correlated with atheroma and fibroatheroma vulnerable plaque regions (β=1.04, 95% CI=0.46, 1.64). CONCLUSION: These findings demonstrate significant NPR-C expression in the intima of advanced carotid artery plaques. Furthermore, NPR-C expression was higher in vulnerable carotid plaque intimal regions, and correlate with features of advanced disease. Our findings suggest that NPR-C may serve as a potential biomarker for carotid plaque vulnerability and progression, in patients with advanced carotid artery occlusive disease

Transchest defibrillation under conditions of hypothermia

This study was conducted to determine whether or not hypothermia changes ventricular defibrillation threshold. Ventricular fibrillation was induced by electrical stimulation of the endocardium in pentobarbital anesthetized dogs, both during normothermia and hypothermia produced by circulating 8 °C water through a rubber bladder implanted in the peritoneal cavity. Defibrillation threshold was determined as the shock strength needed to defibrillate the ventricles and differing no more than 10 percent from a shock strength that failed to defibrillate. Defibrillation threshold current was stable for body temperatures ranging from 37 oC to 22 oC. Threshold energy increased linearly with decreasing temperature in keeping with the expected temperature-dependent changes in body fluid resistance. Normothermic electrical doses are probably appropriate for defibrillation of hypothermic children

Magnetostriction and magnetic texture to 97.4 Tesla in frustrated SrCu2(BO3)2

Strong geometrical frustration in magnets leads to exotic states, such as spin liquids, spin supersolids and complex magnetic textures. SrCu2(BO3)2, a spin-1/2 Heisenberg antiferromagnet in the archetypical Shastry-Sutherland lattice, exhibits a rich spectrum of magnetization plateaus and stripe-like magnetic textures in applied fields. The structure of these plateaus is still highly controversial due to the intrinsic complexity associated with frustration and competing length scales. We reveal new magnetic textures in SrCu2(BO3)2 via magnetostriction and magnetocaloric measurements in fields up to 97.4 Tesla. In addition to observing the low-field fine structure of the plateaus with unprecedented resolution, the data also reveal lattice responses at 82 T and at 73.6 T which we attribute, using a controlled density matrix renormalization group approach, to the long-predicted 1/2-saturation plateau, and to a new 2/5 plateau.Comment: 12 pages, 4 figures, submitte

Optimized preservation of isoforms of creatine kinase MM isoenzyme in plasma specimens and their rapid quantification by semi-automated chromatofocusing

Abstract We report a convenient chromatofocusing procedure for rapid and sensitive quantification of isoforms of the MM isoenzyme of creatine kinase (EC 2.7.3.2) in plasma and efficient methods for preserving isoform profiles during handling of specimens. The assay involves use of prepacked, re-usable Mono P chromatofocusing columns and a "Fast Protein Liquid Chromatograph" (FPLC) system with on-line detection of isoform enzymatic activity in column effluent. Profiles of isoforms are analyzed within 25 min with the use of a 1-mL column; the lower limit of sensitivity for CK activity is 5 mU, and recovery of each isoform is within 1% of the amount added to plasma. Collection of blood specimens in Vacutainer Tubes containing 28.5 mumol of EDTA (final concentration in plasma, 7 to 10 mmol/L) inhibited carboxypeptidase activity in plasma by 76%, sufficient to essentially abolish isoform conversion in vitro at room temperature. These methods should facilitate applications of isoform analysis for diagnosis of myocardial infarction and coronary artery recanalization.</jats:p

Quantitative analysis for isoforms of creatine kinase MM in plasma by chromatofocusing, with on-line monitoring of enzyme activity.

Abstract Changes in the proportions of individual isoforms of the MM isoenzyme of creatine kinase (CK; EC 2.7.3.2) in plasma promptly reflect both myocardial infarction and coronary recanalization. However, quantitative methods developed thus far are too slow or cumbersome for routine use in making clinical decisions. We report a convenient, quantitative chromatofocusing assay with on-line fluorometric detection of isoform activity in the column eluent that provides results within 40 min from the time of sample application. Sample eluted from a microbore chromatofocusing column (1.8-mL bed volume) is split between a reaction stream, into which CK reagents are added, and a reference stream. After incubation at 37 degrees C, NADPH formed by reaction of isoforms with CK reagent is detected at 340 nm. The system can detect activity of individual isoforms in plasma samples having total CK activity greater than or equal to 21 U/L (30 degrees C). Results correlated closely with those obtained by previously validated, but slow, chromatofocusing (r = 0.98, n = 30) and protein immunoblotting (r = 0.90, n = 20) procedures.</jats:p