Search

The sulfonylurea receptor-2 (SUR2) is a subunit of ATP-sensitive potassium channels (KATP) in heart. Mice with the SUR2 gene disrupted (SUR2m) are constitutively protected from ischemia-reperfusion (I/R) cardiac injury. This was surprising because [K.sub.ATP], either sarcolemmal or mitochondrial or both, are thought to be important for cardioprotection. We hypothesized that SUR2m mice have an altered mitochondrial phenotype that protects against I/R. Mitochondrial membrane potential ([DELTA][[PSI].sub.m]), tolerance to [Ca.sup.2+] load, and reactive oxygen species (ROS) generation were studied by fluorescence-based assays, and volumetric changes in response to [K.sup.+] were measured by light scattering in isolated mitochondria. For resting SUR2m mitochondria compared with wild type, the [DELTA][[PSI].sub.m] was less polarized (46.1 [+ or -] 0.4 vs. 51.9 [+ or -] 0.6%), tolerance to [Ca.sup.2+] loading was increased (163 [+ or -] 2 vs. 116 [+ or -] 2 [micro]M), and ROS generation was enhanced with complex I [8.5 [+ or -] 1.2 vs. 4.9 [+ or -] 0.2 arbitrary fluorescence units (afu)/s] or complex II (351 [+ or -] 51.3 vs. 166 [+ or -] 36.2 afu/s) substrates. SUR2m mitochondria had greater swelling in [K.sup.+] medium (30.2 [+ or -] 3.1%) compared with wild type (14.5 [+ or -] 0.6%), indicating greater [K.sup.+] influx. Additionally, [DELTA][[PSI].sub.m] decreased and swelling increased in the absence of ATP in SUR2m, but the sensitivity to ATP was less compared with wild type. When the mitochondria were subjected to hypoxia-reoxygenation, the decrease in respiration rates and respiratory control index was less in SUR2m. [DELTA][[PSI].sub.m] maintenance in the SUR2m intact myocytes was also more tolerant to metabolic inhibition. In conclusion, the cardioprotection observed in the SUR2m mice is associated with a protected mitochondrial phenotype resulting from enhanced K+ conductance that partially dissipated [DELTA][[PSI].sub.m]. These results have implications for possible SUR2 participation in mitochondrial [K.sub.ATP]. adenosine 5-triphosphate-sensitive potassium channel; sulfonylurea receptor 2; ischemia; ischemic-preconditioning; mitochondria; mitochondrial membrane potential; mitochondrial respiration; cellular energetics doi: 10.1152/ajpheart.00363.2010.

Sulfonylurea receptor-containing ATP-sensitive potassium ([K.sub.ATP]) channels have been implicated in cardioprotection, but the cell type and constitution of channels responsible for this protection have not been clear. Mice deleted for the first nucleotide binding region of sulfonylurea receptor 2 (SUR2) are referred to as SUR2 null since they lack full-length SUR2 and glibenclamide-responsive [K.sub.ATP] channels in cardiac, skeletal, and smooth muscle. As previously reported, SUR2 null mice develop electrocardiographic changes of ST segment elevation that were shown to correlate with coronary artery vasospasm. Here we restored expression of the cardiomyocyte SUR2-[K.sub.ATP] channel in SUR2 null mice by generating transgenic mice with ventricular cardiomyocyte-restricted expression of SUR2A. Introduction of the cardiomyocyte SUR2A transgene into the SUR2 null background restored functional cardiac [K.sub.ATP] channels. Hearts isolated from rescued mice, referred to as MLC2A, had significantly reduced infarct size (27 [+ or -] 3% of area at risk) compared with SUR2 null mice (36 [+ or -] 3% of area at risk). Compared with SUR2 null hearts, MLC2A hearts exhibited significantly improved cardiac function during the postischemia reperfusion period primarily because of preservation of low diastolic pressures. Additionally, restoration of cardiac SUR2-[K.sub.ATP] channels significantly reduced the degree and frequency of ST segment elevation episodes in MLC2A mice. Therefore, cardioprotective mechanisms both dependent and independent of SUR2-[K.sub.ATP] channels contribute to cardiac function. ATP-sensitive potassium channel; SUR2; SUR2A; ischemia; vasospasm doi: 10.1152/ajpheart.00084.2010.

15-Lipoxygenase (15-LO-1) metabolizes arachidonic acid (AA) to l l,12,15-trihydroxyeicosatrienoic acids (THETAs) and 15-hydroxy-11,12-epoxyeicosatrienoic acids (HEETA) that dilate rabbit arteries. Increased endothelial 15-LO-1 expression enhances arterial relaxations to agonists. We tested the effect of hypoxia on 15-LO-1 expression, THETA and HEETA synthesis, and relaxations in rabbit arteries. The incubation of rabbit aortic endothelial cells and isolated aortas in 0.7% [O.sub.2] increased 15-LO-1 expression. Rabbits were housed in a hypoxic atmosphere of 12% [O.sub.2] for 5 days. 15-LO-1 expression increased in the endothelium of the arteries of rabbits in 12% [O.sub.2] compared with room air. THETA and HEETA synthesis was also enhanced in aortas and mesenteric arteries. AA hyperpolarized the smooth muscle cells in indomethacinand phenylephrine-treated mesenteric arteries of hypoxic rabbits from -29.4 [+ or -] 1 to -50.1 [+ or -] 3 mV. The hyperpolarization to AA was less in arteries of normoxic rabbits (from -26.0 [+ or -] 2 to -37 [+ or -] 2 mV). This AA-induced hyperpolarization was inhibited by the 15-LO inhibitor BW-755C. Nitric oxide and prostaglandin-independent maximum relaxations to acetylcholine (79.7 [+ or -] 2%) and AA (38.3 [+ or -] 4%) were enhanced in mesenteric arteries from hypoxic rabbits compared with the normoxic rabbits (49.7 [+ or -] 6% and 19.9 [+ or -] 2%, respectively). These relaxations were inhibited by BW-755C and nordihydroguaiaretic acid. Therefore, hypoxia increased the relaxations to agonists in the rabbit mesenteric arteries by enhancing endothelial 15-LO-1 expression and synthesis of the hyperpolarizing factors THETA and HEETA. endothelium; vasodilation; endothelium-derived hyperpolarizing factor

Arachidonic acid (AA) metabolites from the 15-1ipoxygenase-1 (15-LO-1) pathway, trihydroxyeicosatrienoic acids (THETAs) and hydroxy-epoxyeicosatrienoic acids (HEETAs), are endothelium-derived hyperpolarizing factors (EDHFs) and relax rabbit arteries. Rabbit vascular 15-LO-1 expression, THETA and HEETA synthesis, and nitric oxide and prostaglandin-independent relaxations to acetylcholine (ACh) and AA decreased with age (neonates to 16-wk-old). We characterized age-dependent ACh-hypotensive responses in vivo in 1-, 4-, 8-, and 16-wk-old rabbits and the contribution of THETAs and HEETAs to these responses. In anesthetized rabbits, blood pressure responses to ACh (4-4,000 ng/kg) were determined in the presence of vehicle or various inhibitors. ACh responses decreased with age (P > 0.001). In the absence or presence of [N.sup.[omega]]-nitro-L-arginine methyl ester (L-NAME) and indomethacin (Indo), maximum responses in 1 (-54.7 [+ or -] 7.4 and -37.9 [+ or -] 3.9%)- and 4 (-48.8 [+ or -] 2.4 and -35.5 [+ or -] 7.8%)-wk-old rabbits were higher than 8 (-30.0 [+ or -] 2.8 and -26.6 [+ or -] 4.4%)-and 16 (-36.7 [+ or -] 3.5 and -27.3 [+ or -] 10%)-wk-old rabbits. A lipoxygenase inhibitor, BW755C, reduced THETA and HEETA synthesis in mesenteric arteries. In the presence of Indo and [N.sup.[omega]]-nitro-L-arginine, ACh relaxations were reduced by BW755C to a greater extent in the mesenteric arteries from the younger rabbits. In 4-wk-old rabbits treated with L-NAME and Indo, the maximum ACh hypotension was reduced by the potassium channel inhibitors apamin and charybdotoxin to -6.9 [+ or -] 0.9%, by apamin alone to -19.5 [+ or -] 1.4%, and by BW755C to -18.8 [+ or -] 3.5%. The present study indicates that the age-related decrease in ACh-induced hypotension is mediated by the decreased synthesis of the 15-LO-1 metabolites THETAs and HEETAs. endothelium-derived hyperpolarizing factor; arachidonic acid; vasodilation; mean arterial pressure

Arachidonic acid (AA) causes endothelium-dependent smooth muscle hyperpolarizations and relaxations that are mediated by a 15-lipoxygenase-I (15-LO-I) metabolite, 11,12,15-trihydroxyeicosatrienoic acid (11,12,15-THETA). We propose that AA is metabolized sequentially by 15-LO-I and hydroperoxide isomerase to an unidentified hydroxyepoxyeicosatrienoic acid (HEETA), which is hydrolyzed by a soluble epoxide hydrolase (sEH) to 11,12,15-THETA. After incubation of aorta with [sup.4]C-labeled AA, metabolites were extracted and the HEETAs were resolved by performing HPLC. Mass spectrometric analyses identified 15-Hydroxy-11,12-epoxyeicosatrienoic acid (15-H-11,12-EETA). Incubation of aortic incubates with methanol and acetic acid trapped the acidsensitive 15-H-11,12-EETA as methoxydihydroxyeicosatrienoic acids (MDHEs) (367 m/z, M-H). Pretreatment of the aortic tissue with the sEH inhibitor 12-(3-adamantan-l-yl-ureido)-dodecanoic acid (AUDA; [10.sup.-6] M) increased the formation of 15-H-11,12-EETA, measured as MDHEs. Thus 15-H-11,12-EETA is an acid- and sEH-sensitive precursor of 11,12,15-THETA. Aortic homogenates and endothelial cells contain a 57-kDa protein corresponding to the rabbit sEH. In preconstricted aortic rings, AA ([10.sup.-7]-[10.sup.-4] M) and acetylcholine ([10.sup.-9]-[10.sup.-6] M) caused concentration-related relaxations that were enhanced by pretreatment with AUDA. These enhanced relaxations were inhibited by increasing extracellular [[K.sup.+]] from 4.8 to 20 mM. AA (3 x [10.sup.-6] M) induced cell membrane hyperpolarization (from -31.0 [+ or -] 1 to -46.8 [+ or -] 2 mV) in aortic strips with an intact endotfielium, which was enhanced by AUDA. These results indicate that 15-H-11,12-EETA is produced by the aorta, hydrolyzed by sEH to 11,12,15-THETA, and mediates relaxations by membrane hyperpolarization. 15-H-11,12-EETA represents an endothelium-derived hyperpolarizing factor. arachidonic acid; endothelial cells; endothelium-derived hyperpolarizing factor; 15-lipoxygenase

Rabbit 15-1ipoxygenase- 1 (15-LO-1) oxygenates arachidonic acid (AA) into 15-hydroperoxyeicosatetraenoic acid, which is then converted to the vasodilatory 15-hydroxy-11,12-epoxyeicosatrienoic acid (HEETA) and 11,12,15-trihydroxyeicosatrienoic acid (THETA). We studied the age-dependent expression of the 15-LO-1 in rabbit aorta and its effects on the synthesis of THETA, HEETA, and vasoactivity. Aortas of 1-wk-old rabbits express greater amounts of 15-LO-1 mRNA and protein compared with aortas of 4-, 8-, or 16-wk-old rabbits. The synthesis of THETA and HEETA in the rabbit aorta was also reduced with age. THETA synthesis was maximal in 1-wk-old aortas but decreased in aortas of 4- (42%), 8- (4%), and 16-wk-old (1%) rabbits. Similarly, THETA and HEETA synthesis decreased with age in mesenteric arteries from 1-, 4-, 8-, and 16-wk-old rabbits. The maximum vasorelaxation response to acetylcholine ([10.sup.-6] M) in the presence of indomethacin and nitro-L-arginine decreased in the order of 1 wk (64.5 [+ or -] 6.9%), 4 wk (52.6 [+ or -] 8.9%), 8 wk (53.0 [+ or -] 9.4%), and 16 wk (33.3 [+ or -] 6.6%). Similarly, the maximum relaxation to AA (3 x [10.sup.-4] M) decreased with age in the order of 1 wk (60.4 [+ or -] 8.9%), 4 wk (56.3 [+ or -] 5.8%), 8 wk (41.8 [+ or -] 12.3%), and 16 wk (28.9 [+ or -] 1.6%). In contrast, the vasorelaxation to sodium nitroprusside was not significantly altered by age. These data indicate that aortic 15-LO-1 expression and activity are downregulated with aging in rabbits. This decrease is paralleled by the reduced synthesis of vasoactive THETA and HEETA and aortic relaxations to acetylcholine and AA. endothelium-derived hyperpolarizing factor; arachidonic acid; acetylcholine; vasodilation

Endothelium-dependent vasorelaxation of the rabbit aorta is mediated by either nitric oxide (NO) or arachidonic acid (AA) metabolites from cyclooxygenase (COX) and 15-lipoxygenase (15-LO) pathways. 15-LO-1 metabolites of AA, 11,12,15-trihydroxyeicosatrienoic acid (THETA), and 15-hydroxy-11,12-epoxyeicosatrienoic acid (HEETA) cause concentration-dependent relaxation. We tested the hypothesis that in the 15-LO pathway of AA metabolism, 15-LO-1 is sufficient and is the rate-limiting step in inducing relaxations in rabbit aorta. Aorta and rabbit aortic endothelial cells were treated with adenoviruses containing human 15-LO-1 cDNA (Ad-15-LO-1) or [beta]-galactosidase (Ad-[beta]-Gal). Ad-15-LO-l-transduction increased the expression of a 75-kDa protein corresponding to 15-LO-1, detected by immunoblotting with an anti-human15-LO-1 antibody, and increased the production of HEETA and THETA from [[sup.14]C]AA. Immunohistochemical studies on Ad- 15-LO-1-transduced rabbit aorta showed the presence of 15-LO-1 in endothelial cells. Ad-15-LO-1-treated aortic rings showed enhanced relaxation to AA (max 31.7 [+ or -] 3.2%) compared with Ad-[beta]-Gal-treated (max 12.7 [+ or -] 3.2%) or control nontreated rings (max 13.1 [+ or -] 1.6%) (P < 0.01). The relaxations in Ad-15-LO-1-treated aorta were blocked by the 15-LO inhibitor cinnamyl-3,4-dihydroxy-a-cyanocinnamate. Overexpression of 15-LO-1 in the rabbit aortic endothelium is sufficient to increase the production of the vasodilatory HEETA and THETA and enhance the relaxations to AA. This confirms the role of HEETA and THETA as endothelium-derived relaxing factors. vasodilation; trihydroxyeicosatrienoic acid

The problem of determining the location and orientation of straight lines in images arises in many diverse areas of image processing and computer vision, since straight lines occur in various natural and man-made objects, thus many complex objects can often be identified by their distinct combination of linear features. A new approach can alternatively be viewed as representation of the noisy image in terms of elements chosen from a dictionary of lines and this interpretation relates the problem of Hough-based line finding to the body of work on adaptive signal representation.

Chronic diarrhoea following a renal transplant is a common clinical manifestation. A large number of possible aetiologies complicate the diagnosis. Invasive testing is frequently conducted in patients with persistent or intractable diarrhoea. We discuss the case of a kidney transplant recipient who developed persistent diarrhoea with a 10-kg weight loss in a 3-week period. The patient was diagnosed with a Cryptosporidium parvum infection after stool screening for atypical organisms. Cryptosporidium has emerged as one of the most prevalent causes of infectious diarrhoea in post-renal transplant settings, particularly in endemic places such as India. The patient responded well to oral nitazoxanide. Post-renal transplant patients are in an immunocompromised state and are at significantly higher risk for getting infection-associated diarrhoea, so an approach for early stool screening for atypical organisms is advised. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates gender and generational differences in consumers' familiarity, security concern, and intentions to purchase Internet of Things (IoT) devices. Design/methodology/approach: This study surveys 463 undergraduate business students at a large North American university. Findings: Findings suggest that men are more familiar with IoT devices than women (p<0.001), but concerns about the security risks associated with these devices influence women's purchase intentions more than men's (p<0.1). Furthermore, younger generations are found to be more concerned about IoT security risk (p<0.1) and more influenced by risk in their intentions to purchase IoT devices (p<.05), than are older generations. No evidence was found for gender differences in security concern nor for age differences in IoT familiarity. Practical/social implications: The gender and generational differences found here suggest producers of IoT technologies could increase consumers' purchase intentions by developing more secure IoT devices and by providing clearer explanations of their security risks. Originality/value: Despite widespread adoption of IoT devices, few studies consider how demographic characteristics may influence consumers' perceptions of these technologies. This study contributes to both the information systems and marketing literatures by investigating how gender and generation may influence consumers' IoT familiarity, security concern, and purchase intentions. [ABSTRACT FROM AUTHOR]