Endothelium-Dependent Relaxation Effect of Apocynum venetum Leaf Extract via Src/PI3K/Akt Signalling Pathway

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Yeh Siang Lau

2015-06-01

Full Text Available Botanical herbs are consumed globally not only as an essential diet but also as medicines or as functional/recreational food supplements. The extract of the Apocynum venetum leaves (AVLE, also known as Luobuma, exerts its antihypertensive effect via dilating the blood vessels in an endothelium- and concentration-dependent manner with optimal effect seen at as low as 10 µg/mL. A commercial Luoboma “antihypertensive tea” is available commercially in the western province of China. The present study seeks to investigate the underlying cellular mechanisms of the nitric oxide (NO-releasing property of AVLE in rat aortas and human umbilical vein endothelial cells (HUVECs. Endothelium-dependent relaxation induced by AVLE was assessed in organ chambers in the presence or absence of polyethyleneglycol catalase (PP2, 20 µM; inhibitor of Src kinase, wortmannin (30 nM and LY294002 (20 µM; PI3 (phosphatidylinositol3-Kinase inhibitor, NG-nitro-l-arginine (L-NAME, 100 µM; endothelial NO synthase inhibitor (eNOS and ODQ (1 µM; soluble guanylyl cyclase inhibitor. Total nitrite and nitrate (NOx level and protein expression of p-Akt and p-eNOS were measured. AVLE-induced endothelium-dependent relaxation was reduced by PP2, wortmannin and LY294002 and abolished by L-NAME and ODQ. AVLE significantly increased total NOx level in rat aortas and in HUVECs compared to control. It also instigated phosphorylation of Akt and eNOS in cultured HUVECs in a concentration-dependent manner and this was markedly suppressed by PP2, wortmannin and LY294002. AVLE also inhibited superoxide generated from both NADPH oxidase and xanthine/xanthine oxidase system. Taken together, AVLE causes endothelium-dependent NO mediated relaxations of rat aortas through Src/PI3K/Akt dependent NO signalling pathway and possesses superoxide scavenging activity.

Effect of lithium on endothelium-dependent and neurogenic relaxation of rat corpus cavernosum: role of nitric oxide pathway.

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Sadeghipour, Hamed; Ghasemi, Mehdi; Ebrahimi, Farzad; Dehpour, Ahmad Reza

2007-02-01

Some studies have reported erectile dysfunction in patients receiving lithium through a mechanism that has not yet been defined. The aim of the present study was to verify the effect of acute lithium administration on the nonadrenergic noncholinergic (NANC)- and endothelium-mediated relaxation of rat isolated corpus cavernosum. The isolated rat corporeal strips were precontracted with phenylephrine hydrochloride (7.5 microM) and electrical field stimulation (EFS) was applied at different frequencies (2, 5, 10, and 15 Hz) to obtain NANC-mediated relaxation or relaxed by adding cumulative doses of acetylcholine (10nM-1mM) to obtain endothelium-dependent relaxation in the presence or absence of lithium (0.3, 0.5, 1, and 5mM). Also, effects of combining lithium (0.3mM) with 30 nM and 0.1 nM L-NAME (an NO synthase inhibitor) on NANC- and acetylcholine-mediated relaxation was investigated, respectively. Moreover, effects of combining lithium (1mM) with 0.1mM and 10 microM L-arginine (a precursor of NO) on NANC- and endothelium-mediated relaxation was assessed, respectively. Also, the effect of lithium (1mM) on relaxation to sodium nitroprusside (SNP; 1nM-1mM), an NO donor, was investigated. The NANC-mediated relaxation was significantly (Pacetylcholine in a concentration-dependent manner. Combination of lithium (0.3mM) with 30 and 0.1 nM L-NAME, which separately had a minimum effect on NANC- and endothelium-mediated relaxation, significantly (Pacetylcholine and EFS, it improved the inhibition by lithium (1mM) of relaxant responses to acetylcholine and EFS, respectively. Also, SNP produced similar concentration-dependent relaxations from both groups. Our experiments indicated that lithium likely by interfering with NO pathway in both endothelium and nitrergic nerve can result in impairment of both the endothelium- and NANC-mediated relaxation of rat corpus cavernosum.

The ent-15α-Acetoxykaur-16-en-19-oic Acid Relaxes Rat Artery Mesenteric Superior via Endothelium-Dependent and Endothelium-Independent Mechanisms

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Êurica Adélia Nogueira Ribeiro

2012-01-01

Full Text Available The objective of the study was to investigate the mechanism of the relaxant activity of the ent-15α-acetoxykaur-16-en-19-oic acid (KA-acetoxy. In rat mesenteric artery rings, KA-acetoxy induced a concentration-dependent relaxation in vessels precontracted with phenylephrine. In the absence of endothelium, the vasorelaxation was significantly shifted to the right without reduction of the maximum effect. Endothelium-dependent relaxation was significantly attenuated by pretreatment with L-NAME, an inhibitor of the NO-synthase (NOS, indomethacin, an inhibitor of the cyclooxygenase, L-NAME + indomethacin, atropine, a nonselective antagonist of the muscarinic receptors, ODQ, selective inhibitor of the guanylyl cyclase enzyme, or hydroxocobalamin, a nitric oxide scavenger. The relaxation was completely reversed in the presence of L-NAME + 1 mM L-arginine or L-arginine, an NO precursor. Diterpene-induced relaxation was not affected by TEA, a nonselective inhibitor of K+ channels. The KA-acetoxy antagonized CaCl2-induced contractions in a concentration-dependent manner and also inhibited an 80 mM KCl-induced contraction. The KA-acetoxy did not interfere with Ca2+ release from intracellular stores. The vasorelaxant induced by KA-acetoxy seems to involve the inhibition of the Ca2+ influx and also, at least in part, by endothelial muscarinic receptors activation, NO and PGI2 release.

Arginase up-regulation and eNOS uncoupling contribute to impaired endothelium-dependent vasodilation in a rat model of intrauterine growth restriction.

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Grandvuillemin, Isabelle; Buffat, Christophe; Boubred, Farid; Lamy, Edouard; Fromonot, Julien; Charpiot, Philippe; Simoncini, Stephanie; Sabatier, Florence; Dignat-George, Françoise; Peyter, Anne-Christine; Simeoni, Umberto; Yzydorczyk, Catherine

2018-05-09

Individuals born after intrauterine growth restriction (IUGR) are at increased risk of developing cardiovascular diseases in adulthood, notably hypertension (HTN). Alterations in the vascular system, particularly impaired endothelium-dependent vasodilation, may play an important role in long-term effects of IUGR. Whether such vascular dysfunction precedes HTN has not been fully established in individuals born after IUGR. Moreover, the intimate mechanisms of altered endothelium-dependent vasodilation remain incompletely elucidated. We therefore investigated, using a rat model of IUGR, whether impaired endothelium-dependent relaxation precedes the development of HTN and whether key components of the L-Arginine-nitric oxide (NO) pathway are involved in its pathogenesis. Pregnant rats were fed with a control (CTRL, 23% casein) or low-protein diet (LP, 9% casein) to induce IUGR. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography in 5- and 8-week-old male offspring. Aortic rings were isolated to investigate relaxation to acetylcholine, NO production, eNOS protein content, arginase activity, and superoxide anion production. SBP was not different at 5 weeks, but significantly increased in 8-week-old LP vs. CRTL offspring. In 5-week-old LP vs. CRTL males, endothelium-dependent vasorelaxation was significantly impaired, but restored by pre-incubation with L-Arginine or the arginase inhibitor BEC; NO production was significantly reduced, but restored by L-Arginine pretreatment; total eNOS protein, dimer/monomer ratio, and arginase activity were significantly increased; superoxide anion production was significantly enhanced, but normalized by pretreatment with the NOS inhibitor L-NNA. In this model, IUGR leads to early-impaired endothelium-dependent vasorelaxation, resulting from arginase up-regulation and eNOS uncoupling, which precedes the development of HTN.

Effect of subchronic exposure to mainstream cigarette smoke on endothelium-dependent vasodilation in rat arteries

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Helena Lenasi

2005-07-01

Full Text Available Background: Cigarette smoking is reported to impair endothelium-dependent vasodilation. The aim of the present study was to assess the effect of 30-day exposure to mainstream cigarette smoke on vascular reactivity of rat abdominal aorta, carotid, renal and mesenteric artery. Separately, the NO-mediated and the EDHF-mediated, endothelium-dependent vascular relaxations were determined.Methods: Two groups of »Whistar Kyoto« rats were exposed to mainstream cigarette smoke (2 hours/day, 5 days/week for 30 days and to fresh conditioned air, respectively. Rats were sacrificed on the second day after the last exposition to cigarette smoke. Vascular reactivity studies were performed on isolated, endothelium-intact, phenylephrine-preconstricted rat artery rings. Cumulative concentration-relaxation curves to acetylcholine (ACh were obtained in the absence and presence of the endothelial NO synthase (eNOS inhibitor N ω nitro L-arginine (L-NA and the cyclo-oxygenase (COX inhibitor diclofenac, respectively. After washing period of 1 hour, vessels were exposed either to the intracellular superoxide scavenger tiron, to the cytochrome P450 (CYP inhibitor miconazole or the Na-K-ATPase inhibitor ouabain before being preconstricted with phenylephrine and determining the concentration-response curve to ACh.Results: ACh induced concentration-dependent relaxations. In none of the vessels investigated did we observe a significant difference in the relaxations obtained in arteries from control rats and rats exposed to cigarettee smoke. Although smoking is known to cause an increase in oxidative stress, treatment of the vessels with tiron did not affect the NOmediated relaxations. To evaluate the contribution of EDHF to endothelium-dependent vasodilation rings were preincubated with L-NA. The EDHF-mediated relaxations were significantly attenuated compared to the NO-mediated relaxations in renal and mesenteric artery and almost completely abolished in aorta and

Endothelium-dependent relaxation and angiotensin II sensitivity in experimental preeclampsia.

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Anne Marijn van der Graaf

Full Text Available OBJECTIVE: We investigated endothelial dysfunction and the role of angiotensin (Ang-II type I (AT1-R and type II (AT2-R receptor in the changes in the Ang-II sensitivity in experimental preeclampsia in the rat. METHODS: Aortic rings were isolated from low dose lipopolysaccharide (LPS infused pregnant rats (experimental preeclampsia; n=9, saline-infused pregnant rats (n=8, and saline (n=8 and LPS (n=8 infused non-pregnant rats. Endothelium-dependent acetylcholine-mediated relaxation was studied in phenylephrine-preconstricted aortic rings in the presence of vehicle, N(G-nitro-L-arginine methyl ester and/or indomethacin. To evaluate the role for AT1-R and AT2-R in Ang-II sensitivity, full concentration response curves were obtained for Ang-II in the presence of losartan or PD123319. mRNA expression of the AT1-R and AT2-R, eNOS and iNOS, COX1 and COX2 in aorta were evaluated using real-time RT-PCR. RESULTS: The role of vasodilator prostaglandins in the aorta was increased and the role of endothelium-derived hyperpolarizing factor and response of the AT1-R and AT2-R to Ang-II was decreased in pregnant saline infused rats as compared with non-pregnant rats. These changes were not observed during preeclampsia. CONCLUSION: Pregnancy induced adaptations in endothelial function, which were not observed in the rat model for preeclampsia. This role of lack of pregnancy induced endothelial adaptation in the pathophysiology of experimental preeclampsia needs further investigation.

Role of endothelium-derived hyperpolarization in the vasodilatation of rat intrarenal arteries

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Pinilla, Estéfano; Sánchez-Pina, Ana; Muñoz Picos, Mercedes

2016-01-01

Background and purpose: Endothelium-dependent vasodilation plays an important role in the regulation of vascular tone in different vascular beds. Besides the release of prostacyclin (PGI2) and nitric oxide (NO), the endothelium mediates vasodilation through endothelium-derived hyperpolarization (...

Endothelium-Dependent Vasorelaxant Effect of Butanolic Fraction from Caryocar brasiliense Camb. Leaves in Rat Thoracic Aorta

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Lais Moraes de Oliveira

2012-01-01

Full Text Available Caryocar brasiliense Camb. “pequi” is a native plant from the Cerrado region of Brazil that contains bioactive components reported to be antioxidant agents. Previous work has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. We found that the crude hydroalcoholic extract (CHE of C. brasiliense leaves relaxed, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine, and that the butanolic fraction (BF produced an effect similar to that of the CHE. Aortic relaxation induced by BF was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylatecyclase inhibitor ODQ. However, incubation with atropine and pyrilamine had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin and tetraethylammonium. The concentration-response curve to calcium in denuded-endothelium rings was not modified after incubation with BF, and the vasorelaxation by BF in endothelium-intact rings precontracted with KCl was abolished after incubation with L-NAME. In addition, administration of BF in anesthetized rats resulted in a reversible hypotension. The results reveal that C. brasiliense possesses both in vivo and in vitro activities and that the vascular effect of BF involves stimulation of the nitric oxide/cyclic GMP pathway.

Angiotensin-(1-7) augments endothelium-dependent relaxations of porcine coronary arteries to bradykinin by inhibiting angiotensin-converting enzyme 1.

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Raffai, Gábor; Khang, Gilson; Vanhoutte, Paul M

2014-05-01

Angiotensin-converting enzyme 2 (ACE2) converts angiotensin II to angiotensin-(1-7) that activates Mas receptors, inhibits ACE1, and modulates bradykinin receptor sensitivity. This in vitro study compared the direct and indirect effects of angiotensin-(1-7), the ACE1 inhibitor captopril, and diminazene aceturate (DIZE) an alleged ACE2 activator in rings of porcine coronary arteries, by measuring changes of isometric tension. Angiotensin-(1-7), captopril, and DIZE did not cause significant changes in tension before or after desensitization of bradykinin receptors in preparations contracted with U46619. Bradykinin caused concentration-dependent and endothelium-dependent relaxations that were not affected by DIZE but were potentiated to a similar extent by angiotensin-(1-7) and captopril, given alone or in combination. Bradykinin responses potentiated by angiotensin-(1-7) and captopril were not affected by the BK1 antagonist SSR240612 and remained augmented in the presence of either N-nitro-L-arginine methyl ester hydrochloride plus indomethacin or TRAM-34 plus UCL-1684. ACE2 was identified in the coronary endothelium by immunofluorescence, but its basal activity was not influenced by DIZE. These results suggest that in coronary arteries, angiotensin-(1-7) and captopril both improves NO bioavailability and enhances endothelium-dependent hyperpolarization to bradykinin solely by ACE1 inhibition. Endothelial ACE2 activity cannot be increased by DIZE to produce local adequate amounts of angiotensin-(1-7) to influence vascular tone.

Quantifying the abnormal hemodynamics of sickle cell anemia

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Lei, Huan; Karniadakis, George

2012-02-01

Sickle red blood cells (SS-RBC) exhibit heterogeneous morphologies and abnormal hemodynamics in deoxygenated states. A multi-scale model for SS-RBC is developed based on the Dissipative Particle Dynamics (DPD) method. Different cell morphologies (sickle, granular, elongated shapes) typically observed in deoxygenated states are constructed and quantified by the Asphericity and Elliptical shape factors. The hemodynamics of SS-RBC suspensions is studied in both shear and pipe flow systems. The flow resistance obtained from both systems exhibits a larger value than the healthy blood flow due to the abnormal cell properties. Moreover, SS-RBCs exhibit abnormal adhesive interactions with both the vessel endothelium cells and the leukocytes. The effect of the abnormal adhesive interactions on the hemodynamics of sickle blood is investigated using the current model. It is found that both the SS-RBC - endothelium and the SS-RBC - leukocytes interactions, can potentially trigger the vicious ``sickling and entrapment'' cycles, resulting in vaso-occlusion phenomena widely observed in micro-circulation experiments.

Activation of eNOS by D-pinitol Induces an Endothelium-Dependent Vasodilatation in Mouse Mesenteric Artery

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Luciana N. Moreira

2018-05-01

Full Text Available D-pinitol is a cyclitol present in several edible plant species and extensively investigated for the treatment of metabolic diseases in humans, as food supplement, and demonstrated protective effects in the cardiovascular system. For these reasons, the present work aimed at investigating the mechanisms involved in the vascular effects of D-pinitol in mouse mesenteric artery. Mesenteric arteries from male C57BL/6 mice were mounted in a wire myograph. Nitrite was measured by the 2,3-diaminonaphthalene (DAN method. Protein expression and phosphorylation were measured by Western blot. The systolic blood pressure (SBP was measured by tail-cuff plethysmography. D-pinitol induced a concentration-dependent vasodilatation in endothelium-intact, but not in endothelium-denuded arteries. Nω-Nitro-L-arginine methyl ester (300 μM abolished the effect of D-pinitol, while 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μM shifted the concentration-response curve to the right. KN-93 (1 μM blunted the vasodilator effect of D-pinitol, but H-89 (0.1 μM did not change it. 1-[2-(Trifluoromethyl phenyl]imidazole (300 μM, indomethacin (10 μM, celecoxib (5 μM, wortmannin (1 μM, ruthenium red (10 μM, tiron (10 μM, MnTMPyP (30 μM, MPP (0.1 μM, PHTPP (0.1 μM, and atropine (1 μM did not change the effect of D-pinitol. D-pinitol increased the concentration of nitrite, which was inhibited by L-NAME and calmidazolium (10 μM. D-pinitol increased the phosphorylation level of eNOS activation site at Ser1177 and reduced the phosphorylation level of its inactivation site at Thr495. In normotensive mice, the intraperitoneal administration of D-pinitol (10 mg/kg induced a significant reduction of the SBP after 30 min. The present results led us to conclude that D-pinitol has an endothelium- and NO-dependent vasodilator effect in mouse mesenteric artery through a mechanism dependent on the activation of eNOS by the calcium-calmodulin complex, which can explain its

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

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Borgo, M.V.; Claudio, E.R.G.; Silva, F.B.; Romero, W.G.; Gouvea, S.A.; Moysés, M.R.; Santos, R.L.; Almeida, S.A.; Podratz, P.L.; Graceli, J.B.; Abreu, G.R.

2015-01-01

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

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M.V. Borgo

2016-01-01

Full Text Available Drospirenone (DRSP is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2 and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87 at 12 weeks of age were randomly divided into sham operated (Sham, OVX, OVX treated with E2 (E2, and OVX treated with E2 and DRSP (E2+DRSP groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

Hormonal therapy with estradiol and drospirenone improves endothelium-dependent vasodilation in the coronary bed of ovariectomized spontaneously hypertensive rats

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Borgo, M.V.; Claudio, E.R.G.; Silva, F.B.; Romero, W.G.; Gouvea, S.A.; Moysés, M.R.; Santos, R.L.; Almeida, S.A. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES (Brazil); Podratz, P.L.; Graceli, J.B. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Abreu, G.R. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal de Espírito Santo, Vitória, ES (Brazil)

2015-11-17

Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.

Great heterogeneity of commercial fruit juices to induce endothelium-dependent relaxations in isolated porcine coronary arteries: role of the phenolic content and composition.

Science.gov (United States)

Auger, Cyril; Pollet, Brigitte; Arnold, Cécile; Marx, Céline; Schini-Kerth, Valérie B

2015-01-01

Since polyphenol-rich products such as red wine, grape juice, and grape extracts have been shown to induce potent endothelium-dependent relaxations, we have evaluated whether commercial fruit juices such as those from berries are also able to induce endothelium-dependent relaxations of isolated coronary arteries and, if so, to determine whether this effect is related to their phenolic content. Among the 51 fruit juices tested, 2/12 grape juices, 3/7 blackcurrant juices, 4/5 cranberry juices, 1/6 apple juices, 0/5 orange juices, 2/6 red fruit and berry juices, 3/6 blends of red fruit juices, and 0/4 non-red fruit juices were able to induce relaxations achieving more than 50% at a volume of 1%. The active fruit juices had phenolic contents ranging from 0.31 to 1.86 g GAE/L, which were similar to those of most of the less active juices with the exception of one active grape juice (2.14 g GAE/L) and one active blend of red fruit juices (3.48 g GAE/L). Altogether, these findings indicate that very few commercial fruit juices have the ability to induce potent endothelium-dependent relaxations, and that this effect is not related to their quantitative phenolic content, but rather to their qualitative phenolic composition.

Inhibition of PKC-dependent extracellular Ca2+ entry contributes to the depression of contractile activity in long-term pressure-overloaded endothelium-denuded rat aortas

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Padilla, J.; López, R.M.; López, P.; Castillo, M.C.; Querejeta, E.; Ruiz, A.; Castillo, E.F.

2014-01-01

We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT 2 R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT 2 R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca 2+ -free medium or the subsequent tonic constrictions induced by the addition of Ca 2+ in the absence of agonists. Thus, the contractions induced by Ca 2+ release from intracellular stores and Ca 2+ influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca 2+ channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca 2+ . Neither levels of angiotensins nor of AT 2 R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca 2+ entry

Leptin-induced endothelium-dependent vasorelaxation of peripheral arteries in lean and obese rats: role of nitric oxide and hydrogen sulfide.

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Anna Jamroz-Wiśniewska

Full Text Available Adipose tissue hormone leptin induces endothelium-dependent vasorelaxation mediated by nitric oxide (NO and endothelium-derived hyperpolarizing factors (EDHF. Previously it has been demonstrated that in short-term obesity the NO-dependent and the EDHF-dependent components of vascular effect of leptin are impaired and up-regulated, respectively. Herein we examined the mechanism of the EDHF-dependent vasodilatory effect of leptin and tested the hypothesis that alterations of acute vascular effects of leptin in obesity are accounted for by chronic hyperleptinemia. The study was performed in 5 groups of rats: (1 control, (2 treated with exogenous leptin for 1 week to induce hyperleptinemia, (3 obese, fed highly-palatable diet for 4 weeks, (4 obese treated with pegylated superactive rat leptin receptor antagonist (PEG-SRLA for 1 week, (5 fed standard chow and treated with PEG-SRLA. Acute effect of leptin on isometric tension of mesenteric artery segments was measured ex vivo. Leptin relaxed phenylephrine-preconstricted vascular segments in NO- and EDHF-dependent manner. The NO-dependent component was impaired and the EDHF-dependent component was increased in the leptin-treated and obese groups and in the latter group both these effects were abolished by PEG-SRLA. The EDHF-dependent vasodilatory effect of leptin was blocked by either the inhibitor of cystathionine γ-lyase, propargylglycine, or a hydrogen sulfide (H2S scavenger, bismuth (III subsalicylate. The results indicate that NO deficiency is compensated by the up-regulation of EDHF in obese rats and both effects are accounted for by chronic hyperleptinemia. The EDHF-dependent component of leptin-induced vasorelaxation is mediated, at least partially, by H2S.

Endothelium-dependent relaxation of rat aorta to a histamine H3 agonist is reduced by inhibitors of nitric oxide synthase, guanylate cyclase and Na+,K+-ATPase

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D. M. Djuric

1996-01-01

Full Text Available The possible involvement of different effector systems (nitric oxide synthase, guanylate cyclase, β-adrenergic and muscarinic cholinergic receptors, cyclooxygenase and lipoxygenase, and Na+,K+-ATPase was evaluated in a histamine H3 receptor agonist-induced ((Rα-methylhistamine, (Rα-MeHA endothelium-dependent rat aorta relaxation assay. (Rα-MeHA (0.1 nM – 0.01 mM relaxed endothelium-dependent rat aorta, with a pD2 value of 8.22 ± 0.06, compared with a pD2 value of 7.98 ± 0.02 caused by histamine (50% and 70% relaxation, respectively. The effect of (Rα-MeHA (0.1 nM – 0.01 mM was competitively antagonized by thioperamide (1, 10 and 30 nM (pA2 = 9.21 ± 0.40; slope = 1.03 ± 0.35 but it was unaffected by pyrilamine (100 nM, cimetidine (1 μM, atropine (10 μM, propranolol (1 μM, indomethacin (10 μM or nordthydroguaiaretic acid (0.1 mM. Inhibitors of nitric oxide synthase, L-NG-monomethylarginine (L-NMMA, 10 μM and NG-nitro-L-arginine methylester (L-NOARG, 10 μM inhibited the relaxation effect of (Rα-MeHA, by approximately 52% and 70%, respectively. This inhibitory effect of L-NMMA was partially reversed by L-arginine (10 μM. Methylene blue (10 μM and ouabain (10 μM inhibited relaxation (Rα-MeHA-induced by approximately 50% and 90%, respectively. The products of cyclooxygenase and lipoxygenase are not involved in (Rα-MeHA-induced endothelium-dependent rat aorta relaxation nor are the muscarinic cholinergic and β-adrenergic receptors. The results also suggest the involvement of NO synthase, guanylate cyclase and Na+,K+-ATPase in (Rα-MeHA-induced endothelium-dependent rat aorta relaxation.

Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress

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Brouwers, O; Niessen, P M; Haenen, G

2010-01-01

-hydro-5-methylimidazolone (MG-H1) was detected with an antibody against MG-H1 and quantified with ultra-performance liquid chromatography (tandem) mass spectrometry. Reactive oxygen species formation was measured with a 5-(and-6)-chloromethyl-2'7'-dichlorodihydrofluorescein diacetate acetyl ester probe...... for AGE ligand S100b did (p cells and adventitia by fivefold accompanied by an eightfold increase in the oxidative stress marker nitrotyrosine. Antioxidant pre-incubation prevented methylglyoxal......-induced impairment of vasoreactivity. CONCLUSIONS/INTERPRETATION: These data show that hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation is mediated by increased intracellular methylglyoxal levels in a pathway dependent on oxidative stress....

Tocotrienol rich tocomin attenuates oxidative stress and improves endothelium-dependent relaxation in aortae from rats fed a high-fat western diet

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Saher F Ali

2016-10-01

Full Text Available We have previously reported that tocomin, a mixture high in tocotrienol content and also containing tocopherol, acutely preserves endothelial function in the presence of oxidative stress. In this study we investigated whether tocomin treatment would preserve endothelial function in aortae isolated from rats fed a high fat diet known to cause oxidative stress. Wistar hooded rats were fed a western diet (WD, 21% fat or control rat chow (SD, 6% fat for 12 weeks. Tocomin (40 mg/kg/day sc or its vehicle (peanut oil was administered for the last 4 weeks of the feeding regime. Aortae from WD rats showed an impairment of endothelium-dependent relaxation that was associated with an increased expression of the NADPH oxidase Nox2 subunit and an increase in the vascular generation of superoxide measured using L-012 chemiluminescence. The increase in vascular oxidative stress was accompanied by a decrease in basal NO release and impairment of the contribution of NO to ACh-induced relaxation. The impaired relaxation is likely contributed to by a decreased expression of eNOS, calmodulin and phosphorylated Akt and an increase in caveolin-Tocotrienol rich tocomin, which prevented the diet-induced changes in vascular function, reduced vascular superoxide production and abolished the diet-induced changes in eNOS and other protein expression. Using selective inhibitors of nitric oxide synthase (NOS, soluble guanylate cyclase (sGC and calcium activated potassium (KCa channels we demonstrated that tocomin increased NO mediated relaxation, without affecting the contribution of endothelium-dependent hyperpolarization type relaxation to the endothelium-dependent relaxation. The beneficial actions of tocomin in this diet-induced model of obesity suggests that it may have potential to be used as a therapeutic agent to prevent vascular disease in obesity.

Kaempferol enhances endothelium-dependent relaxation in the porcine coronary artery through activation of large-conductance Ca(2+) -activated K(+) channels.

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Xu, Y C; Leung, S W S; Leung, G P H; Man, R Y K

2015-06-01

Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle. The effect of kaempferol on the relaxation of porcine coronary arteries to endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) relaxing agents was studied in an in vitro organ chamber setup. The whole-cell patch-clamp technique was used to determine the effect of kaempferol on potassium channels in porcine coronary artery smooth muscle cells (PCASMCs). At a concentration without direct effect on vascular tone, kaempferol (3 × 10(-6) M) enhanced relaxations produced by bradykinin and sodium nitroprusside. The potentiation by kaempferol of the bradykinin-induced relaxation was not affected by N(ω)-nitro-L-arginine methyl ester, an inhibitor of NO synthase (10(-4) M) or TRAM-34 plus UCL 1684, inhibitors of intermediate- and small-conductance calcium-activated potassium channels, respectively (10(-6) M each), but was abolished by tetraethylammonium chloride, a non-selective inhibitor of calcium-activated potassium channels (10(-3) M), and iberiotoxin, a selective inhibitor of large-conductance calcium-activated potassium channel (KCa 1.1; 10(-7) M). Iberiotoxin also inhibited the potentiation by kaempferol of sodium nitroprusside-induced relaxations. Kaempferol stimulated an outward-rectifying current in PCASMCs, which was abolished by iberiotoxin. The present results suggest that, in smooth muscle cells of the porcine coronary artery, kaempferol enhanced relaxations caused by endothelium-derived and exogenous NO as well as those due to endothelium-dependent hyperpolarization. This vascular effect of kaempferol involved the activation of KCa 1.1 channels. © 2015 The British Pharmacological Society.

Endothelium derived nitric oxide synthase negatively regulates the PDGF-survivin pathway during flow-dependent vascular remodeling.

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Jun Yu

Full Text Available Chronic alterations in blood flow initiate structural changes in vessel lumen caliber to normalize shear stress. The loss of endothelial derived nitric oxide synthase (eNOS in mice promotes abnormal flow dependent vascular remodeling, thus uncoupling mechanotransduction from adaptive vascular remodeling. However, the mechanisms of how the loss of eNOS promotes abnormal remodeling are not known. Here we show that abnormal flow-dependent remodeling in eNOS knockout mice (eNOS (-/- is associated with activation of the platelet derived growth factor (PDGF signaling pathway leading to the induction of the inhibitor of apoptosis, survivin. Interfering with PDGF signaling or survivin function corrects the abnormal remodeling seen in eNOS (-/- mice. Moreover, nitric oxide (NO negatively regulates PDGF driven survivin expression and cellular proliferation in cultured vascular smooth muscle cells. Collectively, our data suggests that eNOS negatively regulates the PDGF-survivin axis to maintain proportional flow-dependent luminal remodeling and vascular quiescence.

Ethanol extract of seeds of Oenothera odorata induces vasorelaxation via endothelium-dependent NO-cGMP signaling through activation of Akt-eNOS-sGC pathway.

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Kim, Hye Yoom; Oh, Hyuncheol; Li, Xiang; Cho, Kyung Woo; Kang, Dae Gill; Lee, Ho Sub

2011-01-27

The vasorelaxant effect of ethanol extract of seeds of Oenothera odorata (Onagraceae) (one species of evening primroses) (ESOO) and its mechanisms involved were defined. Changes in vascular tension, guanosine 3',5'-cyclic monophosphate (cGMP) levels, and Akt expression were measured in carotid arterial rings from rats. Seeds of Oenothera odorata were extracted with ethanol (94%) and the extract was filtered, concentrated and stored at -70°C. ESOO relaxed endothelium-intact, but not endothelium-denuded, carotid arterial rings in a concentration-dependent manner. Similarly, ESOO increased cGMP levels of the carotid arterial rings. Pretreatment of endothelium-intact arterial rings with L-NAME, an inhibitor of nitric oxide synthase (NOS), or ODQ, an inhibitor of soluble guanylyl cyclase (sGC), blocked the ESOO-induced vasorelaxation and increase in cGMP levels. Nominally Ca(2+)-free but not L-typed Ca(2+) channel inhibition attenuated the ESOO-induced vasorelaxation. Thapsigargin, Gd(3+), and 2-aminoethyl diphenylborinate, modulators of store-operated Ca(2+) entry (SOCE), significantly attenuated the ESOO-induced vasorelaxation and increase in cGMP levels. Further, wortmannin, an inhibitor of Akt, attenuated the ESOO-induced vasorelaxation and increases in cGMP levels and phosphorylated Akt2 expression. K(+) channel blockade with TEA, 4-aminopyridine, and glibenclamide attenuated the ESOO-induced vascular relaxation. Taken together, the present study demonstrates that ESOO relaxes vascular smooth muscle via endothelium-dependent NO-cGMP signaling through activation of the Akt-eNOS-sGC pathway. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Factor VIII-associated antigen in human lymphatic endothelium.

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Nagle, R B; Witte, M H; Martinez, A P; Witte, C L; Hendrix, M J; Way, D; Reed, K

1987-03-01

Lymphatic vascular endothelium both on tissue section and in culture exhibits positivity for Factor VIII-associated antigen although staining is generally less intense and more spotty than in comparable blood vascular endothelium. Lymphatic endothelium also exhibits Weibel-Palade bodies. Neither marker, therefore, reliably distinguishes blood vascular endothelium from lymphatic endothelium.

Kaempferol enhances endothelium-dependent relaxation in the porcine coronary artery through activation of large-conductance a2+-activated K+ channels

Science.gov (United States)

Xu, Y C; Leung, S W S; Leung, G P H; Man, R Y K

2015-01-01

Background and Purpose Kaempferol, a plant flavonoid present in normal human diet, can modulate vasomotor tone. The present study aimed to elucidate the signalling pathway through which this flavonoid enhanced relaxation of vascular smooth muscle. Experimental Approach The effect of kaempferol on the relaxation of porcine coronary arteries to endothelium-dependent (bradykinin) and -independent (sodium nitroprusside) relaxing agents was studied in an in vitro organ chamber setup. The whole-cell patch-clamp technique was used to determine the effect of kaempferol on potassium channels in porcine coronary artery smooth muscle cells (PCASMCs). Key Results At a concentration without direct effect on vascular tone, kaempferol (3 × 10−6 M) enhanced relaxations produced by bradykinin and sodium nitroprusside. The potentiation by kaempferol of the bradykinin-induced relaxation was not affected by Nω-nitro-L-arginine methyl ester, an inhibitor of NO synthase (10−4 M) or TRAM-34 plus UCL 1684, inhibitors of intermediate- and small-conductance calcium-activated potassium channels, respectively (10−6 M each), but was abolished by tetraethylammonium chloride, a non-selective inhibitor of calcium-activated potassium channels (10−3 M), and iberiotoxin, a selective inhibitor of large-conductance calcium-activated potassium channel (KCa1.1; 10−7 M). Iberiotoxin also inhibited the potentiation by kaempferol of sodium nitroprusside-induced relaxations. Kaempferol stimulated an outward-rectifying current in PCASMCs, which was abolished by iberiotoxin. Conclusions and Implications The present results suggest that, in smooth muscle cells of the porcine coronary artery, kaempferol enhanced relaxations caused by endothelium-derived and exogenous NO as well as those due to endothelium-dependent hyperpolarization. This vascular effect of kaempferol involved the activation of KCa1.1 channels. PMID:25652142

P2X1 receptors and the endothelium

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LS Harrington

2005-03-01

Full Text Available Adenosine triphosphate (ATP is now established as a principle vaso-active mediator in the vasculature. Its actions on arteries are complex, and are mediated by the P2X and P2Y receptor families. It is generally accepted that ATP induces a bi-phasic response in arteries, inducing contraction via the P2X and P2Y receptors on the smooth muscle cells, and vasodilation via the actions of P2Y receptors located on the endothelium. However, a number of recent studies have placed P2X1 receptors on the endothelium of some arteries. The use of a specific P2X1 receptor ligand, a, b methylene ATP has demonstrated that P2X1 receptors also have a bi-functional role. The actions of ATP on P2X1 receptors is therefore dependant on its location, inducing contraction when located on the smooth muscle cells, and dilation when expressed on the endothelium, comparable to that of P2Y receptors.

Inhibition of PKC-dependent extracellular Ca{sup 2+} entry contributes to the depression of contractile activity in long-term pressure-overloaded endothelium-denuded rat aortas

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Padilla, J.; López, R.M.; López, P.; Castillo, M.C.; Querejeta, E.; Ruiz, A.; Castillo, E.F. [Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, DF (Mexico)

2014-08-01

We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT{sub 2}R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT{sub 2}R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca{sup 2+}-free medium or the subsequent tonic constrictions induced by the addition of Ca{sup 2+} in the absence of agonists. Thus, the contractions induced by Ca{sup 2+} release from intracellular stores and Ca{sup 2+} influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca{sup 2+} channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca{sup 2+}. Neither levels of angiotensins nor of AT{sub 2}R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca{sup 2+} entry.

[The endothelium injuries caused by homocysteine and treatmental effects of Tongxinluo powder].

Science.gov (United States)

Liang, Jun-Qing; Wu, Yi-Ling; Xu, Hai-Bo; Zhao, Shao-Hua; Jia, Zhen-Hua; Zhang, Qiu-Yan; Wei, Cong; Dong, Xiao-Wei

2008-02-01

To observe the effect of homocysteine (HCY) on the function of endothelium cell, and to discuss the possible mechanisms that Tongxinluo super powder affected. Healthy male Wistar rats were divided into randomly the control group, the model group, the Tongxinluo group. The effect of Ach on isolated rat thoracic aorta in vitro was examined, the microcirculation was observed by microcirculation meter, the activity of SOD and GSH-PX and content of NO, MDA, ET, Ang II, TXA2, PGI2 was detected. Compared with control group, the effect of Ach on isolated rat thoracic aorta in vitro weakened markablely (P homocystein might cause the contracted and dilated function decreased, it might get involved in endothelium disfunction as a result of the massive free radicals production and diastolic-contract factors balance disorder induced by high homocystein. (2) Tongxinluo powder could improve the function of endothelium-dependment dilation induced by high homocystein, that associated with inhibitting the excessive production of free radicals, and improved function of endothelium.

Polydatin Restores Endothelium-Dependent Relaxation in Rat Aorta Rings Impaired by High Glucose: A Novel Insight into the PPARβ-NO Signaling Pathway.

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Yang Wu

Full Text Available Polydatin, a natural component from Polygonum Cuspidatum, has important therapeutic effects on metabolic syndrome. A novel therapeutic strategy using polydatin to improve vascular function has recently been proposed to treat diabetes-related cardiovascular complications. However, the biological role and molecular basis of polydatin's action on vascular endothelial cells (VECs-mediated vasodilatation under diabetes-related hyperglycemia condition remain elusive. The present study aimed to assess the contribution of polydatin in restoring endothelium-dependent relaxation and to determine the details of its underlying mechanism. By measuring endothelium-dependent relaxation, we found that acetylcholine-induced vasodilation was impaired by elevated glucose (55 mmol/L; however, polydatin (1, 3, 10 μmol/L could restore the relaxation in a dose-dependent manner. Polydatin could also improve the histological damage to endothelial cells in the thoracic aorta. Polydatin's effects were mediated via promoting the expression of endothelial NO synthase (eNOS, enhancing eNOS activity and decreasing the inducible NOS (iNOS level, finally resulting in a beneficial increase in NO release, which probably, at least in part, through activation of the PPARβ signaling pathway. The results provided a novel insight into polydatin action, via PPARβ-NO signaling pathways, in restoring endothelial function in high glucose conditions. The results also indicated the potential utility of polydatin to treat diabetes related cardiovascular diseases.

Stress susceptibility as a determinant of endothelium-dependent vascular reactivity in rat mesenteric arteries.

NARCIS (Netherlands)

Riksen, N.P.; Ellenbroek, B.A.; Cools, A.R.; Siero, H.L.M.; Rongen, G.A.P.J.M.; Smits, B.W.; Russel, F.G.M.; Smits, P.

2003-01-01

In order to investigate the consequences of stress susceptibility on vascular function, the authors assessed the respective contributions of nitric oxide (NO), prostanoids, and endothelium-derived hyperpolarizing factor to the vascular tone in rats with a constitutionally determined high and low

Effect of Time-Dependent Pinning Pressure on Abnormal Grain Growth: Phase Field Simulation

Science.gov (United States)

Kim, Jeong Min; Min, Guensik; Shim, Jae-Hyeok; Lee, Kyung Jong

2018-05-01

The effect of the time-dependent pinning pressure of precipitates on abnormal grain growth has been investigated by multiphase field simulation with a simple precipitation model. The application of constant pinning pressure is problematic because it always induces abnormal grain growth or no grain growth, which is not reasonable considering the real situation. To produce time-dependent pinning pressure, both precipitation kinetics and precipitate coarsening kinetics have been considered with two rates: slow and fast. The results show that abnormal grain growth is suppressed at the slow precipitation rate. At the slow precipitation rate, the overall grain growth caused by the low pinning pressure in the early stage indeed plays a role in preventing abnormal grain growth by reducing the mobility advantage of abnormal grains. In addition, the fast precipitate coarsening rate tends to more quickly transform abnormal grain growth into normal grain growth by inducing the active growth of grains adjacent to the abnormal grains in the early stage. Therefore, the present study demonstrates that the time dependence of the pinning pressure of precipitates is a critical factor that determines the grain growth mode.

Decreased endothelium-dependent coronary vasomotion in healthy young smokers

International Nuclear Information System (INIS)

Iwado, Yasuyoshi; Yoshinaga, Keiichiro; Furuyama, Hideto; Tsukamoto, Eriko; Tamaki, Nagara; Ito, Yoshinori; Noriyasu, Kazuyuki; Katoh, Chietsugu; Kuge, Yuji

2002-01-01

Chronic cigarette smoking alters coronary vascular endothelial response. To determine whether altered response also occurs in young individuals without manifest coronary disease we quantified coronary blood flow at rest, following adenosine vasodilator stress and during the cold pressor test in healthy young smokers. Myocardial blood flow (MBF) was quantified by oxygen-15 labelled water positron emission tomography in 30 healthy men aged from 20 to 35 years (18 smokers and 12 non-smokers, aged 27.4±4.4 vs 26.3±3.3). The smokers had been smoking cigarettes for 9.4±4.9 pack-years. MBF was measured at rest, during intravenous adenosine triphosphate (ATP: 0.16 mg kg -1 min -1 ) infusion (hyperaemic response), and during cold pressor test (CPT) (endothelial vasodilator response). Rest MBF and hyperaemic MBF did not differ significantly between the smokers and the non-smokers (rest: 0.86±0.11 vs 0.92±0.14 and ATP: 3.20±1.12 vs 3.69±0.76 ml g -1 min -1 ; P=NS). Coronary flow reserve was similar between the two groups (smokers: 3.78±1.83; non-smokers: 4.03±0.68; P=NS). Although CPT induced a similar increase in rate-pressure product (RPP) in the smokers and the non-smokers (10,430±1,820 vs 9,236±1,356 beats min -1 mmHg -1 ), CPT MBF corrected by RPP was significantly decreased in the smokers (0.65±0.12 ml g -1 min -1 ) compared with the non-smokers (0.87±0.12 ml g -1 min -1 ) (P<0.05). In addition, the ratio of CPT MBF to resting MBF was inversely correlated with pack-years (r=-0.57, P=0.014). Endothelium-dependent coronary artery vasodilator function is impaired in apparently healthy young smokers. (orig.)

Decreased endothelium-dependent coronary vasomotion in healthy young smokers

Energy Technology Data Exchange (ETDEWEB)

Iwado, Yasuyoshi; Yoshinaga, Keiichiro; Furuyama, Hideto; Tsukamoto, Eriko; Tamaki, Nagara [Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Kita-Ku, Kita 15 Nishi 7, Sapporo, 060-8638 (Japan); Ito, Yoshinori; Noriyasu, Kazuyuki [Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Katoh, Chietsugu; Kuge, Yuji [Department of Tracer Kinetics, Hokkaido University Graduate School of Medicine, Sapporo (Japan)

2002-08-01

Chronic cigarette smoking alters coronary vascular endothelial response. To determine whether altered response also occurs in young individuals without manifest coronary disease we quantified coronary blood flow at rest, following adenosine vasodilator stress and during the cold pressor test in healthy young smokers. Myocardial blood flow (MBF) was quantified by oxygen-15 labelled water positron emission tomography in 30 healthy men aged from 20 to 35 years (18 smokers and 12 non-smokers, aged 27.4{+-}4.4 vs 26.3{+-}3.3). The smokers had been smoking cigarettes for 9.4{+-}4.9 pack-years. MBF was measured at rest, during intravenous adenosine triphosphate (ATP: 0.16 mg kg{sup -1} min{sup -1}) infusion (hyperaemic response), and during cold pressor test (CPT) (endothelial vasodilator response). Rest MBF and hyperaemic MBF did not differ significantly between the smokers and the non-smokers (rest: 0.86{+-}0.11 vs 0.92{+-}0.14 and ATP: 3.20{+-}1.12 vs 3.69{+-}0.76 ml g{sup -1} min{sup -1}; P=NS). Coronary flow reserve was similar between the two groups (smokers: 3.78{+-}1.83; non-smokers: 4.03{+-}0.68; P=NS). Although CPT induced a similar increase in rate-pressure product (RPP) in the smokers and the non-smokers (10,430{+-}1,820 vs 9,236{+-}1,356 beats min{sup -1} mmHg{sup -1}), CPT MBF corrected by RPP was significantly decreased in the smokers (0.65{+-}0.12 ml g{sup -1} min{sup -1}) compared with the non-smokers (0.87{+-}0.12 ml g{sup -1} min{sup -1}) (P<0.05). In addition, the ratio of CPT MBF to resting MBF was inversely correlated with pack-years (r=-0.57, P=0.014). Endothelium-dependent coronary artery vasodilator function is impaired in apparently healthy young smokers. (orig.)

Rho-kinase inhibitor and nicotinamide adenine dinucleotide phosphate oxidase inhibitor prevent impairment of endothelium-dependent cerebral vasodilation by acute cigarette smoking in rats.

Science.gov (United States)

Iida, Hiroki; Iida, Mami; Takenaka, Motoyasu; Fukuoka, Naokazu; Dohi, Shuji

2008-06-01

We previously reported that acute cigarette smoking can cause a dysfunction of endothelium-dependent vasodilation in cerebral vessels, and that blocking the angiotensin II (Ang II) type 1 (AT1) receptor with valsartan prevented this impairment. Our aim was to investigate the effects of a Rho-kinase inhibitor (fasudil) and a Nicotinamide Adenine Dinucleotide PHosphate (NADPH) oxidase inhibitor (apocynin) on smoking-induced endothelial dysfunction in cerebral arterioles. In Sprague-Dawley rats, we used a closed cranial window preparation to measure changes in pial vessel diameters following topical acetylcholine (ACh) before smoking. After one-minute smoking, we again examined the arteriolar responses to ACh. Finally, after intravenous fasudil or apocynin pre-treatment we re-examined the vasodilator responses to topical ACh (before and after cigarette smoking). Under control conditions, cerebral arterioles were dose-dependently dilated by topical ACh (10(-6) M and 10(-5) M). One hour after a one-minute smoking (1 mg-nicotine cigarette), 10(-5) M ACh constricted cerebral arterioles. However, one hour after a one-minute smoking, 10(-5) M ACh dilated cerebral pial arteries both in the fasudil pre-treatment and the apocynin pre-treatment groups, responses that were significantly different from those obtained without fasudil or apocynin pre-treatment. Thus, inhibition of Rho-kinase and NADPH oxidase activities may prevent the above smoking-induced impairment of endothelium-dependent vasodilation.

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation pursuant to Article 13(5) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

Following an application from Barry Callebaut Belgium nv, submitted pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation...... of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation. Cocoa flavanols are sufficiently characterised. The claimed effect is “help maintain endothelium-dependent vasodilation which contributes to healthy blood flow”. The target population proposed...... by the applicant is the general healthy adult population. The Panel considers that maintenance of normal endothelium-dependent vasodilation is a beneficial physiological effect. In weighing the evidence, the Panel took into account that cocoa flavanols consumed for 12 weeks have been shown to increase fasting ED...

The study of the functional state of the endothelium via a complex of markers with reactive hyperemia

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Berezhniy V.

2016-03-01

Full Text Available Diagnosis of endothelial dysfunction is a key point in the prevention and treatment of cardiovascular diseases. In scientific research the study of the state of the endothelium used test with reactive hyperemia of brachial artery wich present as the value of endothelium dependent and independent artery dilatation. However, the disadvantage of this marker is ignoring the size of arteries, well know that small arteries has a greater degree of dilation more than big arterias, this fact making difficult to compare results between different patients. The aim of our study was to examine the state of endothelium using a complex of markers, compare them informative in children with JRA who are at risk for the development of endothelial dysfunction. Materials and Methods. The study was included 40 children with juvenile rheumatoid arthritis who were treated at the department of children's cardiorheumatology Kyiv City Children's Hospital #1 and Kiev Regional Hospital m. Boyarka. Results. The study found a development of endothelial dysfunction changes in endothelium dependent vasodilation, reactive hyperemia and coefficient of vasodilation. Simultaneous marked change of endothelium vasodilation of the brachial artery and coefficient of vasodilatation. There were no pathological changes in endothelial shear stress in patients compared with healthy children. Conclusions. Evaluate the state of the endothelium is necessary with the help of a set of indicators (RH, EDVD, VC that will help to avoid diagnostic mistakes during the test with the reactive hyperemia.

Adiponectin improves coronary no-reflow injury by protecting the endothelium in rats with type 2 diabetes mellitus.

Science.gov (United States)

Han, Xue; Wu, Ye; Liu, Xin; Ma, Lu; Lv, Tingting; Sun, Qi; Xu, Wenli; Zhang, Suli; Wang, Ke; Wang, Wen; Ma, Xinliang; Liu, Huirong

2017-08-31

To determine the effect of adiponectin (APN) on the coronary no-reflow (NR) injury in rats with Type 2 diabetes mellitus (T2DM), 80 male Sprague-Dawley rats were fed with a high-sugar-high-fat diet to build a T2DM model. Rats received vehicle or APN in the last week and then were subjected to myocardial ischemia reperfusion (MI/R) injury. Endothelium-dependent vasorelaxation of the thoracic aorta was significantly decreased and serum levels of endothelin-1 (ET-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were noticably increased in T2DM rats compared with rats without T2DM. Serum APN was positively correlated with the endothelium-dependent vasorelaxation, but negatively correlated with the serum level of ET-1. Treatment with APN improved T2DM-induced endothelium-dependent vasorelaxation, recovered cardiac function, and decreased both NR size and the levels of ET-1, ICAM-1 and VCAM-1. Hypoadiponectinemia was associated with the aggravation of coronary NR in T2DM rats. APN could alleviate coronary NR injury in T2DM rats by protecting the endothelium and improving microcirculation. © 2017 The Author(s).

Effect of prolonged incubation with copper on endothelium-dependent relaxation in rat isolated aorta

Science.gov (United States)

Chiarugi, Alberto; Pitari, Giovanni Mario; Costa, Rosa; Ferrante, Margherita; Villari, Loredana; Amico-Roxas, Matilde; Godfraind, Théophile; Bianchi, Alfredo; Salomone, Salvatore

2002-01-01

We investigated the effects of prolonged exposure to copper (Cu2+) on vascular functioning of isolated rat aorta. Aortic rings were exposed to CuSO4 (3–24 h) in Dulbecco's modified Eagle medium with or without 10% foetal bovine serum (FBS) and then challenged with vasoconstrictors or vasodilators in the absence of Cu2+. Exposure to 2 μM Cu2+ in the absence of FBS did not modify the response to phenylephrine (PE) or acetylcholine (ACh) in aortic rings incubated for 24 h. Identical exposure in the presence of FBS increased the contractile response to 1 μM PE by 30% (P<0.05) and impaired the relaxant response to 3 μM ACh or 1 μM A23187 (ACh, from 65.7±7.1 to 6.2±1.1%, n=8; A23187, from 74.6±8.2 to 12.0±0.8%, n=6; P<0.01 for both). Cu2+ exposure did not affect the relaxant response to NO-donors. Impairment of vasorelaxation appeared 3 h after incubation with 2 μM Cu2+ and required 12 h to attain a steady state. Vasorelaxation to ACh was partially restored by 1 mM tiron (intracellular scavenger of superoxide ions; maximum relaxation 34.2±6.4%, n=10, P<0.01 vs Cu2+ alone), whereas catalase, superoxide dismutase or cycloheximide were ineffective. Twenty-four hour-exposure to 2 μM Cu2+ did not affect endothelium integrity or eNOS expression, and increased the Cu content in arterial rings from 6.8±1.1 to 18.9±2.9 ng mg−1 wet weight, n=8; P<0.01. Our results show that, in the presence of FBS, prolonged exposure to submicromolar concentrations of Cu2+ impaired endothelium-dependent vasorelaxation in aortic rings, probably through an intracellular generation of superoxide ions. PMID:12163352

Hypertrophy of cultured bovine aortic endothelium following irradiation

International Nuclear Information System (INIS)

Rosen, E.M.; Vinter, D.W.; Goldberg, I.D.

1989-01-01

The vascular endothelium is a vital multifunctional tissue which covers the entire luminal surface of the circulatory system. Loss of continuity of the endothelial lining normally results in cell migration and proliferation to make up for cell loss and to ensure that exposure of the thrombogenic subendothelium to platelets and clotting factors is minimized. We showed that ionizing radiation (400-3000 cGy) causes dose-dependent cell loss from confluent monolayer cultures of bovine aortic endothelium, which cannot immediately be compensated by cell proliferation. Within 24 h, the remaining attached cells undergo substantial somatic hypertrophy (evidenced by increased protein content, cell volume, and attachment area) but remain diploid. If cell loss is not excessive, monolayer continuity is restored within several days. Although reduced protein degradation may contribute, most of the protein accumulation is due to synthesis of new protein. Unlike endothelium, irradiation of smooth muscle cultures causes neither cell loss nor increased protein synthesis. Hypertrophy of irradiated endothelial cells appears to be a consequence of a proliferative stimulus (cell loss) in a population of cells which is unable to divide. It can be modulated by replating irradiated cells at different densities. We suggest that endothelial hypertrophy is an early vascular homeostatic response before clonal proliferation of surviving cells or repopulation by cells from outside of the irradiated field can compensate for cell loss

Excess L-arginine restores endothelium-dependent relaxation impaired by monocrotaline pyrrole

International Nuclear Information System (INIS)

Cheng Wei; Oike, Masahiro; Hirakawa, Masakazu; Ohnaka, Keizo; Koyama, Tetsuya; Ito, Yushi

2005-01-01

The pyrrolizidine alkaloid plant toxin monocrotaline pyrrole (MCTP) causes pulmonary hypertension in experimental animals. The present study aimed to examine the effects of MCTP on the endothelium-dependent relaxation. We constructed an in vitro disease model of pulmonary hypertension by overlaying MCTP-treated bovine pulmonary artery endothelial cells (CPAEs) onto pulmonary artery smooth muscle cell-embedded collagen gel lattice. Acetylcholine (Ach) induced a relaxation of the control CPAEs-overlaid gels that were pre-contracted with noradrenaline, and the relaxation was inhibited by L-NAME, an inhibitor of NO synthase (NOS). In contrast, when MCTP-treated CPAEs were overlaid, the pre-contracted gels did not show a relaxation in response to Ach in the presence of 0.5 mM L-arginine. Expression of endothelial NOS protein, Ach-induced Ca 2+ transients and cellular uptake of L-[ 3 H]arginine were significantly smaller in MCTP-treated CPAEs than in control cells, indicating that these changes were responsible for the impaired NO production in MCTP-treated CPAEs. Since cellular uptake of L-[ 3 H]arginine linearly increased according to its extracellular concentration, we hypothesized that the excess concentration of extracellular L-arginine might restore NO production in MCTP-treated CPAEs. As expected, in the presence of 10 mM L-arginine, Ach showed a relaxation of the MCTP-treated CPAEs-overlaid gels. These results indicate that the impaired NO production in damaged endothelial cells can be reversed by supplying excess L-arginine

Cigarette smoke extract increases albumin flux across pulmonary endothelium in vitro

International Nuclear Information System (INIS)

Holden, W.E.; Maier, J.M.; Malinow, M.R.

1989-01-01

Cigarette smoking causes lung inflammation, and a characteristic of inflammation is an increase in vascular permeability. To determine if cigarette smoke could alter endothelial permeability, we studied flux of radiolabeled albumin across monolayers of porcine pulmonary artery endothelium grown in culture on microporous membranes. Extracts (in either dimethylsulfoxide or phosphate-buffered saline) of cigarette smoke in a range estimate of concentrations simulating cigarette smoke exposure to the lungs in vivo caused a dose-dependent increase in albumin flux that was dependent on extracellular divalent cations and associated with polymerization of cellular actin. The effect was reversible, independent of the surface of endothelial cells exposed (either luminal or abluminal), and due primarily to components of the vapor phase of smoke. The effects occurred without evidence of cell damage, but subtle morphological changes were produced by exposure to the smoke extracts. These findings suggest that cigarette smoke can alter permeability of the lung endothelium through effects on cytoskeletal elements

Endothelium-dependent hyperpolarization-related relaxations diminish with age in murine saphenous arteries of both sexes

DEFF Research Database (Denmark)

Chennupati, R.; Lamers, W. H.; Koehler, S. E.

2013-01-01

nitroprusside and to ACh in the absence of pharmacological inhibitors (indomethacin and L-NAME), were similar in all age groups and sexes, but those mediated by endothelium-derived NO were slightly but significantly increased in 64-week-old male mice. In the presence of inhibitors, 12-week-old animals showed...... pronounced ACh-induced relaxation, which was significantly reduced in 34- and 64-week-old mice of both sexes. The EDH-related component of ACh-induced relaxations was abolished by TRAM-34 (K(Ca)3.1 blocker) or UCL 1684 (K(Ca)2.3 blocker). Although the maximal relaxation induced by NS309 (K-Ca activator......) was not affected by aging, the sensitivity for NS309 significantly decreased with aging. The presence of SKA-31 (K-Ca modulator) potentiated relaxations induced by ACh in arteries of 12-week-old but not older mice. CONCLUSION AND IMPLICATIONS In a small muscular artery of mice of either sex, total endothelium...

Semi-quantitative assessments of dextran toxicity on corneal endothelium: conceptual design of a predictive algorithm.

Science.gov (United States)

Filev, Filip; Oezcan, Ceprail; Feuerstacke, Jana; Linke, Stephan J; Wulff, Birgit; Hellwinkel, Olaf J C

2017-03-01

Dextran is added to corneal culture medium for at least 8 h prior to transplantation to ensure that the cornea is osmotically dehydrated. It is presumed that dextran has a certain toxic effect on corneal endothelium but the degree and the kinetics of this effect have not been quantified so far. We consider that such data regarding the toxicity of dextran on the corneal endothelium could have an impact on scheduling and logistics of corneal preparation in eye banking. In retrospective statistic analyses, we compared the progress of corneal endothelium (endothelium cell loss per day) of 1334 organ-cultured corneal explants in media with and without dextran. Also, the influence of donor-age, sex and cause of death on the observed dextran-mediated effect on endothelial cell counts was studied. Corneas cultured in dextran-free medium showed a mean endothelium cell count decrease of 0.7% per day. Dextran supplementation led to a mean endothelium cell loss of 2.01% per day; this reflects an increase by the factor of 2.9. The toxic impact of dextran was found to be time dependent; while the prevailing part of the effect was observed within the first 24 h after dextran-addition. Donor age, sex and cause of death did not seem to have an influence on the dextran-mediated toxicity. Based on these findings, we could design an algorithm which approximately describes the kinetics of dextran-toxicity. We reproduced the previously reported toxic effect of dextran on the corneal endothelium in vitro. Additionally, this is the first work that provides an algorithmic instrument for the semi-quantitative calculation of the putative endothelium cell count decrease in dextran containing medium for a given incubation time and could thus influence the time management and planning of corneal transplantations.

Nitric oxide, cholesterol oxides and endothelium-dependent vasodilation in plasma of patients with essential hypertension

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P. Moriel

2002-11-01

Full Text Available The objective of the present study was to identify disturbances of nitric oxide radical (·NO metabolism and the formation of cholesterol oxidation products in human essential hypertension. The concentrations of·NO derivatives (nitrite, nitrate, S-nitrosothiols and nitrotyrosine, water and lipid-soluble antioxidants and cholesterol oxides were measured in plasma of 11 patients with mild essential hypertension (H: 57.8 ± 9.7 years; blood pressure, 148.3 ± 24.8/90.8 ± 10.2 mmHg and in 11 healthy subjects (N: 48.4 ± 7.0 years; blood pressure, 119.4 ± 9.4/75.0 ± 8.0 mmHg.Nitrite, nitrate and S-nitrosothiols were measured by chemiluminescence and nitrotyrosine was determined by ELISA. Antioxidants were determined by reverse-phase HPLC and cholesterol oxides by gas chromatography. Hypertensive patients had reduced endothelium-dependent vasodilation in response to reactive hyperemia (H: 9.3 and N: 15.1% increase of diameter 90 s after hyperemia, and lower levels of ascorbate (H: 29.2 ± 26.0, N: 54.2 ± 24.9 µM, urate (H: 108.5 ± 18.9, N: 156.4 ± 26.3 µM, ß-carotene (H: 1.1 ± 0.8, N: 2.5 ± 1.2 nmol/mg cholesterol, and lycopene (H: 0.4 ± 0.2, N: 0.7 ± 0.2 nmol/mg cholesterol, in plasma, compared to normotensive subjects. The content of 7-ketocholesterol, 5alpha-cholestane-3ß,5,6ß-triol and 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol in LDL, and the concentration of endothelin-1 (H: 0.9 ± 0.2, N: 0.7 ± 0.1 ng/ml in plasma were increased in hypertensive patients. No differences were found for ·NO derivatives between groups. These data suggest that an increase in cholesterol oxidation is associated with endothelium dysfunction in essential hypertension and oxidative stress, although ·NO metabolite levels in plasma are not modified in the presence of elevated cholesterol oxides.

Age- and Gene-Dosage–Dependent Cre-Induced Abnormalities in the Retinal Pigment Epithelium

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He, Lizhi; Marioutina, Mariya; Dunaief, Joshua L.; Marneros, Alexander G.

2015-01-01

To conditionally inactivate genes in the retinal pigment epithelium (RPE) transgenic mouse strains have been developed, in which Cre recombinase (Cre) expression is driven by an RPE-specific gene promoter. The RPE is a quiescent epithelium, and continuous expression of Cre could affect its function. Here, we tested the hypothesis that continuous postnatal Cre expression in the RPE may lead to cellular abnormalities, which may depend on both age and Cre gene dosage. We therefore examined the eyes of homozygous and heterozygous VMD2-Cre mice at various ages. In VMD2-Cre heterozygous mice variable progressive age-dependent RPE abnormalities were noticed, including attenuation of phalloidin and cytoplasmic active β-catenin staining, reduced cell size, and loss of the typical honeycomb pattern of RPE morphology in those RPE cells that stained for Cre. These morphological RPE abnormalities were not noticed in Cre-negative RPE cells in VMD2-Cre or age-matched control mice. In addition, an abnormal number and morphology of cell nuclei were noticed in a subset of Cre-expressing RPE cells in aged heterozygous VMD2-Cre mice, whereas more severe nuclear abnormalities were observed already in young homozygous VMD2-Cre mice. Thus, continuous postnatal expression of Cre causes abnormalities in the RPE in an age- and Cre gene dosage-dependent manner, which needs to be considered in the interpretation of gene targeting studies in the RPE. PMID:24854863

Endothelium-dependent vasorelaxant effect of procyanidin B2 on human internal mammary artery.

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Novakovic, Aleksandra; Marinko, Marija; Jankovic, Goran; Stojanovic, Ivan; Milojevic, Predrag; Nenezic, Dragoslav; Kanjuh, Vladimir; Yang, Qin; He, Guo-Wei

2017-07-15

The aim of the present study was to investigate and characterize vasorelaxant effect of procyanidin B2 on human internal mammary artery (HIMA) as one of the mechanisms of its protective effect against vascular risk. Procyanidin B2 induced strong concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Pretreatment with L-NAME, a NO synthase inhibitor, hydroxocobalamin, a NO scavenger, and ODQ, an inhibitor of soluble guanylate cyclase, significantly inhibited procyanidin B2-induced relaxation of HIMA, while indomethacin, a cyclooxygenase inhibitor, considerably reduced effects of low concentrations. Among K + channel blockers, iberiotoxin, a selective blocker of large conductance Ca 2+ -activated K + channels (BK Ca ), abolished procyanidin B2-induced relaxation, glibenclamide, a selective ATP-sensitive K + (K ATP ) channels blocker, induced partial inhibition, while 4-aminopyridine, a blocker of voltage-gated K + (K V ) channels, and TRAM-34, an inhibitor of intermediate-conductance Ca 2+ -activated K + (IK Ca ) channels, slightly reduced maximal relaxation of HIMA. Further, procyanidin B2 relaxed contraction induced by phenylephrine in Ca 2+ -free Krebs solution, but had no effect on contraction induced by caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca 2+ -ATPase inhibitor, significantly reduced relaxation of HIMA produced by procyanidin B2. These results demonstrate that procyanidin B2 produces endothelium-dependent relaxation of HIMA pre-contracted by phenylephrine. This effect is primarily the result of an increased NO synthesis and secretion by endothelial cells and partially of prostacyclin, although it involves activation of BK Ca and K ATP , as well as K V and IK Ca channels in high concentrations of procyanidin B2. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of the endothelium in asthma and chronic obstructive pulmonary disease (COPD).

Science.gov (United States)

Green, Clara E; Turner, Alice M

2017-01-18

COPD and asthma are important chronic inflammatory disorders with a high associated morbidity. Much research has concentrated on the role of inflammatory cells, such as the neutrophil, in these diseases, but relatively little focus has been given to the endothelial tissue, through which inflammatory cells must transmigrate to reach the lung parenchyma and cause damage. There is evidence that there is an abnormal amount of endothelial tissue in COPD and asthma and that this tissue and its' progenitor cells behave in a dysfunctional manner. This article reviews the evidence of the involvement of pulmonary endothelium in COPD and asthma and potential treatment options for this.

The Deletion of Endothelial Sodium Channel α (αENaC Impairs Endothelium-Dependent Vasodilation and Endothelial Barrier Integrity in Endotoxemia in Vivo

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Magdalena Sternak

2018-04-01

Full Text Available The role of epithelial sodium channel (ENaC activity in the regulation of endothelial function is not clear. Here, we analyze the role of ENaC in the regulation of endothelium-dependent vasodilation and endothelial permeability in vivo in mice with conditional αENaC subunit gene inactivation in the endothelium (endo-αENaCKO mice using unique MRI-based analysis of acetylcholine-, flow-mediated dilation and vascular permeability. Mice were challenged or not with lipopolysaccharide (LPS, from Salmonella typhosa, 10 mg/kg, i.p.. In addition, changes in vascular permeability in ex vivo organs were analyzed by Evans Blue assay, while changes in vascular permeability in perfused mesenteric artery were determined by a FITC-dextran-based assay. In basal conditions, Ach-induced response was completely lost, flow-induced vasodilation was inhibited approximately by half but endothelial permeability was not changed in endo-αENaCKO vs. control mice. In LPS-treated mice, both Ach- and flow-induced vasodilation was more severely impaired in endo-αENaCKO vs. control mice. There was also a dramatic increase in permeability in lungs, brain and isolated vessels as evidenced by in vivo and ex vivo analysis in endotoxemic endo-αENaCKO vs. control mice. The impaired endothelial function in endotoxemia in endo-αENaCKO was associated with a decrease of lectin and CD31 endothelial staining in the lung as compared with control mice. In conclusion, the activity of endothelial ENaC in vivo contributes to endothelial-dependent vasodilation in the physiological conditions and the preservation of endothelial barrier integrity in endotoxemia.

Toxicity of methods of implant material sterilization on corneal endothelium

Energy Technology Data Exchange (ETDEWEB)

Singh, G.; Boehnke, Mv.; von Domarus, D.; Draeger, J.

1985-11-01

The toxicity of different procedures utilized for the sterilization of intraocular implant material was assessed on the endothelium of organ-cultured porcine corneas. Polymethylmethacrylate lenses sterilized by treatment with sodium hydroxide (NaOH), ethylene oxide, formaldehyde, and gamma radiation were added to a culture medium containing normal porcine corneas. Considering the viability of endothelial cells, appearance of intracellular degenerative vacuoles, and denudation of corneal Descemet's membrane as criterion for the evaluation of toxicity of different methods of sterilization, the NaOH-treated lenses were found to be the least toxic to porcine corneal endothelium. Phase-contrast microscopy and vital staining of the endothelium permitted direct viewing of the endothelium aiding in the assessment of toxicity.

The Role of the Endothelium in HPS Pathogenesis and Potential Therapeutic Approaches

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Irina Gavrilovskaya

2012-01-01

Full Text Available American hantaviruses cause a highly lethal acute pulmonary edema termed hantavirus pulmonary syndrome (HPS. Hantaviruses nonlytically infect endothelial cells and cause dramatic changes in barrier functions of the endothelium without disrupting the endothelium. Instead hantaviruses cause changes in the function of infected endothelial cells that normally regulate fluid barrier functions of capillaries. The endothelium of arteries, veins, and lymphatic vessels is unique and central to the function of vast pulmonary capillary beds, which regulate pulmonary fluid accumulation. The endothelium maintains vascular barrier functions through a complex series of redundant receptors and signaling pathways that serve to both permit fluid and immune cell efflux into tissues and restrict tissue edema. Infection of the endothelium provides several mechanisms for hantaviruses to alter capillary permeability but also defines potential therapeutic targets for regulating acute pulmonary edema and HPS disease. Here we discuss interactions of HPS causing hantaviruses with the endothelium, potential endothelial cell-directed permeability mechanisms, and therapeutic targeting of the endothelium as a means of reducing the severity of HPS disease.

Glucose-coated gold nanoparticles transfer across human brain endothelium and enter astrocytes in vitro.

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Radka Gromnicova

Full Text Available The blood-brain barrier prevents the entry of many therapeutic agents into the brain. Various nanocarriers have been developed to help agents to cross this barrier, but they all have limitations, with regard to tissue-selectivity and their ability to cross the endothelium. This study investigated the potential for 4 nm coated gold nanoparticles to act as selective carriers across human brain endothelium and subsequently to enter astrocytes. The transfer rate of glucose-coated gold nanoparticles across primary human brain endothelium was at least three times faster than across non-brain endothelia. Movement of these nanoparticles occurred across the apical and basal plasma membranes via the cytosol with relatively little vesicular or paracellular migration; antibiotics that interfere with vesicular transport did not block migration. The transfer rate was also dependent on the surface coating of the nanoparticle and incubation temperature. Using a novel 3-dimensional co-culture system, which includes primary human astrocytes and a brain endothelial cell line hCMEC/D3, we demonstrated that the glucose-coated nanoparticles traverse the endothelium, move through the extracellular matrix and localize in astrocytes. The movement of the nanoparticles through the matrix was >10 µm/hour and they appeared in the nuclei of the astrocytes in considerable numbers. These nanoparticles have the correct properties for efficient and selective carriers of therapeutic agents across the blood-brain barrier.

Low-dose ultraviolet-B irradiation of donor corneal endothelium and graft survival

International Nuclear Information System (INIS)

Dana, M.R.; Olkowski, S.T.; Ahmadian, H.; Stark, W.J.; Young, E.M.

1990-01-01

Donor rabbit corneal endothelium was pretreated with different doses of ultraviolet (UV-B) irradiation (302 nm) before grafting to test whether allograft survival could be favorably affected in comparison with untreated corneas grafted into the same recipients. Endothelial rejection was observed in 19 of 32 (59%) eyes that received no treatment compared with five of 32 (16%) eyes that received UV-B (P less than 0.001), and increasing doses of UV-B were associated with lower rejection rates (P less than 0.05). Although exposure of donor endothelium significantly reduced endothelial rejection at all doses tested, it resulted in primary graft failure in a substantial proportion of corneas treated at high doses. Class II (Ia) antigen staining of corneal tissue was present in conjunction with clinical evidence of rejection, and the magnitude of staining correlated with the histologic extent of inflammation. Scanning electron microscopy revealed various endothelial cell surface irregularities and membrane defects in high-dose UV-treated corneas. Endothelial cell cultures exposed in vitro to UV-B light showed a dose-dependent loss in cell viability. These data suggest that UV-B pretreatment of donor corneal endothelium prolongs graft survival but that toxic side effects must be carefully controlled

Reversible voltage dependent transition of abnormal and normal bipolar resistive switching.

Science.gov (United States)

Wang, Guangyu; Li, Chen; Chen, Yan; Xia, Yidong; Wu, Di; Xu, Qingyu

2016-11-14

Clear understanding the mechanism of resistive switching is the important prerequisite for the realization of high performance nonvolatile resistive random access memory. In this paper, binary metal oxide MoO x layer sandwiched by ITO and Pt electrodes was taken as a model system, reversible transition of abnormal and normal bipolar resistive switching (BRS) in dependence on the maximum voltage was observed. At room temperature, below a critical maximum voltage of 2.6 V, butterfly shaped I-V curves of abnormal BRS has been observed with low resistance state (LRS) to high resistance state (HRS) transition in both polarities and always LRS at zero field. Above 2.6 V, normal BRS was observed, and HRS to LRS transition happened with increasing negative voltage applied. Temperature dependent I-V measurements showed that the critical maximum voltage increased with decreasing temperature, suggesting the thermal activated motion of oxygen vacancies. Abnormal BRS has been explained by the partial compensation of electric field from the induced dipoles opposite to the applied voltage, which has been demonstrated by the clear amplitude-voltage and phase-voltage hysteresis loops observed by piezoelectric force microscopy. The normal BRS was due to the barrier modification at Pt/MoO x interface by the accumulation and depletion of oxygen vacancies.

Jabuticaba-Induced Endothelium-Independent Vasodilating Effect on Isolated Arteries

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Daniela Medeiros Lobo de Andrade

2016-01-01

Full Text Available Abstract Background: Despite the important biological effects of jabuticaba, its actions on the cardiovascular system have not been clarified. Objectives: To determine the effects of jabuticaba hydroalcoholic extract (JHE on vascular smooth muscle (VSM of isolated arteries. Methods: Endothelium-denuded aortic rings of rats were mounted in isolated organ bath to record isometric tension. The relaxant effect of JHE and the influence of K+ channels and Ca2+ intra- and extracellular sources on JHE-stimulated response were assessed. Results: Arteries pre-contracted with phenylephrine showed concentration-dependent relaxation (0.380 to 1.92 mg/mL. Treatment with K+ channel blockers (tetraethyl-ammonium, glibenclamide, 4-aminopyridine hindered relaxation due to JHE. In addition, phenylephrine-stimulated contraction was hindered by previous treatment with JHE. Inhibition of sarcoplasmic reticulum Ca2+ ATPase did not change relaxation due to JHE. In addition, JHE inhibited the contraction caused by Ca2+ influx stimulated by phenylephrine and KCl (75 mM. Conclusion: JHE induces endothelium-independent vasodilation. Activation of K+ channels and inhibition of Ca2+ influx through the membrane are involved in the JHE relaxant effect.

A factorial randomized controlled trial to evaluate the effect of micronutrients supplementation and regular aerobic exercise on maternal endothelium-dependent vasodilatation and oxidative stress of the newborn.

Science.gov (United States)

Ramírez-Vélez, Robinson; Romero, Miryam; Echeverri, Isabella; Ortega, José Guillermo; Mosquera, Mildrey; Salazar, Blanca; Girón, Sandra Lorena; Saldarriaga, Wilmar; Aguilar de Plata, Ana Cecilia; Mateus, Julio Cesar

2011-02-28

Many studies have suggested a relationship between metabolic abnormalities and impaired fetal growth with the development of non-transmissible chronic diseases in the adulthood. Moreover, it has been proposed that maternal factors such as endothelial function and oxidative stress are key mechanisms of both fetal metabolic alterations and subsequent development of non-transmissible chronic diseases. The objective of this project is to evaluate the effect of micronutrient supplementation and regular aerobic exercise on endothelium-dependent vasodilation maternal and stress oxidative of the newborn. 320 pregnant women attending to usual prenatal care in Cali, Colombia will be included in a factorial randomized controlled trial. Women will be assigned to the following intervention groups: 1. usual prenatal care (PC) and placebo (maltodextrine). 2. Exercise group: PC, placebo and aerobic physical exercise. 3. Micronutrients group: PC and a micronutrients capsule consisting of zinc (30 mg), selenium (70 μg), vitamin A (400 μg), alphatocopherol (30 mg), vitamin C (200 mg), and niacin (100 mg). 4. Combined interventions Group: PC, supplementation of micronutrients, and aerobic physical exercise. Anthropometric measures will be taken at the start and at the end of the interventions. Since in previous studies has been showed that the maternal endothelial function and oxidative stress are related to oxidative stress of the newborn, this study proposes that complementation with micronutrients during pregnancy and/or regular physical exercise can be an early and innovative alternative to strengthen the prevention of chronic diseases in the population. NCT00872365.

HOXB4 Promotes Hemogenic Endothelium Formation without Perturbing Endothelial Cell Development

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Nadine Teichweyde

2018-03-01

Full Text Available Summary: Generation of hematopoietic stem cells (HSCs from pluripotent stem cells, in vitro, holds great promise for regenerative therapies. Primarily, this has been achieved in mouse cells by overexpression of the homeotic selector protein HOXB4. The exact cellular stage at which HOXB4 promotes hematopoietic development, in vitro, is not yet known. However, its identification is a prerequisite to unambiguously identify the molecular circuits controlling hematopoiesis, since the activity of HOX proteins is highly cell and context dependent. To identify that stage, we retrovirally expressed HOXB4 in differentiating mouse embryonic stem cells (ESCs. Through the use of Runx1(−/− ESCs containing a doxycycline-inducible Runx1 coding sequence, we uncovered that HOXB4 promoted the formation of hemogenic endothelium cells without altering endothelial cell development. Whole-transcriptome analysis revealed that its expression mediated the upregulation of transcription of core transcription factors necessary for hematopoiesis, culminating in the formation of blood progenitors upon initiation of Runx1 expression. : In this article, Klump and colleagues demonstrate that the human homeotic selector protein HOXB4 promotes ESC-derived hematopoiesis by inducing hemogenic endothelium formation, in vitro. It propels hematopoietic specification by upregulating the transcription of genes essential for hematopoietic development, such as those encoding members of the so-called heptad transcription factors. Keywords: HOXB4, hematopoietic stem cells, hemangioblast, hemogenic endothelium, hematopoietic specification, EHT, RUNX1, pluripotent stem cells

Junctional transfer in cultured vascular endothelium: II. Dye and nucleotide transfer

International Nuclear Information System (INIS)

Larson, D.M.; Sheridan, J.D.

1985-01-01

Vascular endothelial cultures, derived from large vessels, retain many of the characteristics of their in vivo counterparts. However, the observed reduction in size and complexity of intercellular gap and tight junctions in these cultured cells suggests that important functions, thought to be mediated by these structures, may be altered in vitro. In continuing studies on intercellular communication in vessel wall cells, the authors have quantitated the extent of junctional transfer of small molecular tracers (the fluorescent dye Lucifer Yellow CH and tritiated uridine nucleotides) in confluent cultures of calf aortic (BAEC) and umbilical vein (BVEC) endothelium. Both BAEC and BVEC show extensive (and quantitatively equivalent) dye and nucleotide transfer. As an analogue of intimal endothelium, the authors have also tested dye transfer in freshly isolated sheets of endothelium. Transfer in BAEC and BVEC sheets was more rapid, extensive and homogeneous than in the cultured cells, implying a reduction in molecular coupling as endothelium adapts to culture conditions. In addition, they have documented heterocellular nucleotide transfer between cultured endothelium and vascular smooth muscle cells, of particular interest considering the prevalence of ''myo-endothelial'' junctions in vivo. These data yield further information on junctional transfer in cultured vascular endothelium and have broad implications for the functional integration of the vessel wall in the physiology and pathophysiology of the vasculature

Hypotensive effect and endothelium-dependent vascular action of leaves of Alpinia purpurata (Vieill K. Schum

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Alessandra Tesch da Silva

2014-04-01

Full Text Available The aims of this study were to evaluate the chemical profile, vascular reactivity, and acute hypotensive effect (AHE of the ethanolic extract of leaves of Alpinia purpurata (Vieill K. Schum (EEAP. Its chemical profile was evaluated using HPLC-UV, ICP-OES, and colorimetric quantification of total flavonoids and polyphenols. The vascular reactivity of the extract was determined using the mesenteric bed isolated from WKY. AHE dose-response curves were obtained for both EEAP and inorganic material isolated from AP (IAP in WKY and SHR animals. Cytotoxic and mutagenic safety levels were determined by the micronucleus test. Rutin-like flavonoids were quantified in the EEAP (1.8 ± 0.03%, and the total flavonoid and polyphenol ratios were 4.1 ± 1.8% and 5.1 ± 0.3%, respectively. We observed that the vasodilation action of EEAP was partially mediated by nitric oxide (·NO. The IAP showed the presence of calcium (137.76 ± 4.08 μg mg-1. The EEAP and IAP showed an AHE in WKY and SHR animals. EEAP did not have cytotoxic effects or cause chromosomic alterations. The AHE shown by EEAP could result from its endothelium-dependent vascular action. Rutin-like flavonoids, among other polyphenols, could contribute to these biological activities, and the calcium present in EEAP could act in a synergistic way.

Size-dependent abnormal thermo-enhanced luminescence of ytterbium-doped nanoparticles.

Science.gov (United States)

Cui, Xiangshui; Cheng, Yao; Lin, Hang; Huang, Feng; Wu, Qingping; Wang, Yuansheng

2017-09-21

Thermal quenching above 300 K is widely expected in photoluminescence. Luminescence quenching is usually ascribed to the non-radiative relaxation of excited electrons to the ground state of the activators, during which a high temperature always plays a role in pushing the excited electrons towards the quenching channels, leading to thermal quenching. For the lanthanide-doped nanoparticles, however, there is a special luminescence quenching channel that does not exist in their bulk counterparts, i.e., energy migration-induced surface quenching. Herein, a size-dependent abnormal thermal enhancement of luminescence in the temperature range of 300 K to 423 K in the ytterbium-doped fluoride nanoparticles is presented for the first time. Importantly, in this work, we originally demonstrate that the energy migration-induced surface quenching can be suppressed by increasing temperature, which results in the abnormal thermal enhancement of luminescence. According to the temperature-dependent X-ray diffraction and lifetime analyses, an underlying mechanism based on the effect of thermal lattice expansion on ytterbium-mediated energy migration is proposed. This new finding adds new insights to the size effect on the luminescent characteristics of nanoparticles, which could be utilized to construct some unique nanostructures, especially for many important temperature-related purposes, such as thermal sensing technology.

Relative permeability of the endothelium and epithelium of rabbit lungs

International Nuclear Information System (INIS)

Effros, R.M.; Mason, G.R.; Silverman, P.; Hukkanen, J.

1986-01-01

Electron micrographic studies of lungs suggest that the epithelial cells are more tightly joined than the underlying endothelium, and macromolecules penetrate the endothelium more readily than the epithelium. Comparisons of epithelial and endothelial permeability to small molecules have been based upon the relative rates at which solutes traverse the alveolar-capillary barrier in fluid filled lungs and those at which they equilibrate across the capillaries in air-filled lungs. Because the former process is much slower than the latter, it has been concluded that the epithelium is less permeable to small solutes than the endothelium. However this difference may be related to inadequate access of solutes to airway surfaces. In this study, solute losses from the vascular space were compared to those from the airspace in perfused, fluid-filled rabbit lungs. 36 Cl - and 125 I - were lost from air-spaces almost twice as rapidly as 22 Na + . In contrast, the endothelium is equally permeable to 22 Na + and these anions. Loss of 3 H-mannitol from the perfusate resembled that of 22 Na + for about 30 minutes, after which diffusion of 3 H-mannitol into the tissue nearly ceased. These observations suggest that the epithelium is more permselective than the endothelium. By resisting solute and water transport, the epithelium tends to prevent alveolar flooding and confines edema to the interstitium, where it is less likely to interfere with gas exchange

Effects of Buddhism walking meditation on depression, functional fitness, and endothelium-dependent vasodilation in depressed elderly.

Science.gov (United States)

Prakhinkit, Susaree; Suppapitiporn, Siriluck; Tanaka, Hirofumi; Suksom, Daroonwan

2014-05-01

The objectives of this study were to determine the effects of the novel Buddhism-based walking meditation (BWM) and the traditional walking exercise (TWE) on depression, functional fitness, and vascular reactivity. This was a randomized exercise intervention study. The study was conducted in a university hospital setting. Forty-five elderly participants aged 60-90 years with mild-to-moderate depressive symptoms were randomly allocated to the sedentary control, TWE, and BWM groups. The BWM program was based on aerobic walking exercise incorporating the Buddhist meditations performed 3 times/week for 12 weeks. Depression score, functional fitness, and endothelium-dependent vasodilation as measured by the flow-mediated dilation (FMD) were the outcome measures used. Muscle strength, flexibility, agility, dynamic balance, and cardiorespiratory endurance increased in both exercise groups (p<0.05). Depression score decreased (p<0.05) only in the BWM group. FMD improved (p<0.05) in both exercise groups. Significant reduction in plasma cholesterol, triglyceride, high-density lipoprotein cholesterol, and C-reactive protein were found in both exercise groups, whereas low-density lipoprotein cholesterol, cortisol, and interleukin-6 concentrations decreased only in the BWM group. Buddhist walking meditation was effective in reducing depression, improving functional fitness and vascular reactivity, and appears to confer greater overall improvements than the traditional walking program.

Influence of endothelium on the membrane-stabilizing effect of calcium

African Journals Online (AJOL)

Dr Olaleye

increase in [Ca2+]o (low bicarbonate PSS) from 5.0 to 25.0mM in rings with intact endothelium resulted in relaxation responses. These relaxation responses were attenuated in endothelium- denuded rings as well as following exposure to methylene blue. Conclusion: The results show that relaxation responses induced by ...

Abnormal intrinsic functional hubs in alcohol dependence: evidence from a voxelwise degree centrality analysis

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Luo X

2017-07-01

Full Text Available Xiaoping Luo,1,2 Linghong Guo,1 Xi-Jian Dai,3 Qinglai Wang,2 Wenzhong Zhu,2 Xinjun Miao,2 Honghan Gong1 1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nangchang, Jiangxi, People’s Republic of China; 2Department of Radiology, Wenzhou Chinese Medicine Hospital, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China Objective: To explore the abnormal intrinsic functional hubs in alcohol dependence using voxelwise degree centrality analysis approach, and their relationships with clinical features.Materials and methods: Twenty-four male alcohol dependence subjects free of medicine (mean age, 50.21±9.62 years and 24 age- and education-matched male healthy controls (mean age, 50.29±8.92 years were recruited. The alcohol use disorders identification test and the severity of alcohol dependence questionnaire (SADQ were administered to assess the severity of alcohol craving. Voxelwise degree centrality approach was used to assess the abnormal intrinsic functional hubs features in alcohol dependence. Simple linear regression analysis was performed to investigate the relationships between the clinical features and abnormal intrinsic functional hubs.Results: Compared with healthy controls, alcohol dependence subjects exhibited significantly different degree centrality values in widespread left lateralization brain areas, including higher degree centrality values in the left precentral gyrus (BA 6, right hippocampus (BA 35, 36, and left orbitofrontal cortex (BA 11 and lower degree centrality values in the left cerebellum posterior lobe, bilateral secondary visual network (BA 18, and left precuneus (BA 7, 19. SADQ revealed a negative linear correlation with the degree centrality value in the left precentral gyrus (R2=0.296, P=0.006.Conclusion: The specific abnormal intrinsic functional hubs appear

An in vitro model of hemogenic endothelium commitment and hematopoietic production

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Yvernogeau, Laurent; Gautier, Rodolphe; Khoury, Hanane; Menegatti, Sara; Schmidt, Melanie; Gilles, Jean Francois; Jaffredo, Thierry

2016-01-01

Adult-type hematopoietic stem and progenitor cells are formed during ontogeny from a specialized subset of endothelium, termed the hemogenic endothelium, via an endothelial-to-hematopoietic transition (EHT) that occurs in the embryonic aorta and the associated arteries. Despite efforts to generate

A factorial randomized controlled trial to evaluate the effect of micronutrients supplementation and regular aerobic exercise on maternal endothelium-dependent vasodilatation and oxidative stress of the newborn

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Girón Sandra

2011-02-01

Full Text Available Abstract Background Many studies have suggested a relationship between metabolic abnormalities and impaired fetal growth with the development of non-transmissible chronic diseases in the adulthood. Moreover, it has been proposed that maternal factors such as endothelial function and oxidative stress are key mechanisms of both fetal metabolic alterations and subsequent development of non-transmissible chronic diseases. The objective of this project is to evaluate the effect of micronutrient supplementation and regular aerobic exercise on endothelium-dependent vasodilation maternal and stress oxidative of the newborn. Methods and design 320 pregnant women attending to usual prenatal care in Cali, Colombia will be included in a factorial randomized controlled trial. Women will be assigned to the following intervention groups: 1. Control group: usual prenatal care (PC and placebo (maltodextrine. 2. Exercise group: PC, placebo and aerobic physical exercise. 3. Micronutrients group: PC and a micronutrients capsule consisting of zinc (30 mg, selenium (70 μg, vitamin A (400 μg, alphatocopherol (30 mg, vitamin C (200 mg, and niacin (100 mg. 4. Combined interventions Group: PC, supplementation of micronutrients, and aerobic physical exercise. Anthropometric measures will be taken at the start and at the end of the interventions. Discussion Since in previous studies has been showed that the maternal endothelial function and oxidative stress are related to oxidative stress of the newborn, this study proposes that complementation with micronutrients during pregnancy and/or regular physical exercise can be an early and innovative alternative to strengthen the prevention of chronic diseases in the population. Trial registration NCT00872365.

In vitro study of histamine and histamine receptor ligands influence on the adhesion of purified human eosinophils to endothelium.

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Grosicki, Marek; Wójcik, Tomasz; Chlopicki, Stefan; Kieć-Kononowicz, Katarzyna

2016-04-15

It is a well-known fact that histamine is involved in eosinophil-dependent inflammatory responses including cellular chemotaxis and migration. Nevertheless, the relative role of histamine receptors in the mechanisms of eosinophils adhesion to endothelial cells is not known. Therefore the aim of presented study was to examine the effect of selective histamine receptors ligands on eosinophils adhesion to endothelium. For that purpose the highly purified human eosinophils have been isolated from the peripheral blood. The viability and functional integrity of isolated eosinophils have been validated in several tests. Histamine as well as 4-methylhistamine (selective H4 agonist) in concentration-dependent manner significantly increased number of eosinophils that adhere to endothelium. Among the selective histamine receptors antagonist or H1 inverse agonist only JNJ7777120 (histamine H4 antagonist) and thioperamide (dual histamine H3/H4 antagonist) had direct effect on eosinophils adhesion to endothelial cells. Antagonists of H1 (diphenhydramine, mepyramine) H2 (ranitidine and famotidine) and H3 (pitolisant) histamine receptors were ineffective. To the best of our knowledge, this is the first study to demonstrate that histamine receptor H4 plays a dominant role in histamine-induced eosinophils adhesion to endothelium. Copyright © 2016 Elsevier B.V. All rights reserved.

Endothelium-Independent Vasorelaxant Effect of Ligusticum jeholense Root and Rhizoma on Rat Thoracic Aorta

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Bumjung Kim

2015-06-01

Full Text Available Ligusticum jeholense has been used as the traditional medicine ‘Go-Bon’ (Chinese name, Gao-ben in China and Korea. Considering the increased use of medicinal herbs to treat hypertension, in this study, we aimed to investigate the mechanisms of the vasorelaxation effect caused by L. jeholense. We tested the methanol (MeOH extract of L. jeholense root and rhizoma for vasorelaxant effects; while using an isolated organ-chamber technique, L. jeholense extract (LJE induced relaxation in the rat aortic rings by stimulating vascular endothelial and smooth muscle cells. LJE showed concentration-dependent relaxant effects on endothelium-intact and endothelium-denuded aortic rings pre-contracted with both phenylephrine (PE and potassium chloride (KCl in Krebs-Henseleit (KH buffer. The vasorelaxant effect of LJE was partly attenuated by pre-treatment with glibenclamide or 4-aminopyridine (4-AP as K+ channel blockers. Moreover, LJE showed concentration-dependent inhibition of vasoconstriction by Ca2+ supplementation in the aortic rings that were pre-contracted with PE or KCl in Ca2+-free KH buffer. In addition, a combination of LJE and nifedipine, pre-incubated further, decreased PE-induced contractions. The results suggested that LJE-induced vasorelaxation were related to blocking K+ channels and inhibiting entry of extracellular Ca2+ via receptor-operative Ca2+ channels (ROCCs or voltage-dependent Ca2+ channels (VDCCs.

Role of coronary endothelium in cyclic AMP formation by the heart

International Nuclear Information System (INIS)

Kroll, K.; Schrader, J.

1986-01-01

In order to quantify the activation of adenylate cyclase of the coronary endothelium in vivo, endothelial adenine nucleotides of isolated guinea pig hearts were selectively pre-labeled by intracoronary infusion of tritiated (H3)-adenosine, and the coronary efflux of H3-cAMP was measured. The adenosine receptor agonist, NECA (12 μM), increased total cAMP release 4 fold, and raised H3-cAMP release 22 fold. Several classes of coronary vasodilators (adenosine, L-PIA, D-PIA, the beta 2-adrenergic agonist procaterol, and PGE1) caused dose-dependent increases in endothelial-derived H3-cAMP release. These increases were accompanied by decreases in vascular resistance, at agonist doses without positive intropic effects. Hypoxic perfusion also raised H3-cAMP release, and this was antagonized by theophylline. It is concluded: (1) cyclic AMP formation by coronary endothelium can dominate total cAMP production by the heart; (2) coronary endothelial adenylate cyclase-coupled receptors for adenosine (A2), catecholamines (beta2) and prostaglandins are activated in parallel with coronary vasodilation; (3) endothelial adenylate cyclase can be activated by endogenous adenosine

Confocal microscopy and electrophysiological study of single patient corneal endothelium cell cultures

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Tatini, Francesca; Rossi, Francesca; Coppi, Elisabetta; Magni, Giada; Fusco, Irene; Menabuoni, Luca; Pedata, Felicita; Pugliese, Anna Maria; Pini, Roberto

2016-04-01

The characterization of the ion channels in corneal endothelial cells and the elucidation of their involvement in corneal pathologies would lead to the identification of new molecular target for pharmacological treatments and to the clarification of corneal physiology. The corneal endothelium is an amitotic cell monolayer with a major role in preserving corneal transparency and in regulating the water and solute flux across the posterior surface of the cornea. Although endothelial cells are non-excitable, they express a range of ion channels, such as voltage-dependent Na+ channels and K+ channels, L-type Ca2 channels and many others. Interestingly, purinergic receptors have been linked to a variety of conditions within the eye but their presence in the endothelium and their role in its pathophysiology is still uncertain. In this study, we were able to extract endothelial cells from single human corneas, thus obtaining primary cultures that represent the peculiarity of each donor. Corneas were from tissues not suitable for transplant in patients. We characterized the endothelial cells by confocal microscopy, both within the intact cornea and in the primary endothelial cells cultures. We also studied the functional role of the purinergic system (adenosine, ATP and their receptors) by means of electrophysiological recordings. The experiments were performed by patch clamp recordings and confocal time-lapse microscopy and our results indicate that the application of purinergic compounds modulates the amplitude of outward currents in the isolated endothelial cells. These findings may lead to the proposal of new therapies for endothelium-related corneal diseases.

Hypoxia and hydrogen sulfide differentially affect normal and tumor-derived vascular endothelium

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Serena Bianco

2017-08-01

Full Text Available Background: endothelial cells play a key role in vessels formation both under physiological and pathological conditions. Their behavior is influenced by blood components including gasotransmitters (H2S, NO and CO. Tumor cells are subjected to a cyclic shift between pro-oxidative and hypoxic state and, in this scenario, H2S can be both cytoprotective and detrimental depending on its concentration. H2S effects on tumors onset and development is scarcely studied, particularly concerning tumor angiogenesis. We previously demonstrated that H2S is proangiogenic for tumoral but not for normal endothelium and this may represent a target for antiangiogenic therapeutical strategies. Methods: in this work, we investigate cell viability, migration and tubulogenesis on human EC derived from two different tumors, breast and renal carcinoma (BTEC and RTEC, compared to normal microvascular endothelium (HMEC under oxidative stress, hypoxia and treatment with exogenous H2S. Results: all EC types are similarly sensitive to oxidative stress induced by hydrogen peroxide; chemical hypoxia differentially affects endothelial viability, that results unaltered by real hypoxia. H2S neither affects cell viability nor prevents hypoxia and H2O2-induced damage. Endothelial migration is enhanced by hypoxia, while tubulogenesis is inhibited for all EC types. H2S acts differentially on EC migration and tubulogenesis. Conclusions: these data provide evidence for a great variability of normal and altered endothelium in response to the environmental conditions. Keywords: Hydrogen sulfide, Human microvascular endothelial cells, Human breast carcinoma-derived EC, Human renal carcinoma-derived EC, Tumor angiogenesis

Visualization of three pathways for macromolecule transport across cultured endothelium and their modification by flow.

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Ghim, Mean; Alpresa, Paola; Yang, Sung-Wook; Braakman, Sietse T; Gray, Stephen G; Sherwin, Spencer J; van Reeuwijk, Maarten; Weinberg, Peter D

2017-11-01

Transport of macromolecules across vascular endothelium and its modification by fluid mechanical forces are important for normal tissue function and in the development of atherosclerosis. However, the routes by which macromolecules cross endothelium, the hemodynamic stresses that maintain endothelial physiology or trigger disease, and the dependence of transendothelial transport on hemodynamic stresses are controversial. We visualized pathways for macromolecule transport and determined the effect on these pathways of different types of flow. Endothelial monolayers were cultured under static conditions or on an orbital shaker producing different flow profiles in different parts of the wells. Fluorescent tracers that bound to the substrate after crossing the endothelium were used to identify transport pathways. Maps of tracer distribution were compared with numerical simulations of flow to determine effects of different shear stress metrics on permeability. Albumin-sized tracers dominantly crossed the cultured endothelium via junctions between neighboring cells, high-density lipoprotein-sized tracers crossed at tricellular junctions, and low-density lipoprotein-sized tracers crossed through cells. Cells aligned close to the angle that minimized shear stresses across their long axis. The rate of paracellular transport under flow correlated with the magnitude of these minimized transverse stresses, whereas transport across cells was uniformly reduced by all types of flow. These results contradict the long-standing two-pore theory of solute transport across microvessel walls and the consensus view that endothelial cells align with the mean shear vector. They suggest that endothelial cells minimize transverse shear, supporting its postulated proatherogenic role. Preliminary data show that similar tracer techniques are practicable in vivo. NEW & NOTEWORTHY Solutes of increasing size crossed cultured endothelium through intercellular junctions, through tricellular

On the relationship between emotional state and abnormal unfairness sensitivity in alcohol dependence

OpenAIRE

Brevers, Damien; Noël, Xavier; Hanak, Catherine; Verbanck, Paul; Kornreich, Charles

2015-01-01

Recent empirical findings suggest that alcohol dependence is characterized by heightened sensitivity to unfairness during social transactions. The present study went a step further and aimed to ascertain whether this abnormal level of sensitivity to unfairness is underlined by an increased emotional reactivity. Twenty-six recently abstinent alcohol-dependent (AD) individuals and 32 controls performed an ultimatum game (UG), in which participants had to respond to take-it-or-leave-it offers, r...

Thrombin-induced increase in albumin permeability across the endothelium

International Nuclear Information System (INIS)

Garcia, J.G.; Siflinger-Birnboim, A.; Bizios, R.; Del Vecchio, P.J.; Fenton, J.W. II; Malik, A.B.

1986-01-01

We studied the effect of thrombin on albumin permeability across the endothelial monolayer in vitro. Bovine pulmonary artery endothelial cells were grown on micropore membranes. Morphologic analysis confirmed the presence of a confluent monolayer with interendothelial junctions. Albumin permeability was measured by the clearance of 125I-albumin across the endothelial monolayer. The control 125I-albumin clearance was 0.273 +/- 0.02 microliter/min. The native enzyme, alpha-thrombin (10(-6) to 10(-10) M), added to the luminal side of the endothelium produced concentration-dependent increases in albumin clearance (maximum clearance of 0.586 +/- 0.08 microliter/min at 10(-6) M). Gamma (gamma) thrombin (10(-6) M and 10(-8) M), which lacks the fibrinogen recognition site, also produced a concentration-dependent increase in albumin clearance similar to that observed with alpha-thrombin. Moreover, the two proteolytically inactive forms of the native enzyme, i-Pr2 P-alpha-thrombin and D-Phe-Pro-Arg-CH2-alpha-thrombin, increased the 125I-albumin clearance (0.610 +/- 0.09 microliter/min and 0.609 +/- 0.02 microliter/min for i-Pr2 P-alpha-thrombin and D-Phe-Pro-Arg-CH2-alpha-thrombin at 10(-6) M, respectively). Since the modified forms of thrombin lack the fibrinogen recognition and active serine protease sites, the results indicate that neither site is required for increased albumin permeability. The increase in albumin clearance with alpha-thrombin was not secondary to endothelial cell lysis because lactate dehydrogenase concentration in the medium following thrombin was not significantly different from baseline values. There was also no morphological evidence of cell lysis. Moreover, the increase in 125I-albumin clearance induced by alpha-thrombin was reversible by washing thrombin from the endothelium

Effects of a Single Bout of Resistance Exercise in Different Volumes on Endothelium Adaptations in Healthy Animals

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Marcelo Mendonça Mota

Full Text Available Abstract Background: Resistance exercise (RE has been recommended for patients with cardiovascular diseases. Recently, a few studies have demonstrated that the intensity of a single bout of RE has an effect on endothelial adaptations to exercise. However, there is no data about the effects of different volumes of RE on endothelium function. Objective: The aim of the study was to evaluate the effects of different volumes of RE in a single bout on endothelium-dependent vasodilatation and nitric oxide (NO synthesis in the mesenteric artery of healthy animals. Methods: Male Wistar rats were divided into three groups: Control (Ct; low-volume RE (LV, 5 sets x 10 repetitions and high-volume RE (HV, 15 sets x 10 repetitions. The established intensity was 70% of the maximal repetition test. After the exercise protocol, rings of mesenteric artery were used for assessment of vascular reactivity, and other mesenteric arteries were prepared for detection of measure NO production by DAF-FM fluorescence. Insulin responsiveness on NO synthesis was evaluated by stimulating the vascular rings with insulin (10 nM. Results: The maximal relaxation response to insulin increased in the HV group only as compared with the Ct group. Moreover, the inhibition of nitric oxide synthesis (L-NAME completely abolished the insulin-induced vasorelaxation in exercised rats. NO production showed a volume-dependent increase in the endothelial and smooth muscle layer. In endothelial layer, only Ct and LV groups showed a significant increase in NO synthesis when compared to their respective group under basal condition. On the other hand, in smooth muscle layer, NO fluorescence increased in all groups when compared to their respective group under basal condition. Conclusions: Our results suggest that a single bout of RE promotes vascular endothelium changes in a volume-dependent manner. The 15 sets x 10 repetitions exercise plan induced the greatest levels of NO synthesis.

Targeted Delivery of Neutralizing Anti-C5 Antibody to Renal Endothelium Prevents Complement-Dependent Tissue Damage

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Paolo Durigutto

2017-09-01

Full Text Available Complement activation is largely implicated in the pathogenesis of several clinical conditions and its therapeutic neutralization has proven effective in preventing tissue and organ damage. A problem that still needs to be solved in the therapeutic control of complement-mediated diseases is how to avoid side effects associated with chronic neutralization of the complement system, in particular, the increased risk of infections. We addressed this issue developing a strategy based on the preferential delivery of a C5 complement inhibitor to the organ involved in the pathologic process. To this end, we generated Ergidina, a neutralizing recombinant anti-C5 human antibody coupled with a cyclic-RGD peptide, with a distinctive homing property for ischemic endothelial cells and effective in controlling tissue damage in a rat model of renal ischemia/reperfusion injury (IRI. As a result of its preferential localization on renal endothelium, the molecule induced complete inhibition of complement activation at tissue level, and local protection from complement-mediated tissue damage without affecting circulating C5. The ex vivo binding of Ergidina to surgically removed kidney exposed to cold ischemia supports its therapeutic use to prevent posttransplant IRI leading to delay of graft function. Moreover, the finding that the ex vivo binding of Ergidina was not restricted to the kidney, but was also seen on ischemic heart, suggests that this RGD-targeted anti-C5 antibody may represent a useful tool to treat organs prior to transplantation. Based on this evidence, we propose preliminary data showing that Ergidina is a novel targeted drug to prevent complement activation on the endothelium of ischemic kidney.

Enhanced K+-channel-mediated endothelium-dependent local and conducted dilation of small mesenteric arteries from ApoE−/− mice

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Beleznai, Timea; Takano, Hiromichi; Hamill, Claire; Yarova, Polina; Douglas, Gillian; Channon, Keith; Dora, Kim

2011-01-01

Aims Agonists that evoke smooth muscle cell hyperpolarization have the potential to stimulate both local and conducted dilation. We investigated whether the endothelium-dependent vasodilators acetylcholine (ACh) and SLIGRL stimulated conducted dilation and whether this was altered by deficiency in apolipoprotein E (ApoE−/−). Methods and results Isolated mesenteric arteries were cannulated, pressurized, and precontracted with phenylephrine. Agonists were either added to the bath to study local dilation or were restricted to one end of arteries to study conducted dilation. An enhanced sensitivity to both ACh and SLIGRL was observed in mesenteric arteries from ApoE−/− mice compared with wild-type controls. Inhibition of nitric oxide (NO) synthase blocked ACh responses, but had no effect on maximum dilation to SLIGRL. SLIGRL increased endothelial cell Ca2+, hyperpolarized smooth muscle cells, and fully dilated arteries. The NO-independent dilation to SLIGRL was blocked with high [KCl] or Ca2+-activated K+-channel blockers. The hyperpolarization and dilation to SLIGRL passed through the artery to at least 2.5 mm upstream. The conducted dilation was not affected by a deficit in ApoE and could also be stimulated by ACh, suggesting NO itself could stimulate conducted dilation. Conclusion In small mesenteric arteries of ApoE−/− mice, NO-independent dilation is enhanced. Since both NO-dependent and -independent pathways can stimulate local and conducted dilation, the potential for reducing vascular resistance is improved in these vessels. PMID:21690174

Human haemato-endothelial precursors: cord blood CD34+ cells produce haemogenic endothelium.

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Elvira Pelosi

Full Text Available Embryologic and genetic evidence suggest a common origin of haematopoietic and endothelial lineages. In the murine embryo, recent studies indicate the presence of haemogenic endothelium and of a common haemato-endothelial precursor, the haemangioblast. Conversely, so far, little evidence supports the presence of haemogenic endothelium and haemangioblasts in later stages of development. Our studies indicate that human cord blood haematopoietic progenitors (CD34+45+144-, triggered by murine hepatocyte conditioned medium, differentiate into adherent proliferating endothelial precursors (CD144+CD105+CD146+CD31+CD45- capable of functioning as haemogenic endothelium. These cells, proven to give rise to functional vasculature in vivo, if further instructed by haematopoietic growth factors, first switch to transitional CD144+45+ cells and then to haematopoietic cells. These results highlight the plasticity of haemato-endhothelial precursors in human post-natal life. Furthermore, these studies may provide highly enriched populations of human post-fetal haemogenic endothelium, paving the way for innovative projects at a basic and possibly clinical level.

Molecular imaging of the human pulmonary vascular endothelium in pulmonary hypertension: a phase II safety and proof of principle trial

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Harel, Francois [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Nuclear Medicine, Montreal, Quebec (Canada); Langleben, David; Abikhzer, Gad [McGill University, Lady Davis Institute and Jewish General Hospital, Montreal, Quebec (Canada); Provencher, Steve; Guimond, Jean [Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec (Canada); Fournier, Alain; Letourneau, Myriam [INRS-Institut Armand-Frappier, Laval, Quebec (Canada); Finnerty, Vincent; Nguyen, Quang T.; Levac, Xavier [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Mansour, Asmaa; Guertin, Marie-Claude [Montreal Health Innovation Coordination Center, Montreal, QC (Canada); Dupuis, Jocelyn [Montreal Heart Institute, Research Center, Montreal, QC (Canada); Universite de Montreal, Department of Medicine, Montreal, Quebec (Canada)

2017-07-15

The adrenomedullin receptor is densely expressed in the pulmonary vascular endothelium. PulmoBind, an adrenomedullin receptor ligand, was developed for molecular diagnosis of pulmonary vascular disease. We evaluated the safety of PulmoBind SPECT imaging and its capacity to detect pulmonary vascular disease associated with pulmonary hypertension (PH) in a human phase II study. Thirty patients with pulmonary arterial hypertension (PAH, n = 23) or chronic thromboembolic PH (CTEPH, n = 7) in WHO functional class II (n = 26) or III (n = 4) were compared to 15 healthy controls. Lung SPECT was performed after injection of 15 mCi {sup 99m}Tc-PulmoBind in supine position. Qualitative and semi-quantitative analyses of lung uptake were performed. Reproducibility of repeated testing was evaluated in controls after 1 month. PulmoBind injection was well tolerated without any serious adverse event. Imaging was markedly abnormal in PH with ∝50% of subjects showing moderate to severe heterogeneity of moderate to severe extent. The abnormalities were unevenly distributed between the right and left lungs as well as within each lung. Segmental defects compatible with pulmonary embolism were present in 7/7 subjects with CTEPH and in 2/23 subjects with PAH. There were no segmental defects in controls. The PulmoBind activity distribution index, a parameter indicative of heterogeneity, was elevated in PH (65% ± 28%) vs. controls (41% ± 13%, p = 0.0003). In the only subject with vasodilator-responsive idiopathic PAH, PulmoBind lung SPECT was completely normal. Repeated testing 1 month later in healthy controls was well tolerated and showed no significant variability of PulmoBind distribution. In this phase II study, molecular SPECT imaging of the pulmonary vascular endothelium using {sup 99m}Tc-PulmoBind was safe. PulmoBind showed potential to detect both pulmonary embolism and abnormalities indicative of pulmonary vascular disease in PAH. Phase III studies with this novel tracer and

Amiodarona causa vasodilatação dependente do endotélio em artérias coronárias caninas Amiodarone causes endothelium-dependent vasodilation in canine coronary arteries

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Alfredo José Rodrigues

2005-03-01

polysorbate 80, amiodarone dissolved in water, amiodarone dissolved in polysorbate 80, and a commercial presentation of amiodarone (Cordarone. The experiments were conducted in the presence of the following enzymatic blockers: only indomethacin, Nw-nitro-L-arginine associated with indomethacin, and only Nw-nitro-L-arginine. RESULTS: Polysorbate 80 caused a small degree of nonendothelium-dependent relaxation. Cordarone, amiodarone dissolved in water, and amiodarone dissolved in polysorbate 80 caused endothelium-dependent relaxation, which was greater for amiodarone dissolved in polysorbate and for Cordarone. Only the association of indomethacin and Nw-nitro-L-arginine could eliminate the endothelium-dependent relaxation caused by amiodarone dissolved in polysorbate 80. CONCLUSION: The results obtained indicate that vasodilation promoted by amiodarone in canine coronary arteries is mainly caused by stimulation of the release of nitric oxide and cyclooxygenase-dependent relaxing endothelial factors.

ABNORMAL PLASMA NORADRENALINE RESPONSE AND EXERCISE INDUCED ALBUMINURIA IN TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS

NARCIS (Netherlands)

HOOGENBERG, K; DULLAART, RPF

1992-01-01

Submaximal exercise provokes an abnormal elevation in albuminuria in type 1 (insulin-dependent) diabetes mellitus. Plasma catecholamines might be involved in this phenomenon by a renal vasoconstrictive effect. Twelve healthy subjects (Controls: albuminuria It is concluded that the exercise-induced

[Otoneurologic abnormalities in insulin-dependent diabetes].

Science.gov (United States)

Jáuregui-Renaud, K; Domínguez-Rubio, B; Ibarra-Olmos, A; González-Bárcena, D

1998-01-01

To assess the auditory and vestibular function in patients with diabetes. We studied and followed for three years, 10 patients (6 females) of 20.6 years of age (SD 5.5 years), with insulindependent diabetes mellitus of 9.5 years (SD 3.7 years). The patients were selected for having peripheral neuropathy without prolipherative retinopathy and otologic disease or individual factors which could cause neurootologic symptoms. Their glomerular filtration rate and renal plasma flow were 150 mL/min (SD 50) and 543 mL/min (SD 113). Initially all patients had normal audiologic responses, including auditory brainstem responses, but had abnormally and simetrically diminished horizontal vestibulo-ocular responses. A year later one patient had vertigo and asymmetric vestibulo-ocular responses. In the third year, another patient showed similar abnormalities and a third one showed sensorineural hearing loss. Our results suggest that patients with insulindependent diabetes mellitus may suffer neuro-otological deterioration.

Circulating microparticles from patients with valvular heart disease and cardiac surgery inhibit endothelium-dependent vasodilation.

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Fu, Li; Hu, Xiao-Xia; Lin, Ze-Bang; Chang, Feng-Jun; Ou, Zhi-Jun; Wang, Zhi-Ping; Ou, Jing-Song

2015-09-01

Vascular function is very important for maintaining circulation after cardiac surgery. Circulating microparticles (MPs) generated in various diseases play important roles in causing inflammation, coagulation, and vascular injury. However, the impact of MPs generated from patients who have valvular heart disease (VHD), before and after cardiac surgery, on vascular function remains unknown. This study is designed to investigate the impact of such MPs on vasodilation. Microparticles were isolated from age-matched healthy subjects and patients who had VHD, before cardiac surgery, and at 12 hours and 72 hours afterward. The number of MPs was measured and compared. Effects evaluated were of the impact of MPs on: vasodilation of mice aorta; the phosphorylation and expression of Akt, endothelial nitric oxide synthase (eNOS), protein kinase C-βII (PKC-βII), and p70 ribosomal protein S6 kinase (p70S6K); expression of caveolin-1; the association of eNOS with heat shock protein 90 (HSP90); and generation of nitric oxide and superoxide anion of human umbilical vein endothelial cells. Compared with the healthy subjects, VHD patients had significantly higher levels of circulating MPs and those MPs before cardiac surgery can: impair endothelium-dependent vasodilation; inhibit phosphorylation of Akt and eNOS; increase activation of PKC-βII and p70S6K; enhance expression of caveolin-1; reduce the association of HSP90 with eNOS; decrease nitric oxide production, and increase superoxide anion generation. These deleterious effects were even stronger in postoperative MPs. Our data demonstrate that MPs generated from VHD patients before and after cardiac surgery contributed to endothelial dysfunction, by uncoupling and inhibiting eNOS. Circulating MPs are potential therapeutic targets for the maintenance of vascular function postoperatively. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Monoclonal antibody PAL-E specific for endothelium

NARCIS (Netherlands)

Schlingemann, R. O.; Dingjan, G. M.; Emeis, J. J.; Blok, J.; Warnaar, S. O.; Ruiter, D. J.

1985-01-01

A monoclonal antibody, PAL-E, is described that is specific for endothelial cells. The monoclonal antibody, an IgG2a, markedly stains endothelium of capillaries, medium-sized and small veins, and venules in frozen sections of human and some animal tissues tested. It reacts not at all or only weakly

Consequences of PAI-1 specific deletion in endothelium on radiation-induced intestinal damage

International Nuclear Information System (INIS)

Rannou, Emilie

2015-01-01

Radiation-induced injury to healthy tissues is a real public health problem, since they are one of the most limiting factors that restrict efficiency of radiation therapy. This problematic is also part of the French Cancer Plan 2014-2017, and involves clinical research. Concepts surrounding the development of radiation-induced damage have gradually evolved into a contemporary and integrated view of the pathogenesis, involving all compartments of target tissue. Among them, endothelium seems to be central in the sequence of interrelated events that lead to the development of radiation-induced damage, although there are rare concrete elements that support this concept. By using new transgenic mouse models, this PhD project provides a direct demonstration of an endothelium-dependent continuum in evolution of radiation-induced intestinal damage. Indeed, changes in the endothelial phenotype through targeted deletion of the gene SERPINE1, chosen because of its key role in the development of radiation enteritis, influences various parameters of the development of the disease. Thus, lack of PAI-1 secretion by endothelial cells significantly improves survival of the animals, and limits severity of early and late tissue damage after a localized small bowel irradiation. Furthermore, these mice partially KO for PAI-1 showed a decrease in the number of apoptotic intestinal stem cells in the hours following irradiation, a decrease in the macrophages infiltrate density one week after irradiation, and a change in the polarization of macrophages throughout the pathophysiological process. In an effort to protect healthy tissues from radiation therapy side effects, without hindering the cancer treatment, PAI-1 seems to be an obvious therapeutic target. Conceptually, this work represents the direct demonstration of the link between endothelium phenotype and radiation enteritis pathogenesis. (author)

Hemodynamics, functional state of endothelium and renal function, platelets depending on the body mass index in patients with chronic heart failure and preserved systolic function

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Kushnir Yu.

2014-03-01

Full Text Available The aim of the study was to evaluate hemodynamics, endothelium function of kidneys and platelets depending on the body mass index (BMI in patients with chronic heart failure (CHF and preserved systolic function. 42 patients (mean age - 76,690,83 years with CHF II-III FC NYHA with preserved systolic function (LVEF>45% were enrolled. Echocardiography was performed, endothelial function, serum creatinine levels and microalbuminuria were determined in patients. BMI and glomerulation filtration rate were calculated by formulas. The morphological and functional status of platelets was estimated by electronic microscopy. It was defined that increased BMI in patients with CHF and preserved systolic function determines the structural and functional changes of the myocardium and leads to the endothelial and renal functional changes. An increased risk of thrombogenesis was established in patients with overweight and obesity.

Helium induces preconditioning in human endothelium in vivo

NARCIS (Netherlands)

Smit, Kirsten F.; Oei, Gezina T. M. L.; Brevoord, Daniel; Stroes, Erik S.; Nieuwland, Rienk; Schlack, Wolfgang S.; Hollmann, Markus W.; Weber, Nina C.; Preckel, Benedikt

2013-01-01

Helium protects myocardium by inducing preconditioning in animals. We investigated whether human endothelium is preconditioned by helium inhalation in vivo. Forearm ischemia-reperfusion (I/R) in healthy volunteers (each group n = 10) was performed by inflating a blood pressure cuff for 20 min.

HIF-1α Deletion in the Endothelium, but Not in the Epithelium, Protects From Radiation-Induced Enteritis

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Aurore Toullec

2018-01-01

Conclusions: We demonstrate in vivo that HIF-1α impacts radiation-induced enteritis and that this role differs according to the targeted cell type. Our work provides a new role for HIF-1α and endothelium-dependent mechanisms driving inflammatory processes in gut mucosae. Results presented show that effects on normal tissues have to be taken into account in approaches aiming to modulate hypoxia or hypoxia-related molecular mechanisms.

Plxnd1 expression in thymocytes regulates their intrathymic migration while that in thymic endothelium impacts medullary topology

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Young Il Choi

2013-11-01

Full Text Available An important role for plexinD1 in thymic development is inferred from studies of germline Plxnd1 knockout (KO mice where mislocalized CD69+ thymocytes as well as ectopic thymic subcapsular medullary structures were observed. Given embryonic lethality of the Plxnd1-/- genotype, fetal liver transplantation was employed in these prior analyses. Such embryonic hematopoietic reconstitution may have transferred Plxnd1 KO endothelial and/or epithelial stem cells in addition to Plxnd1 KO lymphoid progenitors, thereby contributing to that phenotype. Here we use Plxnd1flox/flox mice crossed to pLck-Cre, pKeratin14-Cre or pTek-Cre transgenic animals to create cell-type specific conditional knockout (CKO lines involving thymocytes (D1ThyCKO, thymic epithelium (D1EpCKO and thymic endothelium (D1EnCKO, respectively. These CKOs allowed us to directly assess the role of plexinD1 in each lineage. Loss of plexinD1 expression on double positive (DP thymocytes leads to their aberrant migration and cortical retention after TCR-mediated positive selection. In contrast, ectopic medulla formation is a consequence of loss of plexinD1 expression on endothelial cells, in turn linked to dysregulation of thymic angiogenesis. D1EpCKO thymi manifest neither abnormality. Collectively, our findings underscore the non-redundant roles for plexinD1 on thymocytes and endothelium, including the dynamic nature of medulla formation resulting from crosstalk between these thymic cellular components.

Efeito dos ácidos graxos ômega-3 sobre o relaxamento-dependente do endotélio em coelhos hipercolesterolêmicos Effects of omega-3 fatty acids on endothelium-dependent relaxation in hypercholesterolemic rabbits

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Paulo Afonso Ribeiro Jorge

1997-07-01

Full Text Available OBJETIVO: Estudar o efeito dos ácidos graxos ômega-3 sobre o relaxamento-dependente do endotélio, o colesterol plasmático, as LDL, VLDL, HDL, triglicérides e a peroxidação lipídica das partículas de LDL-nativas, oxidadas e da parede arterial. MÉTODOS: Coelhos da raça Nova Zelândia foram submetidos a dieta enriquecida com colesterol (0,5% e gordura de coco (2%, por 30 dias e separados em grupo hipercolesterolemia (H e ômega-3 (O-3, sendo administrado ao O-3 ácidos graxos ômega-3 na dose de 300mg/kg/dia, durante 15 dias, através de gavagem. O colesterol plasmático, triglicérides, LDL-colesterol, VLDL e HDL-colesterol foram medidos através de kits enzimáticos e os resultados expressos em mg/dl. As LDL foram obtidas por ultracentrifugação e oxidadas através da exposição ao Cu++. A peroxidação lipídica das LDL e da parede da aorta foi mensurada pela dosagem do malondialdeido (MDA. A função endotelial foi avaliada por curvas de concentração-efeito obtidas pela acetilcolina e nitroprussiato, após contração com norepinefrina. RESULTADOS: Houve aumento do colesterol plasmático e das VLDL, sem interferência nos níveis de LDL e HDL, no O-3. Observou-se redução significante dos triglicérides. Verificou-se aumento significante do teor de MDA nas LDL-nativas e oxidadas, assim como na parede arterial. O relaxamento-dependente do endotélio foi significativamente menor no O-3. CONCLUSÃO: A administração de ácidos graxos ômega-3 na dosagem de 300/mg/kg/dia, a coelhos hipercolesterolêmicos aumentou o colesterol e as VLDL plasmáticas, enquanto reduziu os triglicérides. O relaxamento-dependente do endotélio foi menor que no grupo H.PURPOSE: To study the effect of omega-3 fatty acid on endothelium-dependent relaxation, total plasma cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides levels as well as, the malondialdehyde (MDA content of the LDL particles and arterial wall. METHODS: Fourteen male rabbits

Rat Liver Enzyme Release Depends on Blood Flow-Bearing Physical Forces Acting in Endothelium Glycocalyx rather than on Liver Damage

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Julieta A. Díaz-Juárez

2017-01-01

Full Text Available We have found selective elevation of serum enzyme activities in rats subjected to partial hepatectomy (PH, apparently controlled by hemodynamic flow-bearing physical forces. Here, we assess the involvement of stretch-sensitive calcium channels and calcium mobilization in isolated livers, after chemical modifications of the endothelial glycocalyx and changing perfusion directionality. Inhibiting in vivo protein synthesis, we found that liver enzyme release is influenced by de novo synthesis of endothelial glycocalyx components, and released enzymes are confined into a liver “pool.” Moreover, liver enzyme release depended on extracellular calcium entry possibly mediated by stretch-sensitive calcium channels, and this endothelial-mediated mechanotransduction in liver enzyme release was also evidenced by modifying the glycocalyx carbohydrate components, directionality of perfusing flow rate, and the participation of nitric oxide (NO and malondialdehyde (MDA, leading to modifications in the intracellular distribution of these enzymes mainly as nuclear enrichment of “mitochondrial” enzymes. In conclusion, the flow-induced shear stress may provide fine-tuned control of released hepatic enzymes through mediation by the endothelium glycocalyx, which provides evidence of a biological role of the enzyme release rather to be merely a biomarker for evaluating hepatotoxicity and liver damage, actually positively influencing progression of liver regeneration in mammals.

Gastrin-releasing peptide induces monocyte adhesion to vascular endothelium by upregulating endothelial adhesion molecules

International Nuclear Information System (INIS)

Kim, Mi-Kyoung; Park, Hyun-Joo; Kim, Yeon; Kim, Hyung Joon; Bae, Soo-Kyung; Bae, Moon-Kyoung

2017-01-01

Gastrin-releasing peptide (GRP) is a neuropeptide that plays roles in various pathophysiological conditions including inflammatory diseases in peripheral tissues; however, little is known about whether GRP can directly regulate endothelial inflammatory processes. In this study, we showed that GRP promotes the adhesion of leukocytes to human umbilical vein endothelial cells (HUVECs) and the aortic endothelium. GRP increased the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by activating nuclear factor-κB (NF-κB) in endothelial cells. In addition, GRP activated extracellular signal-regulated kinase 1/2 (ERK1/2), p38MAPK, and AKT, and the inhibition of these signaling pathways significantly reduced GRP-induced monocyte adhesion to the endothelium. Overall, our results suggested that GRP may cause endothelial dysfunction, which could be of particular relevance in the development of vascular inflammatory disorders. - Highlights: • GRP induces adhesion of monocytes to vascular endothelium. • GRP increases the expression of endothelial adhesion molecules through the activation of NF-κB. • ERK1/2, p38MAPK, and Akt pathways are involved in the GRP-induced leukocyte adhesiveness to endothelium.

Binding of human endothelium to Ulex europaeus I-coated Dynabeads: application to the isolation of microvascular endothelium.

Science.gov (United States)

Jackson, C J; Garbett, P K; Nissen, B; Schrieber, L

1990-06-01

A major problem encountered when isolating human microvascular endothelium is the presence of contaminating cells such as fibroblasts that rapidly over-grow the endothelial cells. We describe here a simple, rapid technique for purifying endothelial cells derived from the microvasculature of neonatal foreskin and osteoarthritic and rheumatoid arthritic synovium. This technique is based on the selective binding of the lectin Ulex europaeus I (UEA I) to the endothelial cell surface via fucose residues. Initially UEA I was covalently bound to tosyl-activated super-paramagnetic polystyrene beads (Dynabeads) by incubation for 24 h at room temperature. Cells were isolated by extracting microvascular segments from enzyme-treated (trypsin and Pronase) cubes of tissue. The mixed population of cells obtained were purified by incubating them at 4 degrees C for 10 min with the UEA I-coated Dynabeads. Endothelium bound to the beads whilst contaminating cells were removed by five washes with HBSS using a magnetic particle concentrator. The endothelial cells thus obtained grew to confluence as a cobblestone-like monolayer and expressed von Willebrand factor antigen. The cells were released from the Dynabeads by the competitive binding of fucose (10 min at 4 degrees C). This new method is simple and reproducible and allows pure human microvascular endothelial cells to be cultured within 2 h of obtaining a specimen.

Incidence of fetal chromosome abnormalities in insulin dependent diabetic women

DEFF Research Database (Denmark)

Henriques, C U; Damm, P; Tabor, A

1991-01-01

-diabetic women with little risk of contracting genetic disorders. The results suggest that maternal IDDM does not increase the risk of fetal chromosome abnormality and consequently screening by amniocentesis for chromosome abnormalities among diabetic women does not seem to be indicated....

Ultrastructure of endothelium in ovules of Penstemon gentianoides Poir. (Scrophulariaceae) at mature embryo sac phase.

Science.gov (United States)

Dane, Feruzan; Olgun, Göksel; Ekici, Nuran

2007-06-01

In this study ultrastructural differences between endothelial cells of different location in Penstemon gentianoides have been examined with electron microscope at mature embryo sac phase. Embryo sac is of the Polygonum type and surrounded by endothelium except the micropylar region. The cuticle is located primarily around the chalazal three-fourths of the embryo sac. Endothelium cells around the chalaza and toward the micropylar region are rich in cytoplasmic organelles. The cytoplasm of endothelial cells near the central cell has large vacuoles and few organelles. There are also plasmodesmas on the anticlinal walls of endothelial cells. The endothelium and the micropylar integumentary cells play a role in transport of metabolites into the embryo sac.

Corneal endothelium in xeroderma pigmentosum: clinical specular microscopy study.

Science.gov (United States)

Mohamed, Ashik; Peguda, Rajini; Ramappa, Muralidhar; Ali, Mohammad Javed; Chaurasia, Sunita

2016-06-01

Xeroderma pigmentosum is a condition caused due to a defective DNA repair mechanism when exposed to ultraviolet radiation. Many of the patients with this disorder develop severely oedematous cornea with varying degrees of anterior corneal haze, which necessitates a full-thickness keratoplasty or selective endothelial keratoplasty. Presence of corneal oedema suggests that these patients have a dysfunctional endothelium. The purpose of this study is to evaluate the corneal endothelium in the patients with xeroderma pigmentosum when clinical specular microscopy was feasible. Thirteen patients with classic skin changes of xeroderma pigmentosum were included in the study conducted during January 2010-December 2012. An age-matched group of 13 volunteers were included as controls who were emmetropes without any history of ocular or systemic illness. Corneal endothelium was assessed using specular microscopy from the central clear area of cornea. The mean age of the patients with xeroderma pigmentosum was 16.6±7.2 years and that of the controls was 17.4±6.9 years (p=0.78). The number of analysed cells and endothelial cell density were significantly higher in controls (pxeroderma pigmentosum (p≤0.007). The specular microscopic findings in patients with xeroderma pigmentosum are suggestive of an accelerated endothelial cell loss. It is pertinent that the treating physicians must be involved in emphasising proper ocular protection from ultraviolet radiation to prevent avoidable blindness from xeroderma pigmentosum. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Quantitative Index and Abnormal Alarm Strategy Using Sensor-Dependent Vibration Data for Blade Crack Identification in Centrifugal Booster Fans.

Science.gov (United States)

Chen, Jinglong; Sun, Hailiang; Wang, Shuai; He, Zhengjia

2016-05-09

Centrifugal booster fans are important equipment used to recover blast furnace gas (BFG) for generating electricity, but blade crack faults (BCFs) in centrifugal booster fans can lead to unscheduled breakdowns and potentially serious accidents, so in this work quantitative fault identification and an abnormal alarm strategy based on acquired historical sensor-dependent vibration data is proposed for implementing condition-based maintenance for this type of equipment. Firstly, three group dependent sensors are installed to acquire running condition data. Then a discrete spectrum interpolation method and short time Fourier transform (STFT) are applied to preliminarily identify the running data in the sensor-dependent vibration data. As a result a quantitative identification and abnormal alarm strategy based on compound indexes including the largest Lyapunov exponent and relative energy ratio at the second harmonic frequency component is proposed. Then for validation the proposed blade crack quantitative identification and abnormality alarm strategy is applied to analyze acquired experimental data for centrifugal booster fans and it has successfully identified incipient blade crack faults. In addition, the related mathematical modelling work is also introduced to investigate the effects of mistuning and cracks on the vibration features of centrifugal impellers and to explore effective techniques for crack detection.

Quantitative Index and Abnormal Alarm Strategy Using Sensor-Dependent Vibration Data for Blade Crack Identification in Centrifugal Booster Fans

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Jinglong Chen

2016-05-01

Full Text Available Centrifugal booster fans are important equipment used to recover blast furnace gas (BFG for generating electricity, but blade crack faults (BCFs in centrifugal booster fans can lead to unscheduled breakdowns and potentially serious accidents, so in this work quantitative fault identification and an abnormal alarm strategy based on acquired historical sensor-dependent vibration data is proposed for implementing condition-based maintenance for this type of equipment. Firstly, three group dependent sensors are installed to acquire running condition data. Then a discrete spectrum interpolation method and short time Fourier transform (STFT are applied to preliminarily identify the running data in the sensor-dependent vibration data. As a result a quantitative identification and abnormal alarm strategy based on compound indexes including the largest Lyapunov exponent and relative energy ratio at the second harmonic frequency component is proposed. Then for validation the proposed blade crack quantitative identification and abnormality alarm strategy is applied to analyze acquired experimental data for centrifugal booster fans and it has successfully identified incipient blade crack faults. In addition, the related mathematical modelling work is also introduced to investigate the effects of mistuning and cracks on the vibration features of centrifugal impellers and to explore effective techniques for crack detection.

Abnormal endothelium-dependent microvascular dilator reactivity in pregnancies complicated by normotensive intrauterine growth restriction

NARCIS (Netherlands)

Koopmans, C.M.; Blaauw, Judith; van Pampus, Maria; Rakhorst, G.; Aarnoudse, J.G.

OBJECTIVE: Normotensive intrauterine growth restriction and preeclampsia share a similar placenta pathophysiology, whereas maternal clinical manifestations differ. Clinical symptoms of preeclampsia are partly attributed to vascular endothelial dysfunction, but it is unclear whether this phenomenon

Differential effect of amylin on endothelial-dependent vasodilation in mesenteric arteries from control and insulin resistant rats.

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Mariam El Assar

Full Text Available Insulin resistance (IR is frequently associated with endothelial dysfunction and has been proposed to play a major role in cardiovascular disease (CVD. On the other hand, amylin has long been related to IR. However the role of amylin in the vascular dysfunction associated to IR is not well addressed. Therefore, the aim of the study was to assess the effect of acute treatment with amylin on endothelium-dependent vasodilation of isolated mesenteric arteries from control (CR and insulin resistant (IRR rats and to evaluate the possible mechanisms involved. Five week-old male Wistar rats received 20% D-fructose dissolved in drinking water for 8 weeks and were compared with age-matched CR. Plasmatic levels of glucose, insulin and amylin were measured. Mesenteric microvessels were dissected and mounted in wire myographs to evaluate endothelium-dependent vasodilation to acetylcholine. IRR displayed a significant increase in plasmatic levels of glucose, insulin and amylin and reduced endothelium-dependent relaxation when compared to CR. Acute treatment of mesenteric arteries with r-amylin (40 pM deteriorated endothelium-dependent responses in CR. Amylin-induced reduction of endothelial responses was unaffected by the H2O2 scavenger, catalase, but was prevented by the extracellular superoxide scavenger, superoxide dismutase (SOD or the NADPH oxidase inhibitor (VAS2870. By opposite, amylin failed to further inhibit the impaired relaxation in mesenteric arteries of IRR. SOD, or VAS2870, but not catalase, ameliorated the impairment of endothelium-dependent relaxation in IRR. At concentrations present in insulin resistance conditions, amylin impairs endothelium-dependent vasodilation in mircrovessels from rats with preserved vascular function and low levels of endogenous amylin. In IRR with established endothelial dysfunction and elevated levels of amylin, additional exposure to this peptide has no effect on endothelial vasodilation. Increased superoxide

Dynamic, nondestructive imaging of a bioengineered vascular graft endothelium.

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Bryce M Whited

Full Text Available Bioengineering of vascular grafts holds great potential to address the shortcomings associated with autologous and conventional synthetic vascular grafts used for small diameter grafting procedures. Lumen endothelialization of bioengineered vascular grafts is essential to provide an antithrombogenic graft surface to ensure long-term patency after implantation. Conventional methods used to assess endothelialization in vitro typically involve periodic harvesting of the graft for histological sectioning and staining of the lumen. Endpoint testing methods such as these are effective but do not provide real-time information of endothelial cells in their intact microenvironment, rather only a single time point measurement of endothelium development. Therefore, nondestructive methods are needed to provide dynamic information of graft endothelialization and endothelium maturation in vitro. To address this need, we have developed a nondestructive fiber optic based (FOB imaging method that is capable of dynamic assessment of graft endothelialization without disturbing the graft housed in a bioreactor. In this study we demonstrate the capability of the FOB imaging method to quantify electrospun vascular graft endothelialization, EC detachment, and apoptosis in a nondestructive manner. The electrospun scaffold fiber diameter of the graft lumen was systematically varied and the FOB imaging system was used to noninvasively quantify the affect of topography on graft endothelialization over a 7-day period. Additionally, results demonstrated that the FOB imaging method had a greater imaging penetration depth than that of two-photon microscopy. This imaging method is a powerful tool to optimize vascular grafts and bioreactor conditions in vitro, and can be further adapted to monitor endothelium maturation and response to fluid flow bioreactor preconditioning.

Influence of metabolism modifiers of cyclic nucleotides on contractility of right ventricle of rat heart with intact and removed endocardial endothelium

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Savić Slađana

2010-01-01

Full Text Available Introduction. Endocardial endothelium, a natural biological barrier between circulating blood in heart ventricle and cells, creates a complex yet finely tuned balance of interactions with the immediate environment. Objective. We investigated the roles of theophylline, nonspecific phosphodiesterase inhibitor, and imidazole, an activator of phosphodiesterase on contractility of the right ventricle of rat heart, with intact and removed endocardial endothelium. Methods. Adult rats, of both sexes, type Wistar albino, were used in this experiment. All experiments were conducted on the preparations of the right ventricle using two experimental models. In the first experimental model, an endocardial endothelium (EE was preserved, and in the second model, an endocardial endothelium (-EE was removed using 1% solution Triton X-100. Results. Theophylline (1x10-2 mol/l expressed the positive inotropic effect on the heart, regardless of the presence of the endocardial endothelium. Inotropic response as multiple process can be induced by inhibition of phosphodiesterase, accumulation of cyclic nucleotides and activation of Ca2+ channels. Imidazole (2x10-3 mol/l increased the contractility of the right ventricle of the heart with EE. The modulator effect of endocardial endothelium on contractility of imidazole proved to be significant. As imidazole influenced the contractility of the right ventricle only in the presence of the endocardial endothelium, it is assumed that its effect is mediated via deliverance of endothelial mediators with positive inotropic effect. Conclusion. An intact endocardial endothelium is necessary for completion of contractile performance of the heart.

Diet-induced obesity impairs endothelium-derived hyperpolarization via altered potassium channel signaling mechanisms.

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Rebecca E Haddock

Full Text Available BACKGROUND: The vascular endothelium plays a critical role in the control of blood flow. Altered endothelium-mediated vasodilator and vasoconstrictor mechanisms underlie key aspects of cardiovascular disease, including those in obesity. Whilst the mechanism of nitric oxide (NO-mediated vasodilation has been extensively studied in obesity, little is known about the impact of obesity on vasodilation to the endothelium-derived hyperpolarization (EDH mechanism; which predominates in smaller resistance vessels and is characterized in this study. METHODOLOGY/PRINCIPAL FINDINGS: Membrane potential, vessel diameter and luminal pressure were recorded in 4(th order mesenteric arteries with pressure-induced myogenic tone, in control and diet-induced obese rats. Obesity, reflecting that of human dietary etiology, was induced with a cafeteria-style diet (∼30 kJ, fat over 16-20 weeks. Age and sexed matched controls received standard chow (∼12 kJ, fat. Channel protein distribution, expression and vessel morphology were determined using immunohistochemistry, Western blotting and ultrastructural techniques. In control and obese rat vessels, acetylcholine-mediated EDH was abolished by small and intermediate conductance calcium-activated potassium channel (SK(Ca/IK(Ca inhibition; with such activity being impaired in obesity. SK(Ca-IK(Ca activation with cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl-6-methyl-pyrimidin-4-yl]-amine (CyPPA and 1-ethyl-2-benzimidazolinone (1-EBIO, respectively, hyperpolarized and relaxed vessels from control and obese rats. IK(Ca-mediated EDH contribution was increased in obesity, and associated with altered IK(Ca distribution and elevated expression. In contrast, the SK(Ca-dependent-EDH component was reduced in obesity. Inward-rectifying potassium channel (K(ir and Na(+/K(+-ATPase inhibition by barium/ouabain, respectively, attenuated and abolished EDH in arteries from control and obese rats, respectively; reflecting differential K

Plant abnormality inspection device

International Nuclear Information System (INIS)

Takenaka, Toshio.

1990-01-01

The present invention concerns a plant abnormality inspection device for conducting remote or automatic patrolling inspection in a plant and, more particularly, relates to such a device as capable of detecting abnormal odors. That is, the device comprises a moving device for moving to a predetermined position in the plant, a plurality of gas sensors for different kind of gases to be inspected mounted thereon, a comparator for comparing the concentration of a gas detected by the gas sensor with the normal gas concentration at the predetermined position and a judging means for judging the absence or presence of abnormality depending on the combination of the result of the comparison and deliverying a signal if the state is abnormal. As a result, a slight amount of gas responsible to odors released upon abnormality of the plant can be detected by a plurality of gas sensors for different kinds gases to rapidly and easily find abnormal portions in the plant. (I.S.)

Gap junctions and hydrogen peroxide are involved in endothelium-derived hyperpolarising responses to bradykinin in omental arteries and veins isolated from pregnant women.

Science.gov (United States)

Hammond, Stephanie; Mathewson, Alastair M; Baker, Philip N; Mayhew, Terry M; Dunn, William R

2011-10-01

Altered endothelial function may underlie human cardiovascular diseases, including hypertension, diabetes and pre-eclampsia. While much is known about endothelial function in small arteries, very little is known about endothelial responses in small veins isolated from humans. Therefore, we assessed endothelium-dependent responses in omental arteries and veins isolated from healthy pregnant women, focussing on endothelium-dependent hyperpolarising (EDH) mechanisms. Human omental arteries and veins were obtained from women undergoing elective caesarean sections and examined using pressure myography. In pressurised vessels, the effects of proposed inhibitors of EDH production/function were examined on responses to bradykinin. The expression of connexins Cx37, 40 and 43 was assessed using immunohistochemistry. Bradykinin caused vasodilatation in human pressurised omental arteries and veins. In both vessels, responses to bradykinin were partially blocked in the presence of the gap junction uncoupler, carbenoxolone, and reduced further with the addition of catalase, which acts to degrade H(2)O(2). The effect of catalase alone was more pronounced in venous preparations. All three connexins were expressed in both arteries and veins, with a similar distribution pattern, where Cx37 and Cx40 were located mainly in the endothelium and Cx43 located mostly in the media. These data show that, in human omental vessels, an EDH mechanism is produced in response to bradykinin that involves gap junction communication and the production of H(2)O(2). These mechanisms may be involved in the haemodynamic alterations that take place during pregnancy, and any aberration in their function could contribute to raised blood pressure in hypertensive disorders of pregnancy, such as pre-eclampsia. Copyright © 2011 Elsevier B.V. All rights reserved.

Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals

International Nuclear Information System (INIS)

Morbidelli, Lucia; Monici, Monica; Marziliano, Nicola; Cogoli, Augusto; Fusi, Franco; Waltenberger, Johannes; Ziche, Marina

2005-01-01

Health hazards in astronauts are represented by cardiovascular problems and impaired bone healing. These disturbances are characterized by a common event, the loss of function by vascular endothelium, leading to impaired angiogenesis. We investigated whether the exposure of cultured endothelial cells to hypogravity condition could affect their behaviour in terms of functional activity, biochemical responses, morphology, and gene expression. Simulated hypogravity conditions for 72 h produced a reduction of cell number. Genomic analysis of endothelial cells exposed to hypogravity revealed that proapoptotic signals increased, while antiapoptotic and proliferation/survival genes were down-regulated by modelled low gravity. Activation of apoptosis was accompanied by morphological changes with mitochondrial disassembly and organelles/cytoplasmic NAD(P)H redistribution, as evidenced by autofluorescence analysis. In this condition cells were not able to respond to angiogenic stimuli in terms of migration and proliferation. Our study documents functional, morphological, and transcription alterations in vascular endothelium exposed to simulated low gravity conditions, thus providing insights on the occurrence of vascular tissue dysregulation in crewmen during prolonged space flights. Moreover, the alteration of vascular endothelium can intervene as a concause in other systemic effects, like bone remodelling, observed in weightlessness

Cultivation of Human Microvascular Endothelial Cells on Topographical Substrates to Mimic the Human Corneal Endothelium

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Jie Shi Chua

2013-03-01

Full Text Available Human corneal endothelial cells have a limited ability to replicate in vivo and in vitro. Allograft transplantation becomes necessary when an accident or trauma results in excessive cell loss. The reconstruction of the cornea endothelium using autologous cell sources is a promising alternative option for therapeutic or in vitro drug testing applications. The native corneal endothelium rests on the Descemet’s membrane, which has nanotopographies of fibers and pores. The use of synthetic topographies mimics the native environment, and it is hypothesized that this can direct the behavior and growth of human microvascular endothelial cells (HMVECs to resemble the corneal endothelium. In this study, HMVECs are cultivated on substrates with micron and nano-scaled pillar and well topographies. Closely packed HMVEC monolayers with polygonal cells and well-developed tight junctions were formed on the topographical substrates. Sodium/potassium (Na+/K+ adenine triphosphatase (ATPase expression was enhanced on the microwells substrate, which also promotes microvilli formation, while more hexagonal-like cells are found on the micropillars samples. The data obtained suggests that the use of optimized surface patterning, in particular, the microtopographies, can induce HMVECs to adopt a more corneal endothelium-like morphology with similar barrier and pump functions. The mechanism involved in cell contact guidance by the specific topographical features will be of interest for future studies.

Potentiation of phorbol ester-induced coronary vasoconstriction in dogs following endothelium disruption

International Nuclear Information System (INIS)

Roberts, R.B.; Ku, D.D.

1986-01-01

In the present study, the effect of phorbol ester, 12-0-tetradecanoylphorbol 13-acetate (TPA), activation of protein kinase C on coronary vascular reactivity was studied in isolated dog coronary arteries. Addition of TPA (10-100 nM) produced a slow, time- and dose-dependent contraction reaching a maximum at approx 2-3 hrs and was essentially irreversible upon washing. Disruption of the endothelium(EC) greatly accelerated the development as well as increase the magnitude of TPA contraction (50-100%). Prior treatment of vessels with phentolamine (1μM), cyproheptadine (1μH) and ibuprofen (1μg/ml) did not alter the TPA contraction. Furthermore, in contrast to previously reported calcium-dependence of TPA contraction in other vessels, complete removal of extracellular calcium (Ca 0 ) or addition of 1μM nimodipine after TPA(30nM) resulted in only 32 +/- 4% and 25 +/- 3% reversal of TPA contraction, respectively. Addition of amiloride (10μM to 1mM), however, resulted in a dose-dependent reversal of TPA contraction. The results of the present study indicate that a similar activation of protein kinase C by TPA leads to potent coronary vasoconstriction, which is not completely dependent on Ca 0 . More importantly, these results further support their hypothesis that EC also functions as an inhibitory barrier to prevent circulating vasoconstrictors from exerting their deleterious constrictory effects

Changes in corneal endothelium cell characteristics after cataract surgery with and without use of viscoelastic substances during intraocular lens implantation

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Schulze SD

2015-11-01

Full Text Available Stephan D Schulze,1 Thomas Bertelmann,1 Irena Manojlovic,2 Stefan Bodanowitz,2 Sebastian Irle,3 Walter Sekundo11Department of Ophthalmology, Philipps University of Marburg, Marburg, 2Private Practice and Ambulatory Surgical Center, Bremen, 3Freelance Statistician, Friedberg, GermanyPurpose: To evaluate whether the use of balanced salt solution (BSS or an ophthalmic viscoelastic device (OVD during hydrophilic acrylic intraocular lens (IOL implantation variously impacts corneal endothelial cell characteristics in eyes undergoing uneventful phacoemulsifications.Methods: Prospective nonrandomized observational clinical trial. Patients were assigned either to the BSS plus® or to the OVD Z-Celcoat™ group depending on the substance used during IOL implantation. Corneal endothelium cell characteristics were obtained before, 1 week, and 6 weeks after surgery. Intraoperative parameters (eg, surgery time, phacoemulsification energy were recorded.Results: Ninety-seven eyes were assigned to the BSS plus and 86 eyes to the Z-Celcoat group. Preoperative corneal endothelium cell density (ECD and endothelium cell size were 2,506±310 cells/mm2/2,433±261 cells/mm2 and 406±47 µm2/416±50 µm2 (P=0.107/P=0.09. After 1 and 6 weeks, ECD decreased and endothelium cell size increased significantly in both groups (each P<0.001 without significant differences between both groups (each P>0.05. Irrigation–aspiration suction time (30.3±16.6 versus 36.3±14.5 seconds and overall surgical time (7.2±1.2 versus 8.0±1.4 minutes were significantly longer in the OVD Z-Celcoat group (each P<0.001. No complications or serious side effects occurred.Conclusion: Implantation of a hydrophilic acrylic IOL under BSS infusion seems to be a useful and faster alternative in experienced hands without generating higher ECD loss rates.Keywords: phacoemulsification, ophthalmic viscoelastic device, endothelial cell density, IOL

EFFECTS OF ENALAPRIL ON ENDOTHELIUM FUNCTION IN PATIENTS WITH ISCHEMIC HEART DISEASE

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L. I. Katelnizkaya

2006-01-01

Full Text Available Aim. To study endothelium vasomotor function (EF in patients with ischemic heart disease (IHD and the influence of angiotensin converting enzyme inhibitor enalapril (Enam, Dr .Reddy’s, India on it. Material and methods. 87 patients were examined totally. 49 patients were suffering from IHD: 18 patients were younger than 60 years old and 31 patients were older . The combination of arterial hypertension (HT and IHD were registered in 38 patients: 18 patients were below and 20 patients were above 60 years old. All patients additionally to basic IHD therapy took enalapril in dose 2,5-30 mg/daily during 12 weeks. Before the beginning and in the end of treatment cuff test, test with nitroglycerine, bicycle exercise test and Holter monitoring were made, the thickness of intima-media complex of carotid artery and the level of endothelin-1 in blood plasma were defined. Results. EF disorders were shown in IHD, maximal disorders were determined in patients with combination of IHD and HT. EF disorders were also more expressive in patients of elder group. Enalapril restored of cuff tests results, nitroglycerine tests results, reduced a number of myocardial ischemia episodes and provided target blood pressure in 60, 5% patients with HT. Conclusion. Enalapril improves endothelium vasomotor function, endothelium reaction on nitroglycerine and clinical course of IHD and HT.

Tocotrienol Rich Palm Oil Extract Is More Effective Than Pure Tocotrienols at Improving Endothelium-Dependent Relaxation in the Presence of Oxidative Stress

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Saher F. Ali

2015-01-01

Full Text Available Oxidative endothelial dysfunction is a critical initiator of vascular disease. Vitamin E is an effective antioxidant but attempts to use it to treat vascular disorders have been disappointing. This study investigated whether tocotrienols, the less abundant components of vitamin E compared to tocopherols, might be more effective at preserving endothelial function. Superoxide generated by hypoxanthine/xanthine oxidase or rat aorta was measured using lucigenin-enhanced chemiluminescence. The effect of α-tocopherol, α-, δ-, and γ-tocotrienols and a tocotrienol rich palm oil extract (tocomin on levels of superoxide was assessed. Endothelial function in rat aorta was assessed in the presence of the auto-oxidant pyrogallol. Whilst all of the compounds displayed antioxidant activity, the tocotrienols were more effective when superoxide was produced by hypoxanthine/xanthine oxidase whereas tocomin and α-tocopherol were more effective in the isolated aorta. Tocomin and α-tocopherol restored endothelial function in the presence of oxidant stress but α-, δ-, and γ-tocotrienols were ineffective. The protective effect of tocomin was replicated when the tocotrienols were present with, but not without, α-tocopherol. Tocotrienol rich tocomin is more effective than α-tocopherol at reducing oxidative stress and restoring endothelium-dependent relaxation in rat aortae and although α-, δ-, and γ-tocotrienols effectively scavenged superoxide, they did not improve endothelial function.

Tocotrienol Rich Palm Oil Extract Is More Effective Than Pure Tocotrienols at Improving Endothelium-Dependent Relaxation in the Presence of Oxidative Stress

Science.gov (United States)

Ali, Saher F.; Woodman, Owen L.

2015-01-01

Oxidative endothelial dysfunction is a critical initiator of vascular disease. Vitamin E is an effective antioxidant but attempts to use it to treat vascular disorders have been disappointing. This study investigated whether tocotrienols, the less abundant components of vitamin E compared to tocopherols, might be more effective at preserving endothelial function. Superoxide generated by hypoxanthine/xanthine oxidase or rat aorta was measured using lucigenin-enhanced chemiluminescence. The effect of α-tocopherol, α-, δ-, and γ-tocotrienols and a tocotrienol rich palm oil extract (tocomin) on levels of superoxide was assessed. Endothelial function in rat aorta was assessed in the presence of the auto-oxidant pyrogallol. Whilst all of the compounds displayed antioxidant activity, the tocotrienols were more effective when superoxide was produced by hypoxanthine/xanthine oxidase whereas tocomin and α-tocopherol were more effective in the isolated aorta. Tocomin and α-tocopherol restored endothelial function in the presence of oxidant stress but α-, δ-, and γ-tocotrienols were ineffective. The protective effect of tocomin was replicated when the tocotrienols were present with, but not without, α-tocopherol. Tocotrienol rich tocomin is more effective than α-tocopherol at reducing oxidative stress and restoring endothelium-dependent relaxation in rat aortae and although α-, δ-, and γ-tocotrienols effectively scavenged superoxide, they did not improve endothelial function. PMID:26075031

Intracavitary ultrasound impairs left ventricular performance: presumed role of endocardial endothelium

NARCIS (Netherlands)

Gillebert, T. C.; de Hert, S. G.; Andries, L. J.; Jageneau, A. H.; Brutsaert, D. L.

1992-01-01

Irradiation of isolated cardiac muscle by high-power, high-frequency, continuous wave ultrasound selectively damages endocardial endothelium (EE). We evaluated this ultrasound effect in vivo on the performance of the intact ejecting canine left ventricle (LV). A cylindrical ultrasound probe (0.9

Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats

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Delgado, Nathalie T. B.; Rouver, Wender do N.; Freitas-Lima, Leandro C.; de Paula, Tiago D.-C.; Duarte, Andressa; Silva, Josiane F.; Lemos, Virgínia S.; Santos, Alexandre M. C.; Mauad, Helder; Santos, Roger L.; Moysés, Margareth R.

2017-01-01

prevented the decreasing in plasmatic nitrite. We observed a reduction in total cholesterol and LDL in the Sham-PHE group. The treatment with PHE enhances the endothelium-dependent coronary relaxation and improves cardiovascular parameters, which suggests a therapeutic role of PHE. PMID:28101057

CYP epoxygenase-derived H2O2 is involved in the endothelium-derived hyperpolarization (EDH) and relaxation of intrarenal arteries.

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Muñoz, Mercedes; López-Oliva, Maria Elvira; Pinilla, Estéfano; Martínez, María Pilar; Sánchez, Ana; Rodríguez, Claudia; García-Sacristán, Albino; Hernández, Medardo; Rivera, Luis; Prieto, Dolores

2017-05-01

Reactive oxygen species (ROS) like hydrogen peroxide (H 2 O 2 ) are involved in the in endothelium-derived hyperpolarization (EDH)-type relaxant responses of coronary and mesenteric arterioles. The role of ROS in kidney vascular function has mainly been investigated in the context of harmful ROS generation associated to kidney disease. The present study was sought to investigate whether H 2 O 2 is involved in the endothelium-dependent relaxations of intrarenal arteries as well the possible endothelial sources of ROS generation involved in these responses. Under conditions of cyclooxygenase (COX) and nitric oxide (NO) synthase inhibition, acetylcholine (ACh) induced relaxations and stimulated H 2 O 2 release that were reduced by catalase and by the glutathione peroxidase (GPx) mimetic ebselen in rat renal interlobar arteries, suggesting the involvement of H 2 O 2 in the endothelium-dependent responses. ACh relaxations were also blunted by the CYP2C inhibitor sulfaphenazole and by the NADPH oxidase inhibitor apocynin. Acetylcholine stimulated both superoxide (O 2 •- ) and H 2 O 2 production that were reduced by sulfaphenazole and apocynin. Expression of the antioxidant enzyme CuZnSOD and of the H 2 O 2 reducing enzymes catalase and GPx-1 was found in both intrarenal arteries and renal cortex. On the other hand, exogenous H 2 O 2 relaxed renal arteries by decreasing vascular smooth muscle (VSM) intracellular calcium concentration [Ca 2+ ] i and markedly enhanced endothelial K Ca currents in freshly isolated renal endothelial cells. CYP2C11 and CYP2C23 epoxygenases were highly expressed in interlobar renal arteries and renal cortex, respectively, and were co-localized with eNOS in renal endothelial cells. These results demonstrate that H 2 O 2 is involved in the EDH-type relaxant responses of renal arteries and that CYP 2C epoxygenases are physiologically relevant endothelial sources of vasodilator H 2 O 2 in the kidney. Copyright © 2017 Elsevier Inc. All rights

A null mutation of Hhex results in abnormal cardiac development, defective vasculogenesis and elevated Vegfa levels.

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Hallaq, Haifa; Pinter, Emese; Enciso, Josephine; McGrath, James; Zeiss, Caroline; Brueckner, Martina; Madri, Joseph; Jacobs, Harris C; Wilson, Christine M; Vasavada, Hemaxi; Jiang, Xiaobing; Bogue, Clifford W

2004-10-01

The homeobox gene Hhex has recently been shown to be essential for normal liver, thyroid and forebrain development. Hhex(-/-) mice die by mid-gestation (E14.5) and the cause of their early demise remains unclear. Because Hhex is expressed in the developing blood islands at E7.0 in the endothelium of the developing vasculature and heart at E9.0-9.5, and in the ventral foregut endoderm at E8.5-9.0, it has been postulated to play a critical role in heart and vascular development. We show here, for the first time, that a null mutation of Hhex results in striking abnormalities of cardiac and vascular development which include: (1) defective vasculogenesis, (2) hypoplasia of the right ventricle, (3) overabundant endocardial cushions accompanied by ventricular septal defects, outflow tract abnormalities and atrio-ventricular (AV) valve dysplasia and (4) aberrant development of the compact myocardium. The dramatic enlargement of the endocardial cushions in the absence of Hhex is due to decreased apoptosis and dysregulated epithelial-mesenchymal transformation (EMT). Interestingly, vascular endothelial growth factor A (Vegfa) levels in the hearts of Hhex(-/-) mice were elevated as much as three-fold between E9.5 and E11.5, and treatment of cultured Hhex(-/-) AV explants with truncated soluble Vegfa receptor 1, sFlt-1, an inhibitor of Vegf signaling, completely abolished the excessive epithelial-mesenchymal transformation seen in the absence of Hhex. Therefore, Hhex expression in the ventral foregut endoderm and/or the endothelium is necessary for normal cardiovascular development in vivo, and one function of Hhex is to repress Vegfa levels during development.

Gamma irradiation induces acetylcholine-evoked, endothelium-independent relaxation and activatesk-channels of isolated pulmonary artery of rats

International Nuclear Information System (INIS)

Eder, Veronique; Gautier, Mathieu; Boissiere, Julien; Girardin, Catherine; Rebocho, Manuel; Bonnet, Pierre

2004-01-01

Purpose: To test the effects of irradiation (R*) on the pulmonary artery (PA). Methods and materials: Isolated PA rings were submitted to gamma irradiation (cesium, 8 Gy/min -1 ) at doses of 20 Gy-140 Gy. Rings were placed in an organ chamber, contracted with serotonin (10 -4 M 5-hydroxytryptamine [5-HT]), then exposed to acetylcholine (ACh) in incremental concentrations. Smooth muscle cell (SMC) membrane potential was measured with microelectrodes. Results: A high dose of irradiation (60 Gy) increased 5HT contraction by 20%, whereas lower (20 Gy) doses slightly decreased it compared with control. In the absence of the endothelium, 5-HT precontracted rings exposed to 20 Gy irradiation developed a dose-dependent relaxation induced by acetylcholine (EI-ACh) with maximal relaxation of 60 ± 17% (n = 13). This was totally blocked by L-NAME (10 -4 M), partly by 7-nitro indazole; it was abolished by hypoxia and iberiotoxin, decreased by tetra-ethyl-ammonium, and not affected by free radical scavengers. In irradiated rings, hypoxia induced a slight contraction which was never observed in control rings. No differences in SMC membrane potential were observed between irradiated and nonirradiated PA rings. Conclusion: Irradiation mediates endothelium independent relaxation by a mechanism involving the nitric oxide pathway and K-channels

[Combined G-banded karyotyping and multiplex ligation-dependent probe amplification for the detection of chromosomal abnormalities in fetuses with congenital heart defects].

Science.gov (United States)

Liu, Yang; Xie, Jiansheng; Geng, Qian; Xu, Zhiyong; Wu, Weiqin; Luo, Fuwei; Li, Suli; Wang, Qin; Chen, Wubin; Tan, Hongxi; Zhang, Hu

2017-02-10

To assess the value of G-banded karyotyping in combination with multiplex ligation-dependent probe amplification (MLPA) as a tool for the detection of chromosomal abnormalities in fetuses with congenital heart defects. The combined method was used to analyze 104 fetuses with heart malformations identified by ultrasonography. Abnormal findings were confirmed with chromosomal microarray analysis (CMA). Nineteen (18%) fetuses were found to harbor chromosomal aberrations by G-banded karyotyping and MLPA. For 93 cases, CMA has detected abnormalities in 14 cases including 10 pathogenic copy number variations (CNVs) and 4 CNVs of uncertain significance (VOUS). MLPA was able to detect all of the pathogenic CNVs and 1 VOUS CNV. Combined use of G-banded karyotyping and MLPA is a rapid, low-cost and effective method to detect chromosomal abnormalities in fetuses with various heart malformations.

The atypical structure and function of newborn arterial endothelium is mediated by Rho/Rho kinase signaling.

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Flavahan, Sheila; Flavahan, Nicholas A

2014-08-15

Endothelium of fetal or newborn arteries is atypical, displaying actin stress fibers and reduced nitric oxide (NO)-mediated dilatation. This study tested the hypothesis that Rho/Rho kinase signaling, which promotes endothelial stress fibers and inhibits endothelial dilatation, contributed to this phenotype. Carotid arteries were isolated from newborn [postnatal day 1 (P1)], P7, and P21 mice. Endothelial dilatation to acetylcholine (pressure myograph) was minimal at P1, increased at P7, and further increased at P21. Inhibition of Rho (C3 transferase) or Rho kinase (Y27632, fasudil) significantly increased dilatation to acetylcholine in P1 arteries but had no effect in P7 or P21 arteries. After inhibition of NO synthase (N(G)-nitro-l-arginine methyl ester), Rho kinase inhibition no longer increased acetylcholine responses in P1 arteries. Rho kinase inhibition did not affect dilatation to the NO donor DEA-NONOate. The endothelial actin cytoskeleton was labeled with phalloidin and visualized by laser-scanning microscopy. In P1 arteries, the endothelium had prominent transcytoplasmic stress fibers, whereas in P7 and P21 arteries, the actin fibers had a significantly reduced intensity and were restricted to cell borders. Phosphorylation of myosin light chains, a Rho kinase substrate, was highest in P1 endothelium and significantly reduced in P7 and P21 endothelium (laser-scanning microscopy). In P1 arteries, inhibition of Rho (C3 transferase) or Rho kinase (Y27632) significantly reduced the intensity of actin fibers, which were restricted to cell borders. Similarly, in P1 arteries, Rho inhibition significantly reduced endothelial levels of phosphorylated myosin light chains. These results indicate that the atypical function and morphology of newborn endothelium is mediated by Rho/Rho kinase signaling. Copyright © 2014 the American Physiological Society.

Vitamin D and the endothelium: basic, translational and clinical research updates

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Rinkoo Dalan

2014-09-01

Results and conclusion: Vitamin D deficiency is associated with endothelial dysfunction and cardiovascular diseases. Vitamin D stabilizes the quiescent endothelium, modulates certain stages of endothelial activation, and is involved in the repair of the damaged endothelium in vitro and in vivo. Twelve recent cross sectional studies, including 2086 subjects of varying ethnic groups, show an association between endothelial dysfunction and vitamin D deficiency. Yet 10 recent RCTs of vitamin D supplementation involving 824 subjects have failed to show significant improvements in endothelial function in the short term. So far, RCTs have not been able to confirm or refute the benefit of vitamin D supplementation on vascular mortality. Longer term randomized controlled trials using doses of vitamin D to optimize serum 25(OHD concentrations to 20.0–40.0 ng/mL (50.0–100.0 nmol/L or using vitamin D analogues with no calciotropic effects are needed to assess endothelial function and cardiovascular outcomes.

ENDOTHELIUM LESION MARKERS AND THROMBOCYTE AGGREGATION IN CHRONIC HEPATITIS AND HEPATIC CIRRHOSIS

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A. P. Shchekotova

2012-01-01

Full Text Available Aim — to estimate endothelium lesion, quantity and thrombocyte aggregation function correlation in viral chronic hepatitis C (CHC and hepatic cirrhosis (HC.Materials and methods. 50 CHC patients and 28 HC patients were examined. Using IFA method the total nitric oxide, endothelin‑1, vasculoendothelial growth factor levels, Willebrand factor (vWF activity were investigated, blood plasma desquamated endotheliocyte (DEC number was calculated with Hladovec method, 1978, thrombocyte aggregation (TA with ADP, collagen, ristocetine was determined.Results. DEC and vWF demonstrated correlation in CHC (p = 0.014 and HC (p = 0.000004. In HC patients reliable correlation of all the investigated indices of endothelium lesion with the thrombocyte number and TA was detected, but in CHC patients no correlations were revealed. Thus, significant elevation of TA with ristocetine was noted only in CHC. Decrease in thrombocyte amount among CHC patients and,especially in HC, and heightened vWF activity could change true TA indices. The corrected TA, whose indices in hepatic diseases significantlyincreased, was calculated taking into account the correction factor vWF / thrombocytes that in CHC did not differ from that of healthy patients and in HC was essentially higher.Conclusion. Endothelium dysfunction markers in CH and HC demonstrate correlation with thrombocyte reduction and TA elevation. Determinationof corrected TA permits to reveal disturbances of thrombocyte hemostasis in the form of elevated aggregation in all CHC and HC patients.

Metabolic syndrome enhances endoplasmic reticulum, oxidative stress and leukocyte-endothelium interactions in PCOS.

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Bañuls, Celia; Rovira-Llopis, Susana; Martinez de Marañon, Aranzazu; Veses, Silvia; Jover, Ana; Gomez, Marcelino; Rocha, Milagros; Hernandez-Mijares, Antonio; Victor, Victor M

2017-06-01

Polycystic ovary syndrome (PCOS) is associated with insulin resistance, which can lead to metabolic syndrome (MetS). Oxidative stress and leukocyte-endothelium interactions are related to PCOS. Our aim was to evaluate whether the presence of MetS in PCOS patients can influence endoplasmic reticulum (ER) and oxidative stress and leukocyte-endothelium interactions. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 148 PCOS women (116 without/32 with MetS) and 112 control subjects (87 without / 25 with MetS). Metabolic parameters, reactive oxygen species (ROS) production, ER stress markers (GRP78, sXBP1, ATF6), leukocyte-endothelium interactions, adhesion molecules (VCAM-1, ICAM-1, E-Selectin), TNF-α and IL-6 were determined. Total ROS, inflammatory parameters and adhesion molecules were enhanced in the presence of MetS (pPCOS+MetS group showed higher levels of IL-6 and ICAM-1 than controls (pPCOS and PCOS+MetS groups vs their respective controls (pPCOS groups (pPCOS+MetS patients exhibited higher GRP78 and ATF6 levels than controls and PCOS patients without MetS (pPCOS women, HOMA-IR was positively correlated with ICAM-1 (r=0.501; pPCOS, all of which are related to vascular complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Permeability of the arterial endothelium of spontaneously hypertensive rats to plasma macromolecules

International Nuclear Information System (INIS)

Yurukova, Z.B.; Georgiev, P.G.

1979-01-01

By means of vascular labelling technique at cellular level, the permeability of the arterial endothelium of spontaneously hypertensive rats has been studied. For this purpose colloidal carbon and plasma lipoproteins were introduced into the jugular vein of the animals. Material for light- and electron-microscopic and radioautographic examinations was taken from the thoracic and abdominal parts of the aorta. The results show that in long-term hypertension substances from plasma enter the aortic wall in increased amounts through two main pathways. First, through the selective physiological pathways of transendothelial transport (through cell junctions and vesicular transport) and secondly, through discontinuities of the endothelial lining (separation of the intercellular junctions, areas of loss of one to several endothelial cells). The alteration of the arterial endothelium barrier function in chronic hypertension seems to be an important mechanism for the progression of hypertensive arterial lesions. (A.B.)

[Effects of sodium ethamsylate on anticoagulant and anti-aggregation activity of vascular endothelium in hemorrhagic fever patients with renal syndrome].

Science.gov (United States)

Davidovich, I M; Sirotin, B Z; Parshina, T A

1999-01-01

To elucidate effects of sodium ethamsylate (SE) on anticoagulant and antiaggregation activity of vascular endothelium in patients suffering from hemorrhagic fever with renal syndrome (HFRS). A trial of SE enrolled 70 HFRS patients (58 males, 12 females aged under 30 years) compatible by the disease severity. They were divided into two groups. 42 patients of the control group received standard therapy, 28 patients of the study group received adjuvant 12% solution of SE in daily dose 1500-2000 mg in the course of HFRS oliguria period. Hemostatic parameters were measured before and after the cuff test to investigate the condition of vascular wall with calculation of the athrombogenicity index (the ratio of the relevant indices before and after the cuff test). SE effects on vascular endothelium was assessed by a blind method. In oliguria, both groups had baseline antiaggregation indices significantly higher than in the control. After the cuff test, control patients' indices tended to an increase while in the study group there was a marked decrease. The trend in anticoagulant activity of microvascular endothelium did not differ much with the groups. This picture persisted also in polyuria. In convalescence hemostasis was similar in both groups. SE enhances antiaggregant activity of vascular endothelium in oliguria period of HFRS without affecting its anticoagulant properties. This is explained by a direct effect of SE on vascular endothelium.

Targeted modulation of reactive oxygen species in the vascular endothelium.

Science.gov (United States)

Shuvaev, Vladimir V; Muzykantov, Vladimir R

2011-07-15

'Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-modified enzymes. Targeting of ROS generating enzymes (e.g., glucose oxidase) provides ROS- and site-specific models of endothelial oxidative stress, whereas targeting of antioxidant enzymes SOD and catalase offers site-specific quenching of superoxide anion and H(2)O(2). These targeted antioxidant interventions help to clarify specific role of endothelial ROS in vascular and pulmonary pathologies and provide basis for design of targeted therapeutics for treatment of these pathologies. In particular, antibody/catalase conjugates alleviate acute lung ischemia/reperfusion injury, whereas antibody/SOD conjugates inhibit ROS-mediated vasoconstriction and inflammatory endothelial signaling. Encapsulation in protease-resistant, ROS-permeable carriers targeted to endothelium prolongs protective effects of antioxidant enzymes, further diversifying the means for targeted modulation of endothelial ROS. Copyright © 2011 Elsevier B.V. All rights reserved.

Abnormal Size-Dependent Modulation of Motion Perception in Children with Autism Spectrum Disorder (ASD).

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Sysoeva, Olga V; Galuta, Ilia A; Davletshina, Maria S; Orekhova, Elena V; Stroganova, Tatiana A

2017-01-01

Excitation/Inhibition (E/I) imbalance in neural networks is now considered among the core neural underpinnings of autism psychopathology. In motion perception at least two phenomena critically depend on E/I balance in visual cortex: spatial suppression (SS), and spatial facilitation (SF) corresponding to impoverished or improved motion perception with increasing stimuli size, respectively. While SS is dominant at high contrast, SF is evident for low contrast stimuli, due to the prevalence of inhibitory contextual modulations in the former, and excitatory ones in the latter case. Only one previous study (Foss-Feig et al., 2013) investigated SS and SF in Autism Spectrum Disorder (ASD). Our study aimed to replicate previous findings, and to explore the putative contribution of deficient inhibitory influences into an enhanced SF index in ASD-a cornerstone for interpretation proposed by Foss-Feig et al. (2013). The SS and SF were examined in 40 boys with ASD, broad spectrum of intellectual abilities (63 ASD. The presence of abnormally enhanced SF in children with ASD was the only consistent finding between our study and that of Foss-Feig et al. While the SS and SF indexes were strongly interrelated in TD participants, this correlation was absent in their peers with ASD. In addition, the SF index but not the SS index correlated with the severity of autism and the poor registration abilities. The pattern of results is partially consistent with the idea of hypofunctional inhibitory transmission in visual areas in ASD. Nonetheless, the absence of correlation between SF and SS indexes paired with a strong direct link between abnormally enhanced SF and autism symptoms in our ASD sample emphasizes the role of the enhanced excitatory influences by themselves in the observed abnormalities in low-level visual phenomena found in ASD.

Cytokine-free directed differentiation of human pluripotent stem cells efficiently produces hemogenic endothelium with lymphoid potential.

Science.gov (United States)

Galat, Yekaterina; Dambaeva, Svetlana; Elcheva, Irina; Khanolkar, Aaruni; Beaman, Kenneth; Iannaccone, Philip M; Galat, Vasiliy

2017-03-17

The robust generation of human hematopoietic progenitor cells from induced or embryonic pluripotent stem cells would be beneficial for multiple areas of research, including mechanistic studies of hematopoiesis, the development of cellular therapies for autoimmune diseases, induced transplant tolerance, anticancer immunotherapies, disease modeling, and drug/toxicity screening. Over the past years, significant progress has been made in identifying effective protocols for hematopoietic differentiation from pluripotent stem cells and understanding stages of mesodermal, endothelial, and hematopoietic specification. Thus, it has been shown that variations in cytokine and inhibitory molecule treatments in the first few days of hematopoietic differentiation define primitive versus definitive potential of produced hematopoietic progenitor cells. The majority of current feeder-free, defined systems for hematopoietic induction from pluripotent stem cells include prolonged incubations with various cytokines that make the differentiation process complex and time consuming. We established that the application of Wnt agonist CHIR99021 efficiently promotes differentiation of human pluripotent stem cells in the absence of any hematopoietic cytokines to the stage of hemogenic endothelium capable of definitive hematopoiesis. The hemogenic endothelium differentiation was accomplished in an adherent, serum-free culture system by applying CHIR99021. Hemogenic endothelium progenitor cells were isolated on day 5 of differentiation and evaluated for their endothelial, myeloid, and lymphoid potential. Monolayer induction based on GSK3 inhibition, described here, yielded a large number of CD31 + CD34 + hemogenic endothelium cells. When isolated and propagated in adherent conditions, these progenitors gave rise to mature endothelium. When further cocultured with OP9 mouse stromal cells, these progenitors gave rise to various cells of myeloid lineages as well as natural killer lymphoid, T

Targeted modulation of reactive oxygen species in the vascular endothelium

OpenAIRE

Shuvaev, Vladimir V.; Muzykantov, Vladimir R.

2011-01-01

Endothelial cells lining vascular luminal surface represent an important site of signaling and injurious effects of reactive oxygen species (ROS) produced by other cells and endothelium itself in ischemia, inflammation and other pathological conditions. Targeted delivery of ROS modulating enzymes conjugated with antibodies to endothelial surface molecules (vascular immunotargeting) provides site-specific interventions in the endothelial ROS, unattainable by other formulations including PEG-mo...

Enhanced diffusion with abnormal temperature dependence in underdamped space-periodic systems subject to time-periodic driving

Science.gov (United States)

Marchenko, I. G.; Marchenko, I. I.; Zhiglo, A. V.

2018-01-01

We present a study of the diffusion enhancement of underdamped Brownian particles in a one-dimensional symmetric space-periodic potential due to external symmetric time-periodic driving with zero mean. We show that the diffusivity can be enhanced by many orders of magnitude at an appropriate choice of the driving amplitude and frequency. The diffusivity demonstrates abnormal (decreasing) temperature dependence at the driving amplitudes exceeding a certain value. At any fixed driving frequency Ω normal temperature dependence of the diffusivity is restored at low enough temperatures, T oscillation frequency at the potential minimum, the diffusivity is shown to decrease with Ω according to a power law, with the exponent related to the transient superdiffusion exponent. This behavior is found similar for the cases of sinusoidal in time and piecewise constant periodic ("square") driving.

Hierarchical nitrogen-doped porous carbon with high surface area derived from endothelium corneum gigeriae galli for high-performance supercapacitor

International Nuclear Information System (INIS)

Hong, Xiaoting; Hui, K.S.; Zeng, Zhi; Hui, K.N.; Zhang, Luojiang; Mo, Mingyue; Li, Min

2014-01-01

Highlights: • Porous carbons were prepared using endothelium corneum gigeriae galli as precursor. • Surface and structural properties strongly depend on carbonization temperatures. • Resultant carbons possess nitrogen heteroatom and high surface areas. • ECGG-900 sample exhibits excellent electrochemical capacitive performances. - Abstract: Endothelium corneum gigeriae galli derived 3D hierarchical nitrogen-doped porous carbon was for the first time prepared by preliminary carbonization at 450 °C and final KOH activation at high temperatures. The surface and structural properties of the as-synthesized samples are analyzed with Brunauer–Emmett–Teller surface analyzer apparatus, X-Ray Diffractometer, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectrometer. The electrochemical performances are analyzed by cyclic voltammetry, galvanostatic charge/discharge cycling and electrochemical impedance spectroscopy. The obtained results show that the sample carbonized at 900 °C possesses the SSA of 2149.9 m 2 g −1 , average micropore diameter of 1.78 nm, and exhibits the highest initial specific capacitance of 198.0 F g −1 at current density of 1 A g −1 in 6 M KOH solution. It retains good specific capacitance retention of 91.6% after 3000 charge/discharge cycles at current density of 2 A g −1

THE ROLE OF ENDOTHELIUM FUNCTIONAL STATUS IN PULMONARY HYPERTENSION DEVELOPMENT AMONG CHILDREN

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S.N. Ivanov

2008-01-01

Full Text Available The background paper approaches the problems of functional status of endothelium, significance of vasоactive substances as markers of endothelial dysfunction and reason of its development, role of endothelial dysfunction in the pathogenesis of primary and secondary pulmonary hypertension.Key words: pulmonary hypertension, endothelial dysfunction, vasoactive substances.

Early dynamic fate changes in haemogenic endothelium characterized at the single-cell level

Science.gov (United States)

Swiers, Gemma; Baumann, Claudia; O'Rourke, John; Giannoulatou, Eleni; Taylor, Stephen; Joshi, Anagha; Moignard, Victoria; Pina, Cristina; Bee, Thomas; Kokkaliaris, Konstantinos D.; Yoshimoto, Momoko; Yoder, Mervin C.; Frampton, Jon; Schroeder, Timm; Enver, Tariq; Göttgens, Berthold; de Bruijn, Marella F. T. R.

2013-12-01

Haematopoietic stem cells (HSCs) are the founding cells of the adult haematopoietic system, born during ontogeny from a specialized subset of endothelium, the haemogenic endothelium (HE) via an endothelial-to-haematopoietic transition (EHT). Although recently imaged in real time, the underlying mechanism of EHT is still poorly understood. We have generated a Runx1 +23 enhancer-reporter transgenic mouse (23GFP) for the prospective isolation of HE throughout embryonic development. Here we perform functional analysis of over 1,800 and transcriptional analysis of 268 single 23GFP+ HE cells to explore the onset of EHT at the single-cell level. We show that initiation of the haematopoietic programme occurs in cells still embedded in the endothelial layer, and is accompanied by a previously unrecognized early loss of endothelial potential before HSCs emerge. Our data therefore provide important insights on the timeline of early haematopoietic commitment.

Assessment of endothelium: Dependent vasodilation with a non-invasive method in patients with preeclampsia compared to normotensive pregnant women

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Seyedeh Zahra Allameh

2014-01-01

Full Text Available Background: To assess the endothelial function via noninvasive method, in pregnant women with preeclampsia compared to to normotensive pregnant women. Materials and Methods: Brachial artery diameter was measured via ultrasound, in 28 women with preeclampcia in case group and normotensive pregnant women in control group, at rest, after inflation of sphygmomanometer cuff up to 250-300 mmHg, immediately after deflation of the cuff, 60-90 minutes later and 5 min after administration of sublingual trinitroglycerin (TNG. Results of these measurements as well as demographic characteristics of participants in both groups were recorded in special forms. Data were analyzed via Statistical Package for Social Sciences (SPSS version 16, using t-test and repeated measures analysis of variance (ANOVA. P-value < 0.05 was considered statistically significant. The results were presented as mean ± standard deviation (SD. Results: The mean of brachial artery diameter at rest in the case and control groups was 4.49 ± 0.39 and 4.08 ± 0.38 mm, respectively (P = 0.1. Also the results showed that the brachial artery diameter, immediately after deflation of the cuff, was 4.84 ± 0.4 and 4.37 ± 0.30 mm in the case and control groups (P < 0.001, respectively. The mean brachial artery diameter, 60-90 s after deflation of the cuff, was 4.82 ± 0.41 and 4.42 ± 0.38 mm in the case and control groups (P < 0.00, respectively. The brachial artery diameter, 5 min after sublingual NO administration, was 4.95 ± 0.6 and 4.40 ± 0.45 mm in case and control groups (P < 0.001, respectively. Applying of repeated measures ANOVA showed that the mean difference between case and control groups was statistically significant (P < 0.001. Conclusion: Current study concluded that there is no difference in endothelium-dependent vasodilation between women with preeclampsia and pregnant women with normal blood pressure.

The Anti-Apoptotic Properties of APEX1 in the Endothelium Require the First 20 Amino Acids and Converge on Thioredoxin-1.

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Dyballa-Rukes, Nadine; Jakobs, Philipp; Eckers, Anna; Ale-Agha, Niloofar; Serbulea, Vlad; Aufenvenne, Karin; Zschauer, Tim-Christian; Rabanter, Lothar L; Jakob, Sascha; von Ameln, Florian; Eckermann, Olaf; Leitinger, Norbert; Goy, Christine; Altschmied, Joachim; Haendeler, Judith

2017-04-20

The APEX nuclease (multifunctional DNA repair enzyme) 1 (APEX1) has a disordered N-terminus, a redox, and a DNA repair domain. APEX1 has anti-apoptotic properties, which have been linked to both domains depending on cell type and experimental conditions. As protection against apoptosis is a hallmark of vessel integrity, we wanted to elucidate whether APEX1 acts anti-apoptotic in primary human endothelial cells and, if so, what the underlying mechanisms are. APEX1 inhibits apoptosis in endothelial cells by reducing Cathepsin D (CatD) cleavage, potentially by binding to the unprocessed form. Diminished CatD activation results in increased Thioredoxin-1 protein levels leading to reduced Caspase 3 activation. Consequently, apoptosis rates are decreased. This depends on the first twenty amino acids in APEX1, because APEX1 (21-318) induces CatD activity, decreases Thioredoxin-1 protein levels, and, thus, increases Caspase 3 activity and apoptosis. Along the same lines, APEX1 (1-20) inhibits Caspase 3 cleavage and apoptosis. Furthermore, re-expression of Thioredoxin-1 via lentiviral transduction rescues endothelial cells from APEX1 (21-318)-induced apoptosis. In an in vivo model of restenosis, which is characterized by oxidative stress, endothelial activation, and smooth muscle cell proliferation, Thioredoxin-1 protein levels are reduced in the endothelium of the carotids. APEX1 acts anti-apoptotic in endothelial cells. This anti-apoptotic effect depends on the first 20 amino acids of APEX1. As proper function of the endothelium during life span is a hallmark for individual health span, a detailed characterization of the functions of the APEX1N-terminus is required to understand all its cellular properties. Antioxid. Redox Signal. 26, 616-629.

Activation of the Arterial Program Drives Development of Definitive Hemogenic Endothelium with Lymphoid Potential

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Mi Ae Park

2018-05-01

Full Text Available Summary: Understanding the pathways guiding the development of definitive hematopoiesis with lymphoid potential is essential for advancing human pluripotent stem cell (hPSC technologies for the treatment of blood diseases and immunotherapies. In the embryo, lymphoid progenitors and hematopoietic stem cells (HSCs arise from hemogenic endothelium (HE lining arteries but not veins. Here, we show that activation of the arterial program through ETS1 overexpression or by modulating MAPK/ERK signaling pathways at the mesodermal stage of development dramatically enhanced the formation of arterial-type HE expressing DLL4 and CXCR4. Blood cells generated from arterial HE were more than 100-fold enriched in T cell precursor frequency and possessed the capacity to produce B lymphocytes and red blood cells expressing high levels of BCL11a and β-globin. Together, these findings provide an innovative strategy to aid in the generation of definitive lymphomyeloid progenitors and lymphoid cells from hPSCs for immunotherapy through enhancing arterial programming of HE. : Park et al. find that activation of the arterial program through ETS1 overexpression or by modulating MAPK/ERK signaling pathways at the mesodermal stage of development dramatically enhances formation of arterial-type hemogenic endothelium (HE from hPSCs. Blood cells generated from arterial HE are highly enriched in definitive lymphomyeloid progenitors. Keywords: human pluripotent stem cells, hemogenic endothelium, T cells, hematopoietic stem cells, hematopoiesis, ETS1, MAPK/ERK signaling

SH2 domain-containing protein tyrosine phosphatase 2 and focal adhesion kinase protein interactions regulate pulmonary endothelium barrier function.

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Chichger, Havovi; Braza, Julie; Duong, Huetran; Harrington, Elizabeth O

2015-06-01

Enhanced protein tyrosine phosphorylation is associated with changes in vascular permeability through formation and dissolution of adherens junctions and regulation of stress fiber formation. Inhibition of the protein tyrosine phosphorylase SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) increases tyrosine phosphorylation of vascular endothelial cadherin and β-catenin, resulting in disruption of the endothelial monolayer and edema formation in the pulmonary endothelium. Vascular permeability is a hallmark of acute lung injury (ALI); thus, enhanced SHP2 activity offers potential therapeutic value for the pulmonary vasculature in diseases such as ALI, but this has not been characterized. To assess whether SHP2 activity mediates protection against edema in the endothelium, we assessed the effect of molecular activation of SHP2 on lung endothelial barrier function in response to the edemagenic agents LPS and thrombin. Both LPS and thrombin reduced SHP2 activity, correlated with decreased focal adhesion kinase (FAK) phosphorylation (Y(397) and Y(925)) and diminished SHP2 protein-protein associations with FAK. Overexpression of constitutively active SHP2 (SHP2(D61A)) enhanced baseline endothelial monolayer resistance and completely blocked LPS- and thrombin-induced permeability in vitro and significantly blunted pulmonary edema formation induced by either endotoxin (LPS) or Pseudomonas aeruginosa exposure in vivo. Chemical inhibition of FAK decreased SHP2 protein-protein interactions with FAK concomitant with increased permeability; however, overexpression of SHP2(D61A) rescued the endothelium and maintained FAK activity and FAK-SHP2 protein interactions. Our data suggest that SHP2 activation offers the pulmonary endothelium protection against barrier permeability mediators downstream of the FAK signaling pathway. We postulate that further studies into the promotion of SHP2 activation in the pulmonary endothelium may offer a therapeutic approach for patients

Serum galectin-2, -4, and -8 are greatly increased in colon and breast cancer patients and promote cancer cell adhesion to blood vascular endothelium

DEFF Research Database (Denmark)

Barrow, Hannah; Guo, Xiuli; Wandall, Hans H

2011-01-01

Adhesion of disseminating tumor cells to the blood vascular endothelium is a pivotal step in metastasis. Previous investigations have shown that galectin-3 concentrations are increased in the bloodstream of patients with cancer and that galectin-3 promotes adhesion of disseminating tumor cells...... to vascular endothelium in vitro and experimental metastasis in vivo. This study determined the levels of galectin-1, -2, -3, -4, -8, and -9 in the sera of healthy people and patients with colon and breast cancer and assessed the influence of these galectins on cancer-endothelium adhesion....

Vascular endothelium receptors and transduction mechanisms

CERN Document Server

Gillis, C; Ryan, Una; Proceedings of the Advanced Studies Institute on "Vascular Endothelium: Receptors and Transduction Mechanisms"

1989-01-01

Beyond their obvious role of a barrier between blood and tissue, vascular endothelial cells are now firmly established as active and essential participants in a host of crucial physiological and pathophysiological functions. Probably the two most important factors responsible for promoting the current knowledge of endothelial functions are 1) observations in the late sixties-early seventies that many non-ventilatory properties of the lung could be attributed to the pulmonary endothelium and 2) the establishment, in the early and mid-seventies of procedures for routine culture of vascular endothelial cells. Many of these endothelial functions require the presence of receptors on the surface of the plasma membrane. There is now evidence for the existence among others of muscarinic, a-and /3-adrenergic, purine, insulin, histamine, bradykinin, lipoprotein, thrombin, paf, fibronectin, vitronectin, interleukin and albumin receptors. For some of these ligands, there is evidence only for the existence of endothelial ...

Ulex europaeus I lectin as a marker for vascular endothelium in human tissues.

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Holthöfer, H; Virtanen, I; Kariniemi, A L; Hormia, M; Linder, E; Miettinen, A

1982-07-01

Ulex europaeus I agglutinin, a lectin specific for some alpha-L-fucose-containing glycocompounds, was used in fluorescence microscopy to stain cryostat sections of human tissues. The endothelium of vessels of all sizes was stained ubiquitously in all tissues studied as judged by double staining with a known endothelial marker, antibodies against human clotting factor VIII. Cultured human umbilical vein endothelial cells, but not fibroblasts, also bound Ulex lectin. The staining was not affected by the blood group type of the tissue donor. In some tissues Ulex lectin presented additional binding to epithelial structures. Also, this was independent on the blood group or the ability of the tissue donor to secrete soluble blood group substances. Lotus tetragonolobus agglutinin, another lectin specific for some alpha-L-fucose-containing moieties failed to react with endothelial cells. Our results suggest that Ulex europaeus I agglutinin is a good histologic marker for endothelium in human tissues.

Opening of small and intermediate calcium-activated potassium channels induces relaxation mainly mediated by nitric-oxide release in large arteries and endothelium-derived hyperpolarizing factor in small arteries from rat

DEFF Research Database (Denmark)

Stankevicius, Edgaras; Dalsgaard, Thomas; Kroigaard, Christel

2011-01-01

This study was designed to investigate whether calcium-activated potassium channels of small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance activated by 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) are involved in both nitric oxide (NO) and endothelium-derived hyperpolar......This study was designed to investigate whether calcium-activated potassium channels of small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance activated by 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) are involved in both nitric oxide (NO) and endothelium...... in human umbilical vein endothelial cells (HUVECs), and calcium concentrations were investigated in both HUVECs and mesenteric arterial endothelial cells. In both superior (∼1093 μm) and small mesenteric (∼300 μm) arteries, NS309 evoked endothelium- and concentration-dependent relaxations. In superior....... In small mesenteric arteries, NS309 relaxations were reduced slightly by ADMA, whereas apamin plus an IK(Ca) channel blocker almost abolished relaxation. Iberiotoxin did not change NS309 relaxation. HUVECs expressed mRNA for SK(Ca) and IK(Ca) channels, and NS309 induced increases in calcium, outward...

Activation of the sweet taste receptor, T1R3, by the artificial sweetener sucralose regulates the pulmonary endothelium.

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Harrington, Elizabeth O; Vang, Alexander; Braza, Julie; Shil, Aparna; Chichger, Havovi

2018-01-01

A hallmark of acute respiratory distress syndrome (ARDS) is pulmonary vascular permeability. In these settings, loss of barrier integrity is mediated by cell-contact disassembly and actin remodeling. Studies into molecular mechanisms responsible for improving microvascular barrier function are therefore vital in the development of therapeutic targets for reducing vascular permeability in ARDS. The sweet taste receptor T1R3 is a G protein-coupled receptor, activated following exposure to sweet molecules, to trigger a gustducin-dependent signal cascade. In recent years, extraoral locations for T1R3 have been identified; however, no studies have focused on T1R3 within the vasculature. We hypothesize that activation of T1R3, in the pulmonary vasculature, plays a role in regulating endothelial barrier function in settings of ARDS. Our study demonstrated expression of T1R3 within the pulmonary vasculature, with a drop in expression levels following exposure to barrier-disruptive agents. Exposure of lung microvascular endothelial cells to the intensely sweet molecule sucralose attenuated LPS- and thrombin-induced endothelial barrier dysfunction. Likewise, sucralose exposure attenuated bacteria-induced lung edema formation in vivo. Inhibition of sweet taste signaling, through zinc sulfate, T1R3, or G-protein siRNA, blunted the protective effects of sucralose on the endothelium. Sucralose significantly reduced LPS-induced increased expression or phosphorylation of the key signaling molecules Src, p21-activated kinase (PAK), myosin light chain-2 (MLC2), heat shock protein 27 (HSP27), and p110α phosphatidylinositol 3-kinase (p110αPI3K). Activation of T1R3 by sucralose protects the pulmonary endothelium from edemagenic agent-induced barrier disruption, potentially through abrogation of Src/PAK/p110αPI3K-mediated cell-contact disassembly and Src/MLC2/HSP27-mediated actin remodeling. Identification of sweet taste sensing in the pulmonary vasculature may represent a novel

High-Throughput Screening of Vascular Endothelium-Destructive or Protective Microenvironments: Cooperative Actions of Extracellular Matrix Composition, Stiffness, and Structure.

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Ding, Yonghui; Floren, Michael; Tan, Wei

2017-06-01

Pathological modification of the subendothelial extracellular matrix (ECM) has closely been associated with endothelial activation and subsequent cardiovascular disease progression. To understand regulatory mechanisms of these matrix modifications, the majority of previous efforts have focused on the modulation of either chemical composition or matrix stiffness on 2D smooth surfaces without simultaneously probing their cooperative effects on endothelium function on in vivo like 3D fibrous matrices. To this end, a high-throughput, combinatorial microarray platform on 2D and 3D hydrogel settings to resemble the compositions, stiffness, and structure of healthy and diseased subendothelial ECM has been established, and further their respective and combined effects on endothelial attachment, proliferation, inflammation, and junctional integrity have been investigated. For the first time, the results demonstrate that 3D fibrous structure resembling native ECM is a critical endothelium-protective microenvironmental factor by maintaining the stable, quiescent endothelium with strong resistance to proinflammatory stimuli. It is also revealed that matrix stiffening, in concert with chemical compositions resembling diseased ECM, particularly collagen III, could aggravate activation of nuclear factor kappa B, disruption of endothelium integrity, and susceptibility to proinflammatory stimuli. This study elucidates cooperative effects of various microenvironmental factors on endothelial activation and sheds light on new in vitro model for cardiovascular diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Jabuticaba-Induced Endothelium-Independent Vasodilating Effect on Isolated Arteries.

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Andrade, Daniela Medeiros Lobo de; Borges, Leonardo Luis; Torres, Ieda Maria Sapateiro; Conceição, Edemilson Cardoso da; Rocha, Matheus Lavorenti

2016-09-01

Despite the important biological effects of jabuticaba, its actions on the cardiovascular system have not been clarified. To determine the effects of jabuticaba hydroalcoholic extract (JHE) on vascular smooth muscle (VSM) of isolated arteries. Endothelium-denuded aortic rings of rats were mounted in isolated organ bath to record isometric tension. The relaxant effect of JHE and the influence of K+ channels and Ca2+ intra- and extracellular sources on JHE-stimulated response were assessed. Arteries pre-contracted with phenylephrine showed concentration-dependent relaxation (0.380 to 1.92 mg/mL). Treatment with K+ channel blockers (tetraethyl-ammonium, glibenclamide, 4-aminopyridine) hindered relaxation due to JHE. In addition, phenylephrine-stimulated contraction was hindered by previous treatment with JHE. Inhibition of sarcoplasmic reticulum Ca2+ ATPase did not change relaxation due to JHE. In addition, JHE inhibited the contraction caused by Ca2+ influx stimulated by phenylephrine and KCl (75 mM). JHE induces endothelium-independent vasodilation. Activation of K+ channels and inhibition of Ca2+ influx through the membrane are involved in the JHE relaxant effect. Embora a jabuticaba apresente importantes efeitos biológicos, suas ações sobre o sistema cardiovascular ainda não foram esclarecidas. Determinar os efeitos do extrato de jabuticaba (EHJ) sobre o músculo liso vascular (MLV) em artérias isoladas. Aortas (sem endotélio) de ratos foram montadas em banho de órgãos isolados para registro de tensão isométrica. Foram verificados o efeito relaxante, a influência dos canais de K+ e das fontes de Ca2+ intra- e extracelular sob a resposta estimulada pelo EHJ. Artérias pré-contraídas com fenilefrina apresentaram relaxamento concentração-dependente (0,380 a 1,92 mg/mL). O tratamento com bloqueadores de canais de K+ (tetraetilamônio, glibenclamida, 4-aminopiridina) prejudicaram o relaxamento pelo EHJ. A contração estimulada com fenilefrina tamb

Abnormal mitosis triggers p53-dependent cell cycle arrest in human tetraploid cells.

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Kuffer, Christian; Kuznetsova, Anastasia Yurievna; Storchová, Zuzana

2013-08-01

Erroneously arising tetraploid mammalian cells are chromosomally instable and may facilitate cell transformation. An increasing body of evidence shows that the propagation of mammalian tetraploid cells is limited by a p53-dependent arrest. The trigger of this arrest has not been identified so far. Here we show by live cell imaging of tetraploid cells generated by an induced cytokinesis failure that most tetraploids arrest and die in a p53-dependent manner after the first tetraploid mitosis. Furthermore, we found that the main trigger is a mitotic defect, in particular, chromosome missegregation during bipolar mitosis or spindle multipolarity. Both a transient multipolar spindle followed by efficient clustering in anaphase as well as a multipolar spindle followed by multipolar mitosis inhibited subsequent proliferation to a similar degree. We found that the tetraploid cells did not accumulate double-strand breaks that could cause the cell cycle arrest after tetraploid mitosis. In contrast, tetraploid cells showed increased levels of oxidative DNA damage coinciding with the p53 activation. To further elucidate the pathways involved in the proliferation control of tetraploid cells, we knocked down specific kinases that had been previously linked to the cell cycle arrest and p53 phosphorylation. Our results suggest that the checkpoint kinase ATM phosphorylates p53 in tetraploid cells after abnormal mitosis and thus contributes to proliferation control of human aberrantly arising tetraploids.

On the relationship between emotional state and abnormal unfairness sensitivity in alcohol dependence.

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Brevers, Damien; Noël, Xavier; Hanak, Catherine; Verbanck, Paul; Kornreich, Charles

2015-01-01

Recent empirical findings suggest that alcohol dependence is characterized by heightened sensitivity to unfairness during social transactions. The present study went a step further and aimed to ascertain whether this abnormal level of sensitivity to unfairness is underlined by an increased emotional reactivity. Twenty-six recently abstinent alcohol-dependent (AD) individuals and 32 controls performed an ultimatum game (UG), in which participants had to respond to take-it-or-leave-it offers, ranging from fair to unfair and made by a fictive proposer. Emotional state was recorded during UG offers presentation and was indexed by the amplitude of skin conductance response (SCR). Results showed that AD decided to reject unfair offers more frequently than their controls, confirming previous data. The proportion of rejected unfair UG offers was correlated with SCR, in the AD but not in the control group. This finding suggests that deciding to accept or reject unfair UG offers is influenced by arousal-affective activity in AD, but not in controls. Heightened emotional reactivity may have driven AD to punish the proposer rather than acting as a rational economic agent. An implication of present findings is that AD might have difficult to cope with unfair situations triggered by social interactions. Future studies are needed in order to examine whether-emotional and behavioral-reactivity to unfairness during the UG could impact alcohol consumption and relapse in AD.

Congenital abnormalities associated with hemivertebrae in relation to hemivertebrae location.

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Bollini, Gerard; Launay, Franck; Docquier, Pierre-Louis; Viehweger, Elke; Jouve, Jean-Luc

2010-01-01

Numerous congenital abnormalities have been reported in association with hemivertebrae (HV). No data exist about their incidence depending on the location of the HV. From 1980 to 2003, 75 patients with 80 HV responsible for evolutive congenital scoliosis were managed by HV resection using a double approach and short anterior and posterior convex fusion. The associated abnormalities were evaluated with MRI, echocardiography and renal ultrasound. Associated genitourinary abnormalities were found in 24% of patients, cardiac abnormalities in 8% and intrathecal abnormalities in 15%. Medullar abnormalities were more frequent in case of vertebral malformations at lumbosacral level.

Cardiac abnormality prediction using HMLP network

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Adnan, Ja'afar; Ahmad, K. A.; Mat, Muhamad Hadzren; Rizman, Zairi Ismael; Ahmad, Shahril

2018-02-01

Cardiac abnormality often occurs regardless of gender, age and races but depends on the lifestyle. This problem sometimes does not show any symptoms and usually detected once it already critical which lead to a sudden death to the patient. Basically, cardiac abnormality is the irregular electrical signal that generate by the pacemaker of the heart. This paper attempts to develop a program that can detect cardiac abnormality activity through implementation of Hybrid Multilayer Perceptron (HMLP) network. A certain amount of data of the heartbeat signals from the electrocardiogram (ECG) will be used in this project to train the MLP and HMLP network by using Modified Recursive Prediction Error (MRPE) algorithm and to test the network performance.

Arterial response to shear stress critically depends on endothelial TRPV4 expression.

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Veronika Hartmannsgruber

Full Text Available BACKGROUND: In blood vessels, the endothelium is a crucial signal transduction interface in control of vascular tone and blood pressure to ensure energy and oxygen supply according to the organs' needs. In response to vasoactive factors and to shear stress elicited by blood flow, the endothelium secretes vasodilating or vasocontracting autacoids, which adjust the contractile state of the smooth muscle. In endothelial sensing of shear stress, the osmo- and mechanosensitive Ca(2+-permeable TRPV4 channel has been proposed to be candidate mechanosensor. Using TRPV4(-/- mice, we now investigated whether the absence of endothelial TRPV4 alters shear-stress-induced arterial vasodilation. METHODOLOGY/PRINCIPAL FINDINGS: In TRPV4(-/- mice, loss of the TRPV4 protein was confirmed by Western blot, immunohistochemistry and by in situ-patch-clamp techniques in carotid artery endothelial cells (CAEC. Endothelium-dependent vasodilation was determined by pressure myography in carotid arteries (CA from TRPV4(-/- mice and wild-type littermates (WT. In WT CAEC, TRPV4 currents could be elicited by TRPV4 activators 4alpha-phorbol-12,13-didecanoate (4alphaPDD, arachidonic acid (AA, and by hypotonic cell swelling (HTS. In striking contrast, in TRPV4(-/- mice, 4alphaPDD did not produce currents and currents elicited by AA and HTS were significantly reduced. 4alphaPDD caused a robust and endothelium-dependent vasodilation in WT mice, again conspicuously absent in TRPV4(-/- mice. Shear stress-induced vasodilation could readily be evoked in WT, but was completely eliminated in TRPV4(-/- mice. In addition, flow/reperfusion-induced vasodilation was significantly reduced in TRPV4(-/- vs. WT mice. Vasodilation in response to acetylcholine, vasoconstriction in response to phenylephrine, and passive mechanical compliance did not differ between genotypes, greatly underscoring the specificity of the above trpv4-dependent phenotype for physiologically relevant shear stress

Arterial Response to Shear Stress Critically Depends on Endothelial TRPV4 Expression

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Kacik, Michael; Kaistha, Anuradha; Grgic, Ivica; Harteneck, Christian; Liedtke, Wolfgang; Hoyer, Joachim; Köhler, Ralf

2007-01-01

Background In blood vessels, the endothelium is a crucial signal transduction interface in control of vascular tone and blood pressure to ensure energy and oxygen supply according to the organs' needs. In response to vasoactive factors and to shear stress elicited by blood flow, the endothelium secretes vasodilating or vasocontracting autacoids, which adjust the contractile state of the smooth muscle. In endothelial sensing of shear stress, the osmo- and mechanosensitive Ca2+-permeable TRPV4 channel has been proposed to be candidate mechanosensor. Using TRPV4−/− mice, we now investigated whether the absence of endothelial TRPV4 alters shear-stress-induced arterial vasodilation. Methodology/Principal Findings In TRPV4−/− mice, loss of the TRPV4 protein was confirmed by Western blot, immunohistochemistry and by in situ-patch–clamp techniques in carotid artery endothelial cells (CAEC). Endothelium-dependent vasodilation was determined by pressure myography in carotid arteries (CA) from TRPV4−/− mice and wild-type littermates (WT). In WT CAEC, TRPV4 currents could be elicited by TRPV4 activators 4α-phorbol-12,13-didecanoate (4αPDD), arachidonic acid (AA), and by hypotonic cell swelling (HTS). In striking contrast, in TRPV4−/− mice, 4αPDD did not produce currents and currents elicited by AA and HTS were significantly reduced. 4αPDD caused a robust and endothelium-dependent vasodilation in WT mice, again conspicuously absent in TRPV4−/− mice. Shear stress-induced vasodilation could readily be evoked in WT, but was completely eliminated in TRPV4−/− mice. In addition, flow/reperfusion-induced vasodilation was significantly reduced in TRPV4−/− vs. WT mice. Vasodilation in response to acetylcholine, vasoconstriction in response to phenylephrine, and passive mechanical compliance did not differ between genotypes, greatly underscoring the specificity of the above trpv4-dependent phenotype for physiologically relevant shear stress. Conclusions

Mechanisms underlying epithelium-dependent relaxation in rat bronchioles

DEFF Research Database (Denmark)

Kroigaard, Christel; Dalsgaard, Thomas; Simonsen, Ulf

2010-01-01

This study investigated the mechanisms underlying epithelium-derived hyperpolarizing factor (EpDHF)-type relaxation in rat bronchioles. Immunohistochemistry was performed, and rat bronchioles and pulmonary arteries were mounted in microvascular myographs for functional studies. An opener of small...... (SK(Ca)) and intermediate (IK(Ca))-conductance calcium-activated potassium channels, NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) was used to induce EpDHF-type relaxation. IK(Ca) and SK(Ca)3 positive immunoreactions were observed mainly in the epithelium and endothelium of bronchioles and arteries......, respectively. In 5-hydroxytryptamine (1 microM)-contracted bronchioles (828 +/- 20 microm, n = 84) and U46619 (0.03 microM)-contracted arteries (720 +/- 24 microm, n = 68), NS309 (0.001-10 microM) induced concentration-dependent relaxations that were reduced by epithelium/endothelium removal and by blocking IK...

Relationship between vascular endothelium and periodontal disease in atherosclerotic lesions: Review article

Science.gov (United States)

Saffi, Marco Aurélio Lumertz; Furtado, Mariana Vargas; Polanczyk, Carisi Anne; Montenegro, Márlon Munhoz; Ribeiro, Ingrid Webb Josephson; Kampits, Cassio; Haas, Alex Nogueira; Rösing, Cassiano Kuchenbecker; Rabelo-Silva, Eneida Rejane

2015-01-01

Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease. PMID:25632316

Vascular endothelium as a target of immune response in renal transplant rejection

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Giovanni ePiotti

2014-10-01

Full Text Available This review of clinical and experimental studies aims at analysing the interplay between graft endothelium and host immune system in renal transplantation, and how it affects the survival of the graft. Graft endothelium is indeed the first barrier between self and non-self that is encountered by host lymphocytes upon reperfusion of vascularised solid transplants. Endothelial cells express all the major sets of antigens that elicit host immune response, and therefore represent a preferential target in organ rejection.Some of the antigens expressed by endothelial cells are target of the antibody-mediated response, such as the AB0 blood group system, the HLA and MICA systems, and the endothelial cell-restricted antigens; for each of these systems, the mechanisms of interaction and damage of both preformed and de novo donor-specific antibodies are reviewed along with their impact on renal graft survival. Moreover the rejection process can force injured endothelial cells to expose cryptic self-antigens, toward which an auto-immune response mounts, overlapping to the allo-immune response in the damaging of the graft. Not only are endothelial cells a passive target of the host immune response, but also an active player in lymphocyte activation; therefore their interaction with allogenic T-cells is analysed on the basis of experimental in vitro and in vivo studies, according to the patterns of expression of the HLA class I and II and the co-stimulatory molecules specific for cytotoxic and helper T-cells.Finally, as the response that follows transplantation has proven to be not necessarily destructive, the factors that foster graft endothelium functioning in spite of rejection, and how they could be therapeutically harnessed to promote long-term graft acceptance, are described: accommodation that is resistance of endothelial cells to donor-specific antibodies, and endothelial cell ability to induce Foxp3+ Regulatory T-cells, that are crucial mediators of

Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities.

Science.gov (United States)

McDonald, Robert J; McDonald, Jennifer S; Kallmes, David F; Jentoft, Mark E; Paolini, Michael A; Murray, David L; Williamson, Eric E; Eckel, Laurence J

2017-11-01

Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings

Visual outcomes after deep anterior lamellar keratoplasty using donor corneas without removal of Descemet membrane and endothelium

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Tatiana Moura Bastos Prazeres

Full Text Available ABSTRACT Purpose: The optical quality of the interface after deep anterior lamellar keratoplasty (DALK using the big-bubble technique has been shown to be excellent, leading to results comparable to penetrating keratoplasty. However, there is little in the literature with respect to the controversy surrounding the preparation of the donor cornea. The purpose of this study was to evaluate visual acuity (VA in patients with keratoconus who underwent DALK without removal of the donor graft endothelium. Methods: The records of 90 patients who underwent DALK without the removal of the Descemet membrane (DM and endothelium were retrospectively reviewed. Data collected included uncorrected VA (UCVA and spectacle-corrected VA (SCVA at 7, 30, 180 days, and 1 year postoperatively. Contact lens-corrected visual acuity (CLVA was evaluated after 1 year of the procedure. Results: UCVA was significantly better than preoperative values at 7 days (p<0.001, 30 days (p<0.001, 180 days (p<0.001, and 1 year (p<0.001 after surgery. The 1-year postoperative mean SCVA and CLVA also improved when compared with preoperative SCVA (p<0.001 for both. Conclusions: DALK utilizing donor corneas with attached Descemet membrane and endothelium results in satisfactory VA in patients with keratoconus.

On the relationship between emotional state and abnormal unfairness sensitivity in alcohol dependence

Directory of Open Access Journals (Sweden)

Damien eBrevers

2015-07-01

Full Text Available Recent empirical findings suggest that alcohol dependence is characterized by heightened sensitivity to unfairness during social transactions. The present study went a step further and aimed to ascertain whether this abnormal level of sensitivity to unfairness is underlined by an increased emotional reactivity. Twenty-six recently abstinent alcohol-dependent individuals (AD and 32 controls performed an Ultimatum Game (UG, in which participants had to respond to take-it-or-leave-it offers, ranging from fair to unfair and made by a fictive proposer. Emotional state was recorded during UG offers presentation and was indexed by the amplitude of skin conductance response (SCR. Results showed that AD decided to reject unfair offers more frequently than their controls, confirming previous data. The proportion of rejected unfair UG offers was correlated with SCR, in the AD but not in the control group. This finding suggests that deciding to accept or reject unfair UG offers is influenced by arousal-affective activity in AD, but not in controls. Heightened emotional reactivity may have driven AD to punish the proposer rather than acting as a rational economic agent. An implication of present findings is that AD might have difficult to cope with unfair situations triggered by social interactions. Future studies are needed are needed in order to examine whether - emotional and behavioral - reactivity to unfairness during the UG could impact alcohol consumption and relapse in AD.

Crucial roles of Nox2-derived oxidative stress in deteriorating the function of insulin receptors and endothelium in dietary obesity of middle-aged mice.

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Du, Junjie; Fan, Lampson M; Mai, Anna; Li, Jian-Mei

2013-11-01

Systemic oxidative stress associated with dietary calorie overload plays an important role in the deterioration of vascular function in middle-aged patients suffering from obesity and insulin resistance. However, effective therapy is still lacking. In this study, we used a mouse model of middle-aged obesity to investigate the therapeutic potential of pharmaceutical inhibition (apocynin, 5 mM supplied in the drinking water) or knockout of Nox2, an enzyme generating reactive oxygen species (ROS), in high-fat diet (HFD)-induced obesity, oxidative stress, insulin resistance and endothelial dysfunction. Littermates of C57BL/6J wild-type (WT) and Nox2 knockout (KO) mice (7 months old) were fed with a HFD (45% kcal fat) or normal chow diet (NCD, 12% kcal fat) for 16 weeks and used at 11 months of age. Compared to NCD WT mice, HFD WT mice developed obesity, insulin resistance, dyslipidaemia and hypertension. Aortic vessels from these mice showed significantly increased Nox2 expression and ROS production, accompanied by significantly increased ERK1/2 activation, reduced insulin receptor expression, decreased Akt and eNOS phosphorylation and impaired endothelium-dependent vessel relaxation to acetylcholine. All these HFD-induced abnormalities (except the hyperinsulinaemia) were absent in apocynin-treated WT or Nox2 KO mice given the same HFD. In conclusion, Nox2-derived ROS played a key role in damaging insulin receptor and endothelial function in dietary obesity after middle-age. Targeting Nox2 could represent a valuable therapeutic strategy in the metabolic syndrome. © 2013 The British Pharmacological Society.

Cerebellar cortex development in the weaver condition presents regional and age-dependent abnormalities without differences in Purkinje cells neurogenesis.

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Martí, Joaquín; Santa-Cruz, María C; Hervás, José P; Bayer, Shirley A; Villegas, Sandra

2016-01-01

Ataxias are neurological disorders associated with the degeneration of Purkinje cells (PCs). Homozygous weaver mice (wv/wv) have been proposed as a model for hereditary cerebellar ataxia because they present motor abnormalities and PC loss. To ascertain the physiopathology of the weaver condition, the development of the cerebellar cortex lobes was examined at postnatal day (P): P8, P20 and P90. Three approaches were used: 1) quantitative determination of several cerebellar features; 2) qualitative evaluation of the developmental changes occurring in the cortical lobes; and 3) autoradiographic analyses of PC generation and placement. Our results revealed a reduction in the size of the wv/wv cerebellum as a whole, confirming previous results. However, as distinguished from these reports, we observed that quantified parameters contribute differently to the abnormal growth of the wv/wv cerebellar lobes. Qualitative analysis showed anomalies in wv/wv cerebellar cytoarchitecture, depending on the age and lobe analyzed. Such abnormalities included the presence of the external granular layer after P20 and, at P90, ectopic cells located in the molecular layer following several placement patterns. Finally, we obtained autoradiographic evidence that wild-type and wv/wv PCs presented similar neurogenetic timetables, as reported. However, the innovative character of this current work lies in the fact that the neurogenetic gradients of wv/wv PCs were not modified from P8 to P90. A tendency for the accumulation of late-formed PCs in the anterior and posterior lobes was found, whereas early-generated PCs were concentrated in the central and inferior lobes. These data suggested that wv/wv PCs may migrate properly to their final destinations. The extrapolation of our results to patients affected with cerebellar ataxias suggests that all cerebellar cortex lobes are affected with several age-dependent alterations in cytoarchitectonics. We also propose that PC loss may be regionally

Function of endothelium at adolescents with constitutional exogenous obesity before and after rehabilitation

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Miroshnichenko, O.

2011-01-01

Function of endothelium at 43 adolescents with constitutional exogenous obesity before rehabilitation and at 33 healthy adolescents has been studied. Disorder of endothelial function has been established in 32 (74.4%) adolescents with constitutional exogenous obesity and in 7 (21.2%) healthy adolescents. We showed the efficiency of the rehabilitation program on restoration of endothelial function at adolescents with constitutional exogenous obesity.

Injuries to the vascular endothelium: vascular wall and endothelial dysfunction.

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Fisher, Mark

2008-01-01

Vascular endothelial injury has multiple elements, and this article focuses on ischemia-related processes that have particular relevance to ischemic stroke. Distinctions between necrotic and apoptotic cell death provide a basic science context in which to better understand the significance of classical core and penumbra concepts of acute stroke, with apoptotic processes particularly prominent in the penumbra. The mitochondria are understood to serve as a reservoir of proteins that mediate apoptosis. Oxidative stress pathways generating reactive oxygen species (ROS) are prominent in endothelial injury, both ischemic and nonischemic, with prominent roles of enzyme- and nonenzymemediated pathways; mitochondria once again have a critical role, particularly in the nonenzymatic pathways generating ROS. Inflammation also contributes to vascular endothelial injury, and endothelial cells have the capacity to rapidly increase expression of inflammatory mediators following ischemic challenge; this leads to enhanced leukocyte-endothelial interactions mediated by selectins and adhesion molecules. Preconditioning consists of a minor version of an injurious event, which in turn may protect vascular endothelium from injury following a more substantial event. Presence of the blood-brain barrier creates unique responses to endothelial injury, with permeability changes due to impairment of endothelial-matrix interactions compounding altered vasomotor tone and tissue perfusion mediated by nitric oxide. Pharmacological protection against vascular endothelial injury can be provided by several of the phosphodiesterases (cilostazol and dipyridamole), along with statins. Optimal clinical responses for protection of brain vascular endothelium may use preconditioning as a model, and will likely require combined protection against apoptosis, ROS, and inflammation.

Does abnormal sleep impair memory consolidation in schizophrenia?

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Dara S Manoach

2009-09-01

Full Text Available Although disturbed sleep is a prominent feature of schizophrenia, its relation to the pathophysiology, signs, and symptoms of schizophrenia remains poorly understood. Sleep disturbances are well known to impair cognition in healthy individuals. Yet, in spite of its ubiquity in schizophrenia, abnormal sleep has generally been overlooked as a potential contributor to cognitive deficits. Amelioration of cognitive deficits is a current priority of the schizophrenia research community, but most efforts to define, characterize, and quantify cognitive deficits focus on cross-sectional measures. While this approach provides a valid snapshot of function, there is now overwhelming evidence that critical aspects of learning and memory consolidation happen offline, both over time and with sleep. Initial memory encoding is followed by a prolonged period of consolidation, integration, and reorganization, that continues over days or even years. Much of this evolution of memories is mediated by sleep. This article briefly reviews (i abnormal sleep in schizophrenia, (ii sleep-dependent memory consolidation in healthy individuals, (iii recent findings of impaired sleep-dependent memory consolidation in schizophrenia, and (iv implications of impaired sleep-dependent memory consolidation in schizophrenia. This literature suggests that abnormal sleep in schizophrenia disrupts attention and impairs sleep-dependent memory consolidation and task automation. We conclude that these sleep-dependent impairments may contribute substantially to generalized cognitive deficits in schizophrenia. Understanding this contribution may open new avenues to ameliorating cognitive dysfunction and thereby improve outcome in schizophrenia.

Nitric oxide-dependent vasodilation and Ca2+ signalling induced by erythrodiol in rat aorta

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Fidèle Ntchapda

2015-06-01

Full Text Available Objective: To evaluate the pharmacological property of erythrodiol, a natural triterpenoid contained in propolis, as vasodilatory agent, and to determine its mechanism of action. Methods: Rats aortic rings were isolated and suspended in organ baths, and the effects of erythrodiol were studied by means of isometric tension recording experiments. Nitric oxide (NO was detected by ozone-induced chemiluminescence. The technique used to evaluate changes in intracellular Ca2+ concentration in intact endothelium was opened aortic ring and loaded with 16 µmol Fura-2/AM for 60 min at room temperature, washed and fixed by small pins with the luminal face up. In situ, ECs were visualized by an upright epifluorescence Axiolab microscope (Carl Zeiss, Oberkochen, Germany equipped with a Zeiss×63 Achroplan objective (water immersion, 2.0 mm working distance, 0.9 numerical apertures. ECs were excited alternately at 340 and 380 nm, and the emitted light was detected at 510 nm. Results: In aortic rings with intact endothelium pre-contracted with norepinephrine (10-4 mol/L, the addition of erythrodiol (10-8-10-4 mol/L induced vasorelaxation in a concentration-dependent manner; in endothelium-denuded rings, the relaxant response induced by erythrodiol was almost completely abolished suggesting that vasorelaxation was endothelium-dependent. They had almost no relaxant effect on depolarised or endothelium-denuded aortic segments. The relaxation was significantly attenuated by pre-treatment with the NO synthase inhibitor Nvnitro-L-arginine-methylester. Erythrodiol (10-4 mol/L was able to significantly increase NOx levels. This effect was completely abolished after removal of the vascular endothelium. Erythrodiol (100 µmol/L caused a slow, long-lasting increase in intracellular Ca2+ concentration. These results further supported the hypothesis that erythrodiol can induce activation of the NO/soluble guanylate cyclase/cyclic guanosine monophosphate pathway, as

Comparison and Supervised Learning of Segmentation Methods Dedicated to Specular Microscope Images of Corneal Endothelium

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Yann Gavet

2014-01-01

Full Text Available The cornea is the front of the eye. Its inner cell layer, called the endothelium, is important because it is closely related to the light transparency of the cornea. An in vivo observation of this layer is performed by using specular microscopy to evaluate the health of the cells: a high spatial density will result in a good transparency. Thus, the main criterion required by ophthalmologists is the cell density of the cornea endothelium, mainly obtained by an image segmentation process. Different methods can perform the image segmentation of these cells, and the three most performing methods are studied here. The question for the ophthalmologists is how to choose the best algorithm and to obtain the best possible results with it. This paper presents a methodology to compare these algorithms together. Moreover, by the way of geometric dissimilarity criteria, the algorithms are tuned up, and the best parameter values are thus proposed to the expert ophthalmologists.

Accumulation of the Vitamin D Precursor Cholecalciferol Antagonizes Hedgehog Signaling to Impair Hemogenic Endothelium Formation

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Mauricio Cortes

2015-10-01

Full Text Available Hematopoietic stem and progenitor cells (HSPCs are born from hemogenic endothelium in the dorsal aorta. Specification of this hematopoietic niche is regulated by a signaling axis using Hedgehog (Hh and Notch, which culminates in expression of Runx1 in the ventral wall of the artery. Here, we demonstrate that the vitamin D precursor cholecalciferol (D3 modulates HSPC production by impairing hemogenic vascular niche formation. Accumulation of D3 through exogenous treatment or inhibition of Cyp2r1, the enzyme required for D3 25-hydroxylation, results in Hh pathway antagonism marked by loss of Gli-reporter activation, defects in vascular niche identity, and reduced HSPCs. Mechanistic studies indicated the effect was specific to D3, and not active 1,25-dihydroxy vitamin D3, acting on the extracellular sterol-binding domain of Smoothened. These findings highlight a direct impact of inefficient vitamin D synthesis on cell fate commitment and maturation in Hh-regulated tissues, which may have implications beyond hemogenic endothelium specification.

Ropivacaine-Induced Contraction Is Attenuated by Both Endothelial Nitric Oxide and Voltage-Dependent Potassium Channels in Isolated Rat Aortae

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Seong-Ho Ok

2013-01-01

Full Text Available This study investigated endothelium-derived vasodilators and potassium channels involved in the modulation of ropivacaine-induced contraction. In endothelium-intact rat aortae, ropivacaine concentration-response curves were generated in the presence or absence of the following inhibitors: the nonspecific nitric oxide synthase (NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, the neuronal NOS inhibitor Nω-propyl-L-arginine hydrochloride, the inducible NOS inhibitor 1400W dihydrochloride, the nitric oxide-sensitive guanylyl cyclase (GC inhibitor ODQ, the NOS and GC inhibitor methylene blue, the phosphoinositide-3 kinase inhibitor wortmannin, the cytochrome p450 epoxygenase inhibitor fluconazole, the voltage-dependent potassium channel inhibitor 4-aminopyridine (4-AP, the calcium-activated potassium channel inhibitor tetraethylammonium (TEA, the inward-rectifying potassium channel inhibitor barium chloride, and the ATP-sensitive potassium channel inhibitor glibenclamide. The effect of ropivacaine on endothelial nitric oxide synthase (eNOS phosphorylation in human umbilical vein endothelial cells was examined by western blotting. Ropivacaine-induced contraction was weaker in endothelium-intact aortae than in endothelium-denuded aortae. L-NAME, ODQ, and methylene blue enhanced ropivacaine-induced contraction, whereas wortmannin, Nω-propyl-L-arginine hydrochloride, 1400W dihydrochloride, and fluconazole had no effect. 4-AP and TEA enhanced ropivacaine-induced contraction; however, barium chloride and glibenclamide had no effect. eNOS phosphorylation was induced by ropivacaine. These results suggest that ropivacaine-induced contraction is attenuated primarily by both endothelial nitric oxide and voltage-dependent potassium channels.

Uptake of low density lipoproteins by the hamster lung. Interactions with capillary endothelium

International Nuclear Information System (INIS)

Nistor, A.; Simionescu, M.

1986-01-01

The mechanism by which the circulating low density lipoproteins (LDL) contribute to the lung surfactant cholesterol was investigated by perfusing the hamster lung in situ with LDL either radiolabeled or coupled to gold, or both. Part of [ 125 I]-LDL and [ 3 H]-cholesterol LDL were taken up by a specific process which was time- and concentration-dependent and reached saturation within 20 to 30 min of perfusion. Competition experiments and removal of receptor-bound LDL by heparin suggested that about 50% of LDL uptake is receptor-independent. Experiments using double labeled LDL showed a preferential uptake of 3 H-cholesterol versus 125 I by the lung both in situ and in vivo. LDL-gold particles (LDL-Au), recirculated through the isolated lung, bound to the endothelial luminal plasma membrane and to features potentially involved in receptor-mediated endocytosis (coated pits, coated vesicles, lysosomelike structures) and in transcytosis (plasmalemmal vesicles). The results suggest that LDL uptake by the lung takes place by both receptor-mediated and receptor-independent mechanisms. Cholesterol may be in part transferred to the lung without the apoprotein moiety; the alveolar capillary endothelium appears to be the first monitor of this complex process

Hyperglycemia and Diabetes Downregulate the Functional Expression of TRPV4 Channels in Retinal Microvascular Endothelium

Science.gov (United States)

Monaghan, Kevin; McNaughten, Jennifer; McGahon, Mary K.; Kelly, Catriona; Kyle, Daniel; Yong, Phaik Har

2015-01-01

Retinal endothelial cell dysfunction is believed to play a key role in the etiology and pathogenesis of diabetic retinopathy. Numerous studies have shown that TRPV4 channels are critically involved in maintaining normal endothelial cell function. In the current paper, we demonstrate that TRPV4 is functionally expressed in the endothelium of the retinal microcirculation and that both channel expression and activity is downregulated by hyperglycaemia. Quantitative PCR and immunostaining demonstrated molecular expression of TRPV4 in cultured bovine retinal microvascular endothelial cells (RMECs). Functional TRPV4 activity was assessed in cultured RMECs from endothelial Ca2+-responses recorded using fura-2 microfluorimetry and electrophysiological recordings of membrane currents. The TRPV4 agonist 4α-phorbol 12,13-didecanoate (4-αPDD) increased [Ca2+]i in RMECs and this response was largely abolished using siRNA targeted against TRPV4. These Ca2+-signals were completely inhibited by removal of extracellular Ca2+, confirming their dependence on influx of extracellular Ca2+. The 4-αPDD Ca2+-response recorded in the presence of cyclopiazonic acid (CPA), which depletes the intracellular stores preventing any signal amplification through store release, was used as a measure of Ca2+-influx across the cell membrane. This response was blocked by HC067047, a TRPV4 antagonist. Under voltage clamp conditions, the TRPV4 agonist GSK1016790A stimulated a membrane current, which was again inhibited by HC067047. Following incubation with 25mM D-glucose TRPV4 expression was reduced in comparison with RMECs cultured under control conditions, as were 4αPDD-induced Ca2+-responses in the presence of CPA and ion currents evoked by GSK1016790A. Molecular expression of TRPV4 in the retinal vascular endothelium of 3 months’ streptozotocin-induced diabetic rats was also reduced in comparison with that in age-matched controls. We conclude that hyperglycaemia and diabetes reduce the

Presence of plasma proteins facilitates the uptake of 125I-thrombin by the rabbit thoracic aorta endothelium in vitro

International Nuclear Information System (INIS)

Hatton, M.W.; Moar, S.L.

1986-01-01

Various purified proteins, protein derivatives and two polysaccharides were added individually to a physiological medium in order to effect uptake of 125 I-thrombin by the rabbit aorta endothelium. Over a wide range of concentration (0.004-40 mg/ml), the presence of either purified rabbit or bovine albumin during thrombin uptake encouraged an increase (70-110%) in 125 I-thrombin binding by the endothelium and subendothelium compared to uptake by aorta segments in the absence of added protein. Pretreatment of aorta segments with albumin before incubation with 125 I-thrombin in the absence of albumin did not encourage thrombin uptake to the same extent as having 125 I-thrombin and albumin together. Purified human transferrin, rabbit IgG, chicken ovalbumin or denatured bovine casein could replace albumin to produce a similar enhancement of thrombin uptake. Replacing active concentrations of albumin by either reduced-carboxymethylated albumin, defatted albumin, plasmin-treated or thermolysin-treated albumin also caused an increase (50-130%) in thrombin binding, whereas replacement by acid-hydrolysed albumin or with polyglutamic acid was either ineffective or even inhibitory. Lysine-modified or arginine-modified albumins caused a small enhancement (14-32%) and no enhancement of thrombin uptake, respectively. Dextran, at low concentration (0.04-0.4 mg/ml) did not influence thrombin uptake, and at higher concentration (4-40 mg/ml) caused a decrease in uptake by both the endothelium and subendothelial layers. Low concentration of dextran sulphate inhibited thrombin uptake to 20-30% of control values. These data express the importance of accompanying protein in the response of the vascular endothelium during binding of thrombin. The possibility that other protein-cell interactions may be similarly influenced by macromolecular solutes is also discussed

Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

Science.gov (United States)

Chou, Chu-Lin; Pang, Cheng-Yoong; Lee, Tony J F; Fang, Te-Chao

2015-01-01

Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose

Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

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Chu-Lin Chou

Full Text Available Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group. Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L. These results suggest a protective role of calcitriol treatment on endothelial

Brain perfusion abnormalities associated to drug abuse in recent abstinent patients using SPECT 99m Tc-ethylen-cysteinate-dimer (ECD)

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Massardo, Teresa [University of Chile Clinical Hospital Nuclear Medicine Section, Department of Medicine, Santiago (Chile); Pallavicini, Julio [Addiction Unit, Psychiatric Clinic. University of Chile Clinical Hospital (Chile); Gonzalez, Patricio; Jaimovich, Rodrigo [University of Chile Clinical Hospital Nuclear Medicine Section, Department of Medicine, Santiago (Chile); Servat, Monica [Addiction Unit, Psychiatric Clinic. University of Chile Clinical Hospital (Chile); Lavados, Hugo [University of Chile Clinical Hospital Nuclear Medicine Section, Department of Medicine, Santiago (Chile); Arancibia, Pablo [Addiction Unit, Psychiatric Clinic. University of Chile Clinical Hospital (Chile); Padilla, Pamela [University of Chile Clinical Hospital Nuclear Medicine Section, Department of Medicine, Santiago (Chile)

2009-04-15

Several substances may produce brain perfusion abnormalities in drug-dependent patients. Their mechanism is unclear and several causes might be involved, especially vasospasm in cocaine consumption. Goal: To characterize residual brain perfusion abnormalities in substance-dependent population. We analyzed brain perfusion in 100 dependant patients (DSM-IV criteria) following a month of strict in-hospital abstinence (age:35{+-}12 y.o.; 86% men); 55% corresponded to poly-drug dependents, mainly to cocaine, alcohol and cannabis; 44% mono-drug users, mostly to alcohol. Results: Single Photon Emission Computed Tomography (SPECT) with 99mTc-ethylen-cysteinate-dimer (ECD) was abnormal in 54% of the cases, with bilateral cortical hypo-perfusion in 89%, focal in 54% and diffuse in 46% of them, with moderate or severe intensity in 61%. The abnormal perfusion group's age was 38{+-}12 versus 31{+-}10 years in the normal SPECT group (P=0.005) with a consumption period of 16{+-}11 versus 11{+-}8 years, respectively (P=0.043). Only 29% of women had abnormal perfusion versus 58% of men (P=0.047). Abnormal brain perfusion in 64% of mono and 45% in poly-drug dependents (P=0.07). Psychometric tests performed in 25 patients demonstrated association between perfusion defects and cognitive abnormalities. Relative risk for abnormal psychometric test was 2.5 [95%;CI=1.1-5.6] for abnormal SPECT. Conclusion: Dependent population after a month of abstinence persists with cortical brain perfusion abnormalities, associated to age, sex and type of drug consumption.

Comparison of the effects of intraocular irrigating solutions on the corneal endothelium in intraocular lens implantation.

Science.gov (United States)

Matsuda, M; Kinoshita, S; Ohashi, Y; Shimomura, Y; Ohguro, N; Okamoto, H; Omoto, T; Hosotani, H; Yoshida, H

1991-01-01

We conducted a randomised prospective controlled study to determine the effects of a glucose glutathione bicarbonate solution (BSS Plus) and a citrate acetate bicarbonate solution (S-MA2) on the corneal endothelium in patients undergoing extracapsular cataract extraction with posterior chamber lens implantation. One eye of each patient was randomly assigned to receive BSS Plus, and the other eye to receive S-MA2. BSS Plus caused significantly less corneal swelling on the first postoperative day than did S-MA2. There was no difference between the two solutions in their effect on corneal thickness one week and one month postoperatively. Computer assisted morphometric analysis of wide-field specular microscopic photographs demonstrated minimal changes in endothelial morphological characteristics in the eyes irrigated with BSS Plus. By comparison S-MA2, caused a significant loss of endothelial cells and a marked reduction in the figure coefficient. These results indicated that BSS Plus has a clinical advantage over S-MA2 with respect to the corneal endothelium. PMID:1873266

Proton nuclear magnetic resonance study on the barrier function of pig corneal epithelium and endothelium

International Nuclear Information System (INIS)

Yokoi, Norihiko; Kinoshita, Shigeru; Morimoto, Taketoshi; Yoshizaki, Kazuo.

1995-01-01

Using gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) as a tracer, the barrier function of the corneal epithelium and endothelium was evaluated by proton nuclear magnetic resonance. Whole pig eyes and cornea excised with scleral rim, which had been incubated in dextran-added Gd-DTPA solution, were subjected to T 1 relaxation measurement and magnetic resonance imaging (MRI). After incubation, the T 1 relaxation rate (1/T 1 ) of the excised cornea increased to a steady value, whereas that of the cornea from the whole eye increased only slightly. These results indicated that the increase in the T 1 relaxation rate of the excised cornea was attributable to Gd-DTPA penetration from the corneal endothelium and that the corneal epithelium exhibited a strong barrier function against Gd-DTPA entry. The MRI study also confirmed the strong barrier, enhanced signals being detected within the aqueous fluid in the T 1 -weighted image only when the corneal epithelium was abraded. Since Gd-DTPA scarcely penetrates the intact corneal epithelium, Gd-DTPA-enhanced MRI shows potential as a quantitative tracer in evaluating epithelial barrier disruption. (author)

[The effects of intraocular irrigating solutions on the human corneal endothelium (author's transl)].

Science.gov (United States)

Weekers, J F; Dethinne, M

1978-11-01

Human corneas from enucleated eyes get thicker during perfusion with B.S.S. On the contrary, their thickness decreases when perfused with T.C. Earle solution. Addition of reduced glutathion and adenosine does not change the results obtained with T.C. Earle. Histological study of the endothelium after a 24 hours perfusion demonstrates a better conservation of the cells with T.C. Earle and T.C. Earle glutathion--adenosine than with B.S.S.

Critical Endothelial Regulation by LRP5 during Retinal Vascular Development

Science.gov (United States)

Huang, Wei; Li, Qing; Amiry-Moghaddam, Mahmood; Hokama, Madoka; Sardi, Sylvia H.; Nagao, Masashi; Warman, Matthew L.; Olsen, Bjorn R.

2016-01-01

Vascular abnormalities in the eye are the leading cause of many forms of inherited and acquired human blindness. Loss-of-function mutations in the Wnt-binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The canonical Wnt-β-catenin pathway is known to regulate retinal vascular development. However, it is unclear what precise role LPR5 plays in this process. Here, we show that loss of LRP5 function in mice causes retinal hypovascularization during development as well as retinal neovascularization in adulthood with disorganized and leaky vessels. Using a highly specific Flk1-CreBreier line for vascular endothelial cells, together with several genetic models, we demonstrate that loss of endothelium-derived LRP5 recapitulates the retinal vascular defects in Lrp5-/- mice. In addition, restoring LRP5 function only in endothelial cells in Lrp5-/- mice rescues their retinal vascular abnormalities. Furthermore, we show that retinal vascularization is regulated by LRP5 in a dosage dependent manner and does not depend on LRP6. Our study provides the first direct evidence that endothelium-derived LRP5 is both necessary and sufficient to mediate its critical role in the development and maintenance of retinal vasculature. PMID:27031698

Abnormal Event Detection in Wireless Sensor Networks Based on Multiattribute Correlation

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Mengdi Wang

2017-01-01

Full Text Available Abnormal event detection is one of the vital tasks in wireless sensor networks. However, the faults of nodes and the poor deployment environment have brought great challenges to abnormal event detection. In a typical event detection technique, spatiotemporal correlations are collected to detect an event, which is susceptible to noises and errors. To improve the quality of detection results, we propose a novel approach for abnormal event detection in wireless sensor networks. This approach considers not only spatiotemporal correlations but also the correlations among observed attributes. A dependency model of observed attributes is constructed based on Bayesian network. In this model, the dependency structure of observed attributes is obtained by structure learning, and the conditional probability table of each node is calculated by parameter learning. We propose a new concept named attribute correlation confidence to evaluate the fitting degree between the sensor reading and the abnormal event pattern. On the basis of time correlation detection and space correlation detection, the abnormal events are identified. Experimental results show that the proposed algorithm can reduce the impact of interference factors and the rate of the false alarm effectively; it can also improve the accuracy of event detection.

Extracellular Calcium-Dependent Modulation of Endothelium Relaxation in Rat Mesenteric Small Artery

DEFF Research Database (Denmark)

Hangaard, Lise; Jessen, Peter B; Kamaev, Dmitrii

2015-01-01

The nature of NO- and COX-independent endothelial hyperpolarization (EDH) is not fully understood but activation of small- and intermittent-conductance Ca(2+)-activated K(+) channels (SKCa and IKCa) is important. Previous studies have suggested that the significance of IKCa depends on [Ca(2+)]out...

Phototoxic effects of 8-methoxypsoralen on rabbit corneal endothelium

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Menon, I.A.; Basu, P.K.; Hasany, S.M.; Persad, S.D. (Univ. of Toronto, Ontario (Canada))

1989-01-01

The phototoxic effects of 8-methoxypsoralen (8-MOP) were investigated using the rabbit corneal endothelium in organ culture. The corneas were divided into four groups: (a) irradiated with a mercury vapor lamp (emitting UVA and visible radiation) in the presence of 8-MOP (experimental), (b) irradiated without 8-MOP (control A), (c) incubated with 8-MOP (control B) and (d) incubated without 8-MOP (control C). Specular and light microscopic examination showed that the experimental corneas had greater cellular damage compared to the control corneas. The effects of 8-MOP were restricted to certain localized areas of the cornea. However there was no significant difference in the amounts of 51Cr released from the labelled experimental and control corneas. These results show phototoxic damage of the corneal endothelial cells.

EDRF [endothelium-derived relaxing factor]-release and Ca++-channel blockage by Magnolol, an antiplatelet agent isolated from Chinese herb Magnolia officinalis, in rat thoracic aorta

International Nuclear Information System (INIS)

Teng, Cheming; Yu, Sheumeei; Chen, Chienchih; Huang, Yulin; Huang, Turfu

1990-01-01

Magnolol is an antiplatelet agent isolated from Chinese herb Magnolia officinalis. It inhibited norepinephrine-induced phasic and tonic contractions in rat thoracic aorta. At the plateau of the NE-induced tonic contraction, addition of magnolol caused two phases (fast and slow) of relaxation. These two relaxations were concentration-dependent, and were not inhibited by indomethacin. The fast relaxation was completely antagonized by hemoglobin and methylene blue, and disappeared in de-endothelialized aorta while the slow relaxation was not affected by the above treatments. Magnolol also inhibited high potassium-induced, calcium-dependent contraction of rat aorta in a concentration-dependent manner. 45 Ca ++ influx induced by high potassium or NE was markedly inhibited by magnolol. Cyclic GMP, but not PGI 2 , was increased by magnolol in intact, but not in de-endothelialized aorta. It is concluded that magnolol relaxed vascular smooth muscle by releasing endothelium-derived relaxing factor (EDRF) and by inhibiting calcium influx through voltage-gated calcium channels

[Binding studies with Ulex europaeus agglutinin I (UEA-I) of the vascular endothelium of the synovial membrane].

Science.gov (United States)

Zschäbitz, A; Stofft, E

1988-01-01

The lectin binding sites of the synovium of patients with rheumatoid arthritis and osteoarthritis were investigated. It was shown that Ulex europaeus agglutinin is a constant marker of the vascular endothelium and is not induced during the course of inflammatory process in rheumatoid arthritis.

Sarpogrelate hydrochloride, a selective 5-hydroxytryptamine(2A) antagonist, augments autologous bone marrow mononuclear cell implantation-induced improvement in endothelium-dependent vasodilation in patients with critical limb ischemia.

Science.gov (United States)

Higashi, Yukihito; Miyazaki, Masanori; Goto, Chikara; Sanada, Hiroaki; Sueda, Taijiro; Chayama, Kazuaki

2010-01-01

The purpose of this study was to determine the effect of a combination of bone marrow mononuclear cell (BM-MNC) implantation and sarpogrelate, a selective 5-HT(2A) antagonist, on endothelial function in patients with critical limb ischemia (CLI). We evaluated the leg blood flow (LBF) responses to acetylcholine (ACh) and sodium nitroprusside before and after BM-MNC implantation in 16 patients with CLI. We divided patients with CLI into 2 groups: those cotreated with sarpogrelate orally for 12 weeks (sarpogrelate group, n = 8) and those who remained on conventional therapy (control group, n = 8). LBF was measured by strain gauge plethysmography. BM-MNC implantation improved ankle brachial pressure index, transcutaneous oxygen pressure, and pain-free walking time. There was no significant difference in these parameters between the 2 groups. Before BM-MNC implantation, LBF responses to ACh were similar in the sarpogrelate group and control group. Twelve weeks of BM-MNC implantation enhanced LBF responses to ACh in the sarpogrelate and control groups. After 12 weeks of BM-MNC implantation, LBF response to ACh was significantly greater in the sarpogrelate group than in the control group. BM-MNC implantation did not alter the LBF responses to sodium nitroprusside in either group. These findings suggest that BM-MNC implantation improved not only limb ischemic symptoms but also endothelium-dependent vasodilation in patients with CLI. A combination of BM-MNC implantation and sarpogrelate had a more beneficial effect on vascular function in these patients.

Ca²⁺-dependent nitric oxide release in the injured endothelium of excised rat aorta: a promising mechanism applying in vascular prosthetic devices in aging patients.

Science.gov (United States)

Berra-Romani, Roberto; Avelino-Cruz, José Everardo; Raqeeb, Abdul; Della Corte, Alessandro; Cinelli, Mariapia; Montagnani, Stefania; Guerra, Germano; Moccia, Francesco; Tanzi, Franco

2013-01-01

Nitric oxide is key to endothelial regeneration, but it is still unknown whether endothelial cell (EC) loss results in an increase in NO levels at the wound edge. We have already shown that endothelial damage induces a long-lasting Ca²⁺ entry into surviving cells though connexin hemichannels (CxHcs) uncoupled from their counterparts on ruptured cells. The physiological outcome of injury-induced Ca²⁺ inflow is, however, unknown. In this study, we sought to determine whether and how endothelial scraping induces NO production (NOP) in the endothelium of excised rat aorta by exploiting the NO-sensitive fluorochrome, DAF-FM diacetate and the Ca²⁺-sensitive fluorescent dye, Fura-2/AM. We demonstrated that injury-induced NOP at the lesion site is prevented in presence of the endothelial NO synthase inhibitor, L-NAME, and in absence of extracellular Ca²⁺. Unlike ATP-dependent NO liberation, the NO response to injury is insensitive to BTP-2, which selectively blocks store-operated Ca²⁺ inflow. However, injury-induced NOP is significantly reduced by classic gap junction blockers, and by connexin mimetic peptides specifically targeting Cx37Hcs, Cx40HCs, and Cx43Hcs. Moreover, disruption of caveolar integrity prevents injury-elicited NO signaling, but not the accompanying Ca²⁺ response. The data presented provide the first evidence that endothelial scraping stimulates NO synthesis at the wound edge, which might both exert an immediate anti-thrombotic and anti-inflammatory action and promote the subsequent re-endothelialization.

The partitioning of nanoparticles to endothelium or interstitium during ultrasound-microbubble-targeted delivery depends on peak-negative pressure

Energy Technology Data Exchange (ETDEWEB)

Hsiang, Y.-H.; Song, J.; Price, R. J., E-mail: rprice@virginia.edu [University of Virginia, Department of Biomedical Engineering (United States)

2015-08-15

Patients diagnosed with advanced peripheral arterial disease often face poor prognoses and have limited treatment options. For some patient populations, the therapeutic growth of collateral arteries (i.e. arteriogenesis) that bypass regions affected by vascular disease may become a viable treatment option. Our group and others are developing therapeutic approaches centered on the ability of ultrasound-activated microbubbles to permeabilize skeletal muscle capillaries and facilitate the targeted delivery of pro-arteriogenic growth factor-bearing nanoparticles. The development of such approaches would benefit significantly from a better understanding of how nanoparticle diameter and ultrasound peak-negative pressure affect both total nanoparticle delivery and the partitioning of nanoparticles to endothelial or interstitial compartments. Toward this goal, using Balb/C mice that had undergone unilateral femoral artery ligation, we intra-arterially co-injected nanoparticles (50 and 100 nm) with microbubbles, applied 1 MHz ultrasound to the gracilis adductor muscle at peak-negative pressures of 0.7, 0.55, 0.4, and 0.2 MPa, and analyzed nanoparticle delivery and distribution. As expected, total nanoparticle (50 and 100 nm) delivery increased with increasing peak-negative pressure, with 50 nm nanoparticles exhibiting greater tissue coverage than 100 nm nanoparticles. Of particular interest, increasing peak-negative pressure resulted in increased delivery to the interstitium for both nanoparticle sizes, but had little influence on nanoparticle delivery to the endothelium. Thus, we conclude that alterations to peak-negative pressure may be used to adjust the fraction of nanoparticles delivered to the interstitial compartment. This information will be useful when designing ultrasound protocols for delivering pro-arteriogenic nanoparticles to skeletal muscle.

The partitioning of nanoparticles to endothelium or interstitium during ultrasound-microbubble-targeted delivery depends on peak-negative pressure

International Nuclear Information System (INIS)

Hsiang, Y.-H.; Song, J.; Price, R. J.

2015-01-01

Patients diagnosed with advanced peripheral arterial disease often face poor prognoses and have limited treatment options. For some patient populations, the therapeutic growth of collateral arteries (i.e. arteriogenesis) that bypass regions affected by vascular disease may become a viable treatment option. Our group and others are developing therapeutic approaches centered on the ability of ultrasound-activated microbubbles to permeabilize skeletal muscle capillaries and facilitate the targeted delivery of pro-arteriogenic growth factor-bearing nanoparticles. The development of such approaches would benefit significantly from a better understanding of how nanoparticle diameter and ultrasound peak-negative pressure affect both total nanoparticle delivery and the partitioning of nanoparticles to endothelial or interstitial compartments. Toward this goal, using Balb/C mice that had undergone unilateral femoral artery ligation, we intra-arterially co-injected nanoparticles (50 and 100 nm) with microbubbles, applied 1 MHz ultrasound to the gracilis adductor muscle at peak-negative pressures of 0.7, 0.55, 0.4, and 0.2 MPa, and analyzed nanoparticle delivery and distribution. As expected, total nanoparticle (50 and 100 nm) delivery increased with increasing peak-negative pressure, with 50 nm nanoparticles exhibiting greater tissue coverage than 100 nm nanoparticles. Of particular interest, increasing peak-negative pressure resulted in increased delivery to the interstitium for both nanoparticle sizes, but had little influence on nanoparticle delivery to the endothelium. Thus, we conclude that alterations to peak-negative pressure may be used to adjust the fraction of nanoparticles delivered to the interstitial compartment. This information will be useful when designing ultrasound protocols for delivering pro-arteriogenic nanoparticles to skeletal muscle

Conservative treatment of bone tissue metabolic disorders among patients with vitamin D-dependent rickets type II with genetic abnormality of type I collagen formation

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S.M. Martsyniak

2017-08-01

Full Text Available Background. The purpose of the article is to determine the effect of conservative therapy on genetically caused disorders of bone tissue metabolism in patients with vitamin D-dependent rickets type II and genetic abnormality of type I collagen formation (VDDR(COL1. Materials and methods. At the premises of consulting and outpatient department of SI “Institute of Traumatology and Orthopaedics of the NAMS of Ukraine”, 13 patients having VDDR type II and genetic damage of type I collagen formation were examined and treated. The medical treatment was conducted in four stages. The first stage included full examination of patients (calcium and phosphorus levels in the blood serum and their urinary excretion, as well as determination of calcidiol and calcitriol serum levels, indicators of parathyroid hormone and osteocalcin, and a marker of bone formation P1NP and osteoresorption b-CTx. At this stage, children were obligated to undergo a genetic test to detect changes (polymorphism in alleles of receptors to vitamin D and type I collagen. Besides genetic tests, examinations at the other stages were conducted in full. Results. The study has shown the following. The genetically caused abnormality of reception to vitamin D results into substantial accumulation of vitamin D active metabolite in the blood serum. When combined with gene­tic abnormality of type I collagen formation, it significantly affected bone formation and destruction processes that causes development of osteomalacia (parathormone — vitamin D — osteocalcin system. The comprehensive study of vitamin D metabolism and biochemical vitals of bone tissue in patients having VDDR (COL1 brought us to understanding of some issues related to pathogenesis and nature of osteomalacia and, in future, osteoporotic changes on different levels, ensured us to express these changes by corresponding indices in the biochemical research and, finally, to develop appropriate schemes for the treatment of

Photoreactivation of developmental abnormality in sea urchin embryos induced by UV-irradiated sperm

International Nuclear Information System (INIS)

Ejima, Yosuke; Shiroya, Tuguo.

1980-01-01

The effects of UV-irradiation of sperm on the embryonic development of sea urchins (H. pulcherrimus, Anthocidaris crassispina, Pseudocentrotus depressus, and C. japonicus) were studied. Eggs inseminated with UV-irradiated sperm developed almost normally into blastulae without arrest of cleavage or hatching, even though they showed some division delay. Morphogenesis was disturbed in and after the gastrula stage, and the formation of normal pluteus larvae was inhibited depending on the UV dose (5 - 30 J/m 2 ) given to the sperm. Morphological abnormalities observed were as follows: inhibition of gastrulation; abnormal delamination and random arrangement of primary mesenchymal cells onto the ectodermal wall; abnormal localization or an excess number of spicules; malformed skeletons. These developmental abnormalities were photoreactivated with high efficiency. Inhibition of pluteus formation to less than 5% by the UV-irradiation with 20 J/m 2 completely recovered under fluorescent light illumination with 10 klux. By treating the eggs with brief illumination at various times after insemination, a stage-dependent change of the photoreactivation (PR) efficiency was found. PR treatment after the insemination up to the onset of the first DNA synthesizing phase was highly effective for the recovery, while the PR efficiency began to decrease during the S phase, becoming zero on and after the end of the phase. In eggs fertilized with UV-irradiated sperm, mitoses were abnormal and shromosomal bridges were formed at the anaphase of the first mitosis. Their frequency increased depending on the UV dose. The mitotic abnormality was also photoreactivated with visible light treatment after fertilization. The change in PR efficiency of the illumination was very similar to that of morphological abnormality. (Author)

Platelets are required for enhanced activation of the endothelium and fibrinogen in a mouse thrombosis model of APS.

Science.gov (United States)

Proulle, Valerie; Furie, Richard A; Merrill-Skoloff, Glenn; Furie, Barbara C; Furie, Bruce

2014-07-24

Antiphospholipid syndrome (APS) is defined by thrombosis, fetal loss, and the presence of antiphospholipid antibodies, including anti-β2-glycoprotein-1 autoantibodies (anti-β2GP1) that have a direct role in the pathogenesis of thrombosis in vivo. The cellular targets of the anti-β2GP1 autoantibody/β2GP1 complex in vivo were studied using a laser-induced thrombosis model of APS in a live mouse and human anti-β2GP1 autoantibodies affinity-purified from APS patients. Cell binding of fluorescently labeled β2GP1 and anti-β2GP1 autoantibodies revealed their colocalization on the platelet thrombus but not the endothelium. Anti-β2GP1 autoantibodies enhanced platelet activation, monitored by calcium mobilization, and endothelial activation, monitored by intercellular adhesion molecule-1 expression. When eptifibatide was infused to block platelet thrombus formation, enhanced fibrin generation and endothelial cell activation were eliminated. Thus, the anti-β2GP1 autoantibody/β2GP1 complex binds to the thrombus, enhancing platelet activation, and platelet secretion leads to enhanced endothelium activation and fibrin generation. These results lead to a paradigm shift away from the concept that binding of the anti-β2GP1 autoantibody/β2GP1 complex activates both endothelial cells and platelets toward one in which activation of platelets in response to anti-β2GP1 autoantibody/β2GP1 complex binding leads to subsequent enhanced endothelium activation and fibrin generation. © 2014 by The American Society of Hematology.

Lung volumes and emphysema in smokers with interstitial lung abnormalities.

Science.gov (United States)

Washko, George R; Hunninghake, Gary M; Fernandez, Isis E; Nishino, Mizuki; Okajima, Yuka; Yamashiro, Tsuneo; Ross, James C; Estépar, Raúl San José; Lynch, David A; Brehm, John M; Andriole, Katherine P; Diaz, Alejandro A; Khorasani, Ramin; D'Aco, Katherine; Sciurba, Frank C; Silverman, Edwin K; Hatabu, Hiroto; Rosas, Ivan O

2011-03-10

Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; Ppulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation; ClinicalTrials.gov number, NCT00608764.).

Analysis of biological characteristics of corneal endothelium in old patients with high myopia

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Ya-Qiong Chen

2014-11-01

Full Text Available AIM: To analyze quantitatively the biological characteristics of corneal endothelium in old patients of high myopia with non-contact automatic corneal endothelial microscope.METHODS:A total of 189 old patients(197 eyeswere divided into the high myopia group and the normal control group according to refractive diopter, in which the former 98 cases(103 eyes, the latter 91 cases(94 eyes. The hexagonal cell(6A, the coefficient of variation(CV, the average cell area(AVE, the average cell density(CDand the central corneal thickness(CCTwere measured by non-contact automatic corneal endothelium. SPSS 14.0 software was used to analyze their percentage. Z-test was used to compare the mean and Chi-square test was used to compare the rate in between. RESULTS: The average cell density in high myopia patients decreased, but there were 14 eyes >3 000/mm2, 11 eyes 2 and 78 eyes in the 2 000～3 000/mm2, there were each 0 eye, 3 eyes and 91 eyes respectively in the normal control group. There was statistically significant difference between high myopia group and control(χ2=19.11, PPP>0.05. CONCLUSION: There will provide a reference valuable for clinical surgeon. Because according to the changes of parameters and morphology of the corneal endothelial cells, we can understand the repair ability, to predict the consequence of the treatment, in order to determine the design and the choice of a surgical.

[Nutritional abnormalities in chronic obstructive pulmonary disease].

Science.gov (United States)

Gea, Joaquim; Martínez-Llorens, Juana; Barreiro, Esther

2014-07-22

Nutritional abnormalities are associated with chronic obstructive pulmonary disease with a frequency ranging from 2 to 50%, depending on the geographical area and the study design. Diagnostic tools include anthropometry, bioelectrical impedance, dual energy radioabsortiometry and deuterium dilution, being the body mass and the lean mass indices the most frequently used parameters. While the most important consequences of nutritional abnormalities are muscle dysfunction and exercise limitation, factors implicated include an imbalance between caloric intake and consumption, and between anabolic and catabolic hormones, inflammation, tobacco smoking, poor physical activity, hypoxemia, some drugs and aging/comorbidities. The most important molecular mechanism for malnutrition associated with chronic obstructive pulmonary disease appears to be the mismatching between protein synthesis and breakdown. Among the therapeutic measures proposed for these nutritional abnormalities are improvements in lifestyle and nutritional support, although the use of anabolic drugs (such as secretagogues of the growth hormone) offers a new therapeutic strategy. Copyright © 2013 Elsevier España, S.L. All rights reserved.

The diversity of abnormal hormone receptors in adrenal Cushing's syndrome allows novel pharmacological therapies

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Lacroix A.

2000-01-01

Full Text Available Recent studies from several groups have indicated that abnormal or ectopic expression and function of adrenal receptors for various hormones may regulate cortisol production in ACTH-independent hypercortisolism. Gastric inhibitory polypeptide (GIP-dependent Cushing's syndrome has been described in patients with either unilateral adenoma or bilateral macronodular adrenal hyperplasia; this syndrome results from the large adrenal overexpression of the GIP receptor without any activating mutation. We have conducted a systematic in vivo evaluation of patients with adrenal Cushing's syndrome in order to identify the presence of abnormal hormone receptors. In macronodular adrenal hyperplasia, we have identified, in addition to GIP-dependent Cushing's syndrome, other patients in whom cortisol production was regulated abnormally by vasopressin, ß-adrenergic receptor agonists, hCG/LH, or serotonin 5HT-4 receptor agonists. In patients with unilateral adrenal adenoma, the abnormal expression or function of GIP or vasopressin receptor has been found, but the presence of ectopic or abnormal hormone receptors appears to be less prevalent than in macronodular adrenal hyperplasia. The identification of the presence of an abnormal adrenal receptor offers the possibility of a new pharmacological approach to control hypercortisolism by suppressing the endogenous ligands or by using specific antagonists for the abnormal receptors.

A Combined Impedance and AlphaLISA-Based Approach to Identify Anti-inflammatory and Barrier-Protective Compounds ion Human Endothelium

Czech Academy of Sciences Publication Activity Database

Pfluger, M.; Kapuscik, Alexandra; Lucas, R.; Koppensteiner, A.; Katzlinger, M.; Jokela, J.; Eger, A.; Jacobi, N.; Wiesner, Ch.; Hofmann, E.; Önder, K.; Kopecký, Jiří; Schütt, W.; Hundsberger, H.

2014-01-01

Roč. 18, č. 1 (2014), s. 67-74 ISSN 1087-0571 Grant - others:Oesterreichische Forschungsforderungsgesellschaft(AT) FFG 821021, 822710 Institutional support: RVO:61388971 Keywords : impendance * anti-inflammatory * human endothelium Subject RIV: EE - Microbiology, Virology Impact factor: 2.423, year: 2014

GABAergic influences on ORX receptor-dependent abnormal motor behaviors and neurodegenerative events in fish

International Nuclear Information System (INIS)

Facciolo, Rosa Maria; Crudo, Michele; Giusi, Giuseppina; Canonaco, Marcello

2010-01-01

At date the major neuroreceptors i.e. γ-aminobutyric acid A (GABA A R) and orexin (ORXR) systems are beginning to be linked to homeostasis, neuroendocrine and emotional states. In this study, intraperitoneal treatment of the marine teleost Thalassoma pavo with the highly selective GABA A R agonist (muscimol, MUS; 0,1 μg/g body weight) and/or its antagonist bicuculline (BIC; 1 μg/g body weight) have corroborated a GABA A ergic role on motor behaviors. In particular, MUS induced moderate (p A R was very likely responsible for very strong and strong ORXR mRNA reductions in cerebellum valvula and torus longitudinalis, respectively. Moreover these effects were linked to evident ultra-structural changes such as shrunken cell membranes and loss of cytoplasmic architecture. In contrast, MUS supplied a very low, if any, argyrophilic reaction in hypothalamic and mesencephalic regions plus a scarce level of ultra-structural damages. Interestingly, combined administrations of MUS + BIC were not related to consistent damages, aside mild neuronal alterations in motor-related areas such as optic tectum. Overall it is tempting to suggest, for the first time, a neuroprotective role of GABA A R inhibitory actions against the overexcitatory ORXR-dependent neurodegeneration and consequently abnormal swimming events in fish.

Naltrexone ameliorates functional network abnormalities in alcohol‐dependent individuals

Science.gov (United States)

Baek, Kwangyeol; Tait, Roger; Elliott, Rebecca; Ersche, Karen D.; Flechais, Remy; McGonigle, John; Murphy, Anna; Nestor, Liam J.; Orban, Csaba; Passetti, Filippo; Paterson, Louise M.; Rabiner, Ilan; Reed, Laurence; Smith, Dana; Suckling, John; Taylor, Eleanor M.; Bullmore, Edward T.; Lingford‐Hughes, Anne R.; Deakin, Bill; Nutt, David J.; Sahakian, Barbara J.; Robbins, Trevor W.; Voon, Valerie

2017-01-01

Abstract Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50‐mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly‐drug‐dependent individuals compared with 36 healthy volunteers. Graph theoretic and network‐based statistical analysis of resting‐state functional magnetic resonance imaging (MRI) data revealed that alcohol‐dependent subjects had reduced functional connectivity of a dispersed network compared with both poly‐drug‐dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol‐dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly‐substance‐dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology. PMID:28247526

Interphase death and repair of radiation injuries to thoracic aorta endothelium of mammals

International Nuclear Information System (INIS)

Shcherbova, E.N.; Ivanov, Yu.V.

1978-01-01

Using the method of plane preparations injury to the thoracic aorta endothelium of guinea-pigs, rats and rabbits exposed to various doses of γ-rays ( 60 Co) has been studied. The value of the threshold dose, tested by diminution of the endothelial cell quantity, has been found to be 250 R for guinea-pigs, 830 R, for rats and 880 R, for rabbits. It has been shown by means of the fractionated irradiation model that the interphase endothelial cells of guinea-pigs and rats can recover from sublethal radiation injuries

Binocular combination in abnormal binocular vision.

Science.gov (United States)

Ding, Jian; Klein, Stanley A; Levi, Dennis M

2013-02-08

We investigated suprathreshold binocular combination in humans with abnormal binocular visual experience early in life. In the first experiment we presented the two eyes with equal but opposite phase shifted sine waves and measured the perceived phase of the cyclopean sine wave. Normal observers have balanced vision between the two eyes when the two eyes' images have equal contrast (i.e., both eyes contribute equally to the perceived image and perceived phase = 0°). However, in observers with strabismus and/or amblyopia, balanced vision requires a higher contrast image in the nondominant eye (NDE) than the dominant eye (DE). This asymmetry between the two eyes is larger than predicted from the contrast sensitivities or monocular perceived contrast of the two eyes and is dependent on contrast and spatial frequency: more asymmetric with higher contrast and/or spatial frequency. Our results also revealed a surprising NDE-to-DE enhancement in some of our abnormal observers. This enhancement is not evident in normal vision because it is normally masked by interocular suppression. However, in these abnormal observers the NDE-to-DE suppression was weak or absent. In the second experiment, we used the identical stimuli to measure the perceived contrast of a cyclopean grating by matching the binocular combined contrast to a standard contrast presented to the DE. These measures provide strong constraints for model fitting. We found asymmetric interocular interactions in binocular contrast perception, which was dependent on both contrast and spatial frequency in the same way as in phase perception. By introducing asymmetric parameters to the modified Ding-Sperling model including interocular contrast gain enhancement, we succeeded in accounting for both binocular combined phase and contrast simultaneously. Adding binocular contrast gain control to the modified Ding-Sperling model enabled us to predict the results of dichoptic and binocular contrast discrimination experiments

Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

Science.gov (United States)

Fernald, Charles D.

1980-01-01

Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

The original Pathologische Anatomie Leiden-Endothelium monoclonal antibody recognizes a vascular endothelial growth factor binding site within neuropilin-1

NARCIS (Netherlands)

Jaalouk, Diana E.; Ozawa, Nfichael G.; Sun, Jessica; Lahdenranta, Johanna; Schlingemann, Reinier O.; Pasqualini, Renata; Arap, Wadih

2007-01-01

For two decades, the antigen recognized by the Pathologische Anatomie Leiden-Endothelium (PAL-E) monoclonal antibody, a standard vascular endothelial cell marker, has remained elusive. Here, we used a combinatorial phage display-based approach ("epitope mapping") to select peptides binding to the

Nanoscale abnormal grain growth in (001) epitaxial ceria

International Nuclear Information System (INIS)

Solovyov, Vyacheslav F.; Develos-Bagarinao, Katherine; Nykypanchuk, Dmytro

2009-01-01

X-ray reciprocal-space mapping and atomic force microscopy (AFM) are used to study kinetics and mechanisms of lateral grain growth in epitaxial (001) ceria (CeO 2 ) deposited by pulsed laser deposition on (001) yttria-stabilized zirconia (YSZ) and (12 lowbar 10) (r-cut) sapphire. Rate and character of the grain growth during postannealing at 1050 deg. C are found to be strongly dependent on the type of the epitaxial substrate. Films deposited on YSZ exhibit signatures of normal grain growth, which stagnated after the lateral grain size reaches 40 nm, consistent with the grain-boundary pinning by the thermal grooving. In contrast, when r-cut sapphire substrate was used, abnormal (secondary) grain growth is observed. A small population of grains grow to well over 100 nm consuming smaller, 100 nm large (001) terminations and rendering the sample single-crystalline quality. The grain growth is accompanied by reduction in lateral rms strain, resulting in a universal grain size--rms strain dependence. Analysis of the AFM and x-ray diffraction data leads to the conclusion that bimodal initial grain population consisting of grains with very different sizes is responsible for initiation of the abnormal growth in (001) CeO 2 films on r-cut sapphire. Due to different surface chemistry, when a YSZ substrate is used, the initial grain distribution is monomodal, therefore only normal growth is active. We demonstrate that a 2.2 deg. miscut of the sapphire substrate eliminates the large-grain population, thus suppressing abnormal grain growth. It is concluded that utilization of abnormal grain growth is a promising way for synthesis of large (001) ceria terminations.

Time Window Is Important for Adenosine Preventing Cold-induced Injury to the Endothelium.

Science.gov (United States)

Li, Yan; Hu, Xiao-Xia; Fu, Li; Chen, Jing; Lu, Li-He; Liu, Xiang; Xu, Zhe; Zhou, Li; Wang, Zhi-Ping; Zhang, Xi; Ou, Zhi-Jun; Ou, Jing-Song

2017-06-01

Cold cardioplegia is used to induce heart arrest during cardiac surgery. However, endothelial function may be compromised after this procedure. Accordingly, interventions such as adenosine, that mimic the effects of preconditioning, may minimize endothelial injury. Herein, we investigated whether adenosine prevents cold-induced injury to the endothelium. Cultured human cardiac microvascular endothelial cells were treated with adenosine for different durations. Phosphorylation and expression of endothelial nitric oxide synthase (eNOS), p38MAPK, ERK1/2, and p70S6K6 were measured along with nitric oxide (NO) production using diaminofluorescein-2 diacetate (DAF-2DA) probe. Cold-induced injury by hypothermia to 4°C for 45 minutes to mimic conditions of cold cardioplegia during open heart surgery was induced in human cardiac microvascular endothelial cells. Under basal conditions, adenosine stimulated NO production, eNOS phosphorylation at serine 1177 from 5 minutes to 4 hours and inhibited eNOS phosphorylation at threonine 495 from 5 minutes to 6 hours, but increased phosphorylation of ERK1/2, p38MAPK, and p70S6K only after exposure for 5 minutes. Cold-induced injury inhibited NO production and the phosphorylation of the different enzymes. Importantly, adenosine prevented these effects of hypothermic injury. Our data demonstrated that adenosine prevents hypothermic injury to the endothelium by activating ERK1/2, eNOS, p70S6K, and p38MAPK signaling pathways at early time points. These findings also indicated that 5 minutes after administration of adenosine or release of adenosine is an important time window for cardioprotection during cardiac surgery.

The pleiotropic effects of simvastatin on retinal microvascular endothelium has important implications for ischaemic retinopathies.

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Reinhold J Medina

Full Text Available BACKGROUND: Current guidelines encourage the use of statins to reduce the risk of cardiovascular disease in diabetic patients; however the impact of these drugs on diabetic retinopathy is not well defined. Moreover, pleiotropic effects of statins on the highly specialised retinal microvascular endothelium remain largely unknown. The objective of this study was to investigate the effects of clinically relevant concentrations of simvastatin on retinal endothelium in vitro and in vivo. METHODS AND FINDINGS: Retinal microvascular endothelial cells (RMECs were treated with 0.01-10 microM simvastatin and a biphasic dose-related response was observed. Low concentrations enhanced microvascular repair with 0.1 microM simvastatin significantly increasing proliferation (p<0.05, and 0.01 microM simvastatin significantly promoting migration (p<0.05, sprouting (p<0.001, and tubulogenesis (p<0.001. High concentration of simvastatin (10 microM had the opposite effect, significantly inhibiting proliferation (p<0.01, migration (p<0.01, sprouting (p<0.001, and tubulogenesis (p<0.05. Furthermore, simvastatin concentrations higher than 1 microM induced cell death. The mouse model of oxygen-induced retinopathy was used to investigate the possible effects of simvastatin treatment on ischaemic retinopathy. Low dose simvastatin (0.2 mg/Kg promoted retinal microvascular repair in response to ischaemia by promoting intra-retinal re-vascularisation (p<0.01. By contrast, high dose simvastatin(20 mg/Kg significantly prevented re-vascularisation (p<0.01 and concomitantly increased pathological neovascularisation (p<0.01. We also demonstrated that the pro-vascular repair mechanism of simvastatin involves VEGF stimulation, Akt phosphorylation, and nitric oxide production; and the anti-vascular repair mechanism is driven by marked intracellular cholesterol depletion and related disorganisation of key intracellular structures. CONCLUSIONS: A beneficial effect of low

Chronic exposure to high glucose impairs bradykinin-stimulated nitric oxide production by interfering with the phospholipase-C-implicated signalling pathway in endothelial cells: evidence for the involvement of protein kinase C.

Science.gov (United States)

Tang, Y; Li, G D

2004-12-01

Overwhelming evidence indicates that endothelial cell dysfunction in diabetes is characterised by diminished endothelium-dependent relaxation, but the matter of the underlying molecular mechanism remains unclear. As nitric oxide (NO) production from the endothelium is the major player in endothelium-mediated vascular relaxation, we investigated the effects of high glucose on NO production, and the possible alterations of signalling pathways implicated in this scenario. NO production and intracellular Ca(2+) levels ([Ca(2+)](i)) were assessed using the fluorescent probes 4,5-diaminofluorescein diacetate and fura-2 respectively. Exposure of cultured bovine aortic endothelial cells to high glucose for 5 or 10 days significantly reduced NO production induced by bradykinin (but not by Ca(2+) ionophore) in a time- and dose-dependent manner. This was probably due to an attenuation in bradykinin-induced elevations of [Ca(2+)](i) under these conditions, since a close correlation between [Ca(2+)](i) increases and NO generation was observed in intact bovine aortic endothelial cells. Both bradykinin-promoted intracellular Ca(2+) mobilisation and extracellular Ca(2+) entry were affected. Moreover, bradykinin-induced formation of Ins(1,4,5)P(3), a phospholipase C product leading to increases in [Ca(2+)](i), was also inhibited following high glucose culture. This abnormality was not attributable to a decrease in inositol phospholipids, but possibly to a reduction in the number of bradykinin receptors. The alterations in NO production, the increases in [Ca(2+)](i), and the bradykinin receptor number due to high glucose could be largely reversed by protein kinase C inhibitors and D: -alpha-tocopherol (antioxidant). Chronic exposure to high glucose reduces NO generation in endothelial cells, probably by impairing phospholipase-C-mediated Ca(2+) signalling due to excess protein kinase C activation. This defect in NO release may contribute to the diminished endothelium-dependent

Effect of diatrizoate (Angiografin) on the aortic endothelium in rats during the course of endotoxin shock

Energy Technology Data Exchange (ETDEWEB)

Gospos, C; Freudenberg, N; Hauenstein, K H; Kauffmann, G W; Koch, H K

1982-08-01

Investigations have been carried out on the endothelial changes produced by diatrizoate (Angiografin) during the course of endotoxin shock. A single injection was given directly into the aorta of 1 ml of the contrast medium, with an iodine content of 300 mg/ml. The increased proliferation of the aortic endothelium could be shown to be due to the endotoxin shock, but was not further increased by administration of the contrast medium.

Are premorbid abnormal personality traits associated with behavioural and psychological symptoms in dementia?

Science.gov (United States)

Prior, Jack; Abraham, Rajesh; Nicholas, Helen; Chan, Tom; Vanvlymen, Jeremy; Lovestone, Simon; Boothby, Harry

2016-09-01

The study aims to investigate associations between behavioural and psychological symptoms of dementia (BPSD) and abnormal premorbid personality traits. Data were obtained from 217 patients with a diagnosis of probable Alzheimer's disease. Behavioural and psychological symptoms of late-onset dementia were assessed with the Neuropsychiatric Inventory. Premorbid personality traits were assessed using the Standardised Assessment of Personality. Abnormal premorbid personality traits were categorised with Diagnostic and Statistical Manual of Mental Disorders fourth edition and International Statistical Classification of Diseases and Related Health Problems-10 diagnostic criteria for personality disorders. Abnormal premorbid personality traits were associated with increased behavioural and psychological symptoms in dementia. Cluster A (solitary/paranoid) premorbid personality traits were associated with anxiety, depression and hallucinations. Cluster C (anxious/dependent) traits were associated with a syndrome of depression. The presence of Clusters A (solitary/paranoid) and C (anxious/dependent) abnormal premorbid personality traits seems to affect the expression of certain behavioural and psychological symptoms in dementia, depression in particular. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Exercise-mediated wall shear stress increases mitochondrial biogenesis in vascular endothelium.

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Boa Kim

Full Text Available Enhancing structural and functional integrity of mitochondria is an emerging therapeutic option against endothelial dysfunction. In this study, we sought to investigate the effect of fluid shear stress on mitochondrial biogenesis and mitochondrial respiratory function in endothelial cells (ECs using in vitro and in vivo complementary studies.Human aortic- or umbilical vein-derived ECs were exposed to laminar shear stress (20 dyne/cm2 for various durations using a cone-and-plate shear apparatus. We observed significant increases in the expression of key genes related to mitochondrial biogenesis and mitochondrial quality control as well as mtDNA content and mitochondrial mass under the shear stress conditions. Mitochondrial respiratory function was enhanced when cells were intermittently exposed to laminar shear stress for 72 hrs. Also, shear-exposed cells showed diminished glycolysis and decreased mitochondrial membrane potential (ΔΨm. Likewise, in in vivo experiments, mice that were subjected to a voluntary wheel running exercise for 5 weeks showed significantly higher mitochondrial content determined by en face staining in the conduit (greater and lesser curvature of the aortic arch and thoracic aorta and muscle feed (femoral artery arteries compared to the sedentary control mice. Interestingly, however, the mitochondrial biogenesis was not observed in the mesenteric artery. This region-specific adaptation is likely due to the differential blood flow redistribution during exercise in the different vessel beds.Taken together, our findings suggest that exercise enhances mitochondrial biogenesis in vascular endothelium through a shear stress-dependent mechanism. Our findings may suggest a novel mitochondrial pathway by which a chronic exercise may be beneficial for vascular function.

Endogenous ovarian hormones affect mitochondrial efficiency in cerebral endothelium via distinct regulation of PGC-1 isoforms.

Science.gov (United States)

Kemper, Martin F; Zhao, Yuanzi; Duckles, Sue P; Krause, Diana N

2013-01-01

Mitochondria support the energy-intensive functions of brain endothelium but also produce damaging-free radicals that lead to disease. Previously, we found that estrogen treatment protects cerebrovascular mitochondria, increasing capacity for ATP production while decreasing reactive oxygen species (ROS). To determine whether these effects occur specifically in endothelium in vivo and also explore underlying transcriptional mechanisms, we studied freshly isolated brain endothelial preparations from intact and ovariectomized female mice. This preparation reflects physiologic influences of circulating hormones, hemodynamic forces, and cell-cell interactions of the neurovascular unit. Loss of ovarian hormones affected endothelial expression of the key mitochondrial regulator family, peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1), but in a unique way. Ovariectomy increased endothelial PGC-1α mRNA but decreased PGC-1β mRNA. The change in PGC-1β correlated with decreased mRNA for crucial downstream mitochondrial regulators, nuclear respiratory factor 1 and mitochondrial transcription factor A, as well as for ATP synthase and ROS protection enzymes, glutamate-cysteine ligase and manganese superoxide dismutase. Ovariectomy also decreased mitochondrial biogenesis (mitochondrial/nuclear DNA ratio). These results indicate ovarian hormones normally act through a distinctive regulatory pathway involving PGC-1β to support cerebral endothelial mitochondrial content and guide mitochondrial function to favor ATP coupling and ROS protection.

Prevalence of type 2 diabetes mellitus and other abnormalities of carbohydrate metabolism depending on diagnostic criteria

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Alexander Vasil'evich Dreval'

2010-03-01

Full Text Available Aim. To assess current criteria for type 2 diabetes mellitus. Materials and methods. This screening study involving 2,368 residents of two municipal districts of the Moscow region was designed to elucidate differencesin the prevalence of abnormalities of carbohydrate metabolism depending on diagnostic criteria (WHO and ADA. Results. The prevalence of early disorders of carbohydrate metabolism and DM2 among the adult population of Moscow region is 17,1 and 7,2 respectivelyusing WHO criteria and 40,0 and 5,9% by ADA criteria. Conclusion. Refusal to undergo OGTT during screening decreases detectability of early metabolic disorders by 28,8 and 6,1% using WHO and ADAcriteria respectively. When screening is aimed to diagnose DM2 alone, OGTT can be omitted in subjects with fasting plasma glucose level below4,7 mmol/l. If it is aimed to diagnose both DM2 and impaired glucose tolerance, OGTT is not needed in subjects with fasting plasma glucose levelbelow 4,2 mmol/l. The use of ?combined? diagnostic criteria (i.e. OGTT according to ADA, but not WHO significantly increases the prevalence ofmetabolic disorders from 24,9 to 48,8%.

Effect of 21-day head down bed rest on urine proteins related to endothelium: Correlations with changes in carbohydrate metabolism

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Kashirina, D.; Pastushkova, L.; Custaud, M. A.; Dobrokhotov, I.; Brzhozovsky, A.; Navasiolava, N.; Nosovsky, A.; Kononikhin, A.; Nikolaev, E.; Larina, I.

2017-08-01

We performed liquid chromatography-mass spectrometric study of the urine proteome in 8 healthy volunteers aged between 20 and 44 y.o. who have completed 21-day head-down bed rest. ANDSystem software which builds associative networks was used to identify the urinary proteins functionally related to the endothelium. We identified 7 endothelium-related biological processes, directly linked to 13 urine proteins. We performed manual annotation of the proteins which were the most important in terms of endothelial functions. Analysis of the correlations with biochemical variables revealed a positive correlation between fasting blood glucose and the following urine proteins: albumin, CD44 antigen, endothelial protein C receptor, mucin-1, osteopontin, receptor tyrosine kinase. As well, we found a positive correlation between HOMA-insulin resistance index and the following urine proteins: endothelial protein C receptor and syndecan-4. These results might suggest the involvement of above-mentioned proteins in glucose metabolism and their participation in the response to changes in blood glucose level.

Beneficial Effects of Apelin on Vascular Function in Patients With Central Obesity.

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Schinzari, Francesca; Veneziani, Augusto; Mores, Nadia; Barini, Angela; Di Daniele, Nicola; Cardillo, Carmine; Tesauro, Manfredi

2017-05-01

Patients with central obesity have impaired insulin-stimulated vasodilation and increased ET-1 (endothelin 1) vasoconstriction, which may contribute to insulin resistance and vascular damage. Apelin enhances insulin sensitivity and glucose disposal but also acts as a nitric oxide (NO)-dependent vasodilator and a counter-regulator of AT 1 (angiotensin [Ang] II type 1) receptor-induced vasoconstriction. We, therefore, examined the effects of exogenous (Pyr 1 )apelin on NO-mediated vasodilation and Ang II- or ET-1-dependent vasoconstrictor tone in obese patients. In the absence of hyperinsulinemia, forearm blood flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during saline or apelin administration (both P >0.05). During intra-arterial infusion of regular insulin, however, apelin enhanced the vasodilation induced by both acetylcholine and nitroprusside (both P 0.05). In conclusion, in patients with central obesity, apelin has favorable effects not only to improve insulin-stimulated endothelium-dependent and endothelium-independent vasodilator responses but also to blunt Ang II- and ET-1-dependent vasoconstriction by a mechanism not involving NO. Taken together, our results suggest that targeting the apelin system might favorably impact some hemodynamic abnormalities of insulin-resistant states like obesity. © 2017 American Heart Association, Inc.

Differential expression of the Slc4 bicarbonate transporter family in murine corneal endothelium and cell culture.

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Shei, William; Liu, Jun; Htoon, Hla M; Aung, Tin; Vithana, Eranga N

2013-01-01

To characterize the relative expression levels of all the solute carrier 4 (Slc4) transporter family members (Slc4a1-Slc4a11) in murine corneal endothelium using real-time quantitative (qPCR), to identify further important members besides Slc4a11 and Slc4a4, and to explore how close to the baseline levels the gene expressions remain after cells have been subjected to expansion and culture. Descemet's membrane-endothelial layers of 8-10-week-old C57BL6 mice were stripped from corneas and used for both primary cell culture and direct RNA extraction. Total RNA (from uncultured cells as well as cultured cells at passages 2 and 7) was reverse transcribed, and the cDNA was used for real time qPCR using specific primers for all the Slc4 family members. The geNorm method was applied to determine the most stable housekeeping genes and normalization factor, which was calculated from multiple housekeeping genes for more accurate and robust quantification. qPCR analyses revealed that all Slc4 bicarbonate transporter family members were expressed in mouse corneal endothelium. Slc4a11 showed the highest expression, which was approximately three times higher than that of Slc4a4 (3.4±0.3; p=0.004). All Slc4 genes were also expressed in cultured cells, and interestingly, the expression of Slc4a11 in cultured cells was significantly reduced by approximately 20-fold (0.05±0.001; p=0.000001) in early passage and by approximately sevenfold (0.14±0.002; p=0.000002) in late passage cells. Given the known involvement of SLC4A4 and SLC4A11 in corneal dystrophies, we speculate that the other two highly expressed genes in the uncultured corneal endothelium, SLC4A2 and SLC4A7, are worthy of being considered as potential candidate genes for corneal endothelial diseases. Moreover, as cell culture can affect expression levels of Slc4 genes, caution and careful design of experiments are necessary when undertaking studies of Slc4-mediated ion transport in cultured cells.

Overexpression of PLK3 Mediates the Degradation of Abnormal Prion Proteins Dependent on Chaperone-Mediated Autophagy.

Science.gov (United States)

Wang, Hui; Tian, Chan; Sun, Jing; Chen, Li-Na; Lv, Yan; Yang, Xiao-Dong; Xiao, Kang; Wang, Jing; Chen, Cao; Shi, Qi; Shao, Qi-Xiang; Dong, Xiao-Ping

2017-08-01

Polo-like kinase 3 (PLK3) is the main cause of cell cycle reentry-related neuronal apoptosis which has been implicated in the pathogenesis of prion diseases. Previous work also showed the regulatory activity of exogenous PLK3 on the degradation of PrP (prion protein) mutants and pathogenic PrP Sc ; however, the precise mechanisms remain unknown. In this study, we identified that the overexpression of PLK3-mediated degradation of PrP mutant and PrP Sc was repressed by lysosome rather than by proteasomal and macroautophagy inhibitors. Core components of chaperone-mediated autophagy (CMA) effectors, lysosome-associated membrane protein type 2A (LAMP2a), and heat shock cognate protein 70 (Hsc70) are markedly decreased in the HEK293T cells expressing PrP mutant and scrapie-infected cell line SMB-S15. Meanwhile, PrP mutant showed ability to interact with LAMP2a and Hsc70. Overexpression of PLK3 sufficiently increased the cellular levels of LAMP2a and Hsc70, accompanying with declining the accumulations of PrP mutant and PrP Sc . The kinase domain (KD) of PLK3 was responsible for elevating LAMP2a and Hsc70. Knockdown of endogenous PLK3 enhanced the activity of macroautophagy in the cultured cells. Moreover, time-dependent reductions of LAMP2a and Hsc70 were also observed in the brain tissues of hamster-adapted scrapie agent 263K-infected hamsters, indicating an impairment of CMA during prion infection. Those data indicate that the overexpression of PLK3-mediated degradation of abnormal PrP is largely dependent on CMA pathway.

Abnormal uterine bleeding

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Anovulatory bleeding; Abnormal uterine bleeding - hormonal; Polymenorrhea - dysfunctional uterine bleeding ... ACOG committee opinion no. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Reaffirmed 2015. www. ...

Favorable Vascular Actions of Angiotensin-(1-7) in Human Obesity.

Science.gov (United States)

Schinzari, Francesca; Tesauro, Manfredi; Veneziani, Augusto; Mores, Nadia; Di Daniele, Nicola; Cardillo, Carmine

2018-01-01

Obese patients have vascular dysfunction related to impaired insulin-stimulated vasodilation and increased endothelin-1-mediated vasoconstriction. In contrast to the harmful vascular actions of angiotensin (Ang) II, the angiotensin-converting enzyme 2 product Ang-(1-7) has shown to exert cardiovascular and metabolic benefits in experimental models through stimulation of the Mas receptor. We, therefore, examined the effects of exogenous Ang-(1-7) on vasodilator tone and endothelin-1-dependent vasoconstriction in obese patients. Intra-arterial infusion of Ang-(1-7) (10 nmol/min) resulted in significant increase in unstimulated forearm flow ( P =0.03), an effect that was not affected by the Mas receptor antagonist A779 (10 nmol/min; P >0.05). In the absence of hyperinsulinemia, however, forearm flow responses to graded doses of acetylcholine and sodium nitroprusside were not different during Ang-(1-7) administration compared with saline (both P >0.05). During infusion of regular insulin (0.15 mU/kg per minute), by contrast, endothelium-dependent vasodilator response to acetylcholine was significantly enhanced by Ang-(1-7) ( P =0.04 versus saline), whereas endothelium-independent response to sodium nitroprusside was not modified ( P =0.91). Finally, Ang-(1-7) decreased the vasodilator response to endothelin A receptor blockade (BQ-123; 10 nmol/min) compared with saline (6±1% versus 93±17%; P obese patients Ang-(1-7) has favorable effects not only to improve insulin-stimulated endothelium-dependent vasodilation but also to blunt endothelin-1-dependent vasoconstrictor tone. These findings provide support for targeting Ang-(1-7) to counteract the hemodynamic abnormalities of human obesity. © 2017 American Heart Association, Inc.

Anormalidades de fluxo sangüíneo cerebral em indivíduos dependentes de cocaína Cerebral blood flow abnormalities in cocaine dependent subjects

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Sergio Nicastri

2000-06-01

Full Text Available INTRODUÇÃO: Nos últimos anos, tem havido relatos de anormalidades do fluxo sanguíneo cerebral em indivíduos com o abuso de cocaína, detectadas por meio de tomografia computadorizada por emissão de fóton único (SPECT. Esse padrão anormal de perfusão cerebral tem sido associado a prejuízos cognitivos mas não a alterações observáveis por meio de exames de neuroimagem estrutural. Um problema envolvendo a maioria dos trabalhos publicados sobre esse tema é a inclusão de um grande número de usuários de heroína nas amostras estudadas. Essa outra droga também parece afetar o padrão de perfusão cerebral, particularmente durante estados de abstinência. MÉTODOS: Quatorze pacientes dependentes de cocaína (nenhum com uso de opióides e 14 voluntários normais (grupo controle foram submetidos a exames de SPECT com dímero de etil-cisteína marcado com tecnécio-99m. A análise dos exames de SPECT foi realizada por meio de análise visual qualitativa das imagens obtidas (procedimento padrão na prática clínica, realizada por um radiologista não informado sobre o diagnóstico dos indivíduos avaliados. RESULTADOS: A análise visual revelou um padrão sugestivo de irregularidades do fluxo sangüíneo cerebral em nove pacientes, mas em apenas dois controles (p = 0,018; teste exato de Fisher bicaudal. CONCLUSÕES: Anormalidades de circulação cerebral podem ter relação com prejuízos cognitivos relatados em populações de dependentes de cocaína. Embora déficits de perfusão cerebral associados ao uso de cocaína possam ser irreversíveis, têm surgido relatos na literatura de tratamentos para essas anormalidades de fluxo sangüíneo. Alterações de fluxo sangüíneo cerebral associadas à dependência de cocaína ocorrem mesmo na ausência de abuso ou dependência de opióides.INTRODUCTION: In the last years, there have been reports of abnormalities in brain blood flow of cocaine abusers, detected by single photon computed

Dextran-shelled oxygen-loaded nanodroplets reestablish a normoxia-like pro-angiogenic phenotype and behavior in hypoxic human dermal microvascular endothelium

International Nuclear Information System (INIS)

Basilico, Nicoletta; Magnetto, Chiara; D'Alessandro, Sarah; Panariti, Alice; Rivolta, Ilaria; Genova, Tullio; Khadjavi, Amina; Gulino, Giulia Rossana; Argenziano, Monica; Soster, Marco

2015-01-01

In chronic wounds, hypoxia seriously undermines tissue repair processes by altering the balances between pro-angiogenic proteolytic enzymes (matrix metalloproteinases, MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) released from surrounding cells. Recently, we have shown that in human monocytes hypoxia reduces MMP-9 and increases TIMP-1 without affecting TIMP-2 secretion, whereas in human keratinocytes it reduces MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. Provided that the phenotype of the cellular environment is better understood, chronic wounds might be targeted by new oxygenating compounds such as chitosan- or dextran-shelled and 2H,3H-decafluoropentane-cored oxygen-loaded nanodroplets (OLNs). Here, we investigated the effects of hypoxia and dextran-shelled OLNs on the pro-angiogenic phenotype and behavior of human dermal microvascular endothelium (HMEC-1 cell line), another cell population playing key roles during wound healing. Normoxic HMEC-1 constitutively released MMP-2, TIMP-1 and TIMP-2 proteins, but not MMP-9. Hypoxia enhanced MMP-2 and reduced TIMP-1 secretion, without affecting TIMP-2 levels, and compromised cell ability to migrate and invade the extracellular matrix. When taken up by HMEC-1, nontoxic OLNs abrogated the effects of hypoxia, restoring normoxic MMP/TIMP levels and promoting cell migration, matrix invasion, and formation of microvessels. These effects were specifically dependent on time-sustained oxygen diffusion from OLN core, since they were not achieved by oxygen-free nanodroplets or oxygen-saturated solution. Collectively, these data provide new information on the effects of hypoxia on dermal endothelium and support the hypothesis that OLNs might be used as effective adjuvant tools to promote chronic wound healing processes. - Highlights: • Hypoxia enhances MMP-2 and reduces TIMP-1 secretion by dermal HMEC-1 cell line. • Hypoxia compromises migration and matrix invasion abilities of

Dextran-shelled oxygen-loaded nanodroplets reestablish a normoxia-like pro-angiogenic phenotype and behavior in hypoxic human dermal microvascular endothelium

Energy Technology Data Exchange (ETDEWEB)

Basilico, Nicoletta, E-mail: nicoletta.basilico@unimi.it [Dipartimento di Scienze Biomediche, Chirurgiche e Odontoiatriche, Università di Milano, via Pascal 36, 20133 Milano (Italy); Magnetto, Chiara, E-mail: c.magnetto@inrim.it [Istituto Nazionale di Ricerca Metrologica (INRIM), Strada delle Cacce, 91, 10135 Torino (Italy); D' Alessandro, Sarah, E-mail: sarah.dalessandro@unimi.it [Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, via Pascal 36, 20133 Milano (Italy); Panariti, Alice, E-mail: alice.panariti@mail.mcgill.ca [Dipartimento di Scienze della Salute, Università di Milano Bicocca, Via Cadore 48, 20900 Monza (Italy); Rivolta, Ilaria, E-mail: ilaria.rivolta@unimib.it [Dipartimento di Scienze della Salute, Università di Milano Bicocca, Via Cadore 48, 20900 Monza (Italy); Genova, Tullio, E-mail: tullio.genova@unito.it [Dipartimento di Scienze della Vita e Biologia dei Sistemi, Via Accademia Albertina 13, 10123 Torino (Italy); Khadjavi, Amina, E-mail: amina.khadjavi@unito.it [Dipartimento di Neuroscienze, Università di Torino, Corso Raffaello 30, 10125 Torino (Italy); Gulino, Giulia Rossana, E-mail: giuliarossana.gulino@unito.it [Dipartimento di Oncologia, Università di Torino, Via Santena 5 bis, 10126 Torino (Italy); Argenziano, Monica, E-mail: monica.argenziano@unito.it [Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via Giuria, 9, 10125 Torino (Italy); Soster, Marco, E-mail: marco.soster@unito.it [Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via Giuria, 9, 10125 Torino (Italy); and others

2015-11-01

In chronic wounds, hypoxia seriously undermines tissue repair processes by altering the balances between pro-angiogenic proteolytic enzymes (matrix metalloproteinases, MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) released from surrounding cells. Recently, we have shown that in human monocytes hypoxia reduces MMP-9 and increases TIMP-1 without affecting TIMP-2 secretion, whereas in human keratinocytes it reduces MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. Provided that the phenotype of the cellular environment is better understood, chronic wounds might be targeted by new oxygenating compounds such as chitosan- or dextran-shelled and 2H,3H-decafluoropentane-cored oxygen-loaded nanodroplets (OLNs). Here, we investigated the effects of hypoxia and dextran-shelled OLNs on the pro-angiogenic phenotype and behavior of human dermal microvascular endothelium (HMEC-1 cell line), another cell population playing key roles during wound healing. Normoxic HMEC-1 constitutively released MMP-2, TIMP-1 and TIMP-2 proteins, but not MMP-9. Hypoxia enhanced MMP-2 and reduced TIMP-1 secretion, without affecting TIMP-2 levels, and compromised cell ability to migrate and invade the extracellular matrix. When taken up by HMEC-1, nontoxic OLNs abrogated the effects of hypoxia, restoring normoxic MMP/TIMP levels and promoting cell migration, matrix invasion, and formation of microvessels. These effects were specifically dependent on time-sustained oxygen diffusion from OLN core, since they were not achieved by oxygen-free nanodroplets or oxygen-saturated solution. Collectively, these data provide new information on the effects of hypoxia on dermal endothelium and support the hypothesis that OLNs might be used as effective adjuvant tools to promote chronic wound healing processes. - Highlights: • Hypoxia enhances MMP-2 and reduces TIMP-1 secretion by dermal HMEC-1 cell line. • Hypoxia compromises migration and matrix invasion abilities of

Expression of follicle-stimulating hormone receptor by the vascular endothelium in tumor metastases

International Nuclear Information System (INIS)

Siraj, Ahsan; Gonin, Julie; Radu, Aurelian; Ghinea, Nicolae; Desestret, Virginie; Antoine, Martine; Fromont, Gaëlle; Huerre, Michel; Sanson, Marc; Camparo, Philippe; Pichon, Christophe; Planeix, François

2013-01-01

The Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness. We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients. In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between the density of FSHR-positive vessels inside vs. outside tumors for metastases from lung, breast, colon, and kidney cancers. In contrast, for prostate cancer metastases, the density of FSHR-positive vessels was about 3-fold higher at the exterior of the tumor compared to the interior. Among brain metastases, the density of FSHR-positive vessels was highest in lung and kidney cancer, and lowest in prostate and colon cancer. In metastases of breast cancer to the lung pleura, the percentage of blood vessels expressing FSHR was positively correlated with the progesterone receptor level, but not with either HER-2 or estrogen receptors. In normal tissues corresponding to the host organs for the analyzed metastases, obtained from patients not known to have cancer, FSHR staining was absent, with the exception of approx. 1% of the vessels in non tumoral temporal lobe epilepsy samples. FSHR is expressed by the endothelium of blood vessels in the majority of metastatic tumors

Encapsulated Bacillus anthracis interacts closely with liver endothelium.

Science.gov (United States)

Piris-Gimenez, Alejandro; Corre, Jean-Philippe; Jouvion, Gregory; Candela, Thomas; Khun, Huot; Goossens, Pierre L

2009-11-01

The Bacillus anthracis poly-gamma-D-glutamate capsule is essential for virulence. It impedes phagocytosis and protects bacilli from the immune system, thus promoting systemic dissemination. To further define the virulence mechanisms brought into play by the capsule, we characterized the interactions between encapsulated nontoxinogenic B. anthracis and its host in vivo through histological analysis, perfusion, and competition experiments with purified capsule. Clearance of encapsulated bacilli from the blood was rapid (>90% clearance within 5 min), with 75% of the bacteria being trapped in the liver. Competition experiments with purified capsule polyglutamate inhibited this interaction. At the septicemic phase of cutaneous infection with spores, the encapsulated bacilli were trapped in the vascular spaces of the liver and interacted closely with the liver endothelium in the sinusoids and terminal and portal veins. They often grow as microcolonies containing capsular material shed by the bacteria. We show that, in addition to its inhibitory effect on the interaction with the immune system, the capsule surrounding B. anthracis plays an active role in mediating the trapping of the bacteria within the liver and may thus contribute to anthrax pathogenesis. Because other microorganisms produce polyglutamate, it may also represent a general mechanism of virulence or in vivo survival.

Urine - abnormal color

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... medlineplus.gov/ency/article/003139.htm Urine - abnormal color To use the sharing features on this page, please enable JavaScript. The usual color of urine is straw-yellow. Abnormally colored urine ...

Tooth - abnormal colors

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... medlineplus.gov/ency/article/003065.htm Tooth - abnormal colors To use the sharing features on this page, please enable JavaScript. Abnormal tooth color is any color other than white to yellowish- ...

Contribution of Ca2+-Dependent Cl- Channels to Norepinephrine-Induced Contraction of Femoral Artery Is Replaced by Increasing EDCF Contribution during Ageing

Czech Academy of Sciences Publication Activity Database

Líšková, Silvia; Petrová, M.; Karen, Petr; Behuliak, Michal; Zicha, Josef

2014-01-01

Roč. 2014, č. 2014 (2014), s. 289361 ISSN 2314-6133 R&D Projects: GA ČR(CZ) GAP304/12/0259 Institutional support: RVO:67985823 Keywords : calcium-dependent chloride channels * endothelium-derived contracting factor * ageing Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.579, year: 2014

Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

Energy Technology Data Exchange (ETDEWEB)

Milliat, F

2007-05-15

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

Gamma radiations induced meiotic abnormalities in cape gosseberry (Physalis peruviana Linn.)

International Nuclear Information System (INIS)

Gupta, S.K.

1987-01-01

The cytological alterations were systematically scored in Physalis peruviana after treatment with 5 to 60 Krads of gamma radiation. In control plant diplotenediakinesis revealed 24 bivalents and cytokinesis produced normal tetrads, whereas PMCs of differently treated plants showed various anomalies viz., altered configuration of chromosomes, clumping/sickness, fragments, bridges, laggards, unequal segregation and non-orientation of chromosomes and unequal groupings of chromosomes. Abnormal karyokinesis and/or cytokinesis led to the formation of abnormal sporads which later on causes pollen and plant sterility. While every type of anomaly is dose-dependent and tend to increase with advancing dose showing a fair degree of correlation with the dose of radiation. The persistence of meiotic abnormalities with reduce d frequency in M 2 generation also bears correlation with administered dose. (author). 10 refs

Endothelium-derived fibronectin regulates neonatal vascular morphogenesis in an autocrine fashion.

Science.gov (United States)

Turner, Christopher J; Badu-Nkansah, Kwabena; Hynes, Richard O

2017-11-01

Fibronectin containing alternatively spliced EIIIA and EIIIB domains is largely absent from mature quiescent vessels in adults, but is highly expressed around blood vessels during developmental and pathological angiogenesis. The precise functions of fibronectin and its splice variants during developmental angiogenesis however remain unclear due to the presence of cardiac, somitic, mesodermal and neural defects in existing global fibronectin KO mouse models. Using a rare family of surviving EIIIA EIIIB double KO mice, as well as inducible endothelial-specific fibronectin-deficient mutant mice, we show that vascular development in the neonatal retina is regulated in an autocrine manner by endothelium-derived fibronectin, and requires both EIIIA and EIIIB domains and the RGD-binding α5 and αv integrins for its function. Exogenous sources of fibronectin do not fully substitute for the autocrine function of endothelial fibronectin, demonstrating that fibronectins from different sources contribute differentially to specific aspects of angiogenesis.

Abnormal Structure–Function Relationship in Spasmodic Dysphonia

Science.gov (United States)

Ludlow, Christy L.

2012-01-01

Spasmodic dysphonia (SD) is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. Although recent studies have found abnormal brain function and white matter organization in SD, the extent of gray matter alterations, their structure–function relationships, and correlations with symptoms remain unknown. We compared gray matter volume (GMV) and cortical thickness (CT) in 40 SD patients and 40 controls using voxel-based morphometry and cortical distance estimates. These measures were examined for relationships with blood oxygen level–dependent signal change during symptomatic syllable production in 15 of the same patients. SD patients had increased GMV, CT, and brain activation in key structures of the speech control system, including the laryngeal sensorimotor cortex, inferior frontal gyrus (IFG), superior/middle temporal and supramarginal gyri, and in a structure commonly abnormal in other primary dystonias, the cerebellum. Among these regions, GMV, CT and activation of the IFG and cerebellum showed positive relationships with SD severity, while CT of the IFG correlated with SD duration. The left anterior insula was the only region with decreased CT, which also correlated with SD symptom severity. These findings provide evidence for coupling between structural and functional abnormalities at different levels within the speech production system in SD. PMID:21666131

Effect of topical 0.05% cyclosporine A on corneal endothelium in patients with dry eye disease

OpenAIRE

Pérez-Rico, Consuelo; Germain, Francisco; Castro-Rebollo, María; Moreno-Salgueiro, Agustín; Teus, Miguel Ángel

2013-01-01

AIM:To determine the effect of topical 0.05% cyclosporine A (CsA) on corneal endothelium in patients with dry eye disease.METHODS: Observational, prospective, case series study. Fifty-five eyes of 29 consecutive patients (9 males and 20 females; median age:66.8 years, interquartile range:61-73.2 years) with moderate-severe dry eye disease were evaluated. All patients were treated with topical 0.05% CsA ophthalmic emulsion twice a day in addition to lubricant eyedrops 5 times a day. The follow...

Effects of iodinated contrast media on blood and endothelium

International Nuclear Information System (INIS)

Aspelin, Peter; Stacul, Fulvio; Thomsen, Henrik S.; Morcos, Sameh K.; Molen, Aart J. van der

2006-01-01

The aim of the study was to assess the effects of iodinated contrast media on blood components and endothelium based on experimental and clinical studies and to produce clinically relevant guidelines for reducing thrombotic and hematologic complications following the intravascular use of contrast media. A report was drafted after review of the literature and discussions among the members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology. The final report was produced following discussion at the 12th European Symposium on Urogenital Radiology in Ljubljana, Slovenia (2005). Experimental data indicate that all iodinated contrast media produce an anticoagulant effect and that this effect is greater with ionic contrast media. Several of the in vitro and experimental in vivo studies on haematological effects of contrast media have not been confirmed by clinical studies. Low- or iso-osmolar contrast media should be used for diagnostic and interventional angiographic procedures, including phlebography. Meticulous angiographic technique is the most important factor for reducing the thrombotic complications associated with angiographic procedures. Drugs and interventional devices that decrease the risk of thromboembolic complications during interventional procedures minimize the importance of the effects of contrast media. (orig.)

Effects of iodinated contrast media on blood and endothelium

Energy Technology Data Exchange (ETDEWEB)

Aspelin, Peter [Karolinska Institute/Huddinge University Hospital, Division of Radiology, Centre for Surgical Sciences, Stockholm (Sweden); Stacul, Fulvio [Institute of Radiology, Trieste (Italy); Thomsen, Henrik S. [Copenhagen University Hospital at Herlev, Department of Diagnostic Radiology 54E2, Herlev (Denmark); Morcos, Sameh K. [Sheffield Teaching Hospitals NHS Trust, Department of Diagnostic Imaging, Northern General Hospital, Sheffield (United Kingdom); Molen, Aart J. van der [Leiden University Medical Centre, Department of Radiology, Leiden (Netherlands)

2006-05-15

The aim of the study was to assess the effects of iodinated contrast media on blood components and endothelium based on experimental and clinical studies and to produce clinically relevant guidelines for reducing thrombotic and hematologic complications following the intravascular use of contrast media. A report was drafted after review of the literature and discussions among the members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology. The final report was produced following discussion at the 12th European Symposium on Urogenital Radiology in Ljubljana, Slovenia (2005). Experimental data indicate that all iodinated contrast media produce an anticoagulant effect and that this effect is greater with ionic contrast media. Several of the in vitro and experimental in vivo studies on haematological effects of contrast media have not been confirmed by clinical studies. Low- or iso-osmolar contrast media should be used for diagnostic and interventional angiographic procedures, including phlebography. Meticulous angiographic technique is the most important factor for reducing the thrombotic complications associated with angiographic procedures. Drugs and interventional devices that decrease the risk of thromboembolic complications during interventional procedures minimize the importance of the effects of contrast media. (orig.)

[Abnormal floral meristem development in transgenic tomato plants do not depend on the expression of genes encoding defense-related PR-proteins and antimicrobial peptides].

Science.gov (United States)

Khaliluev, M R; Chaban, I A; Kononenko, N V; Baranova, E N; Dolgov, S V; Kharchenko, P N; Poliakov, V Iu

2014-01-01

In this study, the morphological and cytoembryological analyses of the tomato plants transformed with the genes encoding chitin-binding proteins (ac and RS-intron-Shir) from Amaranthus caudatus L. andA. retroflexus L., respectively, as well as the gene amp2 encoding hevein-like antimicrobial peptides from Stellaria media L., have been performed. The transgenic lines were adapted to soil and grown the greenhouse. The analysis of putative transgenic tomato plants revealed several lines that did not differ phenotypically from the wild type plants and three lines with disruption in differentiation of the inflorescence shoot and the flower, as well as the fruit formation (modified plants of each line were transformed with a single gene as noted before). Abnormalities in the development of the generative organs were maintained for at least six vegetative generations. These transgenic plants were shown to be defective in the mail gametophyte formation, fertilization, and, consequently, led to parthenocarpic fruits. The detailed analysis of growing ovules in the abnormal transgenic plants showed that the replacement tissue was formed and proliferated instead of unfertilized embryo sac. The structure of the replacement tissue differed from both embryonic and endosperm tissue of the normal ovule. The formation of the replacement tissue occurred due to continuing proliferation of the endothelial cells that lost their ability for differentiation. The final step in the development of the replacement tissue was its death, which resulted in the cell lysis. The expression of the genes used was confirmed by RT-PCR in all three lines with abnormal phenotype, as well as in several lines that did not phenotypically differ from the untransformed control. This suggests that abnormalities in the organs of the generative sphere in the transgenic plants do not depend on the expression of the foreign genes that were introduced in the tomato genome. Here, we argue that agrobacterial

Abnormal pressures as hydrodynamic phenomena

Science.gov (United States)

Neuzil, C.E.

1995-01-01

So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

Characterization of VCAM-1-binding peptide-functionalized quantum dots for molecular imaging of inflamed endothelium.

Directory of Open Access Journals (Sweden)

Yun Chen

Full Text Available Inflammation-induced activation of endothelium constitutes one of the earliest changes during atherogenesis. New imaging techniques that allow detecting activated endothelial cells can improve the identification of persons at high cardiovascular risk in early stages. Quantum dots (QDs have attractive optical properties such as bright fluorescence and high photostability, and have been increasingly studied and developed for bio-imaging and bio-targeting applications. We report here the development of vascular cell adhesion molecule-1 binding peptide (VCAM-1 binding peptide functionalized QDs (VQDs from amino QDs. It was found that the QD fluorescence signal in tumor necrosis factor [Formula: see text] (TNF-[Formula: see text] treated endothelial cells in vitro was significantly higher when these cells were labeled with VQDs than amino QDs. The VQD labeling of TNF-[Formula: see text]-treated endothelial cells was VCAM-1 specific since pre-incubation with recombinant VCAM-1 blocked cells' uptake of VQDs. Our ex vivo and in vivo experiments showed that in the inflamed endothelium, QD fluorescence signal from VQDs was also much stronger than that of amino QDs. Moreover, we observed that the QD fluorescence peak was significantly blue-shifted after VQDs interacted with aortic endothelial cells in vivo and in vitro. A similar blue-shift was observed after VQDs were incubated with recombinant VCAM-1 in tube. We anticipate that the specific interaction between VQDs and VCAM-1 and the blue-shift of the QD fluorescence peak can be very useful for VCAM-1 detection in vivo.

Abnormal growth of faceted (WC) grains in a (Co) liquid matrix

International Nuclear Information System (INIS)

Park, Y.J.; Yoon, D.Y.

1996-01-01

If the grains dispersed in a liquid matrix are spherical, their surface atomic structure is expected to be rough (diffuse), and their coarsening has been observed to be controlled by diffusion in the matrix. They do not, furthermore, undergo abnormal growth. On the other hand, in some compound material systems, the grains in liquid matrices are faceted and often show abnormal coarsening behavior. Their faceted surface planes are expected to be singular (atomically flat) and therefore grow by a defect-assisted process and two-dimensional (2-D) nucleation. Contrary to the usual coarsening theories, their growth velocity is not linearly dependent on the driving force arising from the grain size difference. If the growth of the faceted grains occurs by 2-D nucleation, the rate is expected to increase abruptly at a critical supersaturation, as has been observed in crystal growth in melts and solutions. It is proposed that this growth mechanism leads to the abnormal grain coarsening. The 2-D nucleation theory predicts that there is a threshold initial grain size for the abnormal grain growth (AGG), and the propensity for AGG will increase with the heat-treatment temperature. The AGG behavior will also vary with the defects in the grains. These predictions are qualitatively confirmed in the sintered WC-Co alloy prepared from fine (0.85-microm) and coarse (5.48-microm) WC powders and their mixtures. The observed dependence of the AGG behavior on the sintering temperature and the milling of the WC powder is also qualitatively consistent with the predicted behavior

Insulin resistance adds to endothelial dysfunction in hypertensive patients and in normotensive offspring of subjects with essential hypertension.

Science.gov (United States)

Zizek, B; Poredos, P

2001-02-01

To evaluate whether endothelium-dependent (nitric oxide-mediated) dilation of the brachial artery (BA) is impaired in patients being treated for essential hypertension (EH), and whether this abnormality can be detected in normotensive offspring of subjects with EH (familial trait, FT); and to investigate the interrelationship between flow-mediated vasodilation (FMD) and hyperinsulinaemia/insulin resistance. Cross-sectional study. Angiology department at a teaching hospital. The study encompassed 172 subjects, of whom 46 were treated hypertonics aged 40-55 (49) years, and 44 age-matched, normotensive volunteers as controls. We also investigated 41 normotonics with FT aged 20-30 (25) years and 41 age-and sex-matched controls without FT. Using high-resolution ultrasound, BA diameters at rest, during reactive hyperaemia (endothelium-dependent dilation) and after sublingual glyceryl trinitrate (GTN) application (endothelium-independent dilation) were measured. In hypertonics FMD was significantly lower than in controls [2.4 (2.9) vs. 7.4 (2.5)%; P < 0.00005], as was GTN-induced dilation [12.1 (4.3) vs. 16.1 (4.6)%; P=0.0007]. In subjects with FT, FMD was also decreased compared with the control group [5.8 (4.1) vs. 10.0 (3.0)%; P < 0.00005]. The response to GTN was comparable in both groups of young subjects. FMD was negatively related to insulin concentration in all subjects studied (P < 0.00005). In treated patients with EH, flow-mediated dilation of the BA as well as endothelium-independent dilation are decreased. In individuals with FT the endothelial function of the peripheral arteries is also altered in the absence of elevated blood pressure. Endothelial dysfunction is related to hyperinsulinaemia/insulin resistance, which could be one of the pathogenetic determinants of EH and its complications.

Identification of a potent endothelium-derived angiogenic factor.

Directory of Open Access Journals (Sweden)

Vera Jankowski

Full Text Available The secretion of angiogenic factors by vascular endothelial cells is one of the key mechanisms of angiogenesis. Here we report on the isolation of a new potent angiogenic factor, diuridine tetraphosphate (Up4U from the secretome of human endothelial cells. The angiogenic effect of the endothelial secretome was partially reduced after incubation with alkaline phosphatase and abolished in the presence of suramin. In one fraction, purified to homogeneity by reversed phase and affinity chromatography, Up4U was identified by MALDI-LIFT-fragment-mass-spectrometry, enzymatic cleavage analysis and retention-time comparison. Beside a strong angiogenic effect on the yolk sac membrane and the developing rat embryo itself, Up4U increased the proliferation rate of endothelial cells and, in the presence of PDGF, of vascular smooth muscle cells. Up4U stimulated the migration rate of endothelial cells via P2Y2-receptors, increased the ability of endothelial cells to form capillary-like tubes and acts as a potent inducer of sprouting angiogenesis originating from gel-embedded EC spheroids. Endothelial cells released Up4U after stimulation with shear stress. Mean total plasma Up4U concentrations of healthy subjects (N=6 were sufficient to induce angiogenic and proliferative effects (1.34 ± 0.26 nmol L(-1. In conclusion, Up4U is a novel strong human endothelium-derived angiogenic factor.

Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

Energy Technology Data Exchange (ETDEWEB)

Milliat, F

2007-05-15

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

Abnormal sound detection device

International Nuclear Information System (INIS)

Yamada, Izumi; Matsui, Yuji.

1995-01-01

Only components synchronized with rotation of pumps are sampled from detected acoustic sounds, to judge the presence or absence of abnormality based on the magnitude of the synchronized components. A synchronized component sampling means can remove resonance sounds and other acoustic sounds generated at a synchronously with the rotation based on the knowledge that generated acoustic components in a normal state are a sort of resonance sounds and are not precisely synchronized with the number of rotation. On the other hand, abnormal sounds of a rotating body are often caused by compulsory force accompanying the rotation as a generation source, and the abnormal sounds can be detected by extracting only the rotation-synchronized components. Since components of normal acoustic sounds generated at present are discriminated from the detected sounds, reduction of the abnormal sounds due to a signal processing can be avoided and, as a result, abnormal sound detection sensitivity can be improved. Further, since it is adapted to discriminate the occurrence of the abnormal sound from the actually detected sounds, the other frequency components which are forecast but not generated actually are not removed, so that it is further effective for the improvement of detection sensitivity. (N.H.)

Effects of a Single Bout of Resistance Exercise in Different Volumes on Endothelium Adaptations in Healthy Animals.

Science.gov (United States)

Mota, Marcelo Mendonça; Silva, Tharciano Luiz Teixeira Braga da; Macedo, Fabricio Nunes; Mesquita, Thássio Ricardo Ribeiro; Quintans, Lucindo José; Santana-Filho, Valter Joviniano de; Lauton-Santos, Sandra; Santos, Márcio Roberto Viana

2017-05-01

Resistance exercise (RE) has been recommended for patients with cardiovascular diseases. Recently, a few studies have demonstrated that the intensity of a single bout of RE has an effect on endothelial adaptations to exercise. However, there is no data about the effects of different volumes of RE on endothelium function. The aim of the study was to evaluate the effects of different volumes of RE in a single bout on endothelium-dependent vasodilatation and nitric oxide (NO) synthesis in the mesenteric artery of healthy animals. Male Wistar rats were divided into three groups: Control (Ct); low-volume RE (LV, 5 sets x 10 repetitions) and high-volume RE (HV, 15 sets x 10 repetitions). The established intensity was 70% of the maximal repetition test. After the exercise protocol, rings of mesenteric artery were used for assessment of vascular reactivity, and other mesenteric arteries were prepared for detection of measure NO production by DAF-FM fluorescence. Insulin responsiveness on NO synthesis was evaluated by stimulating the vascular rings with insulin (10 nM). The maximal relaxation response to insulin increased in the HV group only as compared with the Ct group. Moreover, the inhibition of nitric oxide synthesis (L-NAME) completely abolished the insulin-induced vasorelaxation in exercised rats. NO production showed a volume-dependent increase in the endothelial and smooth muscle layer. In endothelial layer, only Ct and LV groups showed a significant increase in NO synthesis when compared to their respective group under basal condition. On the other hand, in smooth muscle layer, NO fluorescence increased in all groups when compared to their respective group under basal condition. Our results suggest that a single bout of RE promotes vascular endothelium changes in a volume-dependent manner. The 15 sets x 10 repetitions exercise plan induced the greatest levels of NO synthesis. O exercício resistido (ER) tem sido recomendado para pacientes com doen

Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M

DEFF Research Database (Denmark)

Christoffersen, Christina; Obinata, Hideru; Kumaraswamy, Sunil B

2011-01-01

Protection of the endothelium is provided by circulating sphingosine-1-phosphate (S1P), which maintains vascular integrity. We show that HDL-associated S1P is bound specifically to both human and murine apolipoprotein M (apoM). Thus, isolated human ApoM(+) HDL contained S1P, whereas ApoM(-) HDL did...... not. Moreover, HDL in Apom(-/-) mice contains no S1P, whereas HDL in transgenic mice overexpressing human apoM has an increased S1P content. The 1.7-Å structure of the S1P-human apoM complex reveals that S1P interacts specifically with an amphiphilic pocket in the lipocalin fold of apoM. Human ApoM......(+) HDL induced S1P(1) receptor internalization, downstream MAPK and Akt activation, endothelial cell migration, and formation of endothelial adherens junctions, whereas apoM(-) HDL did not. Importantly, lack of S1P in the HDL fraction of Apom(-/-) mice decreased basal endothelial barrier function in lung...

Effect of inorganic lead on some functions of the cerebral microvessel endothelium

International Nuclear Information System (INIS)

Maxwell, K.; Vinters, H.V.; Berliner, J.A.; Bready, J.V.; Cancilla, P.A.

1986-01-01

The effect of inorganic lead on two functions of cerebral microvessel endothelium, cell division and glucose analog uptake, was investigated. Lead concentrations considered to be toxic in humans inhibited both functions in cultured endothelial cells. Both effects were dependent on the length of lead exposure and dose over the range of 10(-4) to 10(-6) M lead acetate. After 4 days of exposure there were 76% fewer cells in 10(-4) M lead-exposed cultures relative to control cultures. After 4 days of exposure to 10(-5) M lead there were 55% fewer cells, and after 10(-6) M lead exposure there were 15% fewer cells. Two days after 10(-4) M lead exposure [methyl-3H]thymidine incorporation into endothelial cells was inhibited by 71%. Incorporation was inhibited 47% by 10(-5) M lead but 10(-6) M lead did not inhibit incorporation after 2 days of exposure. Glucose analog uptake was inhibited in both contact-inhibited and log-phase cells; however, the latter were more sensitive to lead and this increased sensitivity correlated with a higher lead content in this cell population. Both the specific carrier-mediated and the nonspecific components of glucose analog uptake were inhibited by exposure of the endothelial cells to lead. A lead exposure of 40 min produced a significant effect on the uptake mechanism. In order to manifest its effects the lead had to be present in serum-containing medium, suggesting that some serum component was necessary to present the lead to the endothelial cells. These findings imply that the initial target of inorganic lead in the CNS may be the plasma membrane of the capillary endothelial cells, and that lead may act by altering the physiological function of these membranes

Acrolein induces vasodilatation of rodent mesenteric bed via an EDHF-dependent mechanism

International Nuclear Information System (INIS)

Awe, S.O.; Adeagbo, A.S.O.; D'Souza, S.E.; Bhatnagar, A.; Conklin, D.J.

2006-01-01

Acrolein is generated endogenously during lipid peroxidation and inflammation and is an environmental pollutant. Protein adducts of acrolein are detected in atherosclerotic plaques and neurons of patients with Alzheimer's disease. To understand vascular effects of acrolein exposure, we studied acrolein vasoreactivity in perfused rodent mesenteric bed. Acrolein induced endothelium-dependent vasodilatation that was more robust and more sensitive than dilation induced by 4-hydroxy-trans-2-nonenal, trans-2-hexenal, or propionaldehyde. Acrolein-induced vasodilatation was mediated by K + -sensitive components, e.g., it was abolished in 0 [K + ] o buffer or in 3 mM tetrabutylammonium, inhibited 75% in 50 μM ouabain, and inhibited 64% in 20 mM K + buffer. Moreover, combined treatment with the Ca 2+ -activated K + channel inhibitors 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34, 100 nM) and apamin (5 μM) significantly reduced vasodilatation without altering sensitivity to acrolein. However, acrolein-induced % dilation was unaffected by L-NAME or indomethacin pretreatment indicating mechanistic independence of NO and prostaglandins. Moreover, acrolein induced vasodilatation in cirazoline-precontracted mesenteric bed of eNOS-null mice confirming eNOS independence. Pretreatment with 6-(2-propargyloxyphenyl) hexanoic acid (PPOH 50 μM), an epoxygenase inhibitor, or the superoxide dismutase mimetic Tempol (100 μM) significantly attenuated acrolein-induced vasodilatation. Collectively, these data indicate that acrolein stimulates mesenteric bed vasodilatation due to endothelium-derived signal(s) that is K + -, ouabain-, PPOH-, and Tempol-sensitive, and thus, a likely endothelium-derived hyperpolarizing factor (EDHF). These data indicate that low level acrolein exposure associated with vascular oxidative stress or inflammation stimulates vasodilatation via EDHF release in medium-sized arteries - a novel function

Nitric oxide-dependent vasorelaxation induced by extractive solutions and fractions of Maytenus ilicifolia Mart ex Reissek (Celastraceae) leaves.

Science.gov (United States)

Rattmann, Yanna D; Cipriani, Thales R; Sassaki, Guilherme L; Iacomini, Marcello; Rieck, Lia; Marques, Maria C A; da Silva-Santos, José E

2006-04-06

This study reveals that an ethanolic supernatant obtained from an aqueous extractive solution prepared from residues of methanolic extracts of ground leaves of Maytenus ilicifolia is able to cause a concentration- and endothelium-dependent relaxation in pre-contract rat aorta rings, with EC(50) of 199.7 (190-210) microg/ml. The non-selective nitric oxide synthase inhibitors l-NAME and l-NMMA abolished this effect, while superoxide dismutase and MnTBAP (a non-enzymatic superoxide dismutase mimetic) enhanced it. Further, relaxation induced by this ethanolic supernatant have been strongly inhibited by the guanylate cyclase inhibitors methylene blue and ODQ, as well as by the potassium channel blockers 4-aminopyridine and tetraethylammonium, but was unchanged by the cyclooxygenase inhibitor indomethacin and the membrane receptor antagonists atropine, HOE-140 and pirilamine. Partition of the ethanolic supernatant between H(2)O and EtOAc generated a fraction several times more potent, able to fully relax endothelium-intact aorta rings with an EC(50) of 4.3 (3.9-4.8) microg/ml. (13)C NMR spectrum of this fraction showed signals typical of catechin. This study reveals that the leaves of M. ilicifolia possess one or more potent substances able to relax endothelium-intact rat aorta rings, an event that appears to involve nitric oxide production, guanylate cyclase activation and potassium channel opening.

Electrocardiographic abnormalities in opiate addicts.

Science.gov (United States)

Wallner, Christina; Stöllberger, Claudia; Hlavin, Anton; Finsterer, Josef; Hager, Isabella; Hermann, Peter

2008-12-01

To determine in a cross-sectional study the prevalence of electrocardiographic (ECG) abnormalities in opiate addicts who were therapy-seeking and its association with demographic, clinical and drug-specific parameters. In consecutive therapy-seeking opiate addicts, a 12-lead ECG was registered within 24 hours after admission and evaluated according to a pre-set protocol between October 2004 and August 2006. Additionally, demographic, clinical and drug-specific parameters were recorded. Included were 511 opiate-addicts, 25% female, with a mean age of 29 years (range 17-59 years). One or more ECG abnormalities were found in 314 patients (61%). In the 511 patients we found most commonly ST abnormalities (19%), QTc prolongation (13%), tall R- and/or S-waves (11%) and missing R progression (10%). ECG abnormalities were more common in males than in females (64 versus 54%, P seizures less often (16 versus 27%, P opiate addicts. The most frequent ECG abnormalities are ST abnormalities, QTc prolongation and tall R- and/or S-waves. ST abnormalities are associated with cannabis, and QTc prolongation with methadone and benzodiazepines.

Roentgenologic abnormalities in Down's syndrome

Energy Technology Data Exchange (ETDEWEB)

Higuchi, Takehiko; Russell, W J; Komatsuda, Michio; Neriishi, Shotaro

1968-07-25

Roentgenograms of 28 patients with Down's syndrome were reviewed with emphasis on all previously reported abnormalities and any possible additional ones. Most of the abnormalities occurred with the same frequency as previously reported, but some less frequently reported findings were also seen. One abnormal vertebral measurement found in this series may be an additional stigma of Down's syndrome. All of the 27 cases studied cytogenetically had chromosomal abnormalities consistent with this disease. This study emphasizes the need for roentgenologic norms for the Japanese, and the desirability of combining chromosome studies with roentgenological abnormalities and clinical observations in diagnosing Down's syndrome. 19 references, 2 figures, 5 tables.

Vascular Cognitive Impairment Linked to Brain Endothelium Inflammation in Early Stages of Heart Failure in Mice.

Science.gov (United States)

Adamski, Mateusz G; Sternak, Magdalena; Mohaissen, Tasnim; Kaczor, Dawid; Wierońska, Joanna M; Malinowska, Monika; Czaban, Iwona; Byk, Katarzyna; Lyngsø, Kristina S; Przyborowski, Kamil; Hansen, Pernille B L; Wilczyński, Grzegorz; Chlopicki, Stefan

2018-03-26

Although advanced heart failure (HF) is a clinically documented risk factor for vascular cognitive impairment, the occurrence and pathomechanisms of vascular cognitive impairment in early stages of HF are equivocal. Here, we characterize vascular cognitive impairment in the early stages of HF development and assess whether cerebral hypoperfusion or prothrombotic conditions are involved. Tgαq*44 mice with slowly developing isolated HF triggered by cardiomyocyte-specific overexpression of G-αq*44 protein were studied before the end-stage HF, at the ages of 3, 6, and 10 months: before left ventricle dysfunction; at the stage of early left ventricle diastolic dysfunction (with preserved ejection fraction); and left ventricle diastolic/systolic dysfunction, respectively. In 6- to 10-month-old but not in 3-month-old Tgαq*44 mice, behavioral and cognitive impairment was identified with compromised blood-brain barrier permeability, most significantly in brain cortex, that was associated with myelin sheet loss and changes in astrocytes and microglia. Brain endothelial cells displayed increased E-selectin immunoreactivity, which was accompanied by increased amyloid-β 1-42 accumulation in piriform cortex and increased cortical oxidative stress (8-OHdG immunoreactivity). Resting cerebral blood flow measured by magnetic resonance imaging in vivo was preserved, but ex vivo NO-dependent cortical arteriole flow regulation was impaired. Platelet hyperreactivity was present in 3- to 10-month-old Tgαq*44 mice, but it was not associated with increased platelet-dependent thrombogenicity. We report for the first time that vascular cognitive impairment is already present in the early stage of HF development, even before left ventricle systolic dysfunction. The underlying pathomechanism, independent of brain hypoperfusion, involves preceding platelet hyperreactivity and brain endothelium inflammatory activation. © 2018 The Authors. Published on behalf of the American Heart

Cannabis-related hippocampal volumetric abnormalities specific to subregions in dependent users.

Science.gov (United States)

Chye, Yann; Suo, Chao; Yücel, Murat; den Ouden, Lauren; Solowij, Nadia; Lorenzetti, Valentina

2017-07-01

Cannabis use is associated with neuroanatomical alterations in the hippocampus. While the hippocampus is composed of multiple subregions, their differential vulnerability to cannabis dependence remains unknown. The objective of the study is to investigate gray matter alteration in each of the hippocampal subregions (presubiculum, subiculum, cornu ammonis (CA) subfields CA1-4, and dentate gyrus (DG)) as associated with cannabis use and dependence. A total of 35 healthy controls (HC), 22 non-dependent (CB-nondep), and 39 dependent (CB-dep) cannabis users were recruited. We investigated group differences in hippocampal subregion volumes between HC, CB-nondep, and CB-dep users. We further explored the association between CB use variables (age of onset of regular use, monthly use, lifetime use) and hippocampal subregions in CB-nondep and CB-dep users separately. The CA1, CA2/3, CA4/DG, as well as total hippocampal gray matter were reduced in volume in CB-dep but not in CB-nondep users, relative to HC. The right CA2/3 and CA4/DG volumes were also negatively associated with lifetime cannabis use in CB-dep users. Our results suggest a regionally and dependence-specific influence of cannabis use on the hippocampus. Hippocampal alteration in cannabis users was specific to the CA and DG regions and confined to dependent users.

Role of endothelium in radiation-induced normal tissue damages

International Nuclear Information System (INIS)

Milliat, F.

2007-05-01

More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

Gender discrimination in the influence of hyperglycemia and hyperosmolarity on rat aortic tissue responses to insulin.

Science.gov (United States)

Wong, Nikki L; Achike, Francis I

2010-08-09

Hyperglycaemia initiates endothelial dysfunction causing diabetic macro- and micro-vasculopathy, the main causes of morbidity and mortality in diabetes mellitus. The vasculopathy exhibits gender peculiarities. We therefore explored gender differences in comparing the effects of hyperglycaemia (50 mM) per se with its hyperosmolar (50 mM) effects on vascular tissue responses to insulin. Endothelium-intact or denuded thoracic aortic rings from age-matched male and female Sprague-Dawley rats were incubated for 10 min or 6 h (acute versus chronic exposure) in normal, hyperglycaemic or hyperosmolar Krebs solution. Relaxant responses to insulin (6.9x10(-7)-6.9x10(-5) M) of the phenylephrine-contracted tissues were recorded. Endothelium denudation in both genders inhibited relaxation to insulin in all conditions, more significantly in female than in male tissues, suggesting the female response to insulin is more endothelium-dependent than the male. Acutely and chronically exposed normoglycemic endothelium-intact or -denuded tissues responded similarly to insulin. Chronic hyperglycemic or hyperosmolar exposure did not alter the endothelium-denuded tissue responses to insulin, whereas the responses of the endothelium-intact male and female hyperosmolar, and male hyperglycemic tissues were enhanced. The results show that insulin exerts an endothelium-dependent and independent relaxation with the female tissue responses more endothelium-dependent than the male. The data also suggest that hyperosmolarity per se enhances aortic tissue relaxant responses to insulin whereas hyperglycemia per se inhibits the same and more so in female than male tissues. These effects are endothelium-dependent. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Abnormality diagnosis device for nuclear reactor

Energy Technology Data Exchange (ETDEWEB)

Utsunomiya, Kazuhiro; Oyama, Shinmi; Sakaba, Hideo

1989-02-21

According to the present invention, abnormality such as abnormal increase of temperature in a nuclear reactor is detected to send a signal to control rod drives, etc. thereby stopping the operation of the nuclear reactor. Receiving/transmission device transmits a signal for conducting normal operation of an abnormality information section, as well as receives an echo signal from the abnormality information section to transmit an abnormal signal to a reactor protection system. The abnormality information section is disposed to fuel assemblies, receives a signal from the receiving/transmission device for conducting the normal operation to transmit a normal echo signal, as well as changes the echo signal when detecting the nuclear reactor abnormality. By the foregoing method, since the abnormality information section is disposed to the fuel assemblies, various effects can be attained such as: (1) there is no response delay from the occurrence of abnormality to emergency counter measure after detection, (2) high burnup degree for fuels can thus be possible to improve the economical property, (3) the abnormality information section can be taken out from the reactor container together with fuel assemablies by an existent take-out mechanism and (4) since wireless transmission and reception are established between the receiving/transmission device and the abnormality information section, cables are not required in the container. (K.M.).

Dose-dependent increases in flow-mediated dilation following acute cocoa ingestion in healthy older adults

Science.gov (United States)

Feehan, Robert P.; Kunselman, Allen R.; Preston, Amy G.; Miller, Debra L.; Lott, Mary E. J.

2011-01-01

An inverse relation exists between intake of flavonoid-rich foods, such as cocoa, and cardiovascular-related mortality. Favorable effects of flavonoids on the endothelium may underlie these associations. We performed a randomized, double-blind, placebo-controlled study to test the hypothesis that acute cocoa ingestion dose dependently increases endothelium-dependent vasodilation, as measured by an increase in brachial artery flow-mediated dilation (FMD), in healthy older adults. Measurements were obtained before (preingestion) and after (1- and 2-h postingestion) ingestion of 0 (placebo), 2, 5, 13, and 26 g of cocoa in 23 adults (63 ± 2 yr old, mean ± SE). Changes in brachial artery FMD 1- and 2-h postingestion compared with preingestion were used to determine the effects of cocoa. FMD was unchanged 1 (Δ−0.3 ± 0.2%)- and 2-h (Δ0.1 ± 0.1%) after placebo (0 g cocoa). In contrast, FMD increased both 1-h postingestion (2 g cocoa Δ0.0 ± 0.2%, 5 g cocoa Δ0.8 ± 0.3%, 13 g cocoa Δ1.0 ± 0.3%, and 26 g cocoa Δ1.6 ± 0.3%: P FMD 1- and 2-h postingestion (r = 0.44–0.48; both P FMD in healthy older humans. These responses may help to explain associations between flavonoid intake and cardiovascular-related mortality in humans. PMID:21903881

Enlarged cavum septum pellucidum as a neurodevelopmental marker in adolescent-onset opiate dependence.

Directory of Open Access Journals (Sweden)

Jaeuk Hwang

Full Text Available Adolescent-onset exposure to highly addictive substances such as opiates may induce far-reaching deleterious effects on later mental and physical health. However, little is known about the neurodevelopmental basis for adolescent-onset opiate dependence. Here we examined whether having an abnormally large cavum septum pellucidum (CSP, a putative marker of limbic structural maldevelopment, is associated with opiate dependence particularly beginning in adolescence.The overall length of the CSP and the prevalence of abnormal enlargement of the CSP were assessed and compared in 65 opiate-dependent subjects (41 adolescent-onset opiate users and 24 adult-onset opiate users and 67 healthy subjects.Opiate-dependent subjects showed a greater prevalence of abnormal CSP enlargement relative to healthy subjects (odds ratio [OR]=3.64, p=0.034. The overall CSP length of adolescent-onset opiate-dependent subjects was greater, as compared not only with healthy subjects (F₁,₁₀₄=11.03, p=0.001 but also with those who began opiate use during adulthood (F₁,₆₁=4.43, p=0.039.The current findings provide the first evidence that abnormal CSP enlargement, which reflects limbic system dysgenesis of neurodevelopmental origin, may be linked to later development of opiate dependence. In addition, a greater CSP length, which indicates more severe limbic abnormalities, appears to confer higher risk for earlier onset of opiate use.

Platelet Endothelial Cell Adhesion Molecule-1, a Putative Receptor for the Adhesion of Streptococcus pneumoniae to the Vascular Endothelium of the Blood-Brain Barrier

NARCIS (Netherlands)

Iovino, Federico; Molema, Grietje; Bijlsma, Jetta J. E.

The Gram-positive bacterium Streptococcus pneumoniae is the main causative agent of bacterial meningitis. S. pneumoniae is thought to invade the central nervous system via the bloodstream by crossing the vascular endothelium of the blood-brain barrier. The exact mechanism by which pneumococci cross

Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia.

Science.gov (United States)

Stanhewicz, Anna E; Jandu, Sandeep; Santhanam, Lakshmi; Alexander, Lacy M

2017-08-01

Women who have had preeclampsia have increased cardiovascular disease risk; however, the mechanism(s) responsible for this association remain unclear. Microvascular damage sustained during a preeclamptic pregnancy may persist postpartum. The putative mechanisms mediating this dysfunction include a reduction in NO-dependent dilation and an increased sensitivity to angiotensin II. In this study, we evaluated endothelium-dependent dilation, angiotensin II sensitivity, and the therapeutic effect of angiotensin II receptor blockade (losartan) on endothelium-dependent dilation in vivo in the microvasculature of women with a history of preeclampsia (n=12) and control women who had a healthy pregnancy (n=12). We hypothesized that preeclampsia would have (1) reduced endothelium-dependent dilation, (2) reduced NO-mediated dilation, and (3) increased sensitivity to angiotensin II. We further hypothesized that localized losartan would increase endothelium-dependent vasodilation in preeclampsia. We assessed microvascular endothelium-dependent vasodilator function by measurement of cutaneous vascular conductance responses to graded infusion of acetylcholine (acetylcholine; 10 -7 -102 mmol/L) and a standardized local heating protocol in control sites and sites treated with 15 mmol/L L-NAME ( N G -nitro-l-arginine methyl ester; NO-synthase inhibitor) or 43 µmol/L losartan. Further, we assessed microvascular vasoconstrictor sensitivity to angiotensin II (10 -20 -10 -4 mol/L). Preeclampsia had significantly reduced endothelium-dependent dilation (-0.3±0.5 versus -1.0±0.4 log EC50 ; P Preeclampsia also had augmented vasoconstrictor sensitivity to angiotensin II (-10.2±1.3 versus -8.3±0.5; P =0.006). Angiotensin II type I receptor inhibition augmented endothelium-dependent vasodilation and NO-dependent dilation in preeclampsia but had no effect in healthy pregnancy. These data suggest that women who have had preeclampsia have persistent microvascular dysfunction postpartum

Net Fluorescein Flux Across Corneal Endothelium Strongly Suggests Fluid Transport is due to Electro-osmosis.

Science.gov (United States)

Sanchez, J M; Cacace, V; Kusnier, C F; Nelson, R; Rubashkin, A A; Iserovich, P; Fischbarg, J

2016-08-01

We have presented prior evidence suggesting that fluid transport results from electro-osmosis at the intercellular junctions of the corneal endothelium. Such phenomenon ought to drag other extracellular solutes. We have investigated this using fluorescein-Na2 as an extracellular marker. We measured unidirectional fluxes across layers of cultured human corneal endothelial (HCE) cells. SV-40-transformed HCE layers were grown to confluence on permeable membrane inserts. The medium was DMEM with high glucose and no phenol red. Fluorescein-labeled medium was placed either on the basolateral or the apical side of the inserts; the other side carried unlabeled medium. The inserts were held in a CO2 incubator for 1 h (at 37 °C), after which the entire volume of the unlabeled side was collected. After that, label was placed on the opposite side, and the corresponding paired sample was collected after another hour. Fluorescein counts were determined with a (Photon Technology) DeltaScan fluorometer (excitation 380 nm; emission 550 nm; 2 nm bwth). Samples were read for 60 s. The cells utilized are known to transport fluid from the basolateral to the apical side, just as they do in vivo in several species. We used 4 inserts for influx and efflux (total: 20 1-h periods). We found a net flux of fluorescein from the basolateral to the apical side. The flux ratio was 1.104 ± 0.056. That difference was statistically significant (p = 0.00006, t test, paired samples). The endothelium has a definite restriction at the junctions. Hence, an asymmetry in unidirectional fluxes cannot arise from osmosis, and can only point instead to paracellular solvent drag. We suggest, once more, that such drag is due to electro-osmotic coupling at the paracellular junctions.

Endothelium adhesion molecules ICAM-1, ICAM-2, VCAM-1 and VLA-4 expression in leprosy.

Science.gov (United States)

de Sousa, Juarez; Sousa Aarão, Tinara Leila; Rodrigues de Sousa, Jorge; Hirai, Kelly Emi; Silva, Luciana Mota; Dias, Leonidas Braga; Oliveira Carneiro, Francisca Regina; Fuzii, Hellen Thais; Quaresma, Juarez Antonio Simões

2017-03-01

Leprosy triggers a complex relationship between the pathogen and host immune response. Endothelium plays an important role in this immune response by directly influencing cell migration to infected tissues. The objective of this work is to investigate the possible role of endothelium in M. leprae infection, correlating the characteristics of endothelial markers with the expression pattern of cytokines. Thirty-six skin biopsy samples were cut into 5-μm thick sections and stained with hematoxylin-eosin and Ziehl-Neelsen for morphological analysis and then submitted to immunohistochemical analysis using monoclonal antibodies against ICAM-1, ICAM-2, VCAM-1, and VLA-4. Immunostaining for ICAM-1 showed a significantly larger number of stained endothelial cells in the tuberculoid leprosy (9.92 ± 1.11 cells/mm 2 ) when compared to lepromatous samples (5.87 ± 1.01 cells/mm 2 ) and ICAM-2 revealed no significant difference in the number of endothelial cells expressing this marker between the tuberculoid (13.21 ± 1.27 cells/mm 2 ) and lepromatous leprosy (14.3 ± 1.02 cells/mm 2 ). VCAM-1-immunostained showed 18.28 ± 1.46/mm 2 cells in tuberculoid leprosy and 10.67 ± 1.25 cells/mm 2 in the lepromatous leprosy. VLA-4 exhibited 22.46 ± 1.38 cells/mm 2 in the tuberculoid leprosy 16.04 ± 1.56 cells/mm 2 in the lepromatous leprosy. Samples with characteristics of the tuberculoid leprosy exhibited a larger number of cells stained with ICAM-1, VCAM-1 and VLA-4, demonstrating the importance of these molecules in the migration and selection of cells that reach the inflamed tissue. Copyright © 2017 Elsevier Ltd. All rights reserved.

Normal and abnormal growth plate

International Nuclear Information System (INIS)

Kumar, R.; Madewell, J.E.; Swischuk, L.E.

1987-01-01

Skeletal growth is a dynamic process. A knowledge of the structure and function of the normal growth plate is essential in order to understand the pathophysiology of abnormal skeletal growth in various diseases. In this well-illustrated article, the authors provide a radiographic classification of abnormal growth plates and discuss mechanisms that lead to growth plate abnormalities

A structural abnormality associated with graded levels of thyroid hormone insufficiency: Dose dependent increases in heterotopia volume

Science.gov (United States)

A large number of environmental contaminants reduce circulating levels of thyroid hormone (TH), but clear markers of neurological insult associated with modest TH insufficiency are lacking. We have previously identified the presence of an abnormal cluster of misplaced neurons in ...

Management of Abnormal Uterine Bleeding with Emphasis on Alternatives to Hysterectomy.

Science.gov (United States)

Billow, Megan R; El-Nashar, Sherif A

2016-09-01

Abnormal uterine bleeding (AUB) is a common problem that negatively impacts a woman's health-related quality of life and activity. Initial medical treatment includes hormonal and nonhormonal medications. If bleeding persists and no structural abnormalities are present, a repeat trial of medical therapy, a levonorgestrel intrauterine system, or an endometrial ablation can be used dependent on future fertility wishes. The levonorgestrel intrauterine system and endometrial ablation are effective, less invasive, and safe alternatives to a hysterectomy in women with AUB. A hysterectomy is the definitive treatment of AUB irrespective of the suspected cause when alternative treatments fail. Future studies should focus on detection of predictors for treatment outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

Profile of hematological abnormalities of Indian HIV infected individuals

Directory of Open Access Journals (Sweden)

Sharma Aman

2009-08-01

Full Text Available Abstract Background Hematological abnormalities are a common complication of HIV infection. These abnormalities increase as the disease advances. Bone marrow abnormalities occur in all stages of HIV infection. Methods Two hundred HIV infected individual were screened for hematological abnormalities from March 2007–March 2008. Absolute CD4 cell count analysis was carried out by flowcytometry. Depending on the results of the primary screening further investigations were performed, like iron studies, hemolytic work up, PNH work up and bone marrow evaluation. Other investigations included coagulation profile, urine analysis, blood culture (bacterial, fungal, mycobacterial, serology for Epstein Barr virus (EBV, Cytomegalovirus (CMV, Hepatitis B and C, and Parvo B19 infection. Results The most common hematological abnormality was anemia, seen in 65.5% (131/200 patients. Iron deficiency anemia was seen in 49.2% (/200 cases while anemia of chronic disease occurred in 50.7% (/200 cases. Bone marrow evaluation was carried out in 14 patients out of which staging marrow was performed in 2 cases of non-Hodgkin's lymphoma (NHL and did not show any bone marrow infiltration. In remaining12 cases bone marrow was done for evaluation of pancytopenia. Among patients with pancytopenia 50% (6/12 showed granulomas (4 were positive for AFB, 2 were positive for fungal cryptococci, 25% (3/12 showed hemophagocytosis. There was a strong negative correlation between anemia and CD4 counts in this study. Thrombocytopenia was seen in 7% (14/200 cases and had no significant correlation with CD4 counts. No patient had absolute neutrophil count (ANC Conclusion Anemia in HIV patients can be a good clinical indicator to predict and access the underlying immune status. Patients should be investigated for hematological manifestations and appropriate steps should be taken to identify and treat the reversible factors.

Mitochondrial encephalomyopathy (MELAS) with mental disorder

International Nuclear Information System (INIS)

Suzuki, T.; Koizumi, J.; Shiraishi, H.; Ofuku, K.; Sasaki, M.; Hori, T.; Ishikawa, N.; Anno, I.; Ohkoshi, N.

1990-01-01

A case of mitochondrial encephalomyopathy (MELAS) with mental disorder is reported. The SPECT study using 123 I-iodoamphetamine (IMP) and MRI study revealed abnormality in the left parieto-occipital areas without abnormality in the brain CT or brain scintigram. These findings suggest a localized dysfunction of the brain capillary endothelium in association with the cerebral involvement of mitochondrial encephalomyopathy. (orig.)

Rapid and Weight-Independent Improvement of Glucose Tolerance Induced by a Peptide Designed to Elicit Apoptosis in Adipose Tissue Endothelium

Science.gov (United States)

Kim, Dong-Hoon; Sartor, Maureen A.; Bain, James R.; Sandoval, Darleen; Stevens, Robert D.; Medvedovic, Mario; Newgard, Christopher B.; Woods, Stephen C.; Seeley, Randy J.

2012-01-01

A peptide designed to induce apoptosis of endothelium in white adipose tissue (WAT) decreases adiposity. The goal of this work is to determine whether targeting of WAT endothelium results in impaired glucose regulation as a result of impaired WAT function. Glucose tolerance tests were performed on days 2 and 3 of treatment with vehicle (HF-V) or proapoptotic peptide (HF-PP) and mice pair-fed to HF-PP (HF-PF) in obese mice on a high-fat diet (HFD). Serum metabolic variables, including lipid profile, adipokines, individual fatty acids, and acylcarnitines, were measured. Microarray analysis was performed in epididymal fat of lean or obese mice treated with vehicle or proapoptotic peptide (PP). PP rapidly and potently improved glucose tolerance of obese mice in a weight- and food intake–independent manner. Serum insulin and triglycerides were decreased in HF-PP relative to HF-V. Levels of fatty acids and acylcarnitines were distinctive in HF-PP compared with HF-V or HF-PF. Microarray analysis in AT revealed that pathways involved in mitochondrial dysfunction, oxidative phosphorylation, and branched-chain amino acid degradation were changed by exposure to HFD and were reversed by PP administration. These studies suggest a novel role of the AT vasculature in glucose homeostasis and lipid metabolism. PMID:22733798

A family affair: brain abnormalities in siblings of patients with schizophrenia

Science.gov (United States)

Hulshoff Pol, Hilleke; Gogtay, Nitin

2013-01-01

Schizophrenia is a severe mental disorder that has a strong genetic basis. Converging evidence suggests that schizophrenia is a progressive neurodevelopmental disorder, with earlier onset cases resulting in more profound brain abnormalities. Siblings of patients with schizophrenia provide an invaluable resource for differentiating between trait and state markers, thus highlighting possible endophenotypes for ongoing research. However, findings from sibling studies have not been systematically put together in a coherent story across the broader age span. We review here the cortical grey matter abnormalities in siblings of patients with schizophrenia from childhood to adulthood, by reviewing sibling studies from both childhood-onset schizophrenia, and the more common adult-onset schizophrenia. When reviewed together, studies suggest that siblings of patients with schizophrenia display significant brain abnormalities that highlight both similarities and differences between the adult and childhood populations, with shared developmental risk patterns, and segregating trajectories. Based on current research it appears that the cortical grey matter abnormalities in siblings are likely to be an age-dependent endophenotype, which normalize by the typical age of onset of schizophrenia unless there has been more genetic or symptom burdening. With increased genetic burdening (e.g. discordant twins of patients) the grey matter abnormalities in (twin) siblings are progressive in adulthood. This synthesis of the literature clarifies the importance of brain plasticity in the pathophysiology of the illness, indicating that probands may lack protective factors critical for healthy development. PMID:23698280

Breast cancer drugs dampen vascular functions by interfering with nitric oxide signaling in endothelium

International Nuclear Information System (INIS)

Gajalakshmi, Palanivel; Priya, Mani Krishna; Pradeep, Thangaraj; Behera, Jyotirmaya; Muthumani, Kandasamy; Madhuwanti, Srinivasan; Saran, Uttara; Chatterjee, Suvro

2013-01-01

Widely used chemotherapeutic breast cancer drugs such as Tamoxifen citrate (TC), Capecitabine (CP) and Epirubicin (EP) are known to cause various cardiovascular side-effects among long term cancer survivors. Vascular modulation warrants nitric oxide (NO) signal transduction, which targets the vascular endothelium. We hypothesize that TC, CP and EP interference with the nitric oxide downstream signaling specifically, could lead to cardiovascular dysfunctions. The results demonstrate that while all three drugs attenuate NO and cyclic guanosine mono-phosphate (cGMP) production in endothelial cells, they caused elevated levels of NO in the plasma and RBC. However, PBMC and platelets did not show any significant changes under treatment. This implies that the drug effects are specific to the endothelium. Altered eNOS and phosphorylated eNOS (Ser-1177) localization patterns in endothelial cells were observed following drug treatments. Similarly, the expression of phosphorylated eNOS (Ser-1177) protein was decreased under the treatment of drugs. Altered actin polymerization was also observed following drug treatment, while addition of SpNO and 8Br-cGMP reversed this effect. Incubation with the drugs decreased endothelial cell migration whereas addition of YC-1, SC and 8Br-cGMP recovered the effect. Additionally molecular docking studies showed that all three drugs exhibited a strong binding affinity with the catalytic domain of human sGC. In conclusion, results indicate that TC, CP and EP cause endothelial dysfunctions via the NO–sGC–cGMP pathway and these effects could be recovered using pharmaceutical agonists of NO signaling pathway. Further, the study proposes a combination therapy of chemotherapeutic drugs and cGMP analogs, which would confer protection against chemotherapy mediated vascular dysfunctions in cancer patients. - Highlights: • NO production is reduced in endothelial cells under breast cancer drug treatment. • Cellular cGMP level is decreased under

Breast cancer drugs dampen vascular functions by interfering with nitric oxide signaling in endothelium

Energy Technology Data Exchange (ETDEWEB)

Gajalakshmi, Palanivel; Priya, Mani Krishna; Pradeep, Thangaraj; Behera, Jyotirmaya; Muthumani, Kandasamy; Madhuwanti, Srinivasan; Saran, Uttara; Chatterjee, Suvro, E-mail: soovro@yahoo.ca

2013-06-01

Widely used chemotherapeutic breast cancer drugs such as Tamoxifen citrate (TC), Capecitabine (CP) and Epirubicin (EP) are known to cause various cardiovascular side-effects among long term cancer survivors. Vascular modulation warrants nitric oxide (NO) signal transduction, which targets the vascular endothelium. We hypothesize that TC, CP and EP interference with the nitric oxide downstream signaling specifically, could lead to cardiovascular dysfunctions. The results demonstrate that while all three drugs attenuate NO and cyclic guanosine mono-phosphate (cGMP) production in endothelial cells, they caused elevated levels of NO in the plasma and RBC. However, PBMC and platelets did not show any significant changes under treatment. This implies that the drug effects are specific to the endothelium. Altered eNOS and phosphorylated eNOS (Ser-1177) localization patterns in endothelial cells were observed following drug treatments. Similarly, the expression of phosphorylated eNOS (Ser-1177) protein was decreased under the treatment of drugs. Altered actin polymerization was also observed following drug treatment, while addition of SpNO and 8Br-cGMP reversed this effect. Incubation with the drugs decreased endothelial cell migration whereas addition of YC-1, SC and 8Br-cGMP recovered the effect. Additionally molecular docking studies showed that all three drugs exhibited a strong binding affinity with the catalytic domain of human sGC. In conclusion, results indicate that TC, CP and EP cause endothelial dysfunctions via the NO–sGC–cGMP pathway and these effects could be recovered using pharmaceutical agonists of NO signaling pathway. Further, the study proposes a combination therapy of chemotherapeutic drugs and cGMP analogs, which would confer protection against chemotherapy mediated vascular dysfunctions in cancer patients. - Highlights: • NO production is reduced in endothelial cells under breast cancer drug treatment. • Cellular cGMP level is decreased under

Operation aid system upon occurrence of abnormality and display method therefor

International Nuclear Information System (INIS)

Kubota, Ryuji; Ueno, Takashi.

1995-01-01

The present invention provides an operation aid system for a plant having a large number of systematic equipments upon occurrence of an abnormality and a method of displaying it. Namely, contents of an operation manual upon occurrence of an abnormality is displayed in the form of a flow chart divided into a judging section and an operation section depending on symptoms of plant parameters. Discrimination numbers are provided to a plurality sets of the judging sections and the operation sections respectively. With such procedures, using various measured signals of the plant as inputted data, the discrimination numbers of the judging sections in accordance with the inputted data are stored. Then a flow chart for the judging sections and the operation sections corresponding to the stored discrimination numbers are displayed. Further, an operation manual upon occurrence of abnormalities relevant to the judging sections and the operation sections in the form of writings, and previously determined drawings of relevant systems and trend graphs of the plant are also displayed with reference to the discrimination numbers described above. As a result, both of an appropriate operation manual and relevant information are displayed simultaneously for the occurrence of a plant abnormality and an operator's erroneous operation. (I.S.)

Defining Abnormally Low Tenders

DEFF Research Database (Denmark)

Ølykke, Grith Skovgaard; Nyström, Johan

2017-01-01

The concept of an abnormally low tender is not defined in EU public procurement law. This article takes an interdisciplinary law and economics approach to examine a dataset consisting of Swedish and Danish judgments and verdicts concerning the concept of an abnormally low tender. The purpose...

MR imaging of abnormal synovial processes

International Nuclear Information System (INIS)

Quinn, S.F.; Sanchez, R.; Murray, W.T.; Silbiger, M.L.; Ogden, J.; Cochran, C.

1987-01-01

MR imaging can directly image abnormal synovium. The authors reviewed over 50 cases with abnormal synovial processes. The abnormalities include Baker cysts, semimembranous bursitis, chronic shoulder bursitis, peroneal tendon ganglion cyst, periarticular abscesses, thickened synovium from rheumatoid and septic arthritis, and synovial hypertrophy secondary to Legg-Calve-Perthes disease. MR imaging has proved invaluable in identifying abnormal synovium, defining the extent and, to a limited degree, characterizing its makeup

Abnormal grain growth in Eurofer-97 steel in the ferrite phase field

Energy Technology Data Exchange (ETDEWEB)

Oliveira, V.B. [Lorena School of Engineering, University of Sao Paulo, Lorena, SP, 12602-810 (Brazil); Sandim, H.R.Z., E-mail: hsandim@demar.eel.usp.br [Lorena School of Engineering, University of Sao Paulo, Lorena, SP, 12602-810 (Brazil); Raabe, D. [Max-Planck-Institut für Eisenforschung, Düsseldorf, D-40237 (Germany)

2017-03-15

Reduced-activation ferritic-martensitic (RAFM) Eurofer-97 steel is a candidate material for structural applications in future fusion reactors. Depending on the amount of prior cold rolling strain and annealing temperature, important solid-state softening reactions such as recovery, recrystallization, and grain growth occur. Eurofer-97 steel was cold rolled up to 70, 80 and 90% reductions in thickness and annealed in the ferrite phase field (below ≈ 800 °C). Changes in microstructure, micro-, and mesotexture were followed by orientation mappings provided by electron backscatter diffraction (EBSD). Eurofer-97 steel undergoes abnormal grain growth above 650 °C and this solid-state reaction seems to be closely related to the high mobility of a few special grain boundaries that overcome pinning effects caused by fine particles. This solid-state reaction promotes important changes in the microstructure and microtexture of this steel. Abnormal grain growth kinetics for each condition was determined by means of quantitative metallography. - Highlights: • Abnormal grain growth (AGG) occurs in Eurofer-97 steel deformed to several strains. • Kinetics of abnormal grain growth has been determined at 750 and 800 °C. • Significant changes in crystallographic texture take place during AGG. • Grain boundaries with misorientations above 45° may explain abnormal grain growth. • Local microstructural instabilities (coarsening of M23C6 carbides) also explain AGG.

Abnormal thiamine-dependent processes in Alzheimer's Disease. Lessons from diabetes.

Science.gov (United States)

Gibson, Gary E; Hirsch, Joseph A; Cirio, Rosanna T; Jordan, Barry D; Fonzetti, Pasquale; Elder, Jessica

2013-07-01

Reduced glucose metabolism is an invariant feature of Alzheimer's Disease (AD) and an outstanding biomarker of disease progression. Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional glucose hypometabolism remains unclear. Thiamine-dependent processes are critical in glucose metabolism and are diminished in brains of AD patients at autopsy. Further, the reductions in thiamine-dependent processes are highly correlated to the decline in clinical dementia rating scales. In animal models, thiamine deficiency exacerbates plaque formation, promotes phosphorylation of tau and impairs memory. In contrast, treatment of mouse models of AD with the thiamine derivative benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses memory deficits. Diabetes predisposes to AD, which suggests they may share some common mechanisms. Benfotiamine diminishes peripheral neuropathy in diabetic humans and animals. In diabetes, benfotiamine induces key thiamine-dependent enzymes of the pentose shunt to reduce accumulation of toxic metabolites including advanced glycation end products (AGE). Related mechanisms may lead to reversal of plaque formation by benfotiamine in animals. If so, the use of benfotiamine could provide a safe intervention to reverse biological and clinical processes of AD progression. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'. Copyright © 2012 Elsevier Inc. All rights reserved.

Glioblastoma stem-like cells give rise to tumour endothelium

NARCIS (Netherlands)

Wang, Rong; Chadalavada, Kalyani; Wilshire, Jennifer; Kowalik, Urszula; Hovinga, Koos E.; Geber, Adam; Fligelman, Boris; Leversha, Margaret; Brennan, Cameron; Tabar, Viviane

2010-01-01

Glioblastoma (GBM) is among the most aggressive of human cancers. A key feature of GBMs is the extensive network of abnormal vasculature characterized by glomeruloid structures and endothelial hyperplasia. Yet the mechanisms of angiogenesis and the origin of tumour endothelial cells remain poorly

Oxidant-NO dependent gene regulation in dogs with type I diabetes: impact on cardiac function and metabolism

Directory of Open Access Journals (Sweden)

Ojaimi Caroline

2010-08-01

Full Text Available Abstract Background The mechanisms responsible for the cardiovascular mortality in type I diabetes (DM have not been defined completely. We have shown in conscious dogs with DM that: 1 baseline coronary blood flow (CBF was significantly decreased, 2 endothelium-dependent (ACh coronary vasodilation was impaired, and 3 reflex cholinergic NO-dependent coronary vasodilation was selectively depressed. The most likely mechanism responsible for the depressed reflex cholinergic NO-dependent coronary vasodilation was the decreased bioactivity of NO from the vascular endothelium. The goal of this study was to investigate changes in cardiac gene expression in a canine model of alloxan-induced type 1 diabetes. Methods Mongrel dogs were chronically instrumented and the dogs were divided into two groups: one normal and the other diabetic. In the diabetic group, the dogs were injected with alloxan monohydrate (40-60 mg/kg iv over 1 min. The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n = 4. Results The array data revealed that 797 genes were differentially expressed (P 2+ cycling genes (ryanodine receptor; SERCA2 Calcium ATPase, structural proteins (actin alpha. Of particular interests are genes involved in glutathione metabolism (glutathione peroxidase 1, glutathione reductase and glutathione S-transferase, which were markedly down regulated. Conclusion our findings suggest that type I diabetes might have a direct effect on the heart by impairing NO bioavailability through oxidative stress and perhaps lipid peroxidases.

Developmental abnormalities of the vitreous in mouse fetuses caused by simultaneous irradiation of x-rays and ultrasound

Energy Technology Data Exchange (ETDEWEB)

Shirai, S; Yuguchi, S; Majima, A [Nagoya City Univ. (Japan). Faculty of Medicine

1980-10-01

Eye abnormalities in mouse fetuses caused by irradiation of X-rays alone, or simultaneous irradiation of X-rays and ultrasound on day 7 of gestation were histologically studied on day 18 of gestation. Developmental abnormalities of the vitreous were examined in the present experiment, and the following results were obtained. 1. Developmental abnormalities of the vitreous were observed in 23 fetuses, and unilateral cases were 15 of 23 fetuses. In 31 eyes with these abnormalities, much more abundant mesenchymal tissue of components of primary vitreous was found in the retrolental vitreous cavity than in the normal eyes. 2. The above 31 eyes were also accompanied by a variety of ocular abnormalities such as microphthalmia, faulty closure of the fetal fissure, aplasia and hypoplasia of the optic nerve, goniodysgenesis, and corneolenticular adhesion. Complications observed to be associated with developmental abnormalities of the vitreous were lens abnormalities, retinal traction and fold, fibrovascular anastomosis between mesenchymal tissues of the chamber angle and vitreous cavity, retinal rosette, and anomalies of the optic nerve head. 3. The histological findings of 17 eyes corresponded to anterior persistent hyperplastic primary vitreous (PHPV) encountered clinically, those of 3 eyes to posterior PHPV, those of 6 eyes to mixed type of both anterior and posterior types, and those of 5 eyes to PHPV of the optic nerve head. In 3 bilateral cases, the type was different for either eye. 4. From these results, it was considered that the pathogenesis of PHPV of Reese and congenital retinal fold of Mann consists of the maldevelopment of the components of the primary vitreous, and that the type of defect depends on the portion involved and the degree depends on the time at which the maldevelopment occurs.

Developmental abnormalities of the vitreous in mouse fetuses caused by simultaneous irradiation of x-rays and ultrasound

International Nuclear Information System (INIS)

Shirai, Shoichiro; Yuguchi, Shuji; Majima, Akio

1980-01-01

Eye abnormalities in mouse fetuses caused by irradiation of X-rays alone, or simultaneous irradiation of X-rays and ultrasound on day 7 of gestation were histologically studied on day 18 of gestation. Developmental abnormalities of the vitreous were examined in the present experiment, and the following results were obtained. 1. Developmental abnormalities of the vitreous were observed in 23 fetused, and unilateral cases were 15 of 23 fetuses. In 31 eyes with these abnormalities, much more abundant mesenchymal tissue of components of primary vitreous was found in the retrolental vitreous cavity than in the normal eyes. 2. The above 31 eyes were also accompanied by a variety of ocular abnormalities such as microphthalmia, faulty closure of the fetal fissure, aplasia and hypoplasia of the optic nerve, goniodysgenesis, and corneolenticular adhesion. Complications observed to be associated with developmental abnormalities of the vitreous were lens abnormalities, retinal traction and fold, fibrovascular anastomosis between mesenchymal tissues of the chamber angle and vitrious cavity, retinal rosette, and anomalies of the optic nerve head. 3. The histological findings of 17 eyes corresponded to anterior persistent hyperplastic primary vitreous (PHPV) encountered clinically, those of 3 eyes to posterior PHPV, those of 6 eyes to mixed type of both anterior and posterior types, and those of 5 eyes to PHPV of the optic nerve head. In 3 bilateral cases, the type was different for either eye. 4. From these results, it was considered that the pathogenesis of PHPV of Reese and congenital retinal fold of Mann consists of the maldevelopment of the components of the primary vitreous, and that the type of defect is depends on the portion involved and the degree depends on the time at which the maldevelopment occurs. (author)

Mechanisms of endothelial dysfunction in resistance arteries from patients with end-stage renal disease.

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Leanid Luksha

Full Text Available The study focuses on the mechanisms of endothelial dysfunction in the uremic milieu. Subcutaneous resistance arteries from 35 end-stage renal disease (ESRD patients and 28 matched controls were studied ex-vivo. Basal and receptor-dependent effects of endothelium-derived factors, expression of endothelial NO synthase (eNOS, prerequisites for myoendothelial gap junctions (MEGJ, and associations between endothelium-dependent responses and plasma levels of endothelial dysfunction markers were assessed. The contribution of endothelium-derived hyperpolarizing factor (EDHF to endothelium-dependent relaxation was impaired in uremic arteries after stimulation with bradykinin, but not acetylcholine, reflecting the agonist-specific differences. Diminished vasodilator influences of the endothelium on basal tone and enhanced plasma levels of asymmetrical dimethyl L-arginine (ADMA suggest impairment in NO-mediated regulation of uremic arteries. eNOS expression and contribution of MEGJs to EDHF type responses were unaltered. Plasma levels of ADMA were negatively associated with endothelium-dependent responses in uremic arteries. Preserved responses of smooth muscle to pinacidil and NO-donor indicate alterations within the endothelium and tolerance of vasodilator mechanisms to the uremic retention products at the level of smooth muscle. We conclude that both EDHF and NO pathways that control resistance artery tone are impaired in the uremic milieu. For the first time, we validate the alterations in EDHF type responses linked to kinin receptors in ESRD patients. The association between plasma ADMA concentrations and endothelial function in uremic resistance vasculature may have diagnostic and future therapeutic implications.

The Role of Nitric Oxide Metabolites in the Formation of Endothelial Dysfunction in Children with Persistent Bronchial Asthma

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Yu.V. Odinets

2016-09-01

Full Text Available The aim of the study was to assess the role of nitric oxide metabolites in the development of endothelium dysfunction in children with persistent bronchial asthma in acute period and during remission Material and methods. Fifty eight children aged 6–17 years old suffering from persistent bronchial asthma in the period of exacerbation and remission of disease and 15 healthy children of control group have been exa­mined in order to evaluate the role of the metabolites of nitric oxide levels for the development of endothelium dysfunction in the children with persistent bronchial asthma. There were determined serum blood S-nitrosothiol, NO2, NO3, the intima-media complex by the ultrasound duplex scanning and endothelium-dependent dilation status of the brachial artery by cuff probe. Results. It showed a reduction in the levels of nitric oxide metabolites and endothelium-dependent dilation of the brachial artery, intima-media thickening in the period of exacerbation. There was revealed a significant increase in the levels of nitric oxide metabolites and endothelium-dependent dilation of the brachial artery compared with the period of exacerbation, but these findings are still lower in comparison with the control group, which indicates the presence of persistent changes in the vascular wall. Conclusion. The nitric oxide metabolites as well as the carotid intimal medial thickness and endothelium-dependent dilation of brachial artery should be marders of endothelium dysfunction in the children with bronchial asthma.

An in vivo evaluation of induction of abnormal sperm morphology by ivermectin MSD (Mectizan).

Science.gov (United States)

Otubanjo, O A; Mosuro, A A; Ladipo, T F

2007-01-01

The in vivo effects of orally administered ivermectin (Mectizan) on sperm head morphology of albino mice were evaluated. Four different dose levels of 0.25, 0.5, 1.0 and 1.5 x the human therapeutic dose of 150 g kg(-1) body weight, were administered to the animals. The animals were exposed to a single oral treatment. The sperm of the mice from the cauda epididymes were examined 5 and 7 weeks after treatment. Ivermectin (Mectizan) induced sperm head abnormalities; however, the induction was not significantly elevated above the negative control value. Furthermore, the induction of the sperm head abnormalities was not strictly dose-dependent and there was also no correlation between dose level of administered drug and incidence of abnormal sperms. This indicates that the drug might not be mutagenic.

Special report on abnormal climate in 2010

International Nuclear Information System (INIS)

2010-12-01

This reports on abnormal climate in 2010 with impact on the each field. It is comprised of four chapters, which deal with Introduction with purpose of publish and background, current situation and cause of abnormal climate in 2010 on abnormal climate around the world and Korea, Action and impact against abnormal climate in 2010 to agriculture, industry and energy, prevention of disasters, forest, fishery products, environment and health, Evaluation and policy proposal. It also has an appendix about occurrence and damage on abnormal climate of the world in 2010 and media reports on abnormal climate in Korea in 2010.

Differential Changes of Aorta and Carotid Vasodilation in Type 2 Diabetic GK and OLETF Rats: Paradoxical Roles of Hyperglycemia and Insulin

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Mei-Fang Zhong

2012-01-01

Full Text Available We investigated large vessel function in lean Goto-Kakizaki diabetic rats (GK and Otsuka Long-Evans Tokushima Fatty diabetic rats (OLETF with possible roles of hyperglycemia/hyperosmolarity and insulin. Both young and old GK showed marked hyperglycemia with normal insulin level and well-preserved endothelium-dependent and endothelium-independent vasodilation in aorta and carotid artery. There were significant elevations in endothelial/inducible nitric oxide synthase (eNOS/iNOS and inducible/constitutive heme oxygenase (HO-1/HO-2 in GK. The endothelium-dependent vasodilation in GK was inhibited partly by NOS blockade and completely by simultaneous blocking of HO and NOS. In contrast, OLETF showed hyperinsulinemia and mild hyperglycemia but significant endothelium dysfunction beginning at early ages with concomitantly reduced eNOS. Insulin injection corrected hyperglycemia in GK but induced endothelium dysfunction and intima hyperplasia. Hyperglycemia/hyperosmolarity in vitro enhanced vessel eNOS/HO. We suggest that hyperinsulinemia plays a role in endothelium dysfunction in obese diabetic OLETF, while hyperglycemia/hyperosmolarity-induced eNOS/HO upregulation participates in the adaptation of endothelium function in lean diabetic GK.

Comparison of neuromuscular abnormalities between upper and lower extremities in hemiparetic stroke.

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Mirbagheri, M M; AliBiglou, L; Thajchayapong, M; Lilaonitkul, T; Rymer, W Z

2006-01-01

We studied the neuromuscular mechanical properties of the elbow and ankle joints in chronic, hemiparetic stroke patients and healthy subjects. System identification techniques were used to characterize the mechanical abnormalities of these joints and to identify the contribution of intrinsic and reflex stiffness to these abnormalities. Modulation of intrinsic and reflex stiffness with the joint angle was studied by applying PRBS perturbations to the joint at different joint angles. The experiments were performed for both spastic (stroke) and contralateral (control) sides of stroke patients and one side of healthy (normal) subjects. We found reflex stiffness gain (GR) was significantly larger in the stroke than the control side for both elbow and ankle joints. GR was also strongly position dependent in both joints. However, the modulation of GR with position was slightly different in two joints. GR was also larger in the control than the normal joints but the differences were significant only for the ankle joint. Intrinsic stiffness gain (K) was also significantly larger in the stroke than the control joint at elbow extended positions and at ankle dorsiflexed positions. Modulation of K with the ankle angle was similar for stroke, control and normal groups. In contrast, the position dependency of the elbow was different. K was larger in the control than normal ankle whereas it was lower in the control than normal elbow. However, the differences were not significant for any joint. The findings demonstrate that both reflex and intrinsic stiffness gain increase abnormally in both upper and lower extremities. However, the major contribution of intrinsic and reflex stiffness to the abnormalities is at the end of ROM and at the middle ROM, respectively. The results also demonstrate that the neuromuscular properties of the contralateral limb are not normal suggesting that it may not be used as a suitable control at least for the ankle study.

Effect of topical 0.05% cyclosporine A on corneal endothelium in patients with dry eye disease.

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Pérez-Rico, Consuelo; Germain, Francisco; Castro-Rebollo, María; Moreno-Salgueiro, Agustín; Teus, Miguel Ángel

2013-01-01

To determine the effect of topical 0.05% cyclosporine A (CsA) on corneal endothelium in patients with dry eye disease. Observational, prospective, case series study. Fifty-five eyes of 29 consecutive patients (9 males and 20 females; median age: 66.8 years, interquartile range: 61-73.2 years) with moderate-severe dry eye disease were evaluated. All patients were treated with topical 0.05% CsA ophthalmic emulsion twice a day in addition to lubricant eyedrops 5 times a day. The follow-up period was 12 months. Before treatment and at 3 and 12 months post-treatment central corneal specular microscopy was performed. The endothelial cell density (ECD), coefficient of variation of cell size (CoV), and percentage of hexagonal cells (Hex %) were analyzed. The median ECDs pre-treatment and at 3 and 12 months post-treatment were 2 352.5/mm(2) (interquartile range, 2 178-2 548.5), 2364/mm(2) (interquartile range, 2 174.25-2 657.5), and 2366 cells/mm(2) (interquartile range, 2 174.75-2 539.75), respectively (P=0.927, one way ANOVA). The median CoVs pre-treatment and at 3 and 12 months post-treatment were 34.5 (interquartile range, 30-37), 35 (interquartile range, 30-38), and 34 (interquartile range, 30.75-38.25), respectively (P=0.7193, one way ANOVA). The median Hex % values pre-treatment and at 3 and 12 months post-treatment were 53 (interquartile range, 47-58), 54 (interquartile range, 45.75-59), and 50.5 (interquartile range, 45.75-58), respectively (P=0.824, one way ANOVA). Treatment of patients with dry eye disease for 12 months with topical 0.05% CsA does not seem to cause substantial changes on corneal endothelium.

Abnormal vibration of turbine due to oil whip

International Nuclear Information System (INIS)

Koo, Jae Raeyang; Hwang, Jae Hyeon

2001-01-01

Almost all rotating machinery has bearings. Bearing is one of the most important part of rotating machinery. Vibration of rotating machinery depend on its bearing conditions. Bearing conditions are following; oil gap, bearing type, bearing temperature, bearing oil condition. Especially, bearing oil condition influences on rotating machinery vibration directly. In this paper we have discussed the abnormal vibration of turbine due to oil condition. Oil whip problem was occurred in the certain power plant and we had solved this problem through the control of operating values and alignment

Immuno-Spin Trapping-Based Detection of Oxidative Modifications in Cardiomyocytes and Coronary Endothelium in the Progression of Heart Failure in Tgαq*44 Mice

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Bartosz Proniewski

2018-05-01

Full Text Available Recent studies suggest both beneficial and detrimental role of increased reactive oxygen species and oxidative stress in heart failure (HF. However, it is not clear at which stage oxidative stress and oxidative modifications occur in the endothelium in relation to cardiomyocytes in non-ischemic HF. Furthermore, most methods used to date to study oxidative stress are either non-specific or require tissue homogenization. In this study, we used immuno-spin trapping (IST technique with fluorescent microscopy-based detection of DMPO nitrone adducts to localize and quantify oxidative modifications of the hearts from Tgαq*44 mice; a murine model of HF driven by cardiomyocyte-specific overexpression of Gαq* protein. Tgαq*44 mice and age-matched FVB controls at early, transition, and late stages of HF progression were injected with DMPO in vivo and analyzed ex vivo for DMPO nitrone adducts signals. Progressive oxidative modifications in cardiomyocytes, as evidenced by the elevation of DMPO nitrone adducts, were detected in hearts from 10- to 16-month-old, but not in 8-month-old Tgαq*44 mice, as compared with age-matched FVB mice. The DMPO nitrone adducts were detected in left and right ventricle, septum, and papillary muscle. Surprisingly, significant elevation of DMPO nitrone adducts was also present in the coronary endothelium both in large arteries and in microcirculation simultaneously, as in cardiomyocytes, starting from 10-month-old Tgαq*44 mice. On the other hand, superoxide production in heart homogenates was elevated already in 6-month-old Tgαq*44 mice and progressively increased to high levels in 14-month-old Tgαq*44 mice, while the enzymatic activity of catalase, glutathione reductase, and glutathione peroxidase was all elevated as early as in 4-month-old Tgαq*44 mice and stayed at a similar level in 14-month-old Tgαq*44. In summary, this study demonstrates that IST represents a unique method that allows to quantify oxidative

A key role for the endothelium in NOD1 mediated vascular inflammation: comparison to TLR4 responses.

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Timothy Gatheral

Full Text Available Understanding the mechanisms by which pathogens induce vascular inflammation and dysfunction may reveal novel therapeutic targets in sepsis and related conditions. The intracellular receptor NOD1 recognises peptidoglycan which features in the cell wall of gram negative and some gram positive bacteria. NOD1 engagement generates an inflammatory response via activation of NFκB and MAPK pathways. We have previously shown that stimulation of NOD1 directly activates blood vessels and causes experimental shock in vivo. In this study we have used an ex vivo vessel-organ culture model to characterise the relative contribution of the endothelium in the response of blood vessels to NOD1 agonists. In addition we present the novel finding that NOD1 directly activates human blood vessels. Using human cultured cells we confirm that endothelial cells respond more avidly to NOD1 agonists than vascular smooth muscle cells. Accordingly we have sought to pharmacologically differentiate NOD1 and TLR4 mediated signalling pathways in human endothelial cells, focussing on TAK1, NFκB and p38 MAPK. In addition we profile novel inhibitors of RIP2 and NOD1 itself, which specifically inhibit NOD1 ligand induced inflammatory signalling in the vasculature. This paper is the first to demonstrate activation of whole human artery by NOD1 stimulation and the relative importance of the endothelium in the sensing of NOD1 ligands by vessels. This data supports the potential utility of NOD1 and RIP2 as therapeutic targets in human disease where vascular inflammation is a clinical feature, such as in sepsis and septic shock.

Oxidative stress upregulates the NMDA receptor on cerebrovascular endothelium.

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Betzen, Christian; White, Robin; Zehendner, Christoph M; Pietrowski, Eweline; Bender, Bianca; Luhmann, Heiko J; Kuhlmann, Christoph R W

2009-10-15

N-methyl-d-aspartate receptor (NMDA-R)-mediated oxidative stress has been implicated in blood-brain barrier (BBB) disruption in a variety of neuropathological diseases. Although some interactions between both phenomena have been elucidated, possible influences of reactive oxygen species (ROS) on the NMDA-R itself have so far been neglected. The objective of this study was to examine how the cerebroendothelial NMDA-R is affected by exposure to oxidative stress and to assess possible influences on BBB integrity. RT-PCR confirmed several NMDA-R subunits (NR1, NR2B-D) expressed in the bEnd3 cell line (murine cerebrovascular endothelial cells). NR1 protein expression after exposure to ROS was observed via in-cell Western. The functionality of the expressed NMDA-R was determined by measuring DiBAC fluorescence in ROS-preexposed cells upon stimulation with the specific agonist NMDA. Finally, the effects on barrier integrity were evaluated using the ECIS system to detect changes in monolayer impedance upon NMDA-R stimulation after exposure to ROS. The expression of NR1 significantly (p<0.001) increased 72 h after 30 min exposure to superoxide (+33.8+/-7.5%), peroxynitrite (+84.9+/-10.7%), or hydrogen peroxide (+92.8+/-7.6%), resulting in increased cellular response to NMDA-R stimulation and diminished monolayer impedance. We conclude that oxidative stress upregulates NMDA-R on cerebrovascular endothelium and thus heightens susceptibility to glutamate-induced BBB disruption.

Report on abnormal climate in 2011

International Nuclear Information System (INIS)

2011-12-01

This paper reports of impact on abnormal climate in 2011. It has Introduction with purpose and background of publish and summary of this report. The cause and current state on abnormal climate of the world and Korea in 2011, Measurement and impact against abnormal climate in 2011 to agriculture, land and maritime, industry and energy, prevention of disasters, environment and health, assessment and advice on the policy. It lists the appendix about occurrence and damage on abnormal climate of the world and Korea in 2011 and media report data.

Pregnancy Complications: Umbilical Cord Abnormalities

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... Umbilical cord abnormalities Umbilical cord abnormalities Now playing: E-mail to a friend Please fill in all fields. ... blood supply) to the baby. The two arteries transport waste from the baby to the placenta (where ...

Progranulin protects vascular endothelium against atherosclerotic inflammatory reaction via Akt/eNOS and nuclear factor-κB pathways.

Science.gov (United States)

Hwang, Hwan-Jin; Jung, Tae Woo; Hong, Ho Cheol; Choi, Hae Yoon; Seo, Ji-A; Kim, Sin Gon; Kim, Nan Hee; Choi, Kyung Mook; Choi, Dong Seop; Baik, Sei Hyun; Yoo, Hye Jin

2013-01-01

Atherosclerosis is considered a chronic inflammatory disease, initiated by activation and dysfunction of the endothelium. Recently, progranulin has been regarded as an important modulator of inflammatory processes; however, the role for prgranulin in regulating inflammation in vascular endothelial cells has not been described. Signaling pathways mediated by progranulin were analyzed in human umbilical vein endothelial cells (HUVECs) treated with progranulin. Progranulin significantly induced Akt and endothelial nitric oxide synthase (eNOS) phosphorylation in HUVECs, an effect that was blocked with Akt inhibitor. Furthermore, nitric oxide (NO) level, the end product of Akt/eNOS pathway, was significantly upregulated after progranulin treatment. Next, we showed that progranulin efficiently inhibited lipopolysaccharide (LPS)-mediated pro-inflammatory signaling. LPS-induced phosphorylation of IκB and nuclear factor-κB (NF-κB) levels decreased after progranulin treatment. Also, progranulin blocked translocation of NF-κB from the cytosol to the nucleus. In addition, progranulin significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) by inhibiting binding of NF- κB to their promoter regions and blocked attachment of monocytes to HUVECs. Progranulin also significantly reduced the expression of tumor necrosis factor receptor-α (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1), the crucial inflammatory molecules known to aggravate atherosclerosis. Progranulin efficiently inhibited LPS-mediated pro-inflammatory signaling in endothelial cells through activation of the Akt/eNOS pathway and attenuation of the NF-κB pathway, suggesting its protective roles in vascular endothelium against inflammatory reaction underlying atherosclerosis.

TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role in monocyte adhesion to vascular endothelium.

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Seung Jin Lee

Full Text Available Toll-like receptor 4 (TLR4 is known to mediate monocyte adhesion to endothelial cells, however, its role on the expression of monocyte adhesion molecules is unclear. In the present study, we investigated the role of TLR4 on the expression of monocyte adhesion molecules, and determined the functional role of TLR4-induced adhesion molecules on monocyte adhesion to endothelial cells. When THP-1 monocytes were stimulated with Kdo2-Lipid A (KLA, a specific TLR4 agonist, Mac-1 expression was markedly increased in association with an increased adhesion of monocytes to endothelial cells. These were attenuated by anti-Mac-1 antibody, suggesting a functional role of TLR4-induced Mac-1 on monocyte adhesion to endothelial cells. In monocytes treated with MK886, a 5-lipoxygenase (LO inhibitor, both Mac-1 expression and monocyte adhesion to endothelial cells induced by KLA were markedly attenuated. Moreover, KLA increased the expression of mRNA and protein of 5-LO, suggesting a pivotal role of 5-LO on these processes. In in vivo studies, KLA increased monocyte adhesion to aortic endothelium of wild-type (WT mice, which was attenuated in WT mice treated with anti-Mac-1 antibody as well as in TLR4-deficient mice. Taken together, TLR4-mediated expression of Mac-1 in monocytes plays a pivotal role on monocyte adhesion to vascular endothelium, leading to increased foam cell formation in the development of atherosclerosis.

Esophagogastric junction outflow obstruction is often associated with coexistent abnormal esophageal body motility and abnormal bolus transit.

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Zheng, E; Gideon, R M; Sloan, J; Katz, P O

2017-10-01

Currently, the diagnosis of esophageal motility disorders is in part based upon a hierarchical algorithm in which abnormalities of the esophagogastric junction (EGJ) is prioritized. An important metric in evaluating the EGJ is the integrated relaxation pressure (IRP). Patients who do not have achalasia but are found to have an elevated IRP are diagnosed with EGJ outflow obstruction. It has been our observation that a subset of these patients also has a second named motility disorder and may also have abnormal bolus transit. The aim of this study is to determine the frequency of abnormal body motility and or abnormal bolus movement in patients with EGJ outflow obstruction. Further, in an effort to evaluate the potential clinical value in measuring bolus transit as a complement to esophageal manometry, specifically in patients with EGJ outflow obstruction, we analyzed the presenting symptoms of these patients. A total of 807 patients with a mean age of 53 years completed esophageal function testing with impedance monitoring and high-resolution manometry between January 2012 and October 2016. There were 74 patients with achalasia who were excluded from the study. Of the remaining 733 patients, 138 (19%) had an elevated IRP and were given a diagnosis of EGJ outflow obstruction. Among these patients, 56 (40%) were diagnosed with an abnormal motility pattern to liquids (ineffective esophageal motility = 28, distal esophageal spasm = 19, Jackhammer = 6), of which 44 (76%) had abnormal bolus transit to liquids, viscous, or both. In contrast, there were 82 patients with EGJ outflow obstruction and normal esophageal motility, of which 33 (40%) had abnormal bolus transit. Patients with preserved esophageal motility and EGJ outflow obstruction were then evaluated. Of the 733 patients, 299 (40%) had intact esophageal motility. Of the 299 patients with normal esophageal motility, 56 patients had an elevated IRP, of which 16 (28%) had abnormal bolus transit. There were 243 (33

Exercises to Improve Gait Abnormalities

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... Articles Directories Videos Resources Contact Exercises to Improve Gait Abnormalities Home » Article Categories » Exercise and Fitness Font Size: A A A A Exercises to Improve Gait Abnormalities Next Page The manner of how a ...

Report to Congress on abnormal occurrences

International Nuclear Information System (INIS)

1993-06-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health and safety and requires a quarterly report of such events to be made to Congress. This report covers the period January through March 1993. There is one abnormal occurrence at a nuclear power plant disposed in this report that involved a steam generator tube rupture at Palo Verde Unit 2, and none for fuel cycle facilities. Three abnormal occurrences involving medical misadminstrations (two therapeutic and one diagnostic) at NRC-licensed facilities are also discussed in this report. No abnormal occurrences were reported by NRC's Agreement States. The report also contains information updating previously reported abnormal occurrences

Glutaminolysis is Essential for Energy Production and Ion Transport in Human Corneal Endothelium

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Wenlin Zhang

2017-02-01

Full Text Available Corneal endothelium (CE is among the most metabolically active tissues in the body. This elevated metabolic rate helps the CE maintain corneal transparency by its ion and fluid transport properties, which when disrupted, leads to visual impairment. Here we demonstrate that glutamine catabolism (glutaminolysis through TCA cycle generates a large fraction of the ATP needed to maintain CE function, and this glutaminolysis is severely disrupted in cells deficient in NH3:H+ cotransporter Solute Carrier Family 4 Member 11 (SLC4A11. Considering SLC4A11 mutations leads to corneal endothelial dystrophy and sensorineural deafness, our results indicate that SLC4A11-associated developmental and degenerative disorders result from altered glutamine catabolism. Overall, our results describe an important metabolic mechanism that provides CE cells with the energy required to maintain high level transport activity, reveal a direct link between glutamine metabolism and developmental and degenerative neuronal diseases, and suggest an approach for protecting the CE during ophthalmic surgeries.

Memetics clarification of abnormal behavior

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

AIM: Biological medicine is hard to fully and scientifically explain the etiological factor and pathogenesis of abnormal behaviors; while, researches on philosophy and psychology (including memetics) are beneficial to better understand and explain etiological factor and pathogenesis of abnormal behaviors. At present, the theory of philosophy and psychology is to investigate the entity of abnormal behavior based on the views of memetics.METHODS: Abnormal behavior was researched in this study based on three aspects, including instinctive behavior disorder, poorly social-adapted behavior disorder and mental or body disease associated behavior disorder. Most main viewpoints of memetics were derived from "The Meme Machine", which was written by Susan Blackmore. When questions about abnormal behaviors induced by mental and psychological diseases and conduct disorder of teenagers were discussed, some researching achievements which were summarized by authors previously were added in this study, such as aggressive behaviors, pathologically aggressive behaviors, etc.RESULTS: The abnormal behaviors mainly referred to a part of people's substandard behaviors which were not according with the realistic social environment, culture background and the pathologic behaviors resulted from people's various psychological diseases. According to the theory of "meme", it demonstrated that the relevant behavioral obstacles of various psychological diseases, for example, the unusual behavior of schizophrenia, were caused, because the old meme was destroyed thoroughly but the new meme was unable to establish; psychoneurosis and personality disorder were resulted in hard establishment of meme; the behavioral obstacles which were ill-adapted to society, for example, various additional and homosexual behaviors, were because of the selfish replications and imitations of "additional meme" and "homosexual meme"; various instinct behavioral and congenital intelligent obstacles were not significance

Neurologic abnormalities in murderers.

Science.gov (United States)

Blake, P Y; Pincus, J H; Buckner, C

1995-09-01

Thirty-one individuals awaiting trial or sentencing for murder or undergoing an appeal process requested a neurologic examination through legal counsel. We attempted in each instance to obtain EEG, MRI or CT, and neuropsychological testing. Neurologic examination revealed evidence of "frontal" dysfunction in 20 (64.5%). There were symptoms or some other evidence of temporal lobe abnormality in nine (29%). We made a specific neurologic diagnosis in 20 individuals (64.5%), including borderline or full mental retardation (9) and cerebral palsy (2), among others. Neuropsychological testing revealed abnormalities in all subjects tested. There were EEG abnormalities in eight of the 20 subjects tested, consisting mainly of bilateral sharp waves with slowing. There were MRI or CT abnormalities in nine of the 19 subjects tested, consisting primarily of atrophy and white matter changes. Psychiatric diagnoses included paranoid schizophrenia (8), dissociative disorder (4), and depression (9). Virtually all subjects had paranoid ideas and misunderstood social situations. There was a documented history of profound, protracted physical abuse in 26 (83.8%) and of sexual abuse in 10 (32.3%). It is likely that prolonged, severe physical abuse, paranoia, and neurologic brain dysfunction interact to form the matrix of violent behavior.

Somatosensory abnormalities in knee OA.

Science.gov (United States)

Wylde, Vikki; Palmer, Shea; Learmonth, Ian D; Dieppe, Paul

2012-03-01

The aim of this study was to use quantitative sensory testing (QST) to explore the range and prevalence of somatosensory abnormalities demonstrated by patients with advanced knee OA. One hundred and seven knee OA patients and 50 age- and sex-matched healthy participants attended a 1-h QST session. Testing was performed on the medial side of the knee and the pain-free forearm. Light-touch thresholds were assessed using von Frey filaments, pressure pain thresholds using a digital pressure algometer, and thermal sensation and pain thresholds using a Thermotest MSA. Significant differences in median threshold values from knee OA patients and healthy participants were identified using Mann-Whitney U-tests. The z-score transformations were used to determine the prevalence of the different somatosensory abnormalities in knee OA patients. Testing identified 70% of knee OA patients as having at least one somatosensory abnormality. Comparison of median threshold values between knee OA patients and healthy participants revealed that patients had localized thermal and tactile hypoaesthesia and pressure hyperalgesia at the osteoarthritic knee. Tactile hypoaesthesia and pressure hyperalgesia were also present at the pain-free forearm. The most prevalent somatosensory abnormalities were tactile hypoaesthesia and pressure hyperalgesia, evident in between 20 and 34% of patients. This study found that OA patients demonstrate an array of somatosensory abnormalities, of which the most prevalent were tactile hypoaesthesia and pressure hyperalgesia. Further research is now needed to establish the clinical implications of these somatosensory abnormalities.

CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma.

Science.gov (United States)

Wadkin, James C R; Patten, Daniel A; Kamarajah, Sivesh K; Shepherd, Emma L; Novitskaya, Vera; Berditchevski, Fedor; Adams, David H; Weston, Chris J; Shetty, Shishir

2017-08-01

CD151, a member of the tetraspanin family of receptors, is a lateral organizer and modulator of activity of several families of transmembrane proteins. It has been implicated in the development and progression of several cancers, but its role in chronic inflammatory disease is less well understood. Here we show that CD151 is upregulated by distinct microenvironmental signals in a range of chronic inflammatory liver diseases and in primary liver cancer, in which it supports lymphocyte recruitment. CD151 was highly expressed in endothelial cells of the hepatic sinusoids and neovessels developing in fibrotic septa and tumor margins. Primary cultures of human hepatic sinusoidal endothelial cells (HSECs) expressed CD151 at the cell membrane and in intracellular vesicles. CD151 was upregulated by VEGF and HepG2 conditioned media but not by proinflammatory cytokines. Confocal microscopy confirmed that CD151 colocalized with the endothelial adhesion molecule/immunoglobulin superfamily member, VCAM-1. Functional flow-based adhesion assays with primary human lymphocytes and HSECs demonstrated a 40% reduction of lymphocyte adhesion with CD151 blockade. Inhibition of lymphocyte adhesion was similar between VCAM-1 blockade and a combination of CD151/VCAM-1 blockade, suggesting a collaborative role between the two receptors. These studies demonstrate that CD151 is upregulated within the liver during chronic inflammation, where it supports lymphocyte recruitment via liver endothelium. We propose that CD151 regulates the activity of VCAM-1 during lymphocyte recruitment to the human liver and could be a novel anti-inflammatory target in chronic liver disease and hepatocellular cancer prevention. NEW & NOTEWORTHY Chronic hepatitis is characterized by lymphocyte accumulation in liver tissue, which drives fibrosis and carcinogenesis. Here, we demonstrate for the first time that the tetraspanin CD151 supports lymphocyte adhesion to liver endothelium. We show that CD151 is upregulated

Normal and abnormal grain growth in fine-grained Nd-Fe-B sintered magnets prepared from He jet milled powders

Energy Technology Data Exchange (ETDEWEB)

Bittner, F., E-mail: f.bittner@ifw-dresden.de [IFW Dresden, Institute for Metallic Materials, PO Box 270116, 01171 Dresden (Germany); Technische Universität Dresden, Institute of Materials Science, 01062 Dresden (Germany); Woodcock, T.G. [IFW Dresden, Institute for Metallic Materials, PO Box 270116, 01171 Dresden (Germany); Schultz, L. [IFW Dresden, Institute for Metallic Materials, PO Box 270116, 01171 Dresden (Germany); Technische Universität Dresden, Institute of Materials Science, 01062 Dresden (Germany); Schwöbel, C. [Technische Universität Darmstadt, Materialwissenschaft, Alarich-Weiß-Str. 16, 64287 Darmstadt (Germany); Gutfleisch, O. [Technische Universität Darmstadt, Materialwissenschaft, Alarich-Weiß-Str. 16, 64287 Darmstadt (Germany); Fraunhofer ISC, Projektgruppe für Werkstoffkreisläufe und Ressourcenstrategie IWKS, Rodenbacher Chaussee 4, 63457 Hanau (Germany); Zickler, G.A.; Fidler, J. [Technische Universität Wien, Institute of Solid State Physics, Wiedner Hauptstr. 8-10, 1040 Wien (Austria); Üstüner, K.; Katter, M. [Vacuumschmelze GmbH & Co. KG, 63412 Hanau (Germany)

2017-03-15

Fine-grained, heavy rare earth free Nd-Fe-B sintered magnets were prepared from He jet milled powders with an average particle size of 1.5 µm by low temperature sintering at 920 °C or 980 °C. A coercivity of >1600 kA/m was achieved for an average grain size of 1.68 µm. Transmission electron microscopy showed that the distribution and composition of intergranular and grain boundary junction phases was similar to that in conventionally processed magnets. Microstructural analysis on different length scales revealed the occurrence of abnormal grain growth, which is unexpected for sintering temperatures below 1000 °C. A larger area fraction of abnormal grains was observed in the sample sintered at 920 °C compared to that sintered at 980 °C. Microtexture investigation showed a better crystallographic alignment of the abnormal grains compared to the fine-grained matrix, which is explained by a size dependent alignment of the powder particles during magnetic field alignment prior to sintering. Slightly larger particles in the initial powder show a better alignment and will act as nucleation sites for abnormal grain growth. Magneto-optical Kerr investigations confirmed the lower switching field of the abnormal grains compared to the fine-grained matrix. The demagnetisation curve of the sample sintered at 920 °C showed reduced rectangularity and this was attributed to a cooperative effect of the larger fraction of abnormal grains with low switching field and, as a minor effect, a reduced degree of crystallographic texture in this sample compared to the material sintered at 980 °C, which did not show the reduced rectangularity of the demagnetisation curve. - Highlights: • He Jet milling to reduce Nd-Fe-B grain size and to enhance coercivity. • Normal and abnormal grain growth observed for low temperature sintering. • Well oriented abnormal grown grains explained by size dependent field alignment. • Poor rectangularity is caused by low nucleation field of

Normal and abnormal grain growth in fine-grained Nd-Fe-B sintered magnets prepared from He jet milled powders

International Nuclear Information System (INIS)

Bittner, F.; Woodcock, T.G.; Schultz, L.; Schwöbel, C.; Gutfleisch, O.; Zickler, G.A.; Fidler, J.; Üstüner, K.; Katter, M.

2017-01-01

Fine-grained, heavy rare earth free Nd-Fe-B sintered magnets were prepared from He jet milled powders with an average particle size of 1.5 µm by low temperature sintering at 920 °C or 980 °C. A coercivity of >1600 kA/m was achieved for an average grain size of 1.68 µm. Transmission electron microscopy showed that the distribution and composition of intergranular and grain boundary junction phases was similar to that in conventionally processed magnets. Microstructural analysis on different length scales revealed the occurrence of abnormal grain growth, which is unexpected for sintering temperatures below 1000 °C. A larger area fraction of abnormal grains was observed in the sample sintered at 920 °C compared to that sintered at 980 °C. Microtexture investigation showed a better crystallographic alignment of the abnormal grains compared to the fine-grained matrix, which is explained by a size dependent alignment of the powder particles during magnetic field alignment prior to sintering. Slightly larger particles in the initial powder show a better alignment and will act as nucleation sites for abnormal grain growth. Magneto-optical Kerr investigations confirmed the lower switching field of the abnormal grains compared to the fine-grained matrix. The demagnetisation curve of the sample sintered at 920 °C showed reduced rectangularity and this was attributed to a cooperative effect of the larger fraction of abnormal grains with low switching field and, as a minor effect, a reduced degree of crystallographic texture in this sample compared to the material sintered at 980 °C, which did not show the reduced rectangularity of the demagnetisation curve. - Highlights: • He Jet milling to reduce Nd-Fe-B grain size and to enhance coercivity. • Normal and abnormal grain growth observed for low temperature sintering. • Well oriented abnormal grown grains explained by size dependent field alignment. • Poor rectangularity is caused by low nucleation field of

Estrogen and phytoestrogens: Effect on eNOS expression and in vitro vasodilation in cerebral arteries in ovariectomized Watanabe heritable hyperlipidemic rabbits

DEFF Research Database (Denmark)

Lund, Claus O.; Mortensen, Alicja; Nilas, Lisbeth

2007-01-01

Objectives: To evaluate the effect of estrogen replacement therapy or soy isoflavones supplement on endothelium-dependent relaxation in vitro and gene expression of endothelial nitric oxide synthase (eNOS) in cerebral arteries in a rabbit model of human hypercholesterolemia. Study design: Thirty...... cholesterol was significantly higher at termination in the SoyLife(R) group (P lipoprotein (LDL) cholesterol was comparable in all treatment groups. Neither treatment influenced the endothelium-dependent responses to carbamylcholine chloride or L-NAME or the endothelium...

Postnatal Deletion of Podoplanin in Lymphatic Endothelium Results in Blood Filling of the Lymphatic System and Impairs Dendritic Cell Migration to Lymph Nodes.

Science.gov (United States)

Bianchi, Roberta; Russo, Erica; Bachmann, Samia B; Proulx, Steven T; Sesartic, Marko; Smaadahl, Nora; Watson, Steve P; Buckley, Christopher D; Halin, Cornelia; Detmar, Michael

2017-01-01

The lymphatic vascular system exerts major physiological functions in the transport of interstitial fluid from peripheral tissues back to the blood circulation and in the trafficking of immune cells to lymph nodes. Previous studies in global constitutive knockout mice for the lymphatic transmembrane molecule podoplanin reported perinatal lethality and a complex phenotype with lung abnormalities, cardiac defects, lymphedema, blood-filled lymphatic vessels, and lack of lymph node organization, reflecting the importance of podoplanin expression not only by the lymphatic endothelium but also by a variety of nonendothelial cell types. Therefore, we aimed to dissect the specific role of podoplanin expressed by adult lymphatic vessels. We generated an inducible, lymphatic-specific podoplanin knockout mouse model (Pdpn ΔLEC ) and induced gene deletion postnatally. Pdpn ΔLEC mice were viable, and their lymphatic vessels appeared morphologically normal with unaltered fluid drainage function. Intriguingly, Pdpn ΔLEC mice had blood-filled lymph nodes and vessels, most frequently in the neck and axillary region, and displayed a blood-filled thoracic duct, suggestive of retrograde filling of blood from the blood circulation into the lymphatic system. Histological and fluorescence-activated cell sorter analyses revealed normal lymph node organization with the presence of erythrocytes within lymph node lymphatic vessels but not surrounding high endothelial venules. Moreover, fluorescein isothiocyanate painting experiments revealed reduced dendritic cell migration to lymph nodes in Pdpn ΔLEC mice. These results reveal an important role of podoplanin expressed by lymphatic vessels in preventing postnatal blood filling of the lymphatic vascular system and in contributing to efficient dendritic cell migration to the lymph nodes. © 2016 American Heart Association, Inc.

Imaging findings of sternal abnormalities

International Nuclear Information System (INIS)

Franquet, T.; Gimenez, A.; Alegret, X.; Sanchis, E.; Rivas, A.

1997-01-01

Radiographic findings in the sternal abnormalities are often nonspecific, showing appearances from a localized benign lesion to an aggressive lesion as seen with infections and malignant neoplasms. A specific diagnosis of sternal abnormalities can be suggested on the basis of CT and MR characteristics. Familiarity with the presentation and variable appearance of sternal abnormalities may aid the radiologist is suggesting a specific diagnosis. We present among others characteristic radiographic findings of hemangioma, chondrosarcoma, hydatid disease, and SAPHO syndrome. In those cases in which findings are not specific, cross-sectional imaging modalities may help the clinician in their management. (orig.)

Disk abnormality coexists with any degree of synovial and osseous abnormality in the temporomandibular joints of children with juvenile idiopathic arthritis

International Nuclear Information System (INIS)

Kirkhus, Eva; Smith, Hans-Joergen; Arvidsson, Linda Z.; Larheim, Tore A.; Flatoe, Berit; Hetlevik, Siri O.

2016-01-01

MRI manifestation of temporomandibular joint arthritis is frequently reported in children with juvenile idiopathic arthritis. However, little attention has been paid to temporomandibular joint disk abnormalities. To assess combinations of MRI findings in the symptomatic temporomandibular joint in children with juvenile idiopathic arthritis with focus on disk abnormalities. This was a retrospective study of 46 patients with juvenile idiopathic arthritis, mean age 12 years (range: 5-17 years). Mean disease duration was 70 months (standard deviation: 61 months). MR images of 92 temporomandibular joints were scored for thickness of abnormally enhancing synovium (synovitis), joint effusion, bone marrow oedema, abnormal bone shape, bone erosion and disk abnormalities. The 92 temporomandibular joints were categorized as A: No synovitis and normal bone shape (30/92; 33%), B: Synovitis and normal bone shape (14/92: 15%), C: Synovitis and abnormal bone shape (38/92; 41%) and D: No synovitis but abnormal bone shape (10/92; 11%). Thirty-six of the 46 patients (78%) had synovitis and 33/46 (72%) had abnormal bone shape, most frequently in combination (30/46; 65%). Disk abnormalities (flat disk, fragmented disk, adherent disk and displaced disk) were found in 29/46 patients (63%). Disk abnormalities were found in all categories of juvenile idiopathic arthritis involved temporomandibular joints (B: 8/14 [57%]; C: 25/38 [66%] and D: 7/10 [70%]). Disk displacement was found in half of the joints (7/14) in category B. Synovitis was most pronounced in this category. Disk abnormalities were frequent. Disk displacement also occurred in joints with early temporomandibular joint arthritis, i.e., with normal bone shape. Other disk abnormalities were found in joints with bone abnormalities. Attention should be paid to disk abnormalities both in early and long-standing temporomandibular joint arthritis in children with juvenile idiopathic arthritis. (orig.)

Disk abnormality coexists with any degree of synovial and osseous abnormality in the temporomandibular joints of children with juvenile idiopathic arthritis

Energy Technology Data Exchange (ETDEWEB)

Kirkhus, Eva; Smith, Hans-Joergen [Oslo University Hospital, Rikshospitalet, Department of Radiology and Nuclear Medicine, Oslo (Norway); University of Oslo, Institute of Clinical Medicine, Oslo (Norway); Arvidsson, Linda Z.; Larheim, Tore A. [University of Oslo, Department of Maxillofacial Radiology, Institute of Clinical Dentistry, Oslo (Norway); Flatoe, Berit; Hetlevik, Siri O. [Oslo University Hospital, Rikshospitalet, Department of Rheumatology, Oslo (Norway); University of Oslo, Institute of Clinical Medicine, Oslo (Norway)

2016-03-15

MRI manifestation of temporomandibular joint arthritis is frequently reported in children with juvenile idiopathic arthritis. However, little attention has been paid to temporomandibular joint disk abnormalities. To assess combinations of MRI findings in the symptomatic temporomandibular joint in children with juvenile idiopathic arthritis with focus on disk abnormalities. This was a retrospective study of 46 patients with juvenile idiopathic arthritis, mean age 12 years (range: 5-17 years). Mean disease duration was 70 months (standard deviation: 61 months). MR images of 92 temporomandibular joints were scored for thickness of abnormally enhancing synovium (synovitis), joint effusion, bone marrow oedema, abnormal bone shape, bone erosion and disk abnormalities. The 92 temporomandibular joints were categorized as A: No synovitis and normal bone shape (30/92; 33%), B: Synovitis and normal bone shape (14/92: 15%), C: Synovitis and abnormal bone shape (38/92; 41%) and D: No synovitis but abnormal bone shape (10/92; 11%). Thirty-six of the 46 patients (78%) had synovitis and 33/46 (72%) had abnormal bone shape, most frequently in combination (30/46; 65%). Disk abnormalities (flat disk, fragmented disk, adherent disk and displaced disk) were found in 29/46 patients (63%). Disk abnormalities were found in all categories of juvenile idiopathic arthritis involved temporomandibular joints (B: 8/14 [57%]; C: 25/38 [66%] and D: 7/10 [70%]). Disk displacement was found in half of the joints (7/14) in category B. Synovitis was most pronounced in this category. Disk abnormalities were frequent. Disk displacement also occurred in joints with early temporomandibular joint arthritis, i.e., with normal bone shape. Other disk abnormalities were found in joints with bone abnormalities. Attention should be paid to disk abnormalities both in early and long-standing temporomandibular joint arthritis in children with juvenile idiopathic arthritis. (orig.)

ABNORMAL UTERINE BLEEDING IN ADOLESCENTS — ENDOCRINE PROFILE CONDITION

Directory of Open Access Journals (Sweden)

E. V. Sibirskaya

2014-01-01

Full Text Available Aim: The purpose of the study was to evaluate the endocrine profile condition in adolescent girls with abnormal uterine bleeding. Patients and methods: The participants of the study were 110 adolescent girls in the age between 11 and 15 years taken to hospital by emergency indication in the period between 2010–2013 years with dysfunctional uterine bleeding for the term from 3 to 48 days. In the first day of hospitalization before starting the hormonal therapy all patients underwent the physical examination, ultrasonic examination of pelvic organs and endocrine profile assessment. Concentration of follicle-stimulating hormone (FSH and luteinizing hormone (LH and the levels of mammotropic hormone, thyrotropic hormone, estradiol, progesterone and testosterone in their blood were determined. Besides that physicians assessed the complete blood count indices: hemoglobin concentration, erythrocyte number and hematocrits. Results: It was determined that the predisposing causes of abnormal uterine bleeding development in adolescents: high somatic pathology frequency, abnormalities of neuroendocrinal system and menstrual cycle. Gynecological pathology in adolescents is represented by significant disorders of menstrual function establishment expressed in the later beginning of menstruation, its intensity and duration. The authors also note the higher frequency of inflammatory diseases such as adnexitis, edeitis, vulvovaginitis and coleitis in comparison with the control group (37.3 and 30%, respectively. Another tendency was observed while studying the endocrine profile: in patients with hyperestrogenism the normal or increased content of FSH at the normal or lowered LH concentration is observed. At the same time, in patients with hypestrogenism FSH concentration at the lower limits of the age group is lowered, while LH concentration is lowered or normal. Conclusion: Abnormal uterine bleeding in adolescents in the most cases is developing in the setting

Traction force dynamics predict gap formation in activated endothelium

International Nuclear Information System (INIS)

Valent, Erik T.; Nieuw Amerongen, Geerten P. van; Hinsbergh, Victor W.M. van; Hordijk, Peter L.

2016-01-01

In many pathological conditions the endothelium becomes activated and dysfunctional, resulting in hyperpermeability and plasma leakage. No specific therapies are available yet to control endothelial barrier function, which is regulated by inter-endothelial junctions and the generation of acto-myosin-based contractile forces in the context of cell-cell and cell-matrix interactions. However, the spatiotemporal distribution and stimulus-induced reorganization of these integral forces remain largely unknown. Traction force microscopy of human endothelial monolayers was used to visualize contractile forces in resting cells and during thrombin-induced hyperpermeability. Simultaneously, information about endothelial monolayer integrity, adherens junctions and cytoskeletal proteins (F-actin) were captured. This revealed a heterogeneous distribution of traction forces, with nuclear areas showing lower and cell-cell junctions higher traction forces than the whole-monolayer average. Moreover, junctional forces were asymmetrically distributed among neighboring cells. Force vector orientation analysis showed a good correlation with the alignment of F-actin and revealed contractile forces in newly formed filopodia and lamellipodia-like protrusions within the monolayer. Finally, unstable areas, showing high force fluctuations within the monolayer were prone to form inter-endothelial gaps upon stimulation with thrombin. To conclude, contractile traction forces are heterogeneously distributed within endothelial monolayers and force instability, rather than force magnitude, predicts the stimulus-induced formation of intercellular gaps. - Highlights: • Endothelial monolayers exert dynamic- and heterogeneous traction forces. • High traction forces correlate with junctional areas and the F-actin cytoskeleton. • Newly formed inter-endothelial gaps are characterized by opposing traction forces. • Force stability is a key feature controlling endothelial permeability.

Traction force dynamics predict gap formation in activated endothelium

Energy Technology Data Exchange (ETDEWEB)

Valent, Erik T.; Nieuw Amerongen, Geerten P. van; Hinsbergh, Victor W.M. van; Hordijk, Peter L., E-mail: p.hordijk@vumc.nl

2016-09-10

In many pathological conditions the endothelium becomes activated and dysfunctional, resulting in hyperpermeability and plasma leakage. No specific therapies are available yet to control endothelial barrier function, which is regulated by inter-endothelial junctions and the generation of acto-myosin-based contractile forces in the context of cell-cell and cell-matrix interactions. However, the spatiotemporal distribution and stimulus-induced reorganization of these integral forces remain largely unknown. Traction force microscopy of human endothelial monolayers was used to visualize contractile forces in resting cells and during thrombin-induced hyperpermeability. Simultaneously, information about endothelial monolayer integrity, adherens junctions and cytoskeletal proteins (F-actin) were captured. This revealed a heterogeneous distribution of traction forces, with nuclear areas showing lower and cell-cell junctions higher traction forces than the whole-monolayer average. Moreover, junctional forces were asymmetrically distributed among neighboring cells. Force vector orientation analysis showed a good correlation with the alignment of F-actin and revealed contractile forces in newly formed filopodia and lamellipodia-like protrusions within the monolayer. Finally, unstable areas, showing high force fluctuations within the monolayer were prone to form inter-endothelial gaps upon stimulation with thrombin. To conclude, contractile traction forces are heterogeneously distributed within endothelial monolayers and force instability, rather than force magnitude, predicts the stimulus-induced formation of intercellular gaps. - Highlights: • Endothelial monolayers exert dynamic- and heterogeneous traction forces. • High traction forces correlate with junctional areas and the F-actin cytoskeleton. • Newly formed inter-endothelial gaps are characterized by opposing traction forces. • Force stability is a key feature controlling endothelial permeability.

Heterotaxy syndromes and abnormal bowel rotation

Energy Technology Data Exchange (ETDEWEB)

Newman, Beverley [Stanford University, Lucile Packard Children' s Hospital, Department of Radiology, Stanford, CA (United States); Koppolu, Raji; Sylvester, Karl [Lucile Packard Children' s Hospital at Stanford, Department of Surgery, Stanford, CA (United States); Murphy, Daniel [Lucile Packard Children' s Hospital at Stanford, Department of Cardiology, Stanford, CA (United States)

2014-05-15

Bowel rotation abnormalities in heterotaxy are common. As more children survive cardiac surgery, the management of gastrointestinal abnormalities has become controversial. To evaluate imaging of malrotation in heterotaxy with surgical correlation and provide an algorithm for management. Imaging reports of heterotaxic children with upper gastrointestinal (UGI) and/or small bowel follow-through (SBFT) were reviewed. Subsequently, fluoroscopic images were re-reviewed in conjunction with CT/MR studies. The original reports and re-reviewed images were compared and correlated with surgical findings. Nineteen of 34 children with heterotaxy underwent UGI, 13/19 also had SBFT. In 15/19 reports, bowel rotation was called abnormal: 11 malrotation, 4 non-rotation, no cases of volvulus. Re-review, including CT (10/19) and MR (2/19), designated 17/19 (90%) as abnormal, 10 malrotation (abnormal bowel arrangement, narrow or uncertain length of mesentery) and 7 non-rotation (small bowel and colon on opposite sides plus low cecum with probable broad mesentery). The most useful CT/MR findings were absence of retroperitoneal duodenum in most abnormal cases and location of bowel, especially cecum. Abnormal orientation of mesenteric vessels suggested malrotation but was not universal. Nine children had elective bowel surgery; non-rotation was found in 4/9 and malrotation was found in 5/9, with discrepancies (non-rotation at surgery, malrotation on imaging) with 4 original interpretations and 1 re-review. We recommend routine, early UGI and SBFT studies once other, urgent clinical concerns have been stabilized, with elective laparoscopic surgery in abnormal or equivocal cases. Cross-sectional imaging, usually obtained for other reasons, can contribute diagnostically. Attempting to assess mesenteric width is important in differentiating non-rotation from malrotation and more accurately identifies appropriate surgical candidates. (orig.)

Heterotaxy syndromes and abnormal bowel rotation

International Nuclear Information System (INIS)

Newman, Beverley; Koppolu, Raji; Sylvester, Karl; Murphy, Daniel

2014-01-01

Bowel rotation abnormalities in heterotaxy are common. As more children survive cardiac surgery, the management of gastrointestinal abnormalities has become controversial. To evaluate imaging of malrotation in heterotaxy with surgical correlation and provide an algorithm for management. Imaging reports of heterotaxic children with upper gastrointestinal (UGI) and/or small bowel follow-through (SBFT) were reviewed. Subsequently, fluoroscopic images were re-reviewed in conjunction with CT/MR studies. The original reports and re-reviewed images were compared and correlated with surgical findings. Nineteen of 34 children with heterotaxy underwent UGI, 13/19 also had SBFT. In 15/19 reports, bowel rotation was called abnormal: 11 malrotation, 4 non-rotation, no cases of volvulus. Re-review, including CT (10/19) and MR (2/19), designated 17/19 (90%) as abnormal, 10 malrotation (abnormal bowel arrangement, narrow or uncertain length of mesentery) and 7 non-rotation (small bowel and colon on opposite sides plus low cecum with probable broad mesentery). The most useful CT/MR findings were absence of retroperitoneal duodenum in most abnormal cases and location of bowel, especially cecum. Abnormal orientation of mesenteric vessels suggested malrotation but was not universal. Nine children had elective bowel surgery; non-rotation was found in 4/9 and malrotation was found in 5/9, with discrepancies (non-rotation at surgery, malrotation on imaging) with 4 original interpretations and 1 re-review. We recommend routine, early UGI and SBFT studies once other, urgent clinical concerns have been stabilized, with elective laparoscopic surgery in abnormal or equivocal cases. Cross-sectional imaging, usually obtained for other reasons, can contribute diagnostically. Attempting to assess mesenteric width is important in differentiating non-rotation from malrotation and more accurately identifies appropriate surgical candidates. (orig.)

Abnormal Thiamine-Dependent Processes in Alzheimer’s Disease. Lessons from Diabetes

Science.gov (United States)

Gibson, Gary E.; Hirsch, Joseph A.; Cirio, Rosanna T.; Jordan, Barry D.; Fonzetti, Pasquale; Elder, Jessica

2013-01-01

Reduced glucose metabolism is an invariant feature of Alzheimer’s Disease (AD) and an outstanding biomarker of disease progression. Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional glucose hypometabolism remains unclear. Thiamine-dependent processes are critical in glucose metabolism and are diminished in brains of AD patients at autopsy. Further, the reductions in thiamine-dependent processes are highly correlated to the decline in clinical dementia rating scales. In animal models, thiamine deficiency exacerbates plaque formation, promotes phosphorylation of tau and impairs memory. In contrast, treatment of mouse models of AD with the thiamine derivative benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses memory deficits. Diabetes predisposes to AD, which suggests they may share some common mechanisms. Benfotiamine diminishes peripheral neuropathy in diabetic humans and animals. In diabetes, benfotiamine induces key thiamine-dependent enzymes of the pentose shunt to reduce accumulation of toxic metabolites including advanced glycation end products (AGE). Related mechanisms may lead to reversal of plaque formation by benfotiamine in animals. If so, the use of benfotiamine could provide a safe intervention to reverse biological and clinical processes of AD progression. PMID:22982063

Progranulin protects vascular endothelium against atherosclerotic inflammatory reaction via Akt/eNOS and nuclear factor-κB pathways.

Directory of Open Access Journals (Sweden)

Hwan-Jin Hwang

Full Text Available OBJECTIVE: Atherosclerosis is considered a chronic inflammatory disease, initiated by activation and dysfunction of the endothelium. Recently, progranulin has been regarded as an important modulator of inflammatory processes; however, the role for prgranulin in regulating inflammation in vascular endothelial cells has not been described. METHOD AND RESULTS: Signaling pathways mediated by progranulin were analyzed in human umbilical vein endothelial cells (HUVECs treated with progranulin. Progranulin significantly induced Akt and endothelial nitric oxide synthase (eNOS phosphorylation in HUVECs, an effect that was blocked with Akt inhibitor. Furthermore, nitric oxide (NO level, the end product of Akt/eNOS pathway, was significantly upregulated after progranulin treatment. Next, we showed that progranulin efficiently inhibited lipopolysaccharide (LPS-mediated pro-inflammatory signaling. LPS-induced phosphorylation of IκB and nuclear factor-κB (NF-κB levels decreased after progranulin treatment. Also, progranulin blocked translocation of NF-κB from the cytosol to the nucleus. In addition, progranulin significantly reduced the expression of vascular cell adhesion molecule-1 (VCAM-1 and intercellular adhesion molecule-1 (ICAM-1 by inhibiting binding of NF- κB to their promoter regions and blocked attachment of monocytes to HUVECs. Progranulin also significantly reduced the expression of tumor necrosis factor receptor-α (TNF-α and monocyte chemo-attractant protein-1 (MCP-1, the crucial inflammatory molecules known to aggravate atherosclerosis. CONCLUSION: Progranulin efficiently inhibited LPS-mediated pro-inflammatory signaling in endothelial cells through activation of the Akt/eNOS pathway and attenuation of the NF-κB pathway, suggesting its protective roles in vascular endothelium against inflammatory reaction underlying atherosclerosis.

Accelerated Recovery of Endothelium Function after Stent Implantation with the Use of a Novel Systemic Nanoparticle Curcumin

Directory of Open Access Journals (Sweden)

Qi Lu

2015-01-01

Full Text Available Curcumin was reported to exhibit a wide range of pharmacological effects including antioxidant, anti-inflammatory, and antiproliferative activities and significantly prevent smooth muscle cells migration. In the present study, a novel kind of curcumin loaded nanoparticles (Cur-NP has been prepared and characterized with the aim of inhibiting inflammation formation and accelerating the healing process of the stented arteries. Cur-NP was administrated intravenously after stent implantation twice a week and detailed tissue responses were evaluated. The results demonstrated that intravenous administration of Cur-NP after stent implantation accelerated endothelial cells restoration and endothelium function recovery and may potentially be an effective therapeutic alternative to reduce adverse events for currently available drug eluting stents.

Effect of hypothyroidism on the nitrergic relaxant responses of corpus cavernosal smooth muscle in rabbits.

Science.gov (United States)

Sarac, Bulent; Yildirim, Mustafa K; Bagcivan, Ihsan; Kaya, Kemal; Kilicarslan, Hakan; Yildirim, Sahin

2006-01-01

The incidence of hormonal dysfunction as a cause of impotence remains controversial. However, several recent studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. In the present study, we examined nitrergic responses in hypothyroidism in rabbit corpus cavernosum and compared them with controls. Carbachol-induced relaxation responses and electrical field stimulation (EFS)-induced frequency-dependent relaxations decreased significantly in hypothyroid rabbits. Papaverine and sodium nitroprusside (SNP)-induced relaxation responses did not change significantly in hypothyroid rabbits. The contraction responses of phenylephrine and EFS-induced frequency-dependent contractions were significantly decreased in the hypothyroid group. We can speculate that the reduction of relaxant responses to EFS and carbachol in hypothyroid rabbits can depend on a decreased release of nitric oxide (NO) from nitrergic nerves and endothelium or a reduction of muscarinic receptor density. Also, decreases in contraction responses may depend on diminished adrenoceptor density.

Anisotropic atomic packing model for abnormal grain growth mechanism of WC-25 wt.% Co alloy

International Nuclear Information System (INIS)

Ryoo, H.S.; Hwang, S.K.

1998-01-01

During liquid phase sintering, cemented carbide particles grow into either faceted or non-faceted grain shapes depending on ally system. In case of WC-Co alloy, prism-shape faceted grains with (0001) planes and {1 bar 100} planes on each face are observed, and furthermore an abnormal grain growth has been reported to occur. When abnormal grain growth occurs in WC crystals, dimension ratio, R, of the length of the side of the triangular prism face to the height of the prism is higher than 4 whereas that for normal grains is approximately 2. Abnormal grain growth in this alloy is accelerated by the fineness of starting powders and by high sintering temperature. To account for the mechanism of the abnormal grain growth, there are two proposed models which drew much research attention: nucleation and subsequent carburization and transformation of η (W 3 Co 3 C) phase into WC, and coalescence of coarse WC grains through dissolution and re-precipitation. Park et al. proposed a two-dimensional nucleation theory to explain the abnormal grain growth of faceted grains. There are questions, however, on the role of η phase on abnormal grain growth. The mechanism of coalescence of spherical grains as proposed by Kingery is also unsuitable for faceted grains. So far theories on abnormal grain growth do not provide a satisfactory explanation on the change of R value during the growth process. In the present work a new mechanism of nucleation and growth of faceted WC grains is proposed on the ground of anisotropic packing sequence of each atom

Abnormal Cervical Cancer Screening Test Results

Science.gov (United States)

... AQ FREQUENTLY ASKED QUESTIONS FAQ187 GYNECOLOGIC PROBLEMS Abnormal Cervical Cancer Screening Test Results • What is cervical cancer screening? • What causes abnormal cervical cancer screening test ...

Circulating endothelial progenitor cells do not contribute to regeneration of endothelium after murine arterial injury

DEFF Research Database (Denmark)

Hagensen, Mette; Raarup, Merete Krog; Mortensen, Martin Bødtker

2012-01-01

into endothelial cells (ECs). We tested this theory in a murine arterial injury model using carotid artery transplants and fluorescent reporter mice. METHODS AND RESULTS: Wire-injured carotid artery segments from wild-type mice were transplanted into TIE2-GFP transgenic mice expressing green fluorescent protein...... (GFP) in ECs. We found that the endothelium regenerated with GFP(+) ECs as a function of time, evolving from the anastomosis sites towards the centre of the transplant. A migration front of ECs at Day 7 was verified by scanning electron microscopy and by bright-field microscopy using recipient TIE2-lac......Z mice with endothelial β-galactosidase expression. These experiments indicated migration of flanking ECs rather than homing of circulating cells as the underlying mechanism. To confirm this, we interposed non-injured wild-type carotid artery segments between the denuded transplant and the TIE2-GFP...

An artificial vector model for generating abnormal electrocardiographic rhythms

International Nuclear Information System (INIS)

Clifford, Gari D; Nemati, Shamim; Sameni, Reza

2010-01-01

We present generalizations of our previously published artificial models for generating multi-channel ECG to provide simulations of abnormal cardiac rhythms. Using a three-dimensional vectorcardiogram (VCG) formulation, we generate the normal cardiac dipole for a patient using a sum of Gaussian kernels, fitted to real VCG recordings. Abnormal beats are specified either as perturbations to the normal dipole or as new dipole trajectories. Switching between normal and abnormal beat types is achieved using a first-order Markov chain. Probability transitions can be learned from real data or modeled by coupling to heart rate and sympathovagal balance. Natural morphology changes from beat-to-beat are incorporated by varying the angular frequency of the dipole as a function of the inter-beat (RR) interval. The RR interval time series is generated using our previously described model whereby time- and frequency-domain heart rate (HR) and heart rate variability characteristics can be specified. QT-HR hysteresis is simulated by coupling the Gaussian kernels associated with the T-wave in the model with a nonlinear factor related to the local HR (determined from the last n RR intervals). Morphology changes due to respiration are simulated by introducing a rotation matrix couple to the respiratory frequency. We demonstrate an example of the use of this model by simulating HR-dependent T-wave alternans (TWA) with and without phase-switching due to ectopy. Application of our model also reveals previously unreported effects of common TWA estimation methods

Abnormal mineral metabolism and mortality in hemodialysis patients with secondary hyperparathyroidism: evidence from marginal structural models used to adjust for time-dependent confounding.

Science.gov (United States)

Fukagawa, Masafumi; Kido, Ryo; Komaba, Hirotaka; Onishi, Yoshihiro; Yamaguchi, Takuhiro; Hasegawa, Takeshi; Kurita, Noriaki; Fukuma, Shingo; Akizawa, Tadao; Fukuhara, Shunichi

2014-06-01

Hemodialysis patients with mineral and bone disorders (MBDs) have an abnormally high relative risk of death, but their absolute risk of death is unknown. Further, previous studies have not accounted for possible time-dependent confounding of the association between MBD markers and death due to the effect of markers of MBD on treatments, which subsequently may affect MBD markers. Multicenter, 3-year, prospective, case-cohort study. 8,229 hemodialysis patients with secondary hyperparathyroidism (parathyroid hormone level ≥180 pg/mL and/or receiving vitamin D receptor activators) at 86 facilities in Japan. Serum phosphorus, calcium, and parathyroid hormone levels. All-cause mortality. Marginal structural models were used to compute absolute differences in all-cause mortality associated with different levels of predictors while accounting for time-dependent confounding. The association between phosphorus level and mortality appeared U-shaped, although only higher phosphorus level categories reached statistical significance: compared to those with phosphorus levels of 5.0-5.9 mg/dL (1.61-1.93 mmol/L), patients with the highest (≥9.0 mg/dL [≥2.90 mmol/L]) phosphorus levels had 9.4 excess deaths/100 person-years (rate ratio, 2.79 [95% CI, 1.26-6.15]), whereas no association was found for the lowest phosphorus category (secondary hyperparathyroidism. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Vascular adhesion protein-1 is elevated in primary sclerosing cholangitis, is predictive of clinical outcome and facilitates recruitment of gut-tropic lymphocytes to liver in a substrate-dependent manner.

Science.gov (United States)

Trivedi, Palak J; Tickle, Joseph; Vesterhus, Mette Nåmdal; Eddowes, Peter J; Bruns, Tony; Vainio, Jani; Parker, Richard; Smith, David; Liaskou, Evaggelia; Thorbjørnsen, Liv Wenche; Hirschfield, Gideon M; Auvinen, Kaisa; Hubscher, Stefan G; Salmi, Marko; Adams, David H; Weston, Chris J

2018-06-01

Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of IBD. This clinical association is linked pathologically to the recruitment of mucosal T cells to the liver, via vascular adhesion protein (VAP)-1-dependent enzyme activity. Our aim was to examine the expression, function and enzymatic activation of the ectoenzyme VAP-1 in patients with PSC. We examined VAP-1 expression in patients with PSC, correlated levels with clinical characteristics and determined the functional consequences of enzyme activation by specific enzyme substrates on hepatic endothelium. The intrahepatic enzyme activity of VAP-1 was elevated in PSC versus immune-mediated disease controls and non-diseased liver (pgut-tropic α4β7 + lymphocytes to hepatic endothelial cells in vitro under flow was attenuated by 50% following administration of the VAP-1 inhibitor semicarbazide (pgut bacteria-was the most efficient (yielded the highest enzymatic rate) and efficacious in its ability to induce expression of functional mucosal addressin cell adhesion molecule-1 on hepatic endothelium. In a prospectively evaluated patient cohort with PSC, elevated serum soluble (s)VAP-1 levels predicted poorer transplant-free survival for patients, independently (HR: 3.85, p=0.003) and additively (HR: 2.02, p=0.012) of the presence of liver cirrhosis. VAP-1 expression is increased in PSC, facilitates adhesion of gut-tropic lymphocytes to liver endothelium in a substrate-dependent manner, and elevated levels of its circulating form predict clinical outcome in patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Low-set ears and pinna abnormalities

Science.gov (United States)

Low-set ears; Microtia; "Lop" ear; Pinna abnormalities; Genetic defect - pinna; Congenital defect - pinna ... conditions: Abnormal folds or location of the pinna Low-set ears No opening to the ear canal ...

Influence exerted by new pyrimidine derivatives on cerebral circulation auto-regulation and vasodilatating function of vessels endothelium in rats' brains under chronic hemic hypoxia

Directory of Open Access Journals (Sweden)

A.V. Voronkov

2018-03-01

Full Text Available Our research goal was to examine influences exerted by new pyrimidine derivatives coded as BL0 and BL2 on cerebral hemodynamics auto-regulation parameters and vasodilatating function of vessels endothelium as risk factors causing ischemic and hemorrhagic strokes under chronic hemic hypoxia. We performed an experiment on white Wistar rats to prove that endothelial dysfunction which evolves under chronic hemic hypoxia leads to disorders in endothelium-mediated mechanisms for cerebral circulation auto-regulation in rats. We modeled hypoxia in animals via granting them free access to 0.2 % sodium nitrite solution instead of ordinary drinking water. Endothelial dysfunction was confirmed as per disorders in vasodilatation and vasoconstriction reactions at intravenous introduction of acetyl choline (0.1 mg/kg and methyl ether hydrochloride nitro-L-arginine (10 mg/kg. Cerebral blood flow speed was measured with MM-D-K-Minimax v.2.1. ultrasound Doppler. We assessed cerebral circulation auto-regulation as per compression test results which allowed us to calculate overshoot coefficient and auto-regulation power. Examined pyrimidine derivatives and comparison preparations were introduced orally 60 minutes prior to taking readings. Mexidol doses were calculated on the basis of interspecific recalculation of a maximum daily dose for a man. Nicergoline dose was taken as a most effective one as per literature data. When new pyrimidine derivatives BL0 and BL2 are applied under chronic hemic hypoxia, it causes overshoot coefficient to grow authentically higher than in a negative control group but it doesn't exert any positive influence on collateral reserve parameter, namely auto-regulation power. BL0 and BL2 improve endothelium vasodilatating function at intravenous acetylcholine introduction (0.1 mg/kg and don't exert any influence on vasoconstricting function at L-NAME intravenous introduction (10 mg/kg. The examined substance BL0 has more apparent

Congenital Abnormalities

Science.gov (United States)

... tube defects. However, there is also a genetic influence to this type of congenital anomaly. Unknown Causes The vast majority of congenital abnormalities have no known cause. This is particularly troubling for parents who plan to have more children, because there is no way to predict if ...

Chromosomal Abnormalities Associated With Omphalocele

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Chih-Ping Chen

2007-03-01

Full Text Available Fetuses with omphalocele have an increased risk for chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with umbilical cord cysts, complexity of associated anomalies, and the contents of omphalocele. There is considerable evidence that genetics contributes to the etiology of omphalocele. This article provides an overview of chromosomal abnormalities associated with omphalocele and a comprehensive review of associated full aneuploidy such as trisomy 18, trisomy 13, triploidy, trisomy 21, 45,X, 47,XXY, and 47,XXX, partial aneuploidy such as dup(3q, dup(11p, inv(11, dup(1q, del(1q, dup(4q, dup(5p, dup(6q, del(9p, dup(15q, dup(17q, Pallister-Killian syndrome with mosaic tetrasomy 12p and Miller-Dieker lissencephaly syndrome with deletion of 17p13.3, and uniparental disomy (UPD such as UPD 11 and UPD 14. Omphalocele is a prominent marker for chromosomal abnormalities. Perinatal identification of omphalocele should alert chromosomal abnormalities and familial unbalanced translocations, and prompt thorough cytogenetic investigations and genetic counseling.

Real-time synchrotoron radiation X-ray diffraction and abnormal temperature dependence of photoluminescence from erbium silicates on SiO2/Si substrates

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H. Omi

2012-03-01

Full Text Available The erbium silicate formation processes during annealing in Ar gas were monitored by synchrotron radiation grazing incidence X-ray diffraction (GIXD in real time and the optical properties of the silicates were investigated by photoluminescence measurements in spectral and time-resolved domains. The GIXD measurements show that erbium silicates and erbium oxide are formed by interface reactions between silicon oxide and erbium oxides deposited on silicon oxide by reactive sputtering in Ar gas and O2/Ar mixture gas ambiences. The erbium silicates are formed above 1060 °C in Ar gas ambience and above 1010 °C in O2/Ar gas ambience, and erbium silicides are dominantly formed above 1250 °C. The I15/2-I13/2 Er3+ photoluminescence from the erbium oxide and erbium silicate exhibits abnormal temperature dependence, which can be explained by the phonon-assisted resonant absorption of the 532-nm excitation photons into the 2H11/2 levels of Er3+ ions of the erbium compounds.

Frequency of metabolic abnormalities in urinary stones patients.

Science.gov (United States)

Ahmad, Iftikhar; Pansota, Mudassar Saeed; Tariq, Muhammad; Tabassum, Shafqat Ali

2013-11-01

To determine the frequency of metabolic abnormalities in the serum and urine of patients with urinary stones disease. Two hundred patients with either multiple or recurrent urolithiasis diagnosed on ultrasonography and intravenous urography were included in this study. 24 hour urine sample were collected from each patient and sent for PH, specific gravity, Creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. In addition, blood sample of each patient was also sent for serum levels of urea, creatinine, uric acid, phosphate and calcium. Mean age of patients was 38 ± 7.75 years with male to female ratio of 2:1. The main presenting complaint was lumber pain and 82.5% patients were found to have calcium oxalate stones on chemical analysis. Metabolic abnormalities were found in 90.5% patients, whereas there were no metabolic abnormalities in 19 (9.5%) patients. Forty patients (21.5%) only had one metabolic abnormality and 157 (78.5%) patients had multiple metabolic abnormalities. Hyperoxaluria was the most commonly observed metabolic abnormality and was found in 64.5% patients. Other significant metabolic abnormalities were hypercalciuria, Hypercalcemia, hypocitraturia and hyperuricemia. This study concludes that frequency of metabolic abnormalities is very high in patients with urolithiasis and hyperoxaluria, hypercalciuria and hypocitraturia are the most important metabolic abnormalities observed in these patients.

Altered gene expression of Staphylococcus aureus upon interaction with human endothelial cells

NARCIS (Netherlands)

Vriesema, A.J.M.; Beekhuizen, H.; Hamdi, M.; Soufan, A.; Lammers, A.; Willekens, B.; Bakker, O.; Veltrop, M.H.A.M.; Gevel, van de J.S.; Dankert, J.; Zaat, S.A.J.

2000-01-01

Staphylococcus aureus is isolated from a substantial number of patients with infective endocarditis who are not known to have predisposing heart abnormalities. It has been suggested that the infection is initiated by the direct binding of S. aureus to human vascular endothelium. To determine the

Altered gene expression in Staphylococcus aureus upon interaction with human endothelial cells

NARCIS (Netherlands)

Vriesema, A. J.; Beekhuizen, H.; Hamdi, M.; Soufan, A.; Lammers, A.; Willekens, B.; Bakker, O.; Welten, A. G.; Veltrop, M. H.; van de Gevel, J. S.; Dankert, J.; Zaat, S. A.

2000-01-01

Staphylococcus aureus is isolated from a substantial number of patients with infective endocarditis who are not known to have predisposing heart abnormalities. It has been suggested that the infection is initiated by the direct binding of S. aureus to human vascular endothelium. To determine the

Carotid Artery Intima-Media Thickness and Cutaneous Microvascular Function are Associated With Vitamin C Levels in Young Patients With Type 1 Diabetes

DEFF Research Database (Denmark)

Odermarsky, Michal; Lykkesfeldt, Jens; Liuba, Petru

2008-01-01

Background: Vascular endothelial dysfunction and accelerated thickening of arterial intima contribute to increased cardiovascular morbidity in type 1 diabetes. Although vitamin C has important antioxidant functions, and increased oxidative stress is a central mechanism of vascular abnormalities......, lower plasma levels of vitamin C appears to predispose to more pronounced adverse changes in both microcirculation and peripheral arteries. Further studies are needed to investigate whether dietary supplementation with vitamin C could retard the development of microvasculopathy and atherosclerosis...... in diabetes, the relationship between these two in young patients with this disease has not been yet investigated. Methods: Carotid artery intima-media thickness (cIMT) and cutaneous microvascular reactivity to endothelium-dependent (acetylcholine, ACH) and independent (sodium nitroprusside, SNP) were...

Prevalence of asymptomatic urinary abnormalities among adolescents

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Mohamed Fouad

2016-01-01

Full Text Available To determine the prevalence of asymptomatic urinary abnormalities in adolescents, first morning clean mid-stream urine specimens were obtained from 2500 individuals and examined by dipstick and light microscopy. Adolescents with abnormal screening results were reexamined after two weeks and those who had abnormal results twice were subjected to systemic clinical examination and further clinical and laboratory investigations. Eight hundred and three (32.1% individuals had urinary abnormalities at the first screening, which significantly decreased to 345 (13.8% at the second screening, (P <0.001. Hematuria was the most common urinary abnormalities detected in 245 (9.8% adolescents who had persistent urine abnormalities; 228 (9.1% individuals had non glomerular hematuria. The hematuria was isolated in 150 (6% individuals, combined with leukocyturia in 83 (3.3% individuals, and combined with proteinuria in 12 (0.5% individuals. Leukocyturia was detected in 150 (6% of all studied adolescents; it was isolated in 39 (1.6% individuals and combined with proteinuria in 28 (1.1% of them. Asymp- tomatic bacteriuria was detected in 23 (0.9% of all studied adolescents; all the cases were females. Proteinuria was detected in 65 (2.6% of all the studied adolescents; 45 (1.8% indivi- duals had <0.5 g/day and twenty (0.8% individuals had 0.5-3 g/day. Asymptomatic urinary abnormalities were more common in males than females and adolescents from rural than urban areas (P <0.01 and (P <0.001, respectively. The present study found a high prevalence of asymptomatic urinary abnormalities among adolescents in our population.

The metabolism of L-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: L-glutamine inhibits the generation of L-arginine by cultured endothelial cells

International Nuclear Information System (INIS)

Sessa, W.C.; Hecker, M.; Mitchell, J.A.; Vane, J.R.

1990-01-01

The mechanism by which L-glutamine (L-Gln) inhibits the release of endothelium-derived factor from bovine aortic cultured endothelial cells was investigated. The intracellular concentration of L-arginine (L-Arg) in Arg-depleted endothelial cells was inversely related to the level of L-Gln. Removal of L-Gln from the culture medium (usually containing L-Gln at 2 mM) abolished the inhibitory effect of the culture medium on L-Arg generation. L-Gln (0.2 and 2 mM) but not D-Gln inhibited the generation of L-Arg by both Arg-depleted and nondepleted endothelial cells. L-Gln did not interfere with the uptake of L-Arg or the metabolism of L-Arg-L-Phe to L-Arg but inhibited the formation of L-Arg from L-citrulline (L-Cit), L-Cit-L-Phe, and N G -monomethyl-L-arginine. L-Gln also inhibited the conversion of L-[ 14 C]Cit to L-[ 14 C]Arg by Arg-depleted endothelial cells. However, L-Gln did not inhibit the conversion of L-argininosuccinic acid to L-Arg by endothelial cell homogenates. Thus, L-Gln interferes with the conversion of L-Cit to L-Arg probably by acting on argininosuccinate synthetase rather than argininosuccinate lyase. L-Gln also inhibited the generation of L-Arg by the monocyte-macrophage cell line J774 but had no effect on the conversion of L-Cit to L-Arg by these cells. As the release of endothelium-derived relaxing factor from cultured and non-cultured endothelial cells is limited by the availability of L-Arg, endogenous L-Gln may play a regulatory role in the biosynthesis of endothelium-derived relaxing factor

Circulating microparticles in severe pulmonary arterial hypertension increase intercellular adhesion molecule-1 expression selectively in pulmonary artery endothelium

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Leslie A. Blair

2016-10-01

Full Text Available Abstract Background Microparticles (MPs stimulate inflammatory adhesion molecule expression in systemic vascular diseases, however it is unknown whether circulating MPs stimulate localized ICAM-1 expression in the heterogeneically distinct pulmonary endothelium during pulmonary arterial hypertension (PAH. Pulmonary vascular lesions with infiltrating inflammatory cells in PAH form in the pulmonary arteries and arterioles, but not the microcirculation. Therefore, we sought to determine whether circulating MPs from PAH stimulate pulmonary artery endothelial cell-selective ICAM-1 expression. Results Pulmonary artery endothelial cells (PAECs were exposed to MPs isolated from the circulation of a rat model of severe PAH. During late-stage (8-weeks PAH, but not early-stage (3-weeks, an increase in ICAM-1 was observed. To determine whether PAH MP-induced ICAM-1 was selective for a specific segment of the pulmonary circulation, pulmonary microvascular endothelial cells (PMVECs were exposed to late-stage PAH MPs and no increase in ICAM-1 was detected. A select population of circulating MPs, the late-stage endoglin + MPs, were used to assess their ability to stimulate ICAM-1 and it was determined that the endoglin + MPs were sufficient to promote ICAM-1 increases in the whole cell, but not surface only expression. Conclusions Late-stage, but not early-stage, MPs in a model of severe PAH selectively induce ICAM-1 in pulmonary artery endothelium, but not pulmonary microcirculation. Further, the selected endoglin + PAH MPs, but not endoglin + MPs from control, are sufficient to promote whole cell ICAM-1 in PAECs. The implications of this work are that MPs in late-stage PAH are capable of inducing ICAM-1 expression selectively in the pulmonary artery. ICAM-1 likely plays a significant role in the observed inflammatory cell recruitment, specifically to vascular lesions in the pulmonary artery and not the pulmonary microcirculation.

A Pharmacological Examination of the Cardiovascular Effects of Malayan Krait (Bungarus candidus Venoms

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Janeyuth Chaisakul

2017-03-01

Full Text Available Cardiovascular effects (e.g., tachycardia, hypo- and/or hypertension are often clinical outcomes of snake envenoming. Malayan krait (Bungarus candidus envenoming has been reported to cause cardiovascular effects that may be related to abnormalities in parasympathetic activity. However, the exact mechanism for this effect has yet to be determined. In the present study, we investigated the in vivo and in vitro cardiovascular effects of B. candidus venoms from Southern (BC-S and Northeastern (BC-NE Thailand. SDS-PAGE analysis of venoms showed some differences in the protein profile of the venoms. B. candidus venoms (50 µg/kg–100 µg/kg, i.v. caused dose-dependent hypotension in anaesthetised rats. The highest dose caused sudden hypotension (phase I followed by a return of mean arterial pressure to baseline levels and a decrease in heart rate with transient hypertension (phase II prior to a small decrease in blood pressure (phase III. Prior administration of monovalent antivenom significantly attenuated the hypotension induced by venoms (100 µg/kg, i.v.. The sudden hypotensive effect of BC-NE venom was abolished by prior administration of hexamethonium (10 mg/kg, i.v. or atropine (5 mg/kg, i.v.. BC-S and BC-NE venoms (0.1 µg/kg–100 µg/ml induced concentration-dependent relaxation (EC50 = 8 ± 1 and 13 ± 3 µg/mL, respectively in endothelium-intact aorta. The concentration–response curves were markedly shifted to the right by pre-incubation with L-NAME (0.2 mM, or removal of the endothelium, suggesting that endothelium-derived nitric oxide (NO is likely to be responsible for venom-induced aortic relaxation. Our data indicate that the cardiovascular effects caused by B. candidus venoms may be due to a combination of vascular mediators (i.e., NO and autonomic adaptation via nicotinic and muscarinic acetylcholine receptors.

Report to Congress on abnormal occurrences

International Nuclear Information System (INIS)

1990-10-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from April 1 through June 30, 1990. The report discusses six abnormal occurrences, none involving a nuclear power plant. There were five abnormal occurrences at NRC licensees: (1) deficiencies in brachytherapy program; (2) a radiation overexposure of a radiographer; (3) a medical diagnostic misadministration; (4) administration of iodine-131 to a lactating female with subsequent uptake by her infant; and (5) a medical therapy misadministration. An Agreement State (Arizona) reported an abnormal occurrence involving a medical diagnostic misadministration. The report also contains information that updates a previously reported occurrence

Amplitude of low frequency fluctuation abnormalities in adolescents with online gaming addiction.

Science.gov (United States)

Yuan, Kai; Jin, Chenwang; Cheng, Ping; Yang, Xuejuan; Dong, Tao; Bi, Yanzhi; Xing, Lihong; von Deneen, Karen M; Yu, Dahua; Liu, Junyu; Liang, Jun; Cheng, Tingting; Qin, Wei; Tian, Jie

2013-01-01

The majority of previous neuroimaging studies have demonstrated both structural and task-related functional abnormalities in adolescents with online gaming addiction (OGA). However, few functional magnetic resonance imaging (fMRI) studies focused on the regional intensity of spontaneous fluctuations in blood oxygen level-dependent (BOLD) during the resting state and fewer studies investigated the relationship between the abnormal resting-state properties and the impaired cognitive control ability. In the present study, we employed the amplitude of low frequency fluctuation (ALFF) method to explore the local features of spontaneous brain activity in adolescents with OGA and healthy controls during resting-state. Eighteen adolescents with OGA and 18 age-, education- and gender-matched healthy volunteers participated in this study. Compared with healthy controls, adolescents with OGA showed a significant increase in ALFF values in the left medial orbitofrontal cortex (OFC), the left precuneus, the left supplementary motor area (SMA), the right parahippocampal gyrus (PHG) and the bilateral middle cingulate cortex (MCC). The abnormalities of these regions were also detected in previous addiction studies. More importantly, we found that ALFF values of the left medial OFC and left precuneus were positively correlated with the duration of OGA in adolescents with OGA. The ALFF values of the left medial OFC were also correlated with the color-word Stroop test performance. Our results suggested that the abnormal spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of OGA.

Amplitude of low frequency fluctuation abnormalities in adolescents with online gaming addiction.

Directory of Open Access Journals (Sweden)

Kai Yuan

Full Text Available The majority of previous neuroimaging studies have demonstrated both structural and task-related functional abnormalities in adolescents with online gaming addiction (OGA. However, few functional magnetic resonance imaging (fMRI studies focused on the regional intensity of spontaneous fluctuations in blood oxygen level-dependent (BOLD during the resting state and fewer studies investigated the relationship between the abnormal resting-state properties and the impaired cognitive control ability. In the present study, we employed the amplitude of low frequency fluctuation (ALFF method to explore the local features of spontaneous brain activity in adolescents with OGA and healthy controls during resting-state. Eighteen adolescents with OGA and 18 age-, education- and gender-matched healthy volunteers participated in this study. Compared with healthy controls, adolescents with OGA showed a significant increase in ALFF values in the left medial orbitofrontal cortex (OFC, the left precuneus, the left supplementary motor area (SMA, the right parahippocampal gyrus (PHG and the bilateral middle cingulate cortex (MCC. The abnormalities of these regions were also detected in previous addiction studies. More importantly, we found that ALFF values of the left medial OFC and left precuneus were positively correlated with the duration of OGA in adolescents with OGA. The ALFF values of the left medial OFC were also correlated with the color-word Stroop test performance. Our results suggested that the abnormal spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of OGA.

Ergonomics for enhancing detection of machine abnormalities.

Science.gov (United States)

Illankoon, Prasanna; Abeysekera, John; Singh, Sarbjeet

2016-10-17

Detecting abnormal machine conditions is of great importance in an autonomous maintenance environment. Ergonomic aspects can be invaluable when detection of machine abnormalities using human senses is examined. This research outlines the ergonomic issues involved in detecting machine abnormalities and suggests how ergonomics would improve such detections. Cognitive Task Analysis was performed in a plant in Sri Lanka where Total Productive Maintenance is being implemented to identify sensory types that would be used to detect machine abnormalities and relevant Ergonomic characteristics. As the outcome of this research, a methodology comprising of an Ergonomic Gap Analysis Matrix for machine abnormality detection is presented.

Abnormal functional brain asymmetry in depression: evidence of biologic commonality between major depression and dysthymia.

Science.gov (United States)

Bruder, Gerard E; Stewart, Jonathan W; Hellerstein, David; Alvarenga, Jorge E; Alschuler, Daniel; McGrath, Patrick J

2012-04-30

Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having "pure" dysthymia show the same abnormality of perceptual asymmetry as MDD. It also examined gender differences in lateralization, and the extent to which abnormalities of perceptual asymmetry in depressed patients are dependent on gender. Unmedicated patients having either a MDD (n=96) or "pure" dysthymic disorder (n=42) and healthy controls (n=114) were tested on dichotic fused-words and complex-tone tests. Patient and control groups differed in right hemisphere advantage for complex tones, but not left hemisphere advantage for words. Reduced right hemisphere advantage for tones was equally present in MDD and dysthymia, but was more evident among depressed men than depressed women. Also, healthy men had greater hemispheric asymmetry than healthy women for both words and tones, whereas this gender difference was not seen for depressed patients. Dysthymia and MDD share a common abnormality of hemispheric asymmetry for dichotic listening. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

[Hysteroscopic polypectomy, treatment of abnormal uterine bleeding].

Science.gov (United States)

de Los Rios, P José F; López, R Claudia; Cifuentes, P Carolina; Angulo, C Mónica; Palacios-Barahona, Arlex U

2015-07-01

To evaluate the effectiveness of the hysteroscopic polypectomy in terms of the decrease of the abnormal uterine bleeding. A cross-sectional and analytical study was done with patients to whom a hysteroscopic polypectomy was done for treating the abnormal uterine bleeding, between January 2009 and December 2013. The response to the treatment was evaluated via a survey given to the patients about the behavior of the abnormal uterine bleeding after the procedure and about overall satisfaction. The results were obtained after a hysteroscopic polypectomy done to 128 patients and were as follows. The average time from the polypectomy applied until the survey was 30.5 months, with a standard deviation of 18 months. 67.2% of the patients reported decreased abnormal uterine bleeding and the 32.8% reported a persistence of symptoms. On average 82.8% of the. patients were satisfied with the treatment. Bivariate and multivariate analysis showed no association between the variables studied and no improvement of abnormal uterine bleeding after surgery (polypectomy). There were no complications. Hysteroscopic polypectomy is a safe surgical treatment, which decreases on two of three patients the abnormal uterine bleeding in the presence of endometrial polyps, with an acceptable level of satisfaction.

Abnormalities of Object Visual Processing in Body Dysmorphic Disorder

Science.gov (United States)

Feusner, Jamie D.; Hembacher, Emily; Moller, Hayley; Moody, Teena D.

2013-01-01

Background Individuals with body dysmorphic disorder may have perceptual distortions for their appearance. Previous studies suggest imbalances in detailed relative to configural/holistic visual processing when viewing faces. No study has investigated the neural correlates of processing non-symptom-related stimuli. The objective of this study was to determine whether individuals with body dysmorphic disorder have abnormal patterns of brain activation when viewing non-face/non-body object stimuli. Methods Fourteen medication-free participants with DSM-IV body dysmorphic disorder and 14 healthy controls participated. We performed functional magnetic resonance imaging while participants matched photographs of houses that were unaltered, contained only high spatial frequency (high detail) information, or only low spatial frequency (low detail) information. The primary outcome was group differences in blood oxygen level-dependent signal changes. Results The body dysmorphic disorder group showed lesser activity in the parahippocampal gyrus, lingual gyrus, and precuneus for low spatial frequency images. There were greater activations in medial prefrontal regions for high spatial frequency images, although no significant differences when compared to a low-level baseline. Greater symptom severity was associated with lesser activity in dorsal occipital cortex and ventrolateral prefrontal cortex for normal and high spatial frequency images. Conclusions Individuals with body dysmorphic disorder have abnormal brain activation patterns when viewing objects. Hypoactivity in visual association areas for configural and holistic (low detail) elements and abnormal allocation of prefrontal systems for details is consistent with a model of imbalances in global vs. local processing. This may occur not only for appearance but also for general stimuli unrelated to their symptoms. PMID:21557897

Ca2+ signaling in injured in situ endothelium of rat aorta.

Science.gov (United States)

Berra-Romani, Roberto; Raqeeb, Abdul; Avelino-Cruz, José Everardo; Moccia, Francesco; Oldani, Amanda; Speroni, Francisco; Taglietti, Vanni; Tanzi, Franco

2008-09-01

The inner wall of excised rat aorta was scraped by a microelectrode and Ca2+ signals were investigated by fluorescence microscopy in endothelial cells (ECs) directly coupled with injured cells. The injury caused an immediate increase in the intracellular Ca2+ concentration ([Ca2+]i), followed by a long-lasting decay phase due to Ca2+ influx from extracellular space. The immediate response was mainly due to activation of purinergic receptors, as shown by the effect of P2X and P2Y receptors agonists and antagonists, such as suramin, alpha,beta-MeATP, MRS-2179 and 2-MeSAMP. Inhibition of store-operated Ca2+ influx did not affect either the peak response or the decay phase. Furthermore, the latter was: (i) insensitive to phospholipase C inhibition, (ii) sensitive to the gap junction blockers, palmitoleic acid, heptanol, octanol and oleamide, and (iii) sensitive to La3+ and Ni2+, but not to Gd3+. Finally, ethidium bromide or Lucifer Yellow did not enter ECs facing the scraped area. These results suggest that endothelium scraping: (i) causes a short-lasting stimulation of healthy ECs by extracellular nucleotides released from damaged cells and (ii) uncouples the hemichannels of the ECs facing the injury site; these hemichannels do not fully close and allow a long-lasting Ca2+ entry.

Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone.

Science.gov (United States)

Detremmerie, Charlotte; Vanhoutte, Paul M; Leung, Susan

2017-07-01

The natural compound thymoquinone, extracted from Nigella sativa (black cumin), is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endothelium-independent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously, thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase (sGC) producing inosine 3',5'-cyclic monophosphate (cyclic IMP) rather than guanosine 3',5'-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic IMP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC.

Equipment abnormality monitoring device

International Nuclear Information System (INIS)

Ando, Yasumasa

1991-01-01

When an operator hears sounds in a plantsite, the operator compares normal sounds of equipment which he previously heard and remembered with sounds he actually hears, to judge if they are normal or abnormal. According to the method, there is a worry that abnormal conditions can not be appropriately judged in a case where the number of objective equipments is increased and in a case that the sounds are changed gradually slightly. Then, the device of the present invention comprises a plurality of monitors for monitoring the operation sound of equipments, a recording/reproducing device for recording and reproducing the signals, a selection device for selecting the reproducing signals among the recorded signals, an acoustic device for converting the signals to sounds, a switching device for switching the signals to be transmitted to the acoustic device between to signals of the monitor and the recording/reproducing signals. The abnormality of the equipments can be determined easily by comparing the sounds representing the operation conditions of equipments for controlling the plant operation and the sounds recorded in their normal conditions. (N.H.)

Proximal patellar tendinosis and abnormalities of patellar tracking

International Nuclear Information System (INIS)

Allen, G.M.; Tauro, P.G.; Ostlere, S.J.

1999-01-01

Objective. To assess whether an association exists between patellar tendinosis and abnormal patellar tracking. Design and patients. The MRI examinations of 630 patients (i.e. 860 knees) referred with anterior knee pain over a 4-year period were assessed in retrospect for the presence of patellar tendinosis and abnormal patellar tracking. The images of the patients with patellar tendinosis were reviewed and the location within the patellar tendon was recorded. Results. There were 44 knees with proximal patellar tendinosis. Twenty-four of these were considered to have normal patellar tracking and 20 to have abnormal patellar tracking. In the group of 816 knees without proximal patellar tendinosis, 581 were considered to have normal patellar tracking and 235 knees to have abnormal patellar tracking. When the two groups were compared there was a statistically significant difference in the ratio of patients with and without abnormal tracking. Conclusion. In patients referred with anterior knee pain or suspected abnormal patellar tracking there is a significant association between proximal patellar tendinosis and abnormal patellar tracking. (orig.)

[Correction of the endothelial function damaged by gamma-irradiation with free and liposomal quercetin].

Science.gov (United States)

Kyslova, O V; Sapatyĭ, A L; Kupnovyts'ka, I H; Moĭbenko, O O

2007-01-01

It has been investigation the action of solubil quercetin (corvitin) and quercetin filled liposomes (lipoflavon) on endothelium--dependent r-irradiated isolated rats aortic rings relaxations to acetylcholine. It has been showed, that corvitin addition directly to the buffer solution (0.1 mg/ml) increase endothelium--dependent vascular responses to acetylcholine on 35%, lipoflavon addition--on 25%.

Real-time Multiple Abnormality Detection in Video Data

DEFF Research Database (Denmark)

Have, Simon Hartmann; Ren, Huamin; Moeslund, Thomas B.

2013-01-01

Automatic abnormality detection in video sequences has recently gained an increasing attention within the research community. Although progress has been seen, there are still some limitations in current research. While most systems are designed at detecting specific abnormality, others which...... are capable of detecting more than two types of abnormalities rely on heavy computation. Therefore, we provide a framework for detecting abnormalities in video surveillance by using multiple features and cascade classifiers, yet achieve above real-time processing speed. Experimental results on two datasets...... show that the proposed framework can reliably detect abnormalities in the video sequence, outperforming the current state-of-the-art methods....

Hysterosalpingography: analysis of 473 abnormal examinations

International Nuclear Information System (INIS)

Petta, C.A.; Costa-Paiva, L.H.S. da; Pinto-Neto, A.M.; Martins, R.; Souza, G.A.

1990-01-01

The authors reviewed the reports of 4/3 abnormal hysterosalpingographies from 1,200 medical records of patients at the sterility and infertility out-patient clinic of the School of Medical Sciences of the State University of Campinas (Unicamp), from July, 1974 to December, 1981. The objective was to evaluate the incidence and main alterations diagnosed by hysterosalpingography. The most frequent findings were tuboperitoneal factors in 91% of the examinations, uterine cavity abnormalities in 17.4% and cervical factor in 6.3% of the cases. The examinations showed a great incident of tuboperitoneal abnormalities as cause of sterility from lower social classes. (author) [pt

Numerically abnormal chromosome constitutions in humans

Energy Technology Data Exchange (ETDEWEB)

NONE

1993-12-31

Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

Abnormal Uterine Bleeding

Science.gov (United States)

... especially the progestin-only pill (also called the “mini-pill”) can actually cause abnormal bleeding for some ... Basics Sports Safety Injury Rehabilitation Emotional Well-Being Mental Health Sex and Birth Control Sex and Sexuality ...

Elevated urinary albumin excretion is associated with impaired arterial dilatory capacity in clinically healthy subjects

DEFF Research Database (Denmark)

Clausen, P; Jensen, J S; Jensen, G

2001-01-01

(endothelium-dependent, flow-associated dilation) and to nitroglycerin (endothelium-independent, nitroglycerin-induced dilation). Plasma concentrations of the endothelial markers nitrate/nitrite, thrombomodulin, and von Willebrand factor antigen were also measured. Both flow-associated and nitroglycerin...

The management of women with abnormal cervical cytology in pregnancy.

LENUS (Irish Health Repository)

Flannelly, Grainne

2010-02-01

The management of women with abnormal cytology in pregnancy represents both a diagnostic and a therapeutic challenge for colposcopists. The emphasis should be on diagnosis and confirmation of cervical precancer (Cervical intraepithelial neoplasia (CIN) or Adenocarcinoma in situ (AIS), thus excluding invasive cancer). Following an initial assessment, careful follow-up is essential. This must include colposcopy and take into account the physiological changes of the cervix during pregnancy and the puerperium. The management of women with invasive cancer diagnosed during pregnancy depends on the gestation at diagnosis and requires careful assessment and multidisciplinary planning.

Endothelial function and dysfunction: clinical significance and assessment

Directory of Open Access Journals (Sweden)

Shaghayegh Haghjooyejavanmard

2008-08-01

Full Text Available

• Over the past two decades, investigators have increasingly recognized the importance of the endothelium as a centralregulator of vascular and body homeostasis. The endothelial lining represents an organ of 1.5 kg in an adult, which is distributed throughout the body. The endothelium is versatile and multifunctional. In addition to its role as a selective permeability barrier, it has many synthetic and metabolic properties, including modulation of vascular tone and blood flow, regulation of immune and inflammatory responses, and regulation of coagulation, fibrinolysis and thrombosis. Endothelial dysfunction (ED is a frequently used term, which can be referred to abnormalities in various physiological functions of the endothelium, and it is known as a key variable in the pathogenesis of several diseases and their complications. Finding suitable markers for endothelial damage or ED is certainly of interest. Established and emerging techniques to detect ED are divided into three large families of functional, cellular, and biochemical markers. Instead of performing single assessments, it may be much more valuable to determine various biological aspects of endothelium. It seems that there is likely a spectrum between normality, endothelial activation (by inflammatory cytokines, endothelial dysfunction (e.g., impairment of nitric oxide, resulting in loss of regulation of vascular tone and endothelial damage (e.g., atherosclerosis. In this review we review the importance of endothelium and its activation, biomarkers and dysfunction.
•  KEYWORDS: Endothelial function, endothelium, Disease.

Serotonin Neuron Abnormalities in the BTBR Mouse Model of Autism

Science.gov (United States)

Guo, Yue-Ping; Commons, Kathryn G.

2017-01-01

The inbred mouse strain BTBR T+ Itpr3tf/J (BTBR) i studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region-dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile. PMID:27478061

Chest radiographic abnormalities in HIV-infected African children: a longitudinal study.

Science.gov (United States)

Pitcher, Richard D; Lombard, Carl J; Cotton, Mark F; Beningfield, Stephen J; Workman, Lesley; Zar, Heather J

2015-09-01

There is limited knowledge of chest radiographic abnormalities over time in HIV-infected children in resource-limited settings. To investigate the natural history of chest radiographic abnormalities in HIV-infected African children, and the impact of antiretroviral therapy (ART). Prospective longitudinal study of the association of chest radiographic findings with clinical and immunological parameters. Chest radiographs were performed at enrolment, 6-monthly, when initiating ART and if indicated clinically. Radiographic abnormalities were classified as normal, mild or moderate severity and considered persistent if present for 6 consecutive months or longer. An ordinal multiple logistic regression model assessed the association of enrolment and time-dependent variables with temporal radiographic findings. 258 children (median (IQR) age: 28 (13-51) months; median CD4+%: 21 (15-24)) were followed for a median of 24 (18-42) months. 70 (27%) were on ART at enrolment; 130 (50%) (median age: 33 (18-56) months) commenced ART during the study. 154 (60%) had persistent severe radiographic abnormalities, with median duration 18 (6-24) months. Among children on ART, 69% of radiographic changes across all 6-month transition periods were improvements, compared with 45% in those not on ART. Radiographic severity was associated with previous radiographic severity (OR=120.80; 95% CI 68.71 to 212.38), lack of ART (OR=1.72; 95% CI 1.29 to 2.27), enrolment age ART was beneficial, reducing the risk of radiographic deterioration or increasing the likelihood of radiological improvement. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Prevalence of cervical cytology abnormalities among HIV infected ...

African Journals Online (AJOL)

Objectives: To establish the prevalence of cervical cytology abnormalities, determine the correlation between CD4+ cell count and abnormal Pap smear, determine the correlation between WHO-HIV staging and abnormal pap smear among HIV infected women attending HIV clinic at Rwanda Military Hospital. Design: ...

Abnormal Uterine Bleeding including coagulopathies and other menstrual disorders.

Science.gov (United States)

Deligeoroglou, Efthimios; Karountzos, Vasileios

2018-04-01

Abnormal Uterine Bleeding (AUB) is a frequent cause of visits to the emergency department and a major reason for concern among adolescents and their families. The most common cause of AUB, in otherwise healthy adolescents, is ovulatory dysfunction, although 5-36% of adolescents who present with heavy menstrual bleeding, have an underlying bleeding disorder (BD). The most common form of BDs is von Willebrand Disease, reflecting 13% of adolescents with AUB. Management of AUB depends on the underlying etiology, the bleeding severity, as well as the need for hospitalization. Treatment of adolescents with an underlying coagulopathy depends on the severity of the BD, while therapeutic interventions are summarized in supportive measures, hormonal treatments (e.g. Combined Oral Contraceptives), non-hormonal treatments (e.g. tranexamic acid and desmopressin), surgical options (e.g. dilatation & curettage) and treatment options in specific conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diagnostic value of saline contrast sonohysterography comparing with hysteroscopy for detecting endometrial abnormalities in women with abnormal uterine bleeding

Directory of Open Access Journals (Sweden)

Farzaneh Goharzad

2011-01-01

Full Text Available Background: Abnormal uterine bleeding is a common presentation of uterine abnormalities among premenopausal and postmenopausal women.Objective: To evaluate and compare the diagnostic accuracy of saline contrast sonohysterography and hysteroscopy for detecting the cause of abnormal uterine bleeding.Materials and Methods: A total of 65 women with abnormal uterine bleeding were enrolled in this study. A prior saline contrast sonohysetrography followed by a hysteroscopy was performed in all cases. Sensitivity, specificity, positive and negative predictive value and test accuracy were calculated.Results: As the most common abnormality, SCSH showed hyperplasia in 19 patients while hysteroscopy diagnosed polyp in 15 cases. A sensitivity of 73.3%, 71.4% and 90.9% were reported for polyp, hyperplasia and submucous myoma respectively whereas the specificity was calculated 96% for polyps, 82.3% for hyperplasia and 90.7% for submucous myoma.Conclusion: Comparing with hysteroscopy, sonohysterography showed a high sensitivity and specificity for detecting submucous myoma but not for endometrial polyp and endometrial hyperplasia

Arthropathy of the abnormal temporo-mandibular joint

Energy Technology Data Exchange (ETDEWEB)

Stampfel, G.; Gausch, K.; Waldhart, E.

1984-05-01

Arthrography provides accurate information concerning abnormal changes and function of the soft tissue components of the T.M.J. It is superior to all other clinical and radiological methods of examination for elucidating functional abnormalities. The increasing incidence of functional T.M.J. abnormalities and improvements in treatment make arthrography of the T.M.J. of increasing importance. The importance of views in the sagittal plane and of video recordings is stressed. 3 figs.

How can the process of postnatal adaptation be changed by the presence of congenital abnormalities of lip and palate

Directory of Open Access Journals (Sweden)

Brucknerová Ingrid

2017-12-01

Full Text Available Despite modern approaches in molecular biology and genetics, we are still not able to identify the actual cause in more than 50% of all congenital defects. One-half of the unidentified cases is referred to as “multifactorial”. Detailed prenatal investigation of the fetus can discover the presence of congenital abnormality, which can worsen the process of postnatal adaptation. Retrospective analysis of newborns admitted to the Neonatal Department of Intensive Medicine (NDIM in 2012-2016 with the aim to analyze how the process of postnatal adaptation can be changed by the presence of congenital abnormalities of lip and palate. During a five-year period, 13 newborns were admitted to NDIM (2 premature; 11 term newborns. Chromosomal abnormality was confirmed in one patient (Down syndrome and in one patient suspicion of Patau syndrome was found. Twelve newborns had complete cheilognathopalatoschisis. Two premature newborns and two term newborns had perinatal asphyxia. In this group of patients, 33% had respiratory insufficiency without the presence of congenital heart abnormality, 66% had congenital heart abnormality with respiratory insufficiency, and 2 patients had feeding problems. Only one patient had a positive family history. The diagnosis of complete cheilognathopalatoschisis was confirmed prenatally only in 9 patients. We confirmed that clinical consequences of congenital abnormalities of lip and palate depend on the nature, localization and range of abnormalities, as well as on the genetic background and accompanying congenital abnormalities. Prenatal confirmation of the presence of congenital abnormalities has an important influence on the postnatal management of a patient.

Abnormal Selective Attention Normalizes P3 Amplitudes in PDD

Science.gov (United States)

Hoeksma, Marco R.; Kemner, Chantal; Kenemans, J. Leon; van Engeland, Herman

2006-01-01

This paper studied whether abnormal P3 amplitudes in PDD are a corollary of abnormalities in ERP components related to selective attention in visual and auditory tasks. Furthermore, this study sought to clarify possible age differences in such abnormalities. Children with PDD showed smaller P3 amplitudes than controls, but no abnormalities in…

Bone Abnormalities in Mice with Protein Kinase A (PKA) Defects Reveal a Role of Cyclic AMP Signaling in Bone Stromal Cell-Dependent Tumor Development.

Science.gov (United States)

Liu, S; Shapiro, J M; Saloustros, E; Stratakis, C A

2016-11-01

Protein kinase A (PKA) is an important enzyme for all eukaryotic cells. PKA phosphorylates other proteins, thus, it is essential for the regulation of many diverse cellular functions, including cytoplasmic trafficking and signaling, organelle structure and mitochondrial oxidation, nuclear gene expression, the cell cycle, and cellular division. The PKA holoenzyme is composed of 2 regulatory and 2 catalytic subunits. Four regulatory (R1α, R1β, R2α, and R2β) and 4 catalytic subunits (Cα, Cβ, Cγ, and Prkx) have been identified, giving rise to mainly PKA-I (when the 2 regulatory subunits are either R1α or R1β), or PKA-II (when the 2 regulatory subunits are either R2α or R2β). Mutations in the PKA subunits can lead to altered total PKA activity or abnormal PKA-I to PKA-II ratio, leading to various abnormalities in both humans and mice. These effects can be tissue-specific. We studied the effect of PKA subunit defects on PKA activity and bone morphology of mice that were single or double heterozygous for null alleles of the various PKA subunit genes. Bone lesions including fibrous dysplasia, myxomas, osteo-sarcomas, -chondromas and -chondrosarcomas were found in these mice. Observational and molecular studies showed that these lesions were derived from bone stromal cells (BSCs). We conclude that haploinsufficiency for different PKA subunit genes affected bone lesion formation, new bone generation, organization, and mineralization in variable ways. This work identified a PKA subunit- and activity-dependent pathway of bone lesion formation from BSCs with important implications for understanding how cyclic AMP affects the skeleton and its tumorigenesis. © Georg Thieme Verlag KG Stuttgart · New York.

Activation of KCa 3.1 by SKA-31 induces arteriolar dilation and lowers blood pressure in normo- and hypertensive connexin40-deficient mice

DEFF Research Database (Denmark)

Radtke, J; Schmidt, Kirsten; Wulff, H

2013-01-01

BACKGROUND AND PURPOSE: The calcium-activated potassium channel KCa 3.1 is expressed in the vascular endothelium where its activation causes endothelial hyperpolarization and initiates endothelium-derived hyperpolarization (EDH)-dependent dilations. We here investigated whether pharmacological ac...

Contrast sensitivity abnormalities in deaf individuals

Directory of Open Access Journals (Sweden)

Masoud Khorrami-Nejad

2018-01-01

Conclusion: Hearing impaired boys are at a greater risk for contrast sensitivity abnormalities than boys with normal hearing. The larger frequency of contrast sensitivity abnormalities in high spatial frequencies than in other frequencies may demonstrate greater defects in the central visual system compared with the periphery in individuals with hearing loss.

Hair Shaft Abnormality in Children: a Narrative Review

Directory of Open Access Journals (Sweden)

Ghasem Rahmatpour Rokni

2017-08-01

Full Text Available Background Hair is an ectodermal structure, and its formation is regulated by master genes important in embryology. Hair shaft consists of three major regions: the medulla, cortex and cuticle. Hair shaft abnormality will divide structural hair abnormalities into two broad categories - those associated with increased hair fragility and those not associated with increased hair fragility. We conducted a review study to assess hair shaft abnormality in children. Materials and Methods We conducted a review of all papers published on hair shaft abnormalities. A literature search was performed using PubMed, Scopus and Google Scholar on papers publish from 1990 to 2016. The search terms were: hair shaft abnormality, Hair loss, Hair fragility. All abstracts and full text English-language articles were studied. Results While common developmental and structural features are shared in hair follicles and hair shafts. Anomalies of the hair shaft are separated into those with and those without increased hair fragility. Conclusion Although hair has no vital function, it may serve as an indicator for human health. Clinical and morphological hair abnormalities can be clues to specific complex disorders. Hair shaft abnormalities can be inherited or acquired, can reflect a local problem or a systemic disease.

Chromosome abnormalities in atomic bomb survivors

Energy Technology Data Exchange (ETDEWEB)

Tomonaga, Y [Nagasaki Univ. (Japan). School of Medicine

1976-09-01

Chromosome abnormalities in bone marrow cells were recognized in 6 cases which consisted of one case of chronic myelogenous leukemia, two cases of acute myelogenous leukemia, one case of sideroblastic anemia, and two cases of myelodysplasis. Frequency of stable type chromosome abnormalities in bone marrow cells was investigated in 45 atomic bomb survivors without hematologic disorders and 15 controls. It was 1.4% (15 cases) in the group exposed to atomic bomb within 1 km from the hypocenter, which was significantly higher as compared with 0.1% (15 cases) in the group exposed to atomic bomb over 2.5 km from the hypocenter and 0.2% in normal controls. Examination of chromosome was also made on 2 of 3 cases which were the seconds born of female with high chromosome abnormality, who was exposed to within 1 km from the hypocenter, and healthy male exposed 3 km from the hypocenter. These two cases showed chromosome of normal male type, and balanced translocation was not recognized. There was not a significant difference in chromosome abnormalities between the seconds of atomic bomb survivors and controls.

An abnormal carbohydrate tolerance in acromegaly

International Nuclear Information System (INIS)

Qi Jinwu

1988-01-01

An abnormal secretion of plasma human growth hormore (hGH) and insulin in 67 acromegalic patients had been previously treated by external pituitary radiation were studied. All subjects, following an overnight fast, a standard 100 g oral glucose tolerance test, were performed and venous blood samples were taken at 0, 30, 60, 120 and 180 min. They were measured for blood glucose, plasma insulin and hGH. The results of this study have shown that, of the 67 subjects, 23 cases had an abnormal glucose tolerance(34.32%). Diabetes was detected in 17 cases (23.37%) and 6 patients had decreased glucose tolerance(8.69%). In all, hGH levels were consistantly above 5 ng/ml and were not suppressed after an oral glucose load. In these patients, however, about one-third had abnormal glucose tolerance. Low plasma insulin response to glucose and that of the releasing were evident in them than the normal glucose tolerance and a healthy control group. In addition, the mechanism of the abnormal secretion of hGH and insulin were disscussed

Abnormal increase of cosmic ray on August 7th, 1972

International Nuclear Information System (INIS)

Kodama, Masahiro; Murakami, Kazuaki; Wada, Masami

1974-01-01

The abnormal increase of cosmic ray on Aug. 7th particularly the dependence of its starting time on local time was studied. Cosmic ray increased twice before and after the greatest Forbush decrease in history on August 4th and 7th, 1972. This study is a trial to estimate the anisotropic flow of solar cosmic ray from the time difference time at different places. Further, the past instance of 23 ground-level events were statistically restudied, and the relationship between the time of generation of solar cosmic ray and the time of transmission to the earth was investigated. A list is given regarding the solar cosmic ray of more than 10 9 eV which occurred since the observation had started. The list shows definite three groups. Attention is paid to the transmission time of F type which is considered to have the most simplest transmission mechanism. The dispersion of the transmission time is large regarding flare-starting time and peak wave intensity time, but is small regarding solar wave-starting time, but the dependence on the longitude is systematic. After all, cosmic ray is accelerated after 10 minutes since solar electric wave has started, and arrives at the earth most early in the case of a flare occurred at the root of garden force line toward the earth. In conclusion, the method of studying the difference of the starting time of abnormal increase according to local time may be an effective means for examining in the characteristics of anisotropic flow of solar cosmic ray. (Iwakiri, K.)

Enhanced monitoring of abnormal emergency department demands

KAUST Repository

Harrou, Fouzi; Sun, Ying; Kadri, Farid

2016-01-01

of abnormal situations caused by abnormal patient arrivals to the ED. More specifically, This work proposed the application of autoregressive moving average (ARMA) models combined with the generalized likelihood ratio (GLR) test for anomaly-detection. ARMA

Prediction of heart abnormality using MLP network

Science.gov (United States)

Hashim, Fakroul Ridzuan; Januar, Yulni; Mat, Muhammad Hadzren; Rizman, Zairi Ismael; Awang, Mat Kamil

2018-02-01

Heart abnormality does not choose gender, age and races when it strikes. With no warning signs or symptoms, it can result to a sudden death of the patient. Generally, heart's irregular electrical activity is defined as heart abnormality. Via implementation of Multilayer Perceptron (MLP) network, this paper tries to develop a program that allows the detection of heart abnormality activity. Utilizing several training algorithms with Purelin activation function, an amount of heartbeat signals received through the electrocardiogram (ECG) will be employed to condition the MLP network.

Abnormal Event Detection Using Local Sparse Representation

DEFF Research Database (Denmark)

Ren, Huamin; Moeslund, Thomas B.

2014-01-01

We propose to detect abnormal events via a sparse subspace clustering algorithm. Unlike most existing approaches, which search for optimized normal bases and detect abnormality based on least square error or reconstruction error from the learned normal patterns, we propose an abnormality measurem...... is found that satisfies: the distance between its local space and the normal space is large. We evaluate our method on two public benchmark datasets: UCSD and Subway Entrance datasets. The comparison to the state-of-the-art methods validate our method's effectiveness....

Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone

Directory of Open Access Journals (Sweden)

Charlotte Detremmerie

2017-07-01

Full Text Available The natural compound thymoquinone, extracted from Nigella sativa (black cumin, is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endothelium-independent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously, thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase (sGC producing inosine 3ʹ,5ʹ-cyclic monophosphate (cyclic IMP rather than guanosine 3ʹ,5ʹ-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic IMP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC.

Protective effects of simvastatin on coronary artery function in swine with acute infection

DEFF Research Database (Denmark)

Liuba, Petru; Pesonen, Erkki; Forslid, Anders

2006-01-01

cholesterol) between the groups (p>0.2). CONCLUSION:: Acute infection is associated with impairment of the muscarinic and kinin-related reactivity of coronary circulation. These functional abnormalities are in part prevented by simvastatin through mechanisms unrelated to lipid lowering......BACKGROUND:: The risk for coronary events may rise during acute infection. Perturbation in coronary endothelial function emerges as one important link. We investigated whether simvastatin could protect the coronary arterial function from the adverse effects of acute infection in swine. METHODS......:: Coronary endothelium-dependent and -independent vasomotor responses were assessed by Doppler velocimetry in 12 Chlamydia pneumoniae-infected and 6 sham-infected swine 2 weeks after intratracheal inoculation. Half of animals from the infection group were pre-treated with simvastatin (80mg daily), while...

Abnormal Brain Connectivity Spectrum Disorders Following Thimerosal Administration

Directory of Open Access Journals (Sweden)

David A. Geier

2017-03-01

Full Text Available Background: Autism spectrum disorder (ASD, tic disorder (TD, and hyperkinetic syndrome of childhood (attention deficit disorder [ADD]/attention deficit hyperactivity disorder [ADHD] are disorders recently defined as abnormal connectivity spectrum disorders (ACSDs because they show a similar pattern of abnormal brain connectivity. This study examines whether these disorders are associated with exposure to thimerosal, a mercury (Hg-based preservative. Methods: A hypothesis testing case-control study evaluated the Vaccine Safety Datalink for the potential dose-dependent odds ratios (ORs for diagnoses of ASD, TD, and ADD/ADHD compared to controls, following exposure to Hg from thimerosal-containing Haemophilus influenzae type b vaccines administrated within the first 15 months of life. Febrile seizures, cerebral degeneration, and unspecified disorders of metabolism, which are not biologically plausibly linked to thimerosal, were examined as control outcomes. Results: On a per 25 μg Hg basis, cases diagnosed with ASD (OR = 1.493, TD (OR = 1.428, or ADD/ADHD (OR = 1.503 were significantly (P < .001 more likely than controls to have received increased Hg exposure. Similar relationships were observed when separated by gender. Cases diagnosed with control outcomes were no more likely than controls to have received increased Hg exposure. Conclusion: The results suggest that Hg exposure from thimerosal is significantly associated with the ACSDs of ASD, TD, and ADD/ADHD.

Nitrofurantoin and congenital abnormalities

DEFF Research Database (Denmark)

Czeizel, A.E.; Rockenbauer, M.; Sørensen, Henrik Toft

2001-01-01

or fetuses with Down’s syndrome (patient controls), 23 (2.8%) pregnant women were treated with nitrofurantoin. The above differences between population controls and cases may be connected with recall bias, because the case-control pair analysis did not indicate a teratogenic potential of nitrofurantoin use......Objective: To study human teratogenic potential of oral nitrofurantoin treatment during pregnancy. Materials and Methods: Pair analysis of cases with congenital abnormalities and matched population controls in the population-based dataset of the Hungarian Case-Control Surveillance of Congenital...... during the second and the third months of gestation, i.e. in the critical period for major congenital abnormalities. Conclusion: Treatment with nitrofurantoin during pregnancy does not present detectable teratogenic risk to the fetus....

White matter abnormalities in tuberous sclerosis complex

Energy Technology Data Exchange (ETDEWEB)

Griffiths, P.D. [Sheffield Univ. (United Kingdom). Academic Dept. of Radiology; Bolton, P. [Cambridge Univ. (United Kingdom). Section of Developmental Psychiatry; Verity, C. [Addenbrooke`s NHS Trust, Cambridge (United Kingdom). Dept. of Paediatric Radiology

1998-09-01

The aim of this study was to investigate and describe the range of white matter abnormalities in children with tuberous sclerosis complex by means of MR imaging. Material and Methods: A retrospective cross-sectional study was performed on the basis of MR imaging findings in 20 cases of tuberous sclerosis complex in children aged 17 years or younger. Results: White matter abnormalities were present in 19/20 (95%) cases of tuberous sclerosis complex. These were most frequently (19/20 cases) found in relation to cortical tubers in the supratentorial compartment. White matter abnormalities related to tubers were found in the cerebellum in 3/20 (15%) cases. White matter abnormalities described as radial migration lines were found in relation to 5 tubers in 3 (15%) children. In 4/20 (20%) cases, white matter abnormalities were found that were not related to cortical tubers. These areas had the appearance of white matter cysts in 3 cases and infarction in the fourth. In the latter case there was a definable event in the clinical history, supporting the diagnosis of stroke. Conclusion: A range of white matter abnormalities were found by MR imaging in tuberous sclerosis complex, the commonest being gliosis and hypomyelination related to cortical tubers. Radial migration lines were seen infrequently in relation to cortical tubers and these are thought to represent heterotopic glia and neurons along the expected path of cortical migration. (orig.)

Persistent abnormal coronary flow reserve in association with abnormal glucose metabolism affects prognosis in acute myocardial infarction

DEFF Research Database (Denmark)

Løgstrup, Brian B; Høfsten, Dan E; Christophersen, Thomas B

2011-01-01

baseline CFR (P = 0.004), S' (P = 0.045) and abnormal glucose metabolism (P = 0.001) were predictors of a decreased CFR at 3 months of follow-up. In multivariate analyses abnormal glucose metabolism (OR: 5.3; 95%CI: 1.9-14.4; P = 0.001) remained a predictor of decreased CFR at follow-up, furthermore...

Relaxing Responses to Hydrogen Peroxide and Nitric Oxide in Human Pericardial Resistance Arteries Stimulated with Endothelin-1

DEFF Research Database (Denmark)

Leurgans, Thomas M; Bloksgaard, Maria; Irmukhamedov, Akhmadjon

2018-01-01

In human pericardial resistance arteries, effects of the endothelium-dependent vasodilator bradykinin are mediated by NO during contraction induced by K(+) or the TxA2 analogue U46619 and by H2 O2 during contraction by endothelin-1 (ET-1), respectively. We tested the hypotheses that ET-1 reduces...... also acts as an endothelium-dependent vasodilator. This article is protected by copyright. All rights reserved....

Mechanisms of phytoestrogen biochanin A-induced vasorelaxation in renovascular hypertensive rats

Directory of Open Access Journals (Sweden)

Seok Choi

2014-12-01

Conclusion: These results suggest that the enhanced relaxation caused by biochanin A in aortic rings from hypertensive rats is endothelium dependent. Vascular smooth muscle K+ channels may be involved in biochanin A-induced relaxation in aortae from hypertensive and normotensive rats. In addition, an endothelium-derived activation of voltage-dependent K+ channels contributes, at least in part, to the relaxant effect of biochanin A in renovascular hypertension.

Brain and bone abnormalities of thanatophoric dwarfism.

Science.gov (United States)

Miller, Elka; Blaser, Susan; Shannon, Patrick; Widjaja, Elysa

2009-01-01

The purpose of this article is to present the imaging findings of skeletal and brain abnormalities in thanatophoric dwarfism, a lethal form of dysplastic dwarfism. The bony abnormalities associated with thanatophoric dwarfism include marked shortening of the tubular bones and ribs. Abnormal temporal lobe development is a common associated feature and can be visualized as early as the second trimester. It is important to assess the brains of fetuses with suspected thanatophoric dwarfism because the presence of associated brain malformations can assist in the antenatal diagnosis of thanatophoric dwarfism.

Phenotype abnormality: 35 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 35 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u541i abnormal for trait of behavioral quality... during process named response to gravity ... abnormal ... behavioral quality

Radiographic abnormalities in tricyclic acid overdose

International Nuclear Information System (INIS)

Varnell, R.M.; Richardson, M.L.; Vincent, J.M.; Godwin, J.D.

1987-01-01

Several case reports have described adult respiratory distress syndrome (ARDS) secondary to tricyclic acid (TCA) overdose. During a 1-year period 83 patients requiring intubation secondary to drug overdose were evaluated. Abnormalities on chest radiographs occurred in 26 (50%) of the 54 patients with TCA overdose, compared to six (21%) of the 29 patients overdosed with other drugs. In addition, five (9%) of the patients with TCA overdose subsequently had radiographic and clinical abnormalities meeting the criteria for ARDS. Only one (3%) of the patients with non-TCA overdose subsequently had change suggesting ARDS. TCAs should be added to the list of drugs associated with ARDS, and TCA overdose should be considered a major risk factor in the development of radiographically evident abnormalities

Report on Congress on abnormal occurrences

International Nuclear Information System (INIS)

1991-06-01

Section 208 of the energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from January 1 through March 31, 1991. The report discusses six abnormal occurrences, none of which involved a nuclear power plant. Five of the events occurred at NRC-licensed facilities: one involved a significant degradation of plant safety at a nuclear fuel cycle facility, one involved a medical diagnostic misadministration, and three involved medical therapy misadministrations. An Agreement State (Arizona) reported one abnormal occurrence that involved medical therapy misadministrations

Global gene expression profiling related to temperature-sensitive growth abnormalities in interspecific crosses between tetraploid wheat and Aegilops tauschii.

Directory of Open Access Journals (Sweden)

Ryusuke Matsuda

Full Text Available Triploid wheat hybrids between tetraploid wheat and Aegilops tauschii sometimes show abnormal growth phenotypes, and the growth abnormalities inhibit generation of wheat synthetic hexaploids. In type II necrosis, one of the growth abnormalities, necrotic cell death accompanied by marked growth repression occurs only under low temperature conditions. At normal temperature, the type II necrosis lines show grass-clump dwarfism with no necrotic symptoms, excess tillers, severe dwarfism and delayed flowering. Here, we report comparative expression analyses to elucidate the molecular mechanisms of the temperature-dependent phenotypic plasticity in the triploid wheat hybrids. We compared gene and small RNA expression profiles in crown tissues to characterize the temperature-dependent phenotypic plasticity. No up-regulation of defense-related genes was observed under the normal temperature, and down-regulation of wheat APETALA1-like MADS-box genes, considered to act as flowering promoters, was found in the grass-clump dwarf lines. Some microRNAs, including miR156, were up-regulated, whereas the levels of transcripts of the miR156 target genes SPLs, known to inhibit tiller and branch number, were reduced in crown tissues of the grass-clump dwarf lines at the normal temperature. Unusual expression of the miR156/SPLs module could explain the grass-clump dwarf phenotype. Dramatic alteration of gene expression profiles, including miRNA levels, in crown tissues is associated with the temperature-dependent phenotypic plasticity in type II necrosis/grass-clump dwarf wheat hybrids.

Report to Congress on abnormal occurrences, October--December 1992

International Nuclear Information System (INIS)

1993-03-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from October 1 through December 31, 1992. There are two abnormal occurrences at nuclear power plants and six abnormal occurrences involving medical misadministration (all therapeutic) at NRC-licensed facilities discussed in this report. No abnormal occurrences were reported by the NRC's Agreement States. The report also contains information updating three previously reported abnormal occurrences

Report to congress on abnormal occurrences: January--March 1992

International Nuclear Information System (INIS)

1992-07-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to congress. This report covers the period from January 1 through March 31, 1992. The abnormal occurrences involving medical therapy misadministrations at NRC-licensed facilities are discussed in this report. There were no abnormal occurrences at a nuclear power plant, and none were reported by NRC's Agreement States. The report also contains information updating some previously reported abnormal occurrences

Phenotype abnormality: 31 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 31 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u537i abnormal for trait of behavior...al quality during process named localization of cell ... abnormal ... behavioral quality

Phenotype abnormality: 33 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 33 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u539i abnormal for trait of behavior...al quality during process named response to auxin stimulus ... abnormal ... behavioral quality

Phenotype abnormality: 32 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 32 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u538i abnormal for trait of behavioral quality... during process named organ development ... abnormal ... organ development ... behavioral quality

Phenotype abnormality: 34 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 34 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u540i abnormal for trait of behavioral quality... during process named response to cytokinin stimulus ... abnormal ... behavioral quality

Alterations in Brain Structure and Functional Connectivity in Alcohol Dependent Patients and Possible Association with Impulsivity.

Science.gov (United States)

Wang, Junkai; Fan, Yunli; Dong, Yue; Ma, Mengying; Ma, Yi; Dong, Yuru; Niu, Yajuan; Jiang, Yin; Wang, Hong; Wang, Zhiyan; Wu, Liuzhen; Sun, Hongqiang; Cui, Cailian

2016-01-01

Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity.

Chromosome abnormalities in atomic bomb survivors

International Nuclear Information System (INIS)

Tomonaga, Yu

1976-01-01

Chromosome abnormalities in bone marrow cells were recognized in 6 cases which consisted of one case of chronic myelogenous leukemia, two cases of acute myelogenous leukemia, one case of sideroblastic anemia, and two cases of myelodysplasis. Frequency of stable type chromosome abnormalities in bone marrow cells was investigated in 45 atomic bomb survivors without hematologic disorders and 15 controls. It was 1.4% (15 cases) in the group exposed to atomic bomb within 1 km from the hypocenter, which was significantly higher as compared with 0.1% (15 cases) in the group exposed to atomic bomb over 2.5 km from the hypocenter and 0.2% in normal controls. Examination of chromosome was also made on 2 of 3 cases which were the seconds born of female with high chromosome abnormality, who was exposed to within 1 km from the hypocenter, and healthy male exposed 3 km from the hypocenter. These two cases showed chromosome of normal male type, and balanced translocation was not recognized. There was not a significant difference in chromosome abnormalities between the seconds of atomic bomb survivors and controls. (Kanao, N.)

Additive Effect of Non-Alcoholic Fatty Liver Disease on Metabolic Syndrome-Related Endothelial Dysfunction in Hypertensive Patients

Directory of Open Access Journals (Sweden)

Maria Perticone

2016-03-01

Full Text Available Metabolic syndrome (MS is characterized by an increased risk of incident diabetes and cardiovascular (CV events, identifying insulin resistance (IR and endothelial dysfunction as key elements. Moreover, non-alcoholic fatty liver disease (NAFLD is bidirectionally linked with MS as a consequence of metabolic and inflammatory abnormalities. We addressed the question if the evolution in NAFLD might worsen endothelium-dependent vasodilating response in MS hypertensives. We recruited 272 Caucasian newly-diagnosed never-treated hypertensive outpatients divided into three groups according to the presence/absence of MS alone or in combination with NAFLD. MS and NAFLD were defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII and non-invasive fatty liver index, respectively. We determined IR by using the homeostasis model assessment (HOMA index. Vascular function, as forearm blood flow (FBF, was determined through strain-gauge plethysmography after intra-arterial infusion of acetylcholine (ACh and sodium nitroprusside. MS+NAFLD+ group showed worse metabolic, inflammatory and vascular profiles compared with MS−NAFLD− and MS+NAFLD−. HOMA resulted in being the strongest predictor of FBF both in the MS+NAFLD− and in the MS+NAFLD+ groups, accounting for 20.5% and 33.2% of its variation, respectively. In conclusion, we demonstrated that MS+NAFLD+ hypertensives show a worse endothelium-dependent vasodilation compared with MS+NAFLD−, allowing for consideration of NAFLD as an early marker of endothelial dysfunction in hypertensives.

Phenotype abnormality: 42 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 42 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u548i abnormal for trait of behavior...al quality in organ named root during process named gravitropism ... root ... abnormal ... behavioral quality

Phenotype abnormality: 40 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 40 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u546i abnormal for trait of behavioral quality... in organ named hypocotyl during process named gravitropism ... hypocotyl ... abnormal ... behavioral quality

Phenotype abnormality: 43 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 43 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u549i abnormal for trait of behavioral quality... in organ named root during process named growth ... root ... abnormal ... growth ... behavioral quality

Abnormal duodenal loop demonstrated by X-ray

International Nuclear Information System (INIS)

Thommesen, P.; Funch-Jensen, P.

1986-01-01

The occurrence of dyspeptic symptoms has previously been correlated with the shape of the duodenal loop in patients with X-ray-negative dyspepsia. An abnormal duodenal loop was associated with a significantly higher incidence of symtoms provoked by meals, vomiting, regurgitations, heartburn, and the irritable bowel syndrome. 89% of these patients (26 patients with a normal duodenal loop and 39 patients with abnormal duodenal loop) were available for a 5-year follow-up study of symptomatic outcome. The incidence of symptoms provoked by meals was still significantly higher in patients with an abnormal duodenal loop, and there was also a significant difference concerning symptomatic outcome. Approximately 75% of the patients with a normal duodenal loop had improved, and 25% had unchanged clinical conditions. Approximately 50% of the patients with an abnormal duodenal loop had improved, and 50% had an unchanged or even deteriorated clinical condition

Microcirculatory disorders in scleroderma systematica: an association with vascular wall stiffness

Directory of Open Access Journals (Sweden)

Ulyana Yuryevna Ruzhentsova

2013-01-01

Full Text Available Objective: to study the specific features of regulation of peripheral vascular tone and their association with the endothelial structure and function of large vessels in patients with scleroderma systematica (SDS. Subjects and methods. The investigation enrolled 25 patients with SDS (mean age, 47±2.6 years; mean disease duration, 8.3+1.7 years and 15 apparently healthy individuals matched for age and gender. Comprehensive examination involved laboratory and instrumental studies, laser Doppler study to evaluate endothelium-dependent and endothelium-independent vasodilation, as well as applanation tonometry calculating the pulse wave velocity and augmentation index. Results. All the patients were found to have impaired peripheral vascular responsiveness as compared to the controls. The examination established a relationship between the magnitude of endothelium-dependent vasodilation and the stiffness index of large vessels. There was no association between endothelium-independent vasodilation and vascular elasticity parameters.

Effects of pranoprofen eye drops on corneal endothelium and tears inflammatory factors in perioperative period of cataract

Directory of Open Access Journals (Sweden)

Rong-Rong Wang

2018-01-01

Full Text Available AIM: To observe the effect of pranoprofen eye drops on corneal endothelium and tears inflammatory factors in perioperative period of cataract surgery. METHODS: Totally 60 cases(60 eyesof senile cataract patients were enrolled in this study. Patients with diabetes or other systemic diseases, with other eye diseases or eye surgery, drug allergy were excluded. All the patients were given ophthalmic surgery for the first time. All the patients were randomly divided into 4 groups, 15 patients per group. Each group of patients had been given levofloxacin eye drops preoperatively for 3d, 4 times per day, and tobramycin dexamethasone eye drops postoperatively, 3 times per day for the first week, 2 times per day for the second week. Group A was the control group, without any other drugs. Group B was given pranoprofen eye drops 4 times per day for 3d before the operation. Group C was given pranoprofen eye drops 4 times per day for 1wk after the operation. Group D was given pranoprofen eye drops 4 times per day for 3d before the operation and 1wk after the operation. All the surgeries were done by the same ophthalmologist, using the same phacoemulsification machine and the same ultrasound energy parameters. The loss rate of endothelial cell was measured by corneal endothelium counterometry. Interleukin-6(IL-6and tumor necrosis factor(TNFin the tear fluid were measured by ELISA before surgery(before using eye dropsand 1wk, 1mo and 3mo postoperatively. RESULTS: There was no significant difference in patients' gender, age and phacoemulsification time among 4 groups. The levels of inflammatory cytokines IL-6 in the tear fluid of the Group B before surgery had no significant difference compared to that at 3mo postoperatively(P>0.05, but the differences among the other groups at different time points were statistically significant(PP>0.05. At 1wk after the operation, there was significant difference between the Group A and the other three groups(PPP>0.05. At 1mo

Organelle and cellular abnormalities associated with hippocampal heterotopia in neonatal doublecortin knockout mice.

Directory of Open Access Journals (Sweden)

Reham Khalaf-Nazzal

Full Text Available Heterotopic or aberrantly positioned cortical neurons are associated with epilepsy and intellectual disability. Various mouse models exist with forms of heterotopia, but the composition and state of cells developing in heterotopic bands has been little studied. Dcx knockout (KO mice show hippocampal CA3 pyramidal cell lamination abnormalities, appearing from the age of E17.5, and mice suffer from spontaneous epilepsy. The Dcx KO CA3 region is organized in two distinct pyramidal cell layers, resembling a heterotopic situation, and exhibits hyperexcitability. Here, we characterized the abnormally organized cells in postnatal mouse brains. Electron microscopy confirmed that the Dcx KO CA3 layers at postnatal day (P 0 are distinct and separated by an intermediate layer devoid of neuronal somata. We found that organization and cytoplasm content of pyramidal neurons in each layer were altered compared to wild type (WT cells. Less regular nuclei and differences in mitochondria and Golgi apparatuses were identified. Each Dcx KO CA3 layer at P0 contained pyramidal neurons but also other closely apposed cells, displaying different morphologies. Quantitative PCR and immunodetections revealed increased numbers of oligodendrocyte precursor cells (OPCs and interneurons in close proximity to Dcx KO pyramidal cells. Immunohistochemistry experiments also showed that caspase-3 dependent cell death was increased in the CA1 and CA3 regions of Dcx KO hippocampi at P2. Thus, unsuspected ultrastructural abnormalities and cellular heterogeneity may lead to abnormal neuronal function and survival in this model, which together may contribute to the development of hyperexcitability.

Factors associated with abnormal spirometry among HIV-infected individuals.

Science.gov (United States)

Drummond, M Bradley; Huang, Laurence; Diaz, Philip T; Kirk, Gregory D; Kleerup, Eric C; Morris, Alison; Rom, William; Weiden, Michael D; Zhao, Enxu; Thompson, Bruce; Crothers, Kristina

2015-08-24

HIV-infected individuals are susceptible to development of chronic lung diseases, but little is known regarding the prevalence and risk factors associated with different spirometric abnormalities in this population. We sought to determine the prevalence, risk factors and performance characteristics of risk factors for spirometric abnormalities among HIV-infected individuals. Cross-sectional cohort study. We analyzed cross-sectional US data from the NHLBI-funded Lung-HIV consortium - a multicenter observational study of heterogeneous groups of HIV-infected participants in diverse geographic sites. Logistic regression analysis was performed to determine factors statistically significantly associated with spirometry patterns. A total of 908 HIV-infected individuals were included. The median age of the cohort was 50 years, 78% were men and 68% current smokers. An abnormal spirometry pattern was present in 37% of the cohort: 27% had obstructed and 10% had restricted spirometry patterns. Overall, age, smoking status and intensity, history of Pneumocystis infection, asthma diagnosis and presence of respiratory symptoms were independently associated with an abnormal spirometry pattern. Regardless of the presence of respiratory symptoms, five HIV-infected participants would need to be screened with spirometry to diagnose two individuals with any abnormal spirometry pattern. Nearly 40% of a diverse US cohort of HIV-infected individuals had an abnormal spirometry pattern. Specific characteristics including age, smoking status, respiratory infection history and respiratory symptoms can identify those at risk for abnormal spirometry. The high prevalence of abnormal spirometry and the poor predictive capability of respiratory symptoms to identify abnormal spirometry should prompt clinicians to consider screening spirometry in HIV-infected populations.

Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS.

Science.gov (United States)

Silva, Mauro Sb; Prescott, Melanie; Campbell, Rebecca E

2018-04-05

Androgen excess is a hallmark of polycystic ovary syndrome (PCOS), a prevalent yet poorly understood endocrine disorder. Evidence from women and preclinical animal models suggests that elevated perinatal androgens can elicit PCOS onset in adulthood, implying androgen actions in both PCOS ontogeny and adult pathophysiology. Prenatally androgenized (PNA) mice exhibit a robust increase of progesterone-sensitive GABAergic inputs to gonadotropin-releasing hormone (GnRH) neurons implicated in the pathogenesis of PCOS. It is unclear when altered GABAergic wiring develops in the brain, and whether these central abnormalities are dependent upon adult androgen excess. Using GnRH-GFP-transgenic mice, we determined that increased GABA input to GnRH neurons occurs prior to androgen excess and the manifestation of reproductive impairments in PNA mice. These data suggest that brain circuit abnormalities precede the postpubertal development of PCOS traits. Despite the apparent developmental programming of circuit abnormalities, long-term blockade of androgen receptor signaling from early adulthood rescued normal GABAergic wiring onto GnRH neurons, improved ovarian morphology, and restored reproductive cycles in PNA mice. Therefore, androgen excess maintains changes in female brain wiring linked to PCOS features and the blockade of androgen receptor signaling reverses both the central and peripheral PNA-induced PCOS phenotype.

Report to Congress on abnormal occurrences, July--September 1992

International Nuclear Information System (INIS)

1992-12-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from July 1 through September 30, 1992. There were no abnormal occurrences at a nuclear power plant. Two abnormal occurrences involving medical misadministrations (both therapeutic) and one involving overexposure of a radiographer at NRC-licensed facilities were discussed in this report. In addition, another abnormal occurrence was reported by an NRC Agreement State. The report also contains information updating a previously reported abnormal occurrence

Management of abnormal radioactive wastes at nuclear power plants

International Nuclear Information System (INIS)

1989-01-01

As with any other industrial activity, a certain level of risk is associated with the operation of nuclear power plants and other nuclear facilities. That is, on occasions nuclear power plants or nuclear facilities may operate under conditions which were not specifically anticipated during the design and construction of the plant. These abnormal conditions and situations may cause the production of abnormal waste, which can differ in character or quantity from waste produced during normal routine operation of nuclear facilities. Abnormal waste can also occur during decontamination programmes, replacement of a reactor component, de-sludging of storage ponds, etc. The management of such kinds of waste involves the need to evaluate existing waste management systems in order to determine how abnormal wastes should best be handled and processed. There are no known publications on this subject, and the IAEA believes that the development and exchange of such information among its Member States would be useful for specialists working in the waste management area. The main objective of this report is to review existing waste management practices which can be applied to abnormal waste and provide assistance in the selection of appropriate technologies and processes that can be used when abnormal situations occur. Naturally, the subject of abnormal waste is complex and this report can only be considered as a guide for the management of abnormal waste. Refs, figs and tabs.

Phenotype abnormality: 47 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 47 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u553i abnormal for trait of behavior...al quality in organ named thylakoid membrane during process named thylakoid membrane organization ... abnormal ... behavioral quality

Effects of theophylline administration and intracranial abnormalities ...

African Journals Online (AJOL)

Objective: To determine effects of theophylline therapy for recurrent apnoea of prematurity and abnormal early (within the first 24 hours) cranial ultrasound abnormalities on protective neck turning response in preterm infants. Design: A cross sectional descriptive study. Setting: The Neonatal Unit of Hammersmith Hospital, ...

Phenotype abnormality: 50 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 50 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u556i abnormal for trait of behavioral quality... in organ named whole plant during process named photomorphogenesis ... whole plant ... abnormal ... behavioral quality

Effect of environmental particulates on cultured human and bovine endothelium. Cellular injury via an oxidant-dependent pathway

International Nuclear Information System (INIS)

Garcia, J.G.; Dodson, R.F.; Callahan, K.S.

1989-01-01

The effects of respirable environmental fibers on cultures of human umbilical vein and bovine pulmonary artery endothelial cell monolayers were studied. Interaction among endothelial cell monolayers and amosite and chrysotile asbestos, attapulgite, fiberglass, or latex beads resulted in rapid phagocytosis of the particulates. A gradient of time-dependent and concentration-dependent endothelial cell injury (measured by specific 51Cr release) was observed with amosite and attapulgite being markedly toxic. Chrysotile and fiberglass were much less toxic, and latex beads were not significantly injurious at any time or dose examined. Responses of bovine pulmonary artery and human endothelial vein endothelial cells to fiber phagocytosis and fiber-induced injury were similar. In human umbilical cell monolayers, fiber-mediated stimulation of the arachidonate metabolite prostacyclin paralleled endothelial cell injury; i.e. amosite and attapulgite were stimulatory, whereas fiberglass (0-500 micrograms/ml) and latex beads (10(9) beads/ml) did not significantly increase prostacyclin generation. Although chrysotile was only weakly cytotoxic, significant stimulation of prostacyclin was observed at the highest dose tested (500 micrograms/ml). To investigate whether toxic oxygen species may be involved in fiber-induced cytotoxicity, oxidant scavengers or inhibitors were used in injury studies. Both superoxide dismutase (a scavenger of O2-) and catalase (an inhibitor of H2O2) produced significant protection against fiber-mediated endothelial cell injury. In addition, chelation by deferoxamine of elemental Fe present in the fiber preparations was also protective, suggesting Fe, via the modified Haber-Weiss reaction, may promote hydroxyl radical formation and contribute to endothelial cell injury induced by these particulates

Redox imbalance and mitochondrial abnormalities in the diabetic lung.

Science.gov (United States)

Wu, Jinzi; Jin, Zhen; Yan, Liang-Jun

2017-04-01

Although the lung is one of the least studied organs in diabetes, increasing evidence indicates that it is an inevitable target of diabetic complications. Nevertheless, the underlying biochemical mechanisms of lung injury in diabetes remain largely unexplored. Given that redox imbalance, oxidative stress, and mitochondrial dysfunction have been implicated in diabetic tissue injury, we set out to investigate mechanisms of lung injury in diabetes. The objective of this study was to evaluate NADH/NAD + redox status, oxidative stress, and mitochondrial abnormalities in the diabetic lung. Using STZ induced diabetes in rat as a model, we measured redox-imbalance related parameters including aldose reductase activity, level of poly ADP ribose polymerase (PAPR-1), NAD + content, NADPH content, reduced form of glutathione (GSH), and glucose 6-phophate dehydrogenase (G6PD) activity. For assessment of mitochondrial abnormalities in the diabetic lung, we measured the activities of mitochondrial electron transport chain complexes I to IV and complex V as well as dihydrolipoamide dehydrogenase (DLDH) content and activity. We also measured the protein content of NAD + dependent enzymes such as sirtuin3 (sirt3) and NAD(P)H: quinone oxidoreductase 1 (NQO1). Our results demonstrate that NADH/NAD + redox imbalance occurs in the diabetic lung. This redox imbalance upregulates the activities of complexes I to IV, but not complex V; and this upregulation is likely the source of increased mitochondrial ROS production, oxidative stress, and cell death in the diabetic lung. These results, together with the findings that the protein contents of DLDH, sirt3, and NQO1 all are decreased in the diabetic lung, demonstrate that redox imbalance, mitochondrial abnormality, and oxidative stress contribute to lung injury in diabetes. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Neurological abnormalities associated with CDMA exposure.

Science.gov (United States)

Hocking, B; Westerman, R

2001-09-01

Dysaesthesiae of the scalp and neurological abnormality after mobile phone use have been reported previously, but the roles of the phone per se or the radiations in causing these findings have been questioned. We report finding a neurological abnormality in a patient after accidental exposure of the left side of the face to mobile phone radiation [code division multiple access (CDMA)] from a down-powered mobile phone base station antenna. He had headaches, unilateral left blurred vision and pupil constriction, unilateral altered sensation on the forehead, and abnormalities of current perception thresholds on testing the left trigeminal ophthalmic nerve. His nerve function recovered during 6 months follow-up. His exposure was 0.015-0.06 mW/cm(2) over 1-2 h. The implications regarding health effects of radiofrequency radiation are discussed.

Chromosomal abnormalities and autism

Directory of Open Access Journals (Sweden)

Farida El-Baz

2016-01-01

Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

Chromosomal abnormality in patients with secondary amenorrhea.

Science.gov (United States)

Safai, Akbar; Vasei, Mohammad; Attaranzadeh, Armin; Azad, Fariborz; Tabibi, Narjes

2012-04-01

Secondary amenorrhea is a condition in which there is cessation of menses after at least one menstruation. It is a symptom of different diseases, such as hormonal disturbances which range from pituitary to ovarian origin, as well as chromosomal abnormalities. Knowledge of the distinct cause of secondary amenorrhea is of tremendous benefit for the management and monitoring of patients. In this study, we determine the chromosomal abnormalities in patients with secondary amenorrhea in Southwest Iran. We selected 94 patients with secondary amenorrhea who referred to our Cytogenetic Ward from 2004 until 2009. For karyotyping, peripheral blood lymphocyte cultures were set up by conventional technique. In this study, 5.3% (n=5) of patients with secondary amenorrhea presented with chromosomal abnormalities, of which all contained an X element. The chromosomal abnormalities were: i) 45, X (n=1); ii) 47, XXX (n=1); iii) 45, X [13]/ 45, Xi(X)q[17] (n=1);  iv) 45, X[12]/46,X,+mar[12] (n=1); and v) 46,X,del(Xq)(q23q28) (n=1). Our study revealed that some causes of secondary amenorrhea could be due to chromosomal abnormalities. Therefore, cytogenetic studies should be important tests in the evaluation of patients with secondary amenorrhea.

Inhibition of protein kinase Cbeta does not improve endothelial function in type 2 diabetes.

Science.gov (United States)

Beckman, Joshua A; Goldfine, Allison B; Goldin, Alison; Prsic, Adnan; Kim, Sora; Creager, Mark A

2010-08-01

Antagonism of protein kinase Cbeta (PKCbeta) restores endothelial function in experimental models of diabetes and prevents vascular dysfunction in response to hyperglycemia in healthy humans. We tested the hypothesis that PKCbeta antagonism would improve vascular function in subjects with type 2 diabetes compared with healthy control subjects. The effect of PKCbeta was evaluated in a randomized, placebo-controlled, double-blinded crossover trial. The study was performed in the outpatient setting of a university medical center. Thirteen subjects with type 2 diabetes without evidence of cardiovascular disease and 15 healthy control subjects were recruited via newspaper advertisement. Subjects underwent a randomized, double-blind, crossover, placebo-controlled trial of the selective PKCbeta antagonist ruboxistaurin mesylate. Subjects received each treatment for 14 d. Endothelium-dependent and endothelium-independent vasodilation of forearm resistance vessels was measured with mercury-in-silastic, strain-gauge plethysmography during intraarterial administration of methacholine chloride and verapamil, respectively. Markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress were measured after each treatment. Endothelium-dependent vasodilation of forearm resistance vessels was attenuated in diabetic subjects when compared with healthy subjects (P=0.001). Endothelium-independent vasodilation did not differ between groups (P value not significant). Ruboxistaurin did not significantly change endothelium-dependent or endothelium-independent vasodilation or blood-based markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress in either diabetic or healthy subjects. Endothelial dysfunction of forearm resistance vessels was not improved by 2 wk of selective PKCbeta inhibition in patients with diabetes. These results suggest that PKCbeta does not contribute significantly to vascular dysfunction in otherwise healthy patients with type 2

Prevalence of chromosomal abnormalities and Y chromosome microdeletion among men with severe semen abnormalities and its correlation with successful sperm retrieval

Directory of Open Access Journals (Sweden)

Mariano Mascarenhas

2016-01-01

Full Text Available AIM: To estimate the prevalence of chromosomal abnormalities and Y chromosome microdeletion among men with azoospermia and severe oligozoospermia and its correlation with successful surgical sperm retrieval. SETTING AND DESIGN: A prospective study in a tertiary level infertility unit. MATERIALS AND METHODS: In a prospective observation study, men with azoospermia and severe oligozoospermia (concentration <5 million/ml attending the infertility center underwent genetic screening. Peripheral blood karyotype was done by Giemsa banding. Y chromosome microdeletion study was performed by a multiplex polymerase chain reaction. RESULTS: The study group consisted of 220 men, 133 of whom had azoospermia and 87 had severe oligozoospermia. Overall, 21/220 (9.5% men had chromosomal abnormalities and 13/220 (5.9% men had Y chromosome microdeletions. Chromosomal abnormalities were seen in 14.3% (19/133 of azoospermic men and Y chromosome microdeletions in 8.3% (11/133. Of the 87 men with severe oligozoospermia, chromosomal abnormalities and Y chromosome microdeletions were each seen in 2.3% (2/87. Testicular sperm aspiration was done in 13 men and was successful in only one, who had a deletion of azoospermia factor c. CONCLUSIONS: Our study found a fairly high prevalence of genetic abnormality in men with severe semen abnormalities and a correlation of genetic abnormalities with surgical sperm retrieval outcomes. These findings support the need for genetic screening of these men prior to embarking on surgical sperm retrieval and assisted reproductive technology intracytoplasmic sperm injection.

Report to Congress on abnormal occurrences, January--March 1978

International Nuclear Information System (INIS)

1978-01-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. The report, the twelfth in the series, covers the period from January 1 to March 31, 1978. The following incidents or events in that time period were determined by the Commission to be significant and reportable: (1) There was one abnormal occurrence at the 68 nuclear power plants licensed to operate. The event involved insulation failures in containment electrical penetrations. (2) There were no abnormal occurrences at fuel cycle facilities (other than nuclear power plants). (3) There were no abnormal occurrences at other license facilities. (4) There was one abnormal occurrence reported by an Agreement State Licensee. The event involved an overexposure of a radiographer. The report also contains information updating previously reported abnormal occurrences

Phenotype abnormality: 46 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 46 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u552i abnormal for trait of behavior.../cria224u2ria224u38i stomatal complex ... abnormal ... response to light stimulus ... behavioral quality

Phenotype abnormality: 44 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 44 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u550i abnormal for trait of behavior...al quality in organ named root during process named organ development ... root ... abnormal ... organ development ... behavioral quality

Phenotype abnormality: 45 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 45 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u551i abnormal for trait of behavior...al quality in organ named stamen during process named organ development ... stamen ... abnormal ... organ development ... behavioral quality

Phenotype abnormality: 37 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 37 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u543i abnormal for trait of behavior...al quality in organ named cotyledon during process named organ development ... cotyledon ... abnormal ... organ development ... behavioral quality

Phenotype abnormality: 39 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 39 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u545i abnormal for trait of behavior...al quality in organ named flower during process named organ development ... flower ... abnormal ... organ development ... behavioral quality

Insulin therapy does not interfere with venous endothelial function evaluation in patients with type 2 diabetes mellitus

Directory of Open Access Journals (Sweden)

Antônio Marcos Vargas da Silva

2010-01-01

Full Text Available INTRODUCTION: Endothelium-dependent dilation is improved in insulin-treated diabetic patients, but this effect is probably due to improved glycemic control. The objective of the present study was to compare endothelium-dependent dilation in patients with well-controlled type 2 diabetes who are or are not using insulin as part of their therapy. METHODS: We studied 27 patients with type 2 diabetes (11 women, 60.3 years ± 6 years, with HbA1c < 7% and no nephropathy, including 16 patients treated with anti-diabetic agents (No-Ins, 8 women and 11 patients treated with insulin alone or in combination with anti-diabetic agents (Ins, 3 women. Endothelial function was evaluated by the dorsal hand vein technique, which measures changes in vein diameter in response to phenylephrine, acetylcholine (endothelium-dependent vasodilation and sodium nitroprusside (endothelium-independent vasodilation. RESULTS: Age, systolic blood pressure (No-Ins: 129.4 mmHg ± 11.8 mmHg, Ins: 134.8 mmHg ± 12.0 mmHg; P= 0.257, HbA1c, lipids and urinary albumin excretion rate [No-Ins: 9 mg/24 h (0-14.1 mg/24 h vs. Ins: 10.6 mg/24 h (7.5-14.4 mg/24 h, P=0.398] were similar between groups. There was no difference between endothelium-dependent vasodilation of the No-Ins group (59.3% ± 26.5% vs. the Ins group (54.0% ± 16.3%; P=0.526. Endothelium-independent vasodilation was also similar between the No-Ins (113.7% ± 35.3% and Ins groups (111.9% ± 28.5%; P=0.888. CONCLUSIONS: Subcutaneous insulin therapy does not interfere with venous endothelial function in type 2 diabetes when glycemic and blood pressure control are stable.

Insulin therapy does not interfere with venous endothelial function evaluation in patients with type 2 diabetes mellitus.

Science.gov (United States)

Silva, Antônio Marcos Vargas da; Penno, Luciana de Moraes; Bertoluci, Marcello Casaccia; Irigoyen, Maria Cláudia; Schaan, Beatriz D'Agord

2010-01-01

Endothelium-dependent dilation is improved in insulin-treated diabetic patients, but this effect is probably due to improved glycemic control. The objective of the present study was to compare endothelium-dependent dilation in patients with well-controlled type 2 diabetes who are or are not using insulin as part of their therapy. We studied 27 patients with type 2 diabetes (11 women, 60.3 years ± 6 years, with HbA1c < 7% and no nephropathy), including 16 patients treated with anti-diabetic agents (No-Ins, 8 women) and 11 patients treated with insulin alone or in combination with anti-diabetic agents (Ins, 3 women). Endothelial function was evaluated by the dorsal hand vein technique, which measures changes in vein diameter in response to phenylephrine, acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation). Age, systolic blood pressure (No-Ins: 129.4 mmHg ± 11.8 mmHg, Ins: 134.8 mmHg ± 12.0 mmHg; P= 0.257), HbA1c, lipids and urinary albumin excretion rate [No-Ins: 9 mg/24 h (0-14.1 mg/24 h) vs. Ins: 10.6 mg/24 h (7.5-14.4 mg/24 h), P=0.398] were similar between groups. There was no difference between endothelium-dependent vasodilation of the No-Ins group (59.3% ± 26.5%) vs. the Ins group (54.0% ± 16.3%; P=0.526). Endothelium-independent vasodilation was also similar between the No-Ins (113.7% ± 35.3%) and Ins groups (111.9% ± 28.5%; P=0.888). Subcutaneous insulin therapy does not interfere with venous endothelial function in type 2 diabetes when glycemic and blood pressure control are stable.

Morphological Abnormalities of Thalamic Subnuclei in Migraine

DEFF Research Database (Denmark)

Magon, Stefano; May, Arne; Stankewitz, Anne

2015-01-01

UNLABELLED: The thalamus contains third-order relay neurons of the trigeminal system, and animal models as well as preliminary imaging studies in small cohorts of migraine patients have suggested a role of the thalamus in headache pathophysiology. However, larger studies using advanced imaging te...... is a disorder of the CNS in which not only is brain function abnormal, but also brain structure is undergoing significant remodeling....... a fully automated multiatlas approach. Deformation-based shape analysis was performed to localize surface abnormalities. Differences between patients with migraine and healthy subjects were assessed using an ANCOVA model. After correction for multiple comparisons, performed using the false discovery rate.......9) was observed in patients. This large-scale study indicates structural thalamic abnormalities in patients with migraine. The thalamic nuclei with abnormal volumes are densely connected to the limbic system. The data hence lend support to the view that higher-order integration systems are altered in migraine...

"Jeopardy" in Abnormal Psychology.

Science.gov (United States)

Keutzer, Carolin S.

1993-01-01

Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

Haematological, ocular and skeletal abnormalities in a Samoyed family

International Nuclear Information System (INIS)

Aroch, I.; Ofri, R.; Aizenberg, I.

1996-01-01

Haematological, ocular and skeletal abnormalities were documented in a samoyed male and its five offspring. Haematological abnormalities, found in repeated tests in all the dogs, included marked eosinophilia, eosinophilic bands and absence of Barr bodies. Two of the dogs had bilateral buphthalmia, retinal detachments and other ocular abnormalities. Three of the dogs had skeletal abnormalities including chondrodysplasia (dwarfism) and brachygnathia (undershot jaw). A similar combination of inherited skeletal and ocular disorders, without the haematological abnormalities, has been described in samoyeds. Acquired causes for the haematological findings, which are similar to the inherited Pelger-Huët anomaly described in several species, have been eliminated. Eosinophilic bands and scarcity of Barr bodies could be a marker, or a previously unreported manifestation, of an inherited disorder in samoyeds

Report to Congress on abnormal occurrences, July--September 1988

International Nuclear Information System (INIS)

1989-01-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from July 1 to September 30, 1988. For this reporting period, there were no abnormal occurrences at nuclear power plants licensed to operate. There were two abnormal occurrences under other NRC-issued licenses: multiple medical therapy misadministrations at a single hospital and a medical diagnostic misadministration. There was one abnormal occurrence reported by an Agreement State (Texas) involving a medical diagnostic misadministration. The report also contains information updating some previously reported abnormal occurrences

Phenotype abnormality: 49 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 49 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u555i abnormal for trait of behavior...al quality in organ named whole plant during process named cell growth ... whole plant ... abnormal ... cell growth ... behavioral quality

Phenotype abnormality: 48 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 48 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u554i abnormal for trait of behavior...al quality in organ named vascular leaf during process named organ development ... vascular leaf ... abnormal ... organ development ... behavioral quality

21 CFR 864.7415 - Abnormal hemoglobin assay.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415 Abnormal...

Prevalence of biochemical and immunological abnormalities in ...

African Journals Online (AJOL)

Tile prevalence of biochemical and immunological abnormalities was studied in a group of 256 patients with rheumatoid arthritis (104 coloureds, 100 whites and 52 blacks). The most common biochemical abnormalities detected were a reduction in the serum creatinine value (43,4%), raised globulins (39,7%), raised serum ...

Know abnormal, find evil : frequent pattern mining for ransomware threat hunting and intelligence

OpenAIRE

Homayoun, S; Dehghantanha, A; Ahmadzadeh, M; Hashemi, S; Khayami, R

2017-01-01

Emergence of crypto-ransomware has significantly\\ud changed the cyber threat landscape. A crypto ransomware\\ud removes data custodian access by encrypting valuable data\\ud on victims’ computers and requests a ransom payment to reinstantiate custodian access by decrypting data. Timely detection of ransomware very much depends on how quickly and\\ud accurately system logs can be mined to hunt abnormalities and\\ud stop the evil. In this paper we first setup an environment to\\ud collect activity l...

Gastric emptying abnormal in duodenal ulcer

Energy Technology Data Exchange (ETDEWEB)

Holt, S.; Heading, R.C.; Taylor, T.V.; Forrest, J.A.; Tothill, P.

1986-07-01

To investigate the possibility that an abnormality of gastric emptying exists in duodenal ulcer and to determine if such an abnormality persists after ulcer healing, scintigraphic gastric emptying measurements were undertaken in 16 duodenal ulcer patients before, during, and after therapy with cimetidine; in 12 patients with pernicious anemia, and in 12 control subjects. No difference was detected in the rate or pattern of gastric emptying in duodenal ulcer patients before and after ulcer healing with cimetidine compared with controls, but emptying of the solid component of the test meal was more rapid during treatment with the drug. Comparison of emptying patterns obtained in duodenal ulcer subjects during and after cimetidine treatment with those obtained in pernicious anemia patients and controls revealed a similar relationship that was characterized by a tendency for reduction in the normal differentiation between the emptying of solid and liquid from the stomach. The similarity in emptying patterns in these groups of subjects suggests that gastric emptying of solids may be influenced by changes in the volume of gastric secretion. The failure to detect an abnormality of gastric emptying in duodenal ulcer subjects before and after ulcer healing calls into question the widespread belief that abnormally rapid gastric emptying is a feature with pathogenetic significance in duodenal ulcer disease.

Gastric emptying abnormal in duodenal ulcer

International Nuclear Information System (INIS)

Holt, S.; Heading, R.C.; Taylor, T.V.; Forrest, J.A.; Tothill, P.

1986-01-01

To investigate the possibility that an abnormality of gastric emptying exists in duodenal ulcer and to determine if such an abnormality persists after ulcer healing, scintigraphic gastric emptying measurements were undertaken in 16 duodenal ulcer patients before, during, and after therapy with cimetidine; in 12 patients with pernicious anemia, and in 12 control subjects. No difference was detected in the rate or pattern of gastric emptying in duodenal ulcer patients before and after ulcer healing with cimetidine compared with controls, but emptying of the solid component of the test meal was more rapid during treatment with the drug. Comparison of emptying patterns obtained in duodenal ulcer subjects during and after cimetidine treatment with those obtained in pernicious anemia patients and controls revealed a similar relationship that was characterized by a tendency for reduction in the normal differentiation between the emptying of solid and liquid from the stomach. The similarity in emptying patterns in these groups of subjects suggests that gastric emptying of solids may be influenced by changes in the volume of gastric secretion. The failure to detect an abnormality of gastric emptying in duodenal ulcer subjects before and after ulcer healing calls into question the widespread belief that abnormally rapid gastric emptying is a feature with pathogenetic significance in duodenal ulcer disease

Diverticular Disease of the Colon: Neuromuscular Function Abnormalities.

Science.gov (United States)

Bassotti, Gabrio; Villanacci, Vincenzo; Bernardini, Nunzia; Dore, Maria P

2016-10-01

Colonic diverticular disease is a frequent finding in daily clinical practice. However, its pathophysiological mechanisms are largely unknown. This condition is likely the result of several concomitant factors occurring together to cause anatomic and functional abnormalities, leading as a result to the outpouching of the colonic mucosa. A pivotal role seems to be played by an abnormal colonic neuromuscular function, as shown repeatedly in these patients, and by an altered visceral perception. There is recent evidence that these abnormalities might be related to the derangement of the enteric innervation, to an abnormal distribution of mucosal neuropeptides, and to low-grade mucosal inflammation. The latter might be responsible for the development of visceral hypersensitivity, often causing abdominal pain in a subset of these patients.

Neurological abnormalities predict disability

DEFF Research Database (Denmark)

Poggesi, Anna; Gouw, Alida; van der Flier, Wiesje

2014-01-01

To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed...... at evaluating age-related white matter changes (ARWMC) as an independent predictor of the transition to disability (according to Instrumental Activities of Daily Living scale) or death in independent elderly subjects that were followed up for 3 years. At baseline, a standardized neurological examination.......0 years, 45 % males), 327 (51.7 %) presented at the initial visit with ≥1 neurological abnormality and 242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for MRI features and other determinants of functional decline, showed that the baseline presence of any neurological...

A comprehensive study of sparse codes on abnormality detection

DEFF Research Database (Denmark)

Ren, Huamin; Pan, Hong; Olsen, Søren Ingvor

2017-01-01

Sparse representation has been applied successfully in abnor-mal event detection, in which the baseline is to learn a dic-tionary accompanied by sparse codes. While much empha-sis is put on discriminative dictionary construction, there areno comparative studies of sparse codes regarding abnormal-ity...... detection. We comprehensively study two types of sparsecodes solutions - greedy algorithms and convex L1-norm so-lutions - and their impact on abnormality detection perfor-mance. We also propose our framework of combining sparsecodes with different detection methods. Our comparative ex-periments are carried...

Abnormal global and local event detection in compressive sensing domain

Science.gov (United States)

Wang, Tian; Qiao, Meina; Chen, Jie; Wang, Chuanyun; Zhang, Wenjia; Snoussi, Hichem

2018-05-01

Abnormal event detection, also known as anomaly detection, is one challenging task in security video surveillance. It is important to develop effective and robust movement representation models for global and local abnormal event detection to fight against factors such as occlusion and illumination change. In this paper, a new algorithm is proposed. It can locate the abnormal events on one frame, and detect the global abnormal frame. The proposed algorithm employs a sparse measurement matrix designed to represent the movement feature based on optical flow efficiently. Then, the abnormal detection mission is constructed as a one-class classification task via merely learning from the training normal samples. Experiments demonstrate that our algorithm performs well on the benchmark abnormal detection datasets against state-of-the-art methods.

Abnormal ''Contamination' Levels On Garden Appliances

International Nuclear Information System (INIS)

German, U.; Levinson, S.; Elmelech, V.; Pelled, O.; Tshuva, A.; Laichter, Y.

1999-01-01

During routine contamination checks we encountered an abnormal high level of Alpha and Beta emitting radioisotopes on working gloves of employees of the gardening department. It came out that the source was due to ''contamination'' levels on steering wheels of some gardening machines. In order to ensure that no real contamination of these workers was involved , a series of checks was started to identity the source of the abnormal levels found during monitoring

Hematological abnormalities in adult patients with Down's syndrome.

LENUS (Irish Health Repository)

McLean, S

2012-02-01

BACKGROUND: There is a paucity of data regarding hematological abnormalities in adults with Down\\'s syndrome (DS). AIMS: We aimed to characterize hematological abnormalities in adult patients with DS and determine their long-term significance. METHODS: We retrospectively studied a cohort of nine DS patients referred to the adult hematology service in our institution between May 2001 and April 2008. Data collected were: full blood count (FBC), comorbidities, investigations performed, duration of follow-up and outcome to most recent follow-up. RESULTS: Median follow-up was 26 months (9-71). Of the nine patients, two had myelodysplastic syndrome (MDS) at presentation. Of these, one progressed, with increasing marrow failure, and requiring support with transfusions and gCSF. The remaining eight patients, with a variety of hematological abnormalities including leukopenia, macrocytosis, and thrombocytopenia, had persistently abnormal FBCs. However there was no evidence of progression, and no patient has evolved to acute myeloid leukemia (AML). CONCLUSIONS: MDS is a complication of DS and may require supportive therapy. However, minor hematological abnormalities are common in adult DS patients, and may not signify underlying marrow disease.

Report to Congress on abnormal occurrences, April--June 1988

International Nuclear Information System (INIS)

1988-12-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from April 1 to June 30, 1988. For this reporting period, there were no abnormal occurrences at nuclear power plants licensed to operate. There were two abnormal occurrences at other NRC licensees: a significant breakdown in management and procedural controls at a medical facility and a medical diagnostic misadministration. There was one abnormal occurrence reported by an Agreement State (Texas) involving radioactive material released during a transportation accident. The report also contains information updating some previously reported abnormal occurrences

Effect of intensive lipid-lowering treatment compared to moderate lipid-lowering treatment with rosuvastatin on endothelial function in high risk patients

DEFF Research Database (Denmark)

Egede, Rasmus; Jensen, Lisette Okkels; Hansen, Henrik Steen

2011-01-01

on the endothelial function evaluated with endothelium-dependent and endothelium-independent flow-mediated dilatation (FMD). METHODS: 87 Statin-naive patients with ST-segment elevation myocardial infarction (STEMI) were randomized to 5mg or 40mg rosuvastatin. The FMD was assessed at baseline, 6months and after 12...

Report to Congress on abnormal occurrences, July--September 1989

International Nuclear Information System (INIS)

1990-01-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from July 1 to September 30, 1989. For this reporting period, there were five abnormal occurrences. One abnormal occurrence took place at a licensed nuclear power plant and involved significant deficiencies associated with the containment recirculation sump at the Trojan facility. The other four abnormal occurrences took place under other NRC-issued licenses: the first involved a medical diagnostic misadministration; the second involved a medical therapy misadministration; the third involved a radiation overexposure of a radiographer; and the fourth involved a significant breakdown and careless disregard of the radiation safety program at three of a licensee's manufacturing facilities. The Agreement States reported no abnormal occurrences during the reporting period. The report also contains information that updates some previously reported abnormal occurrences. 17 refs

Report to Congress on abnormal occurrences, July-September 1986

International Nuclear Information System (INIS)

1987-04-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from July 1 to September 30, 1986. The report states that for this reporting period, there were four abnormal occurrences at the nuclear power plants licensed to operate. The events were (1) a differential pressure switch problem in safety systems at LaSalle facility, (2) abnormal cooldown and depressurization transient at Catawba Unit 2, (3) significant safeguards deficiencies at Wolf Creek and Fort St. Vrain, and (4) significant deficiencies in access controls at River Bend Station. There was one abnormal occurrence at the other NRC licensees; it involved a therapeutic medical misadministration. There was one abnormal occurrence reported by an Agreement State; it involved a therapeutic medical misadministration. The report also contains information updating some previously reported abnormal occurrences

Report to Congress on abnormal occurrences, April--June 1978

International Nuclear Information System (INIS)

1978-01-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report, the thirteenth in the series, covers the period from April 1 to June 30, 1978. The following incidents or events in that period were determined by the Commission to be significant and reportable: (1) There were two abnormal occurrences at the 69 nuclear power plants licensed to operate. One involved a generic concern pertaining to fuel assembly control rod guide tube integrity. The second involved an overexposure of two radiation protection technicians. (2) There were no abnormal occurrences at fuel cycle facilities (other than nuclear power plants). (3) There were no abnormal occurrences at other licensee facilities. (4) There was one abnormal occurrence reported by an agreement state. The event involved willful violations of regulations and subsequent termination of a license. This report also contains information updating previously reported abnormal occurrences

An Abnormal Psychology Community Based Interview Assignment

Science.gov (United States)

White, Geoffry D.

1977-01-01

A course option in abnormal psychology involves students in interviewing and observing the activities of individuals in the off-campus community who are concerned with some aspect of abnormal psychology. The technique generates student interest in the field when they interview people about topics such as drug abuse, transsexualism, and abuse of…

Relationship among sera lipoprotein abnormalities in healthy ...

African Journals Online (AJOL)

As the prevalence of lipoprotein abnormalities in adolescents is increasing dramatically, the identification of relevant risk factors is a major public health challenge. The aim of this study was to investigate whether a family history of diabetes could be a risk factor for lipid abnormalities in healthy individuals. This study is a ...

The usefulness of MRI for the diagnosis of abnormal pregnancies

International Nuclear Information System (INIS)

Amano, Yasuo

1994-01-01

The clinical usefulness of MRI for the diagnosis of abnormal pregnancies was evaluated. Pelvic MRI was carried out on 29 cases suspected of abnormal pregnancy by ultrasonography and clinical examinations. The abnormal pregnancies were classified into three categories: (1) maternal abnormalities, (2) fetal abnormalities and (3) placental abnormalities. MRI was of great value for the diagnosis of maternal abnormalities, particularly in cases of coexistent pelvic tumor. MRI allowed diagnosis of uterine leiomyomas and dermoid cyst through its excellent tissue characterization and broad range of vision. MRI was useful in making diagnoses of fetal central nervous anomalies and fetal death, since the lack of fetal movement and the lesions were clear enough to be detected by MRI. However, anomalies in the fetal trunk or extremities could only be demonstrated, but not diagnosed, by MRI owing to its inferior spatial and time resolution. MRI showed placenta accreta and placental hematoma. Although accurate diagnosis was difficult because of their rarity, MRI revealed the hemorrhagic component of the lesions, which was not shown by ultrasonography. The author believes MRI has potential usefulness in making diagnoses of placental abnormalities through its tissue characterization. MRI was superior to ultrasonography in the soft tissue characterization, field of view, while MRI was inferior in time and spatial resolution. In summary, MRI hould be used in case of abnormal pregnancies such as pelvic tumors, fetal nervous anomalies and placental hemorrhagic lesions. MRI will become useful for the diagnosis of other abnormalities as its spatial resolution and fast scan technology advances. (author)

The usefulness of MRI for the diagnosis of abnormal pregnancies

Energy Technology Data Exchange (ETDEWEB)

Amano, Yasuo (Nippon Medical School, Tokyo (Japan))

1994-02-01

The clinical usefulness of MRI for the diagnosis of abnormal pregnancies was evaluated. Pelvic MRI was carried out on 29 cases suspected of abnormal pregnancy by ultrasonography and clinical examinations. The abnormal pregnancies were classified into three categories: (1) maternal abnormalities, (2) fetal abnormalities and (3) placental abnormalities. MRI was of great value for the diagnosis of maternal abnormalities, particularly in cases of coexistent pelvic tumor. MRI allowed diagnosis of uterine leiomyomas and dermoid cyst through its excellent tissue characterization and broad range of vision. MRI was useful in making diagnoses of fetal central nervous anomalies and fetal death, since the lack of fetal movement and the lesions were clear enough to be detected by MRI. However, anomalies in the fetal trunk or extremities could only be demonstrated, but not diagnosed, by MRI owing to its inferior spatial and time resolution. MRI showed placenta accreta and placental hematoma. Although accurate diagnosis was difficult because of their rarity, MRI revealed the hemorrhagic component of the lesions, which was not shown by ultrasonography. The author believes MRI has potential usefulness in making diagnoses of placental abnormalities through its tissue characterization. MRI was superior to ultrasonography in the soft tissue characterization, field of view, while MRI was inferior in time and spatial resolution. In summary, MRI hould be used in case of abnormal pregnancies such as pelvic tumors, fetal nervous anomalies and placental hemorrhagic lesions. MRI will become useful for the diagnosis of other abnormalities as its spatial resolution and fast scan technology advances. (author).

Modified SOGI based shunt active power filter to tackle various grid voltage abnormalities

Directory of Open Access Journals (Sweden)

Kalpeshkumar Patil

2017-10-01

Full Text Available Shunt Active Power Filters (SAPF have been effectively used to compensate the harmonics generated by the non-linear loads. The SAPF’s performance depends on the accurate generation of reference current, which is dependent greatly on the template of supply voltage. When the grid voltage (or its template is characterized by different abnormalities like presence of harmonics, imbalance, dc-offset etc., some of the conventional techniques of frequency estimation may fail to correctly estimate the frequency. This ultimately affects the reference current generation and hence, the SAPF operation, ultimately leading to high distortion of the grid currents. The paper presents modified dual second-order generalized integrator (MDSOGI based SAPF to ensure effective compensation of harmonics, even when the grid voltage is characterized by all the abnormalities mentioned above. It is highlighted with one case that when the sensed voltage is having dc-offset, DSOGI-SAPF results into the source current with THD, dc-offset and harmonic with values 5.82%, 0.8% and 4.5%, respectively. For the same case, the proposed technique yields grid current which is free of dc-offset and 2nd harmonic and has THD = 3.57%. The dynamic performance of the MDSOGI-SAPF is validated and its superior performance over DSOGI-SAPF is illustrated even with experimental results.

Abnormal global and local event detection in compressive sensing domain

Directory of Open Access Journals (Sweden)

Tian Wang

2018-05-01

Full Text Available Abnormal event detection, also known as anomaly detection, is one challenging task in security video surveillance. It is important to develop effective and robust movement representation models for global and local abnormal event detection to fight against factors such as occlusion and illumination change. In this paper, a new algorithm is proposed. It can locate the abnormal events on one frame, and detect the global abnormal frame. The proposed algorithm employs a sparse measurement matrix designed to represent the movement feature based on optical flow efficiently. Then, the abnormal detection mission is constructed as a one-class classification task via merely learning from the training normal samples. Experiments demonstrate that our algorithm performs well on the benchmark abnormal detection datasets against state-of-the-art methods.

Maternal nutrient restriction during pregnancy impairs an endothelium-derived hyperpolarizing factor-like pathway in sheep fetal coronary arteries.

Science.gov (United States)

Shukla, Praveen; Ghatta, Srinivas; Dubey, Nidhi; Lemley, Caleb O; Johnson, Mary Lynn; Modgil, Amit; Vonnahme, Kimberly; Caton, Joel S; Reynolds, Lawrence P; Sun, Chengwen; O'Rourke, Stephen T

2014-07-15

The mechanisms underlying developmental programming are poorly understood but may be associated with adaptations by the fetus in response to changes in the maternal environment during pregnancy. We hypothesized that maternal nutrient restriction during pregnancy alters vasodilator responses in fetal coronary arteries. Pregnant ewes were fed a control [100% U.S. National Research Council (NRC)] or nutrient-restricted (60% NRC) diet from days 50 to 130 of gestation (term = 145 days); fetal tissues were collected at day 130. In coronary arteries isolated from control fetal lambs, relaxation to bradykinin was unaffected by nitro-l-arginine (NLA). Iberiotoxin or contraction with KCl abolished the NLA-resistant response to bradykinin. In fetal coronary arteries from nutrient-restricted ewes, relaxation to bradykinin was fully suppressed by NLA. Large-conductance, calcium-activated potassium channel (BKCa) currents did not differ in coronary smooth muscle cells from control and nutrient-restricted animals. The BKCa openers, BMS 191011 and NS1619, and 14,15-epoxyeicosatrienoic acid [a putative endothelium-derived hyperpolarizing factor (EDHF)] each caused fetal coronary artery relaxation and BKCa current activation that was unaffected by maternal nutrient restriction. Expression of BKCa-channel subunits did not differ in fetal coronary arteries from control or undernourished ewes. The results indicate that maternal undernutrition during pregnancy results in loss of the EDHF-like pathway in fetal coronary arteries in response to bradykinin, an effect that cannot be explained by a decreased number or activity of BKCa channels or by decreased sensitivity to mediators that activate BKCa channels in vascular smooth muscle cells. Under these conditions, bradykinin-induced relaxation is completely dependent on nitric oxide, which may represent an adaptive response to compensate for the absence of the EDHF-like pathway. Copyright © 2014 the American Physiological Society.

The significance of ultrastructural abnormalities of human cilia.

Science.gov (United States)

Fox, B; Bull, T B; Makey, A R; Rawbone, R

1981-12-01

The electronmicroscopic structure of cilia was studied from the inferior turbinate of the nose in 22 adults, and in 84 biopsies from the bronchial tree of 40 adults. The incidence of compound cilia and abnormal microtubular structures was assessed. There were significant variations in the incidence of abnormalities in different parts of the airways and even within different areas of the same electronmicroscopic section. The focal nature of differences in structure of cilia indicate that abnormalities found in a single biopsy do not necessarily reflect a generalized change in the bronchial tree. Thus, such a finding should not be used as evidence that the abnormalities of cilia are the cause of decrease in mucociliary clearance or that they play a role in the pathogenesis of bronchiectasis and sinusitis.

Visual field abnormalities in multiple sclerosis.

OpenAIRE

Patterson, V H; Heron, J R

1980-01-01

Visual fields were examined with a tangent screen in 54 patients with multiple sclerosis (MS) or optic neuritis (ON). Visual fields were abnormal in all patients with definite MS, 94% with probable MS and 81% with possible MS. Three-quarters of the MS patients with no history of visual symptoms had abnormal fields. The commonest defect found was an arcuate scotoma. As a diagnostic test of visual pathway involvement in MS, tangent screen examination compares favourably with more sophisticated ...

Hemostatic abnormalities in Noonan syndrome.

Science.gov (United States)

Artoni, Andrea; Selicorni, Angelo; Passamonti, Serena M; Lecchi, Anna; Bucciarelli, Paolo; Cerutti, Marta; Cianci, Paola; Gianniello, Francesca; Martinelli, Ida

2014-05-01

A bleeding diathesis is a common feature of Noonan syndrome, and various coagulation abnormalities have been reported. Platelet function has never been carefully investigated. The degree of bleeding diathesis in a cohort of patients with Noonan syndrome was evaluated by a validated bleeding score and investigated with coagulation and platelet function tests. If ratios of prothrombin time and/or activated partial thromboplastin time were prolonged, the activity of clotting factors was measured. Individuals with no history of bleeding formed the control group. The study population included 39 patients and 28 controls. Bleeding score was ≥2 (ie, suggestive of a moderate bleeding diathesis) in 15 patients (38.5%) and ≥4 (ie, suggestive of a severe bleeding diathesis) in 7 (17.9%). Abnormal coagulation and/or platelet function tests were found in 14 patients with bleeding score ≥2 (93.3%) but also in 21 (87.5%) of those with bleeding score Noonan syndrome had a bleeding diathesis and >90% of them had platelet function and/or coagulation abnormalities. Results of these tests should be taken into account in the management of bleeding or invasive procedures in these patients. Copyright © 2014 by the American Academy of Pediatrics.

Chromosomal Abnormalities in ADHD

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2002-07-01

Full Text Available The prevalence of fragile X syndrome, velocardiofacial syndrome (VCFS, and other cytogenetic abnormalities among 100 children (64 boys with combined type ADHD and normal intelligence was assessed at the NIMH and Georgetown University Medical Center.

Report to Congress on abnormal occurrences, January--March 1977

International Nuclear Information System (INIS)

1977-01-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report, the eighth in the series, covers the period from January 1 to March 31, 1977. The NRC has determined that during this period: there were no abnormal occurrences at the 63 nuclear power plants licensed to operate; there were no abnormal occurrences at fuel cycle facilities (other than nuclear power plants); and there was one abnormal occurrence at other licensee facilities. The event involved an inadvertent radiation exposure to two painters while working in an area where industrial radiography was being performed. This report also contains information updating previously reported abnormal occurrences

Abnormal Grain Growth Suppression in Aluminum Alloys

Science.gov (United States)

Hales, Stephen J. (Inventor); Claytor, Harold Dale (Inventor); Alexa, Joel A. (Inventor)

2015-01-01

The present invention provides a process for suppressing abnormal grain growth in friction stir welded aluminum alloys by inserting an intermediate annealing treatment ("IAT") after the welding step on the article. The IAT may be followed by a solution heat treatment (SHT) on the article under effectively high solution heat treatment conditions. In at least some embodiments, a deformation step is conducted on the article under effective spin-forming deformation conditions or under effective superplastic deformation conditions. The invention further provides a welded article having suppressed abnormal grain growth, prepared by the process above. Preferably the article is characterized with greater than about 90% reduction in area fraction abnormal grain growth in any friction-stir-welded nugget.

Aspirin suppresses the abnormal lipid metabolism in liver cancer cells via disrupting an NFκB-ACSL1 signaling.

Science.gov (United States)

Yang, Guang; Wang, Yuan; Feng, Jinyan; Liu, Yunxia; Wang, Tianjiao; Zhao, Man; Ye, Lihong; Zhang, Xiaodong

2017-05-06

Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism. Copyright © 2017. Published by Elsevier Inc.

Echocardiographic abnormalities in hypertensive patients

International Nuclear Information System (INIS)

Rodulfo Garcia, Maikel; Tornes Perez, Victor Manuel; Castellanos Tardo, Juan Ramon

2012-01-01

A descriptive cross-sectional study was carried out in 120 hypertensive patients with a course of 5 or more years, who went to the emergency room of 'Saturnino Lora' Provincial Teaching Hospital from November 2010 to November 2011 in order to determine the presence or absence of echocardiographic abnormalities typical of hypertension. Of these, 78,3 % was affected, most of whom reported not to continue with regular previous medical treatment, and 21,7 % had not these abnormalities. Age group of 50-60 years, males and blacks prevailed in the case material. The most significant echocardiographic findings were left ventricular hypertrophy and heart failure with ejection fraction of left ventricle preserved

Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?

LENUS (Irish Health Repository)

Dowdall, J F

2012-02-03

The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +\\/- 8.2 pg\\/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +\\/- 16.8 and 84.1 +\\/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.

Identification of age-dependent motor and neuropsychological behavioural abnormalities in a mouse model of Mucopolysaccharidosis Type II

Science.gov (United States)

Gleitz, Hélène F. E.; O’Leary, Claire; Holley, Rebecca J.

2017-01-01

Severe mucopolysaccharidosis type II (MPS II) is a progressive lysosomal storage disease caused by mutations in the IDS gene, leading to a deficiency in the iduronate-2-sulfatase enzyme that is involved in heparan sulphate and dermatan sulphate catabolism. In constitutive form, MPS II is a multi-system disease characterised by progressive neurocognitive decline, severe skeletal abnormalities and hepatosplenomegaly. Although enzyme replacement therapy has been approved for treatment of peripheral organs, no therapy effectively treats the cognitive symptoms of the disease and novel therapies are in development to remediate this. Therapeutic efficacy and subsequent validation can be assessed using a variety of outcome measures that are translatable to clinical practice, such as behavioural measures. We sought to consolidate current knowledge of the cognitive, skeletal and motor abnormalities present in the MPS II mouse model by performing time course behavioural examinations of working memory, anxiety, activity levels, sociability and coordination and balance, up to 8 months of age. Cognitive decline associated with alterations in spatial working memory is detectable at 8 months of age in MPS II mice using spontaneous alternation, together with an altered response to novel environments and anxiolytic behaviour in the open-field. Coordination and balance on the accelerating rotarod were also significantly worse at 8 months, and may be associated with skeletal changes seen in MPS II mice. We demonstrate that the progressive nature of MPS II disease is also seen in the mouse model, and that cognitive and motor differences are detectable at 8 months of age using spontaneous alternation, the accelerating rotarod and the open-field tests. This study establishes neurological, motor and skeletal measures for use in pre-clinical studies to develop therapeutic approaches in MPS II. PMID:28207863

The Persistence of Abnormal Returns: Analysis of Polish Manufacturing Industry

Directory of Open Access Journals (Sweden)

Marcin Puziak

2017-06-01

Full Text Available The ultimate goal of a company is to build the enterprise value, which is achievable thanks to abnormal profits generated in particular period. Moreover, firms are expected to take measures to maintain abnormal profit in the future. On the other hand, abnormal profits attract competitors, who increase competition and as a result abnormal profits disappear. The persistence of profit is a term that describes a situation, when the company is successful in maintaining the abnormal profit over time. The main aim of this paper is to investigate the persistence of abnormal profit in Polish manufacturing sector. In other words, the question is whether Polish manufacturing companies are able to maintain their abnormal profits over time. The persistence of abnormal profits is investigated using dynamic panel model with generalized method-of-moments estimators. The method is applied to a panel of 5303 Polish companies from manufacturing sector observed over the period 2006-2014. This paper contributes to the existing literature in two ways. First, analysis is performed for developing country. Second, analysis is performed both at the level of entire sector and at division level. Three main conclusions can be drawn from the conducted research: there are significant differences between profit rates within the same industry at division level; estimated persistence of abnormal profit coefficients are at moderate level; there are substantial differences between estimated persistence of profit coefficients for divisions in the same industry.

Abnormal XPD-induced nuclear receptor transactivation in DNA repair disorders: trichothiodystrophy and xeroderma pigmentosum.

Science.gov (United States)

Zhou, Xiaolong; Khan, Sikandar G; Tamura, Deborah; Ueda, Takahiro; Boyle, Jennifer; Compe, Emmanuel; Egly, Jean-Marc; DiGiovanna, John J; Kraemer, Kenneth H

2013-08-01

XPD (ERCC2) is a DNA helicase involved in nucleotide excision repair and in transcription as a structural bridge tying the transcription factor IIH (TFIIH) core with the cdk-activating kinase complex, which phosphorylates nuclear receptors. Mutations in XPD are associated with several different phenotypes, including trichothiodystrophy (TTD), with sulfur-deficient brittle hair, bone defects, and developmental abnormalities without skin cancer, xeroderma pigmentosum (XP), with pigmentary abnormalities and increased skin cancer, or XP/TTD with combined features, including skin cancer. We describe the varied clinical features and mutations in nine patients examined at the National Institutes of Health who were compound heterozygotes for XPD mutations but had different clinical phenotypes: four TTD, three XP, and two combined XP/TTD. We studied TFIIH-dependent transactivation by nuclear receptor for vitamin D (VDR) and thyroid in cells from these patients. The vitamin D stimulation ratio of CYP24 and osteopontin was associated with specific pairs of mutations (reduced in 5, elevated in 1) but not correlated with distinct clinical phenotypes. Thyroid receptor stimulation ratio for KLF9 was not significantly different from normal. XPD mutations frequently were associated with abnormal VDR stimulation in compound heterozygote patients with TTD, XP, or XP/TTD.

Patterns of pulmonary maturation in normal and abnormal pregnancy.

Science.gov (United States)

Goldkrand, J W; Slattery, D S

1979-03-01

Fetal pulmonary maturation may be a variable event depending on various feto-maternal environmental and biochemical influences. The patterns of maturation were studied in 211 amniotic fluid samples from 123 patients (normal 55; diabetes 23; Rh sensitization 19; preeclampsia 26). The phenomenon of globule formation from the amniotic fluid lipid extract and is relation to pulmonary maturity was utilized for this analysis. Validation of this technique is presented. A normal curve was constructed from 22 to 42 weeks; gestation and compared to the abnormal pregnancies. Patients with class A, B, and C diabetes and Rh-sensitized pregnancies had delayed pulmonary maturation. Patients with class D diabetes and preclampsia paralleled the normal course of maturation. A discussion of these results and their possible cause is presented.

Abnormal grain growth: a non-equilibrium thermodynamic model for multi-grain binary systems

International Nuclear Information System (INIS)

Svoboda, J; Fischer, F D

2014-01-01

Abnormal grain growth as the abrupt growth of a group of the largest grains in a multi-grain system is treated within the context of unequal retardation of grain growth due to the segregation of solute atoms from the bulk of the grains into the grain boundaries. During grain boundary migration, the segregated solute atoms are dragged under a small driving force or left behind the migrating grain boundary under a large driving force. Thus, the solute atoms in the grain boundaries of large grains, exhibiting a large driving force, can be released from the grain boundary. The mobility of these grain boundaries becomes significantly higher and abnormal grain growth is spontaneously provoked. The mean-field model presented here assumes that each grain is described by its grain radius and by its individual segregation parameter. The thermodynamic extremal principle is engaged to obtain explicit evolution equations for the radius and segregation parameter of each grain. Simulations of grain growth kinetics for various conditions of segregation with the same initial setting (100 000 grains with a given radius distribution) are presented. Depending on the diffusion coefficients of the solute in the grain boundaries, abnormal grain growth may be strongly or marginally pronounced. Solute segregation and drag can also significantly contribute to the stabilization of the grain structure. Qualitative agreement with several experimental results is reported. (paper)

ECG abnormalities in patients with chronic kidney disease

International Nuclear Information System (INIS)

Shafi, S.; Saleem, M.; Anjum, R.; Abdullah, W.; Shafi, T.

2017-01-01

Chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease. Electrocardiographic (ECG) abnormalities are common in CKD patients. However, there is variation in literature regarding frequency of ECG abnormalities in CKD patients and limited information in local population. Methods: The study design was cross-sectional in nature. All patients between ages of 20-80 years with CKD not previously on renal replacement therapy who were admitted to nephrology ward at a tertiary care facility over a 6-month period were included. All patients underwent 12 lead electrocardiograms (ECG). ECG abnormalities were defined based on accepted standard criteria. Results: Total number of patients included in the study was 124. Mean age of all patients was 49.9+-13.8 years, 106 (84.8%) had hypertension, 84 (70%) had diabetes mellitus, and 35 (29.9%) had known cardiovascular disease. Mean serum creatinine was 7.2+-3.4 mg/dl, mean eGFR was 10.6+-9.2 ml/min/1.73 m/sup 2/. Overall 78.4% of all CKD patients have one or more ECG abnormality. Left ventricular hypertrophy (40%), Q waves (27.2%), ST segment elevation or depression (23.4%), prolonged QRS duration (19.2%), tachycardia (17.6%) and left and right atrial enlargement (17.6%) were the most common abnormalities. Conclusion: ECG abnormalities are common in hospitalized CKD patients in local population. All hospitalized CKD patients should undergo ECG to screen for cardiovascular disease. (author)

Comparisons of stomatal parameters between normal and abnormal ...

African Journals Online (AJOL)

ED), guard cell length (GCL) and guard cell width (GCW) of normal and abnormal leaf of Bougainvillea spectabilis Willd were studied. This can be useful for further research of physical mechanism of abnormal leaf. Epidermal cells were ...

Mechanisms and consequences of paternally transmitted chromosomal abnormalities

Energy Technology Data Exchange (ETDEWEB)

Marchetti, F; Wyrobek, A J

2005-04-05

Paternally transmitted chromosomal damage has been associated with pregnancy loss, developmental and morphological defects, infant mortality, infertility, and genetic diseases in the offspring including cancer. There is epidemiological evidence linking paternal exposure to occupational or environmental agents with an increased risk of abnormal reproductive outcomes. There is also a large body of literature on germ cell mutagenesis in rodents showing that treatment of male germ cells with mutagens has dramatic consequences on reproduction producing effects such as those observed in human epidemiological studies. However, we know very little about the etiology, transmission and early embryonic consequences of paternally-derived chromosomal abnormalities. The available evidence suggests that: (1) there are distinct patterns of germ cell-stage differences in the sensitivity of induction of transmissible genetic damage with male postmeiotic cells being the most sensitive; (2) cytogenetic abnormalities at first metaphase after fertilization are critical intermediates between paternal exposure and abnormal reproductive outcomes; and, (3) there are maternally susceptibility factors that may have profound effects on the amount of sperm DNA damage that is converted into chromosomal aberrations in the zygote and directly affect the risk for abnormal reproductive outcomes.

Herbicide effects on freshwater benthic diatoms: Induction of nucleus alterations and silica cell wall abnormalities

Energy Technology Data Exchange (ETDEWEB)

Debenest, T. [Ecolab UMR 5245 (INP ENSAT, CNRS, UPS), Equipe ECOGEN, Avenue de l' Agrobiopole - BP 32607 Auzeville Tolosane, 31326 Castanet Tolosan Cedex (France); Cemagref, 50 avenue de Verdun, 33612 Cestas Cedex (France); Silvestre, J. [Ecolab UMR 5245 (INP ENSAT, CNRS, UPS), Equipe ECOGEN, Avenue de l' Agrobiopole - BP 32607 Auzeville Tolosane, 31326 Castanet Tolosan Cedex (France); Coste, M.; Delmas, F. [Cemagref, 50 avenue de Verdun, 33612 Cestas Cedex (France); Pinelli, E. [Ecolab UMR 5245 (INP ENSAT, CNRS, UPS), Equipe ECOGEN, Avenue de l' Agrobiopole - BP 32607 Auzeville Tolosane, 31326 Castanet Tolosan Cedex (France)], E-mail: pinelli@ensat.fr

2008-06-02

Benthic diatoms are well known bio-indicators of river pollution by nutrients (nitrogen and phosphorus). Biological indexes, based on diatom sensitivity for non-toxic pollution, have been developed to assess the water quality. Nevertheless, they are not reliable tools to detect pollution by pesticides. Many authors have suggested that toxic agents, like pesticides, induce abnormalities of the diatom cell wall (frustule). High abnormal frustule abundances have been reported in natural diatom communities sampled in streams contaminated by pesticides. However, no direct link was found between the abundances of abnormal frustules in these communities and the pesticide concentrations in stream water. In the present study, a freshwater benthic diatom community, isolated from natural biofilm and cultured under controlled conditions, was treated with a known genotoxic herbicide, maleic hydrazide (MH). Cells were exposed to three concentrations of MH (5 x 10{sup -6}, 10{sup -6}, 10{sup -7} M) for 6 h followed by a 24 h-recovery time. After MH treatments, nucleus alterations were observed: abnormal nucleus location, micronucleus, multinuclear cell or disruption of the nuclear membrane. A dose-dependent increase of nuclear alterations was observed. The difference between the control (9.65 nuclear alterations per 1000 cells observed (9.65 per mille), S.D. = 4.23) and the highest concentrations (29.40 per mille, S.D. = 8.49 for 10{sup -6} M and 35.96 per mille , S.D. = 3.71 for 5 x 10{sup -6} M) was statistically significant (Tukey test, P < 0.05). Diatoms also exhibited frustules with deformed morphology and abnormal ornamentation. Significantly increased abundances of abnormal frustules were observed for the highest concentrations (10{sup -6} and 5 x 10{sup -6} M; Tukey test, P < 0.05). These two parameters tended to increase together (Pearson correlation = 0.702, P < 0.05). The results suggest that the induction of abnormal frustules could be associated with the genotoxic

Abnormal Uterine Bleeding: American College of Nurse-Midwives.

Science.gov (United States)

2016-07-01

Variations in uterine bleeding, termed abnormal uterine bleeding, occur commonly among women and often are physiologic in nature with no significant consequences. However, abnormal uterine bleeding can cause significant distress to women or may signify an underlying pathologic condition. Most women experience variations in menstrual and perimenstrual bleeding in their lifetimes; therefore, the ability of the midwife to differentiate between normal and abnormal bleeding is a key diagnostic skill. A comprehensive history and use of the PALM-COEIN classification system will provide clear guidelines for clinical management, evidence-based treatment, and an individualized plan of care. The purpose of this Clinical Bulletin is to define and describe classifications of abnormal uterine bleeding, review updated terminology, and identify methods of assessment and treatment using a woman-centered approach. © 2016 by the American College of Nurse-Midwives.

DYNAMICS OF HEAT SHOCK PROTEIN-70 SYNTHESIS IN LUNGS DEPENDS ON THE STAGE OF EXPERIMENTAL RESPIRATORY DISTRESS SYNDROME

Directory of Open Access Journals (Sweden)

E. V. Prutkina

2013-01-01

Full Text Available Abstract. Acute respiratory distress syndrome (ARDS was reproduced in a rat model, by means of intratracheal instillation of granulocyte lysates (a method protected by Russian patent. Expression of HSP-70 in lung cells was determined by immunohistochemical technique at each ARDS stage. A significant increase of HSP-70 expression by all cell types was revealed during exudative stage, being more intensive in alveolocytes type 1, and less expressed in endothelium. During proliferative stage of the disorder, a decreased HSP-70 expression was noted in all cell populations. At these terms, it proved to be high in neutrophils and alveveolocytes type 1, whereas lower expression was registered in endothelium. At fibrotic stage, HSP-70 synthesis remained at high levels in neutrophils, macrophages, fibroblasts and alveolocytes type 1. Endothelium and alveolocytes type 2 exhibited a recurrent increase at fibrotic stage of ARDS, however it did not reach the values typical to the initial stage of the syndrome.

Report to Congress on abnormal occurrences, April--June 1989

International Nuclear Information System (INIS)

1989-10-01

The Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. For this reporting period, there was one abnormal occurrence at nuclear power plants licensed to operate involving significant deficiencies in management controls at Slurry Nuclear Power Station. There was one abnormal occurrence under other NRC-issued licenses; the event involved a medical therapy misadministration. One other abnormal occurrence, involving industrial radiography overexposures, was reported by an Agreement State (Texas). 40 refs

Abnormal traffic flow data detection based on wavelet analysis

Directory of Open Access Journals (Sweden)

Xiao Qian

2016-01-01

Full Text Available In view of the traffic flow data of non-stationary, the abnormal data detection is difficult.proposed basing on the wavelet analysis and least squares method of abnormal traffic flow data detection in this paper.First using wavelet analysis to make the traffic flow data of high frequency and low frequency component and separation, and then, combined with least square method to find abnormal points in the reconstructed signal data.Wavelet analysis and least square method, the simulation results show that using wavelet analysis of abnormal traffic flow data detection, effectively reduce the detection results of misjudgment rate and false negative rate.

Device for diagnoising abnormalities of equipments

International Nuclear Information System (INIS)

Nakano, Hiroshi.

1986-01-01

Purpose: To measure the collision energy easily and at high accuracy by applying impact shocks at known collision energy from a simulated acoustic wave generator and using the generated acoustic signal as reference data. Constitution: A plurality of acoustic detectors are attached to the surface of a nuclear reactor pressure vessel. These acoustic detectors are connected respectively to an abnormality diagnosis device for equipments. Then, when metal obstacles collide against the inner surface of the reactor pressure vessel, acoustic signals generated upon collision are detected by the acoustic detectors and acoustic information thus obtained from the acoustic detectors determines the colliding position of the metal obstacles by means of the abnormality diagnosis device and then the collision energy is measured. In this case, by applying impact shocks at known collision energy near the colliding position of metal obstacles determined by the abnormality diagnosis device, collision energy can be determined at a higher accuracy. (Kawakami, Y.)

Spatial characteristics of white matter abnormalities in schizophrenia

NARCIS (Netherlands)

T.J.H. White (Tonya); S.M. Ehrlich (Stefan); B.C. Ho (Beng ); D.S. Manoach (Dara); A. Caprihan (Arvind); S.C. Schulz (S. Charles); N.C. Andreasen; R.L. Gollub (Randy); V.D. Calhoun (Vince); V. Magnotta

2013-01-01

textabstractThere is considerable evidence implicating brain white matter (WM) abnormalities in the pathophysiology of schizophrenia; however, the spatial localization of WM abnormalities reported in the existing studies is heterogeneous. Thus, the goal of this study was to quantify the spatial

Pharmacology of Endothelium-Dependent and Independent Relaxation of Rabbit Aorta

DEFF Research Database (Denmark)

Larsen, Kirsten Vendelbo

2001-01-01

The purpose of this study was to investigate several aspects of the acetylcholine-evoked relaxation of blood vessels: methodologic aspects; gender; storage; elevated glucose incubation; the signal transduction pathway; and effects of prolonged exposure. Furthermore, the relaxing effect of some ad...

Osseous temporomandibular joint abnormalities in rheumatic disease

International Nuclear Information System (INIS)

Larheim, T.A.; Kolbenstvedt, A.; Rikshospitalet, Oslo

1990-01-01

Computed tomography (CT) of the temporomandibular joint (TMJ) was compared with hypocycloidal tomography in 30 joints of 15 adults with rheumatic disease. CT included 1.5 mm thick axial scans (at 1.0 mm intervals) with reformatted oblique sagittal and oblique coronal sections. Multisection (at 2.0 mm intervals) tomography included oblique sagittal and occasionally, oblique coronal sections. CT demonstrated bone abnormalities in 21 and tomography in 20 joints, indicating high agreement between the imaging modalities regarding number of abnormal TMJs. Bone structures were, however, better visualized by multiplanar CT due to superior contrast and spatial resolution particularly in the most lateral and medial parts of the joint, indicating superiority of CT for depicting subtle bony TMJ abnormalities in patients with rheumatic disease. (orig.)

Dynamic upper respiratory abnormalities in Thoroughbred racehorses in South Africa

Directory of Open Access Journals (Sweden)

Javier E. Mirazo

2014-11-01

Full Text Available Upper airway endoscopy at rest has been the diagnostic method of choice for equine upper respiratory tract (URT conditions. Development of high-speed treadmill endoscopy improved the sensitivity of URT endoscopy by allowing observation of the horse’s nasopharynx and larynx during exercise. However, treadmill exercise may not always accurately represent the horse’s normal exercise as track surface, rider, tack and environmental variables are altered. Recently, the development of dynamic overground endoscopy (DOE has addressed some of these shortcomings. A retrospective study was undertaken to describe the URT abnormalities detected during DOE in racehorses presenting with poor performance and/or abnormal respiratory noise. Patient records of Thoroughbred racehorses undergoing DOE from November 2011 to August 2012 were reviewed. Data collected included signalment, primary complaint, distance exercised, maximum speed and dynamic airway abnormalities detected. Fifty-two horses underwent DOE for investigation of poor performance and/or abnormal respiratory noise. The main abnormalities detected included axial deviation of the aryepiglottic folds (40%, vocal cord collapse (35%, abnormal arytenoid function (33% and dorsal displacement of the soft palate (25%. A total of 40 horses were diagnosed with one or more abnormalities of the URT (77%. Fifteen horses (29% had a single abnormality and 25 horses (48% had multiple abnormalities. This study showed that DOE is a useful technique for investigating dynamic disorders of the URT in racehorses in South Africa. The total number and type of dynamic pathological conditions were comparable with those identified in similar populations in other geographical locations.

Abnormally dark or light skin

Science.gov (United States)

Hyperpigmentation; Hypopigmentation; Skin - abnormally light or dark ... Normal skin contains cells called melanocytes. These cells produce melanin , the substance that gives skin its color. Skin with ...

[Penile congenital abnormalities].

Science.gov (United States)

Boillot, B; Teklali, Y; Moog, R; Droupy, S

2013-07-01

Congenital abnormalities of the penis are usually diagnosed at birth and pose aesthetic and functional problems sometimes requiring surgical management. A literature review was conducted on Medline considering the articles listed until January 2012. Hypospadias is the most common malformation (1 in 250 boys. Familial forms: 7%). The causes remain hypothetical but the doubling of the incidence in 30 years could be linked to fetal exposure to endocrine disruptors "estrogen-like" used in the food industry in particular. Surgical treatment is usually intended to improve the aesthetic appearance but sometimes, in case of significant curvature or posterior meatus, necessary for normal sexual life and fertility. Other malformations (epispades, buried penis, transpositions, twists and preputial abnormalities) as well as management for functional or aesthetic consequences of these malformations in adulthood require complex surgical care in a specialized environment. The improvement of surgical techniques and pediatric anesthesia allows an early and effective specialized surgical approach of penile malformations. Management of sequelae in adulthood must be discussed and requires experience of surgical techniques on pediatric and adult penis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Report to Congress on abnormal occurrences, April--June 1977

International Nuclear Information System (INIS)

1977-01-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report, the ninth in the series, covers the period from April 1 to June 30, 1977. The NRC has determined that during this period: there were two abnormal occurrences at the 64 nuclear power plants licensed to operate, one involved a breach of a plant's physical security system and the other involved degraded fuel rods; there were no abnormal occurrences at fuel cycle facilities (other than nuclear power plants); and there were two abnormal occurrences at other licensee facilities, one involved improper radioactive source handling procedures and the other involved overexposure of two radiographers. Information updating previously reported abnormal occurrences is also included

Report to Congress on abnormal occurrences, January--March 1989

International Nuclear Information System (INIS)

1989-08-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health and safety and requires a Quarterly report of such events to be made to Congress. This report covers the period January 1 to March 31, 1989. For this reporting period, there were two abnormal occurrences at nuclear power plants licensed to operate. The first had generic implications and involved a plug failure resulting in a steam generator tube leak at North Anna Unit 1. The second involved a steam generator tube rupture at McGuire Unit 1. There were three abnormal occurrences under other NRC-issued licenses. Two involved medical therapy misadministrations and one involved a medical diagnostic misadministration. There were no abnormal occurrences reported by the Agreement States. The report also contains information updating some previously reported abnormal occurrences

Abnormal interhemispheric connectivity in male psychopathic offenders.

Science.gov (United States)

Hoppenbrouwers, Sylco S; De Jesus, Danilo R; Sun, Yinming; Stirpe, Tania; Hofman, Dennis; McMaster, Jeff; Hughes, Ginny; Daskalakis, Zafiris J; Schutter, Dennis J L G

2014-01-01

Psychopathic offenders inevitably violate interpersonal norms and frequently resort to aggressive and criminal behaviour. The affective and cognitive deficits underlying these behaviours have been linked to abnormalities in functional interhemispheric connectivity. However, direct neurophysiological evidence for dysfunctional connectivity in psychopathic offenders is lacking. We used transcranial magnetic stimulation combined with electroencephalography to examine interhemispheric connectivity in the dorsolateral and motor cortex in a sample of psychopathic offenders and healthy controls. We also measured intracortical inhibition and facilitation over the left and right motor cortex to investigate the effects of local cortical processes on interhemispheric connectivity. We enrolled 17 psychopathic offenders and 14 controls in our study. Global abnormalities in right to left functional connectivity were observed in psychopathic offenders compared with controls. Furthermore, in contrast to controls, psychopathic offenders showed increased intracortical inhibition in the right, but not the left, hemisphere. The relatively small sample size limited the sensitivity to show that the abnormalities in interhemispheric connectivity were specifically related to the dorsolateral prefrontal cortex in psychopathic offenders. To our knowledge, this study provides the first neurophysiological evidence for abnormal interhemispheric connectivity in psychopathic offenders and may further our understanding of the disruptive antisocial behaviour of these offenders.

Motor Control Abnormalities in Parkinson’s Disease

Science.gov (United States)

Mazzoni, Pietro; Shabbott, Britne; Cortés, Juan Camilo

2012-01-01

The primary manifestations of Parkinson’s disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms. Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb’s position and speed, are controlled and coordinated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson’s disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neural prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of understanding, however, remains limited, partly because of limitations in our knowledge of normal motor control. In this article, we review the concept of motor control and describe a few motor symptoms that illustrate the challenges in understanding such symptoms as motor control abnormalities. PMID:22675667

Cognition and brain abnormalities on MRI in pituitary patients

International Nuclear Information System (INIS)

Brummelman, Pauline; Sattler, Margriet G.A.; Meiners, Linda C.; Berg, Gerrit van den; Klauw, Melanie M. van der; Elderson, Martin F.; Dullaart, Robin P.F.; Koerts, Janneke; Werumeus Buning, Jorien; Tucha, Oliver; Wolffenbuttel, Bruce H.R.; Bergh, Alfons C.M. van den; Beek, André P. van

2015-01-01

Highlights: • Cognitive impairments are frequently observed in treated NFA patients. • NFA patients with cognitive impairments do not show brain abnormalities on MRI more frequently than patients without cognitive impairments. • The absence of brain abnormalities on brain MRI does not exclude impairments of cognition. - Abstract: Purpose: The extent to which cognitive dysfunction is related to specific brain abnormalities in patients treated for pituitary macroadenoma is unclear. Therefore, we compared brain abnormalities seen on Magnetic Resonance Imaging (MRI) in patients treated for nonfunctioning pituitary macroadenoma (NFA) with or without impairments in cognitive functioning. Methods: In this cross-sectional design, a cohort of 43 NFA patients was studied at the University Medical Center Groningen. White matter lesions (WMLs), cerebral atrophy, (silent) brain infarcts and abnormalities of the temporal lobes and hippocampi were assessed on pre-treatment and post-treatment MRI scans. Post-treatment cognitive examinations were performed using a verbal memory and executive functioning test. We compared our patient cohort with large reference populations representative of the Dutch population. Results: One or more impairments on both cognitive tests were frequently observed in treated NFA patients. No treatment effects were found with regard to the comparison between patients with and without impairments in executive functioning. Interestingly, in patients with one or more impairments on verbal memory function, treatment with radiotherapy had been given more frequently (74% in the impaired group versus 40% in the unimpaired group, P = 0.025). Patients with or without any brain abnormality on MRI did not differ in verbal memory or executive functioning. Conclusions: Brain abnormalities on MRI are not observed more frequently in treated NFA patients with impairments compared to NFA patients without impairments in verbal memory or executive functioning

Cognition and brain abnormalities on MRI in pituitary patients

Energy Technology Data Exchange (ETDEWEB)

Brummelman, Pauline [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Sattler, Margriet G.A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen (Netherlands); Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Meiners, Linda C. [Department of Radiology, University of Groningen, University Medical Center Groningen (Netherlands); Berg, Gerrit van den; Klauw, Melanie M. van der [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Elderson, Martin F. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); LifeLines Cohort Study and Biobank, University of Groningen, University Medical Center Groningen (Netherlands); Dullaart, Robin P.F. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Koerts, Janneke [Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen (Netherlands); Werumeus Buning, Jorien, E-mail: j.werumeus.buning@umcg.nl [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Tucha, Oliver [Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen (Netherlands); Wolffenbuttel, Bruce H.R. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); LifeLines Cohort Study and Biobank, University of Groningen, University Medical Center Groningen (Netherlands); Bergh, Alfons C.M. van den [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen (Netherlands); Beek, André P. van, E-mail: a.p.van.beek@umcg.nl [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands)

2015-02-15

Highlights: • Cognitive impairments are frequently observed in treated NFA patients. • NFA patients with cognitive impairments do not show brain abnormalities on MRI more frequently than patients without cognitive impairments. • The absence of brain abnormalities on brain MRI does not exclude impairments of cognition. - Abstract: Purpose: The extent to which cognitive dysfunction is related to specific brain abnormalities in patients treated for pituitary macroadenoma is unclear. Therefore, we compared brain abnormalities seen on Magnetic Resonance Imaging (MRI) in patients treated for nonfunctioning pituitary macroadenoma (NFA) with or without impairments in cognitive functioning. Methods: In this cross-sectional design, a cohort of 43 NFA patients was studied at the University Medical Center Groningen. White matter lesions (WMLs), cerebral atrophy, (silent) brain infarcts and abnormalities of the temporal lobes and hippocampi were assessed on pre-treatment and post-treatment MRI scans. Post-treatment cognitive examinations were performed using a verbal memory and executive functioning test. We compared our patient cohort with large reference populations representative of the Dutch population. Results: One or more impairments on both cognitive tests were frequently observed in treated NFA patients. No treatment effects were found with regard to the comparison between patients with and without impairments in executive functioning. Interestingly, in patients with one or more impairments on verbal memory function, treatment with radiotherapy had been given more frequently (74% in the impaired group versus 40% in the unimpaired group, P = 0.025). Patients with or without any brain abnormality on MRI did not differ in verbal memory or executive functioning. Conclusions: Brain abnormalities on MRI are not observed more frequently in treated NFA patients with impairments compared to NFA patients without impairments in verbal memory or executive functioning