Publications
131 results found
Bianca RDEDV, Mitidieri E, Di Minno MND, et al., 2013, The hydrogen sulfide pathway contributes to the enhanced human platelet aggregation in hyperhomocysteinemia, 2nd European Conference on the Biology of Hydrogen Sulfide, Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE, Pages: S24-S25, ISSN: 1089-8603
Kirkby NS, Zaiss AK, Wright WR, et al., 2013, Differential COX-2 induction by viral and bacterial PAMPs: Consequences for cytokine and interferon responses and implications for anti-viral COX-2 directed therapies, Biochemical and Biophysical Research Communications, Vol: 438, Pages: 249-256, ISSN: 0006-291X
Cyclooxygenase 2 (COX)-2 is induced by bacterial and viral infections and has complex, poorly understood roles in anti-pathogen immunity. Here, we use a knock-in luciferase reporter model to image Cox2 expression across a range of tissues in mice following treatment with the either the prototypical bacterial pathogen-associated molecular pattern (PAMP), LPS, which activates Toll-like receptor (TLR)4, or with poly(I:C), a viral PAMP, which activates TLR3. LPS induced Cox2 expression in all tissues examined. In contrast, poly(I:C) elicited a milder response, limited to a subset of tissues. A panel of cytokines and interferons was measured in plasma of wild-type, Cox1−/− and Cox2−/− mice treated with LPS, poly(I:C), MALP2 (TLR2/6), Pam3CSK4 (TLR2/1), R-848 (TLR7/8) or CpG ODN (TLR9), to establish whether/how each COX isoform modulates specific PAMP/TLR responses. Only LPS induced notable loss of condition in mice (inactivity, hunching, piloerection). However, all TLR agonists produced cytokine responses, many of which were modulated in specific fashions by Cox1 or Cox2 gene deletion. Notably we observed opposing effects of Cox2 gene deletion on the responses to the bacterial PAMP, LPS, and the viral PAMP, poly(I:C), consistent with the differing abilities of the PAMPs to induce Cox2 expression. Cox2 gene deletion limited the plasma IL-1β and interferon-γ responses and hypothermia produced by LPS. In contrast, in response to poly(I:C), Cox2−/− mice exhibited enhanced plasma interferon (IFNα,β,γ,λ) and related cytokine responses (IP-10, IL-12). These observations suggest that a COX-2 selective inhibitor, given early in infection, may enhance and/or prolong endogenous interferon responses, and thereby increase anti-viral immunity.
Zhang Q, Milliken P, Kulczynska A, et al., 2013, Development and Characterization of Glutamyl-Protected <i>N</i>-Hydroxyguanidines as Reno-Active Nitric Oxide Donor Drugs with Therapeutic Potential in Acute Renal Failure, JOURNAL OF MEDICINAL CHEMISTRY, Vol: 56, Pages: 5321-5334, ISSN: 0022-2623
- Author Web Link
- Cite
- Citations: 6
Kirkby NS, Zaiss AK, Urquhart P, et al., 2013, LC-MS/MS confirms that COX-1 drives vascular prostacyclin whilst gene expression pattern reveals non-vascular sites of COX-2 expression, PLoS ONE, Vol: 8, ISSN: 1932-6203
Rauzi F, Kirkby NS, Edin M, et al., 2013, PLATELET COX-1 SUPPORTS THE PRODUCTION OF BOTH PROSTANOIDS AND HETES, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, Pages: A114-A114, ISSN: 1355-6037
Lundberg MH, Kirkby NS, Mitchell JA, et al., 2013, P2Y12 INHIBITION GREATLY POTENTIATES THE ANTI-PLATELET EFFECTS OF PROSTACYCLIN AND NITRIC OXIDE, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, Pages: A137-U630, ISSN: 1355-6037
- Author Web Link
- Cite
- Citations: 1
Willeit P, Zampetaki A, Kaudewitz D, et al., 2013, PLASMA MICRORNAS AS BIOMARKERS FOR PLATELET INHIBITION, Annual Conference of the British-Cardiovascular-Society (BCS), Publisher: BMJ PUBLISHING GROUP, ISSN: 1355-6037
- Author Web Link
- Cite
- Citations: 1
Reed DM, Kirkby NS, Foldes G, et al., 2013, Prostacyclin release pathways in stem cell derived endothelial cells, Experimental Biology 2013
Kirkby NS, Zaiss AK, Urquhart P, et al., 2013, <i>Cox2</i> reporter gene expression and prostacylin mass spectrometry confirm vascular COX-1 dominance for prostacyclin production, Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB), Publisher: FEDERATION AMER SOC EXP BIOL, ISSN: 0892-6638
Wright W, Mackenzie L, Kirkby NS, et al., 2013, Nitric oxide-dependent vasodilation is compromised in isolated pulmonary arteries from COX knockout mice, Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB), Publisher: FEDERATION AMER SOC EXP BIOL, ISSN: 0892-6638
- Author Web Link
- Cite
- Citations: 1
Willeit P, Zampetaki A, Dudek K, et al., 2013, Circulating MicroRNAs as Novel Biomarkers for Platelet Activation, CIRCULATION RESEARCH, Vol: 112, Pages: 595-+, ISSN: 0009-7330
- Author Web Link
- Cite
- Citations: 316
Kirkby NS, Lundberg MH, Harrington LS, et al., 2013, Cyclooxygenase-1, not cyclooxygenase-2, is responsible for physiological production of prostacyclin in the cardiovascular system (vol 109, pg 17597, 2012), PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 110, Pages: 1561-1561, ISSN: 0027-8424
- Author Web Link
- Cite
- Citations: 1
Kirkby NS, Lundberg MH, Harrington LS, et al., 2012, Cyclooxygenase-1, not cyclooxygenase-2, is responsiblefor physiological production of prostacyclin in thecardiovascular system, Proceedings of the National Academy of Sciences of the United States of America
Mitidieri E, Bianca RDDV, Kirkby N, et al., 2012, L-Cysteine/H<sub>2</sub>S pathway involvement in human platelet aggregation, 2nd International Conference on H2S Biology and Medicine, Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE, Pages: S31-S32, ISSN: 1089-8603
Kirkby NS, Duthie KM, Miller E, et al., 2012, Non-endothelial cell endothelin-B receptors limit neointima formation following vascular injury, CARDIOVASCULAR RESEARCH, Vol: 95, Pages: 19-28, ISSN: 0008-6363
- Author Web Link
- Cite
- Citations: 10
Warner TD, Mitchell JA, Kirkby NS, 2012, Short thromboelastography and the identification of high platelet reactivity while on and off therapy, HEART, Vol: 98, Pages: 679-680, ISSN: 1355-6037
Leadbeater PDM, Kirkby NS, Thomas S, et al., 2011, Aspirin has little additional anti-platelet effect in healthy volunteers receiving prasugrel, Journal of Thrombosis and Haemostasis, Vol: 9, Pages: 2050-2056, ISSN: 1538-7836
Summary. Background: Strong P2Y12 blockade, as can be achieved with novel anti‐platelet agents such as prasugrel, has been shown in vitro to inhibit both ADP and thromboxane A2‐mediated pathways of platelet aggregation, calling into question the need for the concomitant use of aspirin. Objective: The present study investigated the hypothesis that aspirin provides little additional anti‐aggregatory effect in a group of healthy volunteers taking prasugrel. Study participants/methods: In all, 9 males, aged 18 to 40 years, enrolled into the 21‐day study. Prasugrel was loaded at 60 mg on day 1 and maintained at 10 mg until day 21. At day 8, aspirin 75 mg was introduced and the dose increased to 300 mg on day 15. On days 0, 7, 14 and 21, platelet function was assessed by aggregometry, response to treatments was determined by VerifyNow™ and urine samples were collected for quantification of prostanoid metabolites. Results: At day 7, aggregation responses to a range of platelet agonists were reduced and there was only a small further inhibition of aggregation to TRAP‐6, collagen and epinephrine at days 14 and 21, when aspirin was included with prasugrel. Urinary prostanoid metabolites were unaffected by prasugrel, and were reduced by the addition of aspirin, independent of dose. Conclusions: In healthy volunteers, prasugrel produces a strong anti‐aggregatory effect, which is little enhanced by the addition of aspirin. The addition of aspirin as a dual‐therapy with potent P2Y12 receptor inhibitors warrants further investigation.
Leadbeater PDM, Kirkby NS, Thomas S, et al., 2011, URINARY PROSTANOID METABOLITES IN HEALTHY VOLUNTEERS TAKING PRASUGREL AND ASPIRIN, HEART, Vol: 97, Pages: 16-16, ISSN: 1355-6037
Kirkby NS, Leadbeater PDM, Chan MV, et al., 2011, INHIBITION OF ADP- AND THROMBOXANE-DEPENDENT PATHWAYS OF PLATELET AGGREGATION BY THE P2Y12 ANTAGONISTS, TICAGRELOR AND PRASUGREL, HEART, Vol: 97, Pages: 9-9, ISSN: 1355-6037
Hoefer T, Kirkby NS, Warner TD, 2011, RELATIONSHIP BETWEEN PROPORTIONS OF P2Y12 INHIBITED PLATELETS AND AGGREGATION IN VITRO, HEART, Vol: 97, Pages: 6-6, ISSN: 1355-6037
Kirkby NS, Leadbeater PDM, Chan MV, et al., 2011, Antiplatelet effects of aspirin vary with level of P2Y(12) receptor blockade supplied by either ticagrelor or prasugrel, Journal of Thrombosis and Haemostasis, Vol: 9, Pages: 2103-2105, ISSN: 1538-7836
Kirkby NS, Singhal R, Mitchell JA, et al., 2011, Synergistic inhibition of platelet aggregation by nitric oxide and prostacyclin is potentiated by P2Y<sub>12</sub> blockade, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 9, Pages: 780-781, ISSN: 1538-7933
Kirkby NS, Leadbeater PDM, Chan M, et al., 2011, Aspirin augments the anti-platelet effects of partial but not complete P2Y<sub>12</sub> receptor blockade by ticagrelor, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 9, Pages: 780-780, ISSN: 1538-7933
Kirkby NS, Harrington LS, Lundberg MH, et al., 2011, CONTRIBUTION OF COX1 AND COX2 TO PROSTACYCLIN RELEASE BY HEALTHY MOUSE TISSUES, 10th World Congress on Inflammation, Publisher: BIRKHAUSER VERLAG AG, Pages: 116-117, ISSN: 1023-3830
Wright WR, Kirkby NS, Harrington LS, et al., 2011, ROLE OF COX-1 AND COX-2 IN THE RELEASE OF PROSTANOIDS IN MURINE LUNG AND ISOLATED LUNG FIBROBLASTS, 10th World Congress on Inflammation, Publisher: BIRKHAUSER VERLAG AG, Pages: 232-232, ISSN: 1023-3830
Armstrong PC, Kirkby NS, Zain ZN, et al., 2011, Thrombosis is reduced by inhibition of COX-1, but unaffected by inhibition of COX-2, in an acute model of platelet activation in the mouse, PLoS ONE, Vol: 6, ISSN: 1932-6203
Leadbeater PDL, Kirkby NS, Dhanji A, et al., 2011, Aspirin has little additional ex vivo anti-platelet effects in healthy volunteers receiving prasugrel, BPS Winter Meeting
Armstrong PCJ, Leadbeater PD, Chan MV, et al., 2011, In the presence of strong P2Y<sub>12</sub> receptor blockade, aspirin provides little additional inhibition of platelet aggregation, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 9, Pages: 552-561, ISSN: 1538-7933
- Author Web Link
- Cite
- Citations: 141
Kirkby NS, Low L, Seckl JR, et al., 2011, Quantitative 3-dimensional imaging of murine neointimal and atherosclerotic lesions by optical projection tomography, PLoS ONE, Vol: 6, ISSN: 1932-6203
Chan MV, Armstrong PCJ, Papalia F, et al., 2011, Optical multichannel (optimul) platelet aggregometry in 96-well plates as an additional method of platelet reactivity testing, PLATELETS, Vol: 22, Pages: 485-494, ISSN: 0953-7104
- Author Web Link
- Cite
- Citations: 37
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.