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您的检索式：作者名="Nicholas Skill"
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| 1 | Murine study of portal hypertension associated endothelin-1 hypo-response显示文摘AIM:To investigate endothelin-1 hypo-responsive associated with portal hypertension in order to improve patient treatment outcomes.METHODS:Wild type,e NOS-/-and i NOS-/-mice receivedpartial portal vein ligation surgery to induce portal hypertension or sham surgery.Development of portal hypertension was determined by measuring the splenic pulp pressure,abdominal aortic flow and portal systemic shunting.To measure splenic pulp pressure,a microtip pressure transducer was inserted into the spleen pulp.Abdominal aortic flow was measured by placing an ultrasonic Doppler flow probe around the abdominal aorta between the diaphragm and celiac artery.Portal systemic shunting was calculated by injection of fluorescent microspheres in to the splenic vein and determining the percentage accumulation of spheres in liver and pulmonary beds.Endothelin-1 hypo-response was evaluated by measuring the change in abdominal aortic flow in response to endothelin-1 intravenous administration.In addition,thoracic aorta endothelin-1contraction was measured in 5 mm isolated thoracic aorta rings ex-vivo using an ADI small vessel myograph.RESULTS:In wild type and i NOS-/-mice splenic pulp pressure increased from 7.5±1.1 mm Hg and 7.2±1 mm Hg to 25.4±3.1 mm Hg and 22±4 mm Hg respectively.In e NOS-/-mice splenic pulp pressure was increased after 1 d(P=NS),after which it decreased and by 7 d was not significantly elevated when compared to 7 d sham operated controls(6.9±0.6 mm Hg and 7.3±0.8 mm Hg respectively,P=0.3).Abdominal aortic flow was increased by 80%and 73%in 7 d portal vein ligated wild type and i NOS when compared to shams,whereas there was no significant difference in 7 d portal vein ligated e NOS-/-mice when compared to shams.Endothelin-1 induced a rapid reduction in abdominal aortic blood flow in wild type,e NOS-/-and i NOS-/-sham mice(50%±8%,73%±9%and 47%±9%respectively).Following portal vein ligation endothelin-1 reduction in blood flow was significantly diminished in each mouse group.Abdominal aortic flow was reduced by 19%±9%,32%±10%and 9%±9%in wild type,e NOS-/-and i NOS-/-mice respectively.CONCLUSION:Aberrant endothelin-1 response in murine portal hypertension is NOS isoform independent.Moreover,portal hypertension in the portal vein ligation model is independent of ET-1 function. | Nicholas Theodorakis Mary Maluccio Nicholas Skill | 2015 | World Journal of Gastroenterology2015，21，16： | 3 |
| 2 | Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure显示文摘AIM: Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and morbidity.Previous reports have suggested that the compound thalidomide attenuates portal hypertension(PHT).However, the mechanism for this action is not fully elucidated.One hypothesis is that thalidomide destabilizes tumor necrosis factor α(TNFα) mR NA and therefore diminishes TNFα induction of nitric oxide synthase(NOS) and the production of nitric oxide(NO).To examine this hypothesis, we utilized the murine partial portal vein ligation(PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout mice.METHODS: Wild type, inducible nitric oxide synthase(i NOS)-/- and endothelial nitric oxide synthase(e NOS)-/-mice received either PVL or sham surgery and were given either thalidomide or vehicle.Serum nitrate(total nitrate, NOx) was measured daily for 7 d as a surrogate of NO synthesis.Serum TNFα level was quantified by enzyme-linked immunosorbent assay.TNFα m RNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain reaction.PHT was determined by recording splenic pulp pressure(SPP) and abdominal aortic flow after 0-7 d.Response to thalidomide was determined by measurement of SPP and mean arterial pressure(MAP).RESULTS: SPP, abdominal aortic flow(Qao) and plasma NOx were increased in wild type and i NOS-/-PVL mice when compared to sham operated control mice.In contrast, SPP, Qao and plasma NOx were not increased in e NOS-/- PVL mice when compared to sham controls.Serum TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA used.Therefore, the effect of thalidomide on serum TNFα levels was undetermined in wild type, e NOS-/-or i NOS-/- mice.Thalidomide acutely increased plasma NOx in wild type and e NOS-/- mice but not i NOS-/-mice.Moreover, thalidomide temporarily(0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, e NOS-/- and i NOS-/- PVL mice, after which time levels returned to the respective baseline.CONCLUSION: Thalidomide does not reduce portalpressure in the murine PVL model by modulation of NO biosynthesis.Rather, thalidomide reduces PHT by decreasing MAP by an undetermined mechanism. | Nicholas G Theodorakis Yining N Wang Vyacheslav A Korshunov Mary A Maluccio Nicholas J Skill | 2015 | World Journal of Gastroenterology2015，21，14： | 1 |
| 3 | The role of nitric oxide synthase isoforms in extrahepatic portal hypertension: studies in gene-knockout mice显示文摘 | Nicholas G Theodorakis Yi-ning Wang Nicholas J Skill Matthew A Metz Paul A Cahill Eileen M Redmond James V Sitzmann | 2003 | Gastroenterology2003，，5： | 1 |
| 4 | Targeted metabolic profiling of hepatocellular carcinoma and hepatitis C using LC ‐ MS / MS显示文摘 | Hamid Baniasadi G. A. Nagana Gowda Haiwei Gu Ao Zeng Shui Zhuang Nicholas Skill Mary Maluccio Daniel Raftery | 2013 | ELECTROPHORESIS2013，，19： | 1 |
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