12 research outputs found
The effectiveness of low-dose desmopressin in improving hypothermia-induced impairment of primary haemostasis under influence of aspirin – a randomized controlled trial
Modulation of the vascular system and the actions of lipoproteins
published_or_final_versionPharmacologyDoctoralDoctor of Philosoph
Nanoparticle trapping based on plasmonic devices
Optical trapping of microscopic particles using focused laser beams has fueled new applications in biological and physical sciences. However, trapping particles at the nanometer scale remains a challenging task because of light diffraction. Jingzhi Wu's research explores the optical and thermal properties of metallic nanostructures under laser excitation. The work shows that both thermal effect and optical response of the nanostructure can be exploited for trapping nanoparticles. This makes possible the accurate, controlled placement of nanoparticles at predefined locations, which will facilitate the development of new approaches in nanoscience, and contribute to better biomedical technologies
Calcitriol Supplementation Ameliorates Microvascular Endothelial Dysfunction in Vitamin D-Deficient Diabetic Rats by Upregulating the Vascular eNOS Protein Expression and Reducing Oxidative Stress
Diabetes mellitus contributes to macro- and microvascular complications, leading to adverse cardiovascular events. This study examined the effects of vitamin D deficiency on the vascular function and tissue oxidative status in the microcirculation of diabetic rats and to determine whether these effects can be reversed with calcitriol (active vitamin D metabolite) supplementation. Streptozotocin-induced diabetic rats were fed for 10 weeks with control diet (DC) or vitamin D-deficient diet without (DD) or with oral calcitriol supplementation (0.15 μg/kg) in the last four weeks (DDS) (10 rats each group). A nondiabetic rat group that received control diet was also included (NR). After 10 weeks, rats were sacrificed; mesenteric arterial rings with and without endothelium were studied using wire myograph. Western blotting of the mesenteric arterial tissue was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) enzyme. Antioxidant enzyme superoxide dismutase (SOD) activity and oxidative stress marker malondialdehyde (MDA) levels in the mesenteric arterial tissue were also measured. The DC group had significantly lower acetylcholine-induced relaxation and augmented endothelium-dependent contraction, with reduced eNOS expression, compared to NR rats. In mesenteric arteries of DD, acetylcholine-induced endothelium-dependent and sodium nitroprusside-induced endothelium-independent relaxations were lower than those in DC. Calcitriol supplementation in DDS restored endothelium-dependent relaxation. Mesenteric artery endothelium-dependent contraction of DD was greater than DC; it was not affected by calcitriol supplementation. The eNOS protein expression and SOD activity were significantly lower while MDA levels were greater in DD compared to DC; these effects were not observed in DDS that received calcitriol supplementation. In conclusion, vitamin D deficiency causes eNOS downregulation and oxidative stress, thereby impairing the vascular function and posing an additional risk for microvascular complications in diabetes. Calcitriol supplementation to diabetics with vitamin D deficiency could potentially be useful in the management of or as an adjunct to diabetes-related cardiovascular complications
Effect of SCC-1 on high-K<sup>+</sup>-induced airway smooth muscle contraction.
<p>A) Concentration-response curves for the relaxant effect of SCC-1 on the rat tracheal rings contracted by 60 mM KCl in the absence (▪) or presence (□) of atropine (10<sup>−6</sup> M). B) Concentration-response curves for the relaxing effect of SCC-1 in the rat tracheal rings contracted by 60 mM KCl (▪), high-K<sup>+</sup> solution (•) and high-K<sup>+</sup>-Cl<sup>–</sup>-free solution (▽), high-K<sup>+</sup>-Cl<sup>−/</sup>HCO<sub>3</sub><sup>−</sup>-free solution (△). */<sup>#</sup><i>p</i><0.05, **/<sup>##</sup><i>p</i><0.01, ***/<sup>###/+++</sup><i>p</i><0.0001, two-way ANOVA followed by Bonferroni <i>post hoc</i> test. *, high-K<sup>+</sup> versus high-K<sup>+</sup>-Cl<sup>–</sup>-free solution. <sup>#</sup>, 60 mM KCl versus high-K<sup>+</sup>-Cl<sup>–</sup>-free solution, <sup>+</sup>, high-K<sup>+</sup>-Cl<sup>−/</sup>HCO<sub>3</sub><sup>−</sup>-free solution versus all groups. C) In the presence of 3×10<sup>−5</sup> M of SCC-1 addition of 60 mM KCl to the organ chamber containing high-K<sup>+</sup>-Cl<sup>−/</sup>HCO<sub>3</sub><sup>−</sup>-free solution caused relaxation of airway smooth muscles. ***<i>p</i><0.0001, one-way ANOVA followed by Dunnett’s <i>post hoc</i> test. Data are presented as mean ± SEM, <i>n</i> = 4.</p
Contractile responses of isolated rat trachea rings to 60 mM KCl in the absence (▪) or presence (□) of SCC-1 (A an B, 1 and 5×10<sup>−6</sup> M respectively).
<p>Contractions are expressed as a percentage of the response to 60 mM KCl. Data are presented as mean ± SEM, <i>n</i> = 4. *<i>p</i><0.05, **<i>p</i><0.01, Student’s <i>t</i>-test.</p
Cyclic IMP-synthesized by sGC as a mediator of hypoxic contraction of coronary arteries
cGMP is considered the only mediator synthesized by soluble guanylyl cyclase (sGC) in response to nitric oxide (NO). However, purified sGC can synthesize several other cyclic nucleotides, including inosine 3',5'-cyclic monophosphate (cIMP). The present study was designed to determine the role of cIMP in hypoxic contractions of isolated porcine coronary arteries. Vascular responses were examined by measuring isometric tension. Cyclic nucleotides were assayed by HPLC tandem mass spectroscopy. Rho kinase (ROCK) activity was determined by measuring the phosphorylation of myosin phosphatase target subunit 1 using Western blot analysis and an ELISA kit. The level of cIMP, but not that of cGMP, was elevated by hypoxia in arteries with, but not in those without, endothelium [except if treated with diethylenetriamine (DETA) NONOate]; the increases in cIMP were inhibited by the sGC inhibitor 1H-[1,2,4] oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ). Hypoxia (PO2: 25-30 mmHg) augmented contractions of arteries with and without endothelium if treated with DETA NONOate; these hypoxic contractions were blocked by ODQ. In arteries without endothelium, hypoxic augmentation of contraction was also obtained with exogenous cIMP. In arteries with endothelium, hypoxic augmentation of contraction was further enhanced by inosine 5'-triphosphate, the precursor for cIMP. The augmentation of contraction caused by hypoxia or cIMP was accompanied by increased phosphorylation of myosin phosphatase target subunit 1 at Thr(853), which was prevented by the ROCK inhibitor Y-27632. ROCK activity in the supernatant of isolated arteries was stimulated by cIMP in a concentration-dependent fashion. These results demonstrate that cIMP synthesized by sGC is the likely mediator of hypoxic augmentation of coronary vasoconstriction, in part by activating ROCK.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000341080300007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Cardiac & Cardiovascular SystemsPhysiologyPeripheral Vascular DiseaseSCI(E)[email protected]