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Vu, Thom Thi,Dieterich, Peter,Vu, Thu Thi,Deussen, Andreas The Korean Society of Pharmacology 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.5
Docosahexaenoic acid (DHA), an omega-3-fatty acid, modulates multiple cellular functions. In this study, we addressed the effects of DHA on human umbilical vein endothelial cell calcium transient and endothelial nitric oxide synthase (eNOS) phosphorylation under control and adenosine triphosphate (ATP, $100{\mu}M$) stimulated conditions. Cells were treated for 48 h with DHA concentrations from 3 to $50{\mu}M$. Calcium transient was measured using the fluorescent dye Fura-2-AM and eNOS phosphorylation was addressed by western blot. DHA dose-dependently reduced the ATP stimulated $Ca^{2+}$-transient. This effect was preserved in the presence of BAPTA (10 and $20{\mu}M$) which chelated the intracellular calcium, but eliminated after withdrawal of extracellular calcium, application of 2-aminoethoxy-diphenylborane ($75{\mu}M$) to inhibit store-operated calcium channel or thapsigargin ($2{\mu}M$) to delete calcium store. In addition, DHA ($12{\mu}M$) increased ser1177/thr495 phosphorylation of eNOS under baseline conditions but had no significant effect on this ratio under conditions of ATP stimulation. In conclusion, DHA dose-dependently inhibited the ATP-induced calcium transient, probably via store-operated calcium channels. Furthermore, DHA changed eNOS phosphorylation suggesting activation of the enzyme. Hence, DHA may shift the regulation of eNOS away from a $Ca^{2+}$ activated mode to a preferentially controlled phosphorylation mode.
Thom Thi Vu,Peter Dieterich,Thu Thi Vu,Andreas Deussen 대한약리학회 2019 The Korean Journal of Physiology & Pharmacology Vol.23 No.5
Docosahexaenoic acid (DHA), an omega-3-fatty acid, modulates multiple cellular functions. In this study, we addressed the effects of DHA on human umbilical vein endothelial cell calcium transient and endothelial nitric oxide synthase (eNOS) phosphorylation under control and adenosine triphosphate (ATP, 100 M) stimulated conditions. Cells were treated for 48 h with DHA concentrations from 3 to 50 M. Calcium transient was measured using the fluorescent dye Fura-2-AM and eNOS phosphorylation was addressed by western blot. DHA dose-dependently reduced the ATP stimulated Ca2+-transient. This effect was preserved in the presence of BAPTA (10 and 20 M) which chelated the intracellular calcium, but eliminated after withdrawal of extracellular calcium, application of 2-aminoethoxy-diphenylborane (75 M) to inhibit store-operated calcium channel or thapsigargin (2 M) to delete calcium store. In addition, DHA (12 M) increased ser1177/thr495 phosphorylation of eNOS under baseline conditions but had no significant effect on this ratio under conditions of ATP stimulation. In conclusion, DHA dose-dependently inhibited the ATP-induced calcium transient, probably via store-operated calcium channels. Furthermore, DHA changed eNOS phosphorylation suggesting activation of the enzyme. Hence, DHA may shift the regulation of eNOS away from a Ca2+ activated mode to a preferentially controlled phosphorylation mode.
( Eungeol Sim ),( Chizoba Nwankwo ),( Bruce Bacon ),( Michael P. Curry ),( Douglas T. Dieterich ),( Steven L. Flamm ),( Kris V. Kowdley ),( Scott Milligan ),( Naoky C. Tsai ),( Zobair M. Younossi ),( 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: Lengthening treatment with elbasvir/grazoprevir (EBR/ GZR) to 16 weeks and/or adding ribavirin (RBV) is recommended for select patients with HCV GT1 infection. However, realworld data (J Hepatol 2017;66:S295) suggest that utilization of this regimen is low. This study examined the use of 12- and 16- week EBR/GZR ±RBV regimens in different patient subgroups. Methods: Data were collected from providers and specialty pharmacies through Trio Health’s disease management program. Patients (n=442) with HCV GT1 infection who initiated EBR/GZR therapy between Jan 28, 2016 (FDA approval) to Dec 31, 2016 were included. Results: 401 (91%) patients received EBR/GZR for 12 weeks, 12 (3%) received EBR/GZR+RBV for 12 weeks, 11 (2%) received EBR/GZR for 16 weeks, and 18 (4%) received EBR/GZR+RBV for 16 weeks. Possible baseline NS5A resistance was identified in 13/285 patients with GT1a infection: 3 (23%) received EBR/ GZR for 12 weeks, 1 (8%) received EBR/GZR+RBV for 12 weeks, 2 (15%) received EBR/GZR for 16 weeks, and 7 (54%) received EBR/GZR+RBV for 16 weeks. Across all patients, the +RBV subgroup had a higher proportion of treatment-experienced patients (43%, 13/30) than the -RBV group (17%, 69/412); and the 16-week subgroup had a higher proportion of GT1A subtype (93%, 27/29) than the 12-week group (62%, 258/413). Other characteristics including gender, age, baseline viral load, and cirrhosis were similar between regimens and between groups defined by RBV addition or therapy duration. SVR12 results at time of abstract submission were available for 262/442 patients. Overall per protocol (PP) SVR12 was 97% (253/262). Across GT1 subgroups (defined by subtype, prior treatment experience, and fibrosis) that received EBR/GZR for 12 weeks without RBV, the PP SVR12 was ≥94% (TABLE). Conclusions: In real-world practice, EBR/GZR was highly effective, with the majority of patients treated for 12 weeks without RBV. Full SVR12 data will be presented at the conference.
General Anesthesia versus Conscious Sedation in Mechanical Thrombectomy
Katharina Feil,Moriz Herzberg,Franziska Dorn,Steffen Tiedt,Clemens Küpper,Dennis C. Thunstedt,Ludwig C. Hinske,Konstanze Mühlbauer,Sebastian Goss,Thomas Liebig,Marianne Dieterich,Andreas Bayer,Lars Ke 대한뇌졸중학회 2021 Journal of stroke Vol.23 No.1
Background and Purpose: Anesthesia regimen in patients undergoing mechanical thrombectomy (MT) is still an unresolved issue. Methods: We compared the effect of anesthesia regimen using data from the German StrokeRegistry- Endovascular Treatment (GSR-ET) between June 2015 and December 2019. Degreeof disability was rated by the modified Rankin Scale (mRS), and good outcome was defined as mRS 0–2. Successful reperfusion was assumed when the modified thrombolysis in cerebral infarction scale was 2b–3. Results: Out of 6,635 patients, 67.1% (n=4,453) patients underwent general anesthesia (GA), 24.9% (n=1,650) conscious sedation (CS), and 3.3% (n=219) conversion from CS to GA. Rate of successful reperfusion was similar across all three groups (83.0% vs. 84.2% vs. 82.6%, P=0.149). Compared to the CA-group, the GA-group had a delay from admission to groin (71.0 minutes vs. 61.0 minutes, P<0.001), but a comparable interval from groin to flow restoration (41.0 minutes vs. 39.0 minutes). The CS-group had the lowest rate of periprocedural complications (15.0% vs. 21.0% vs. 28.3%, P<0.001). The CS-group was more likely to have a good outcome at follow-up (42.1% vs. 34.2% vs. 33.5%, P<0.001) and a lower mortality rate (23.4% vs. 34.2% vs. 26.0%, P<0.001). In multivariable analysis, GA was associated with reduced achievement of good functional outcome (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.71 to 0.94; P=0.004) and increased mortality (OR, 1.42; 95% CI, 1.23 to 1.64; P<0.001). Subgroup analysis for anterior circulation strokes (n=5,808) showed comparable results. Conclusions: We provide further evidence that CS during MT has advantages over GA in terms of complications, time intervals, and functional outcome.