A novel biodegradable polymer-coated sirolimus-eluting stent: 1-year results of the HELIOS registry / 中华医学杂志(英文版)

BACKGROUND@#The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting.@*METHODS@#The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves.@*RESULTS@#A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year.@*CONCLUSION@#The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent.@*CLINICAL TRIAL REGISTRATION@#ClinicalTrials.gov, NCT03916432.

Simultaneous determination of metolazone and valsartan in beagle dog plasma using liquid chromatography-tandem mass spectrometry / 军事医学

Objective To develop an LC-MS/MS method for simultaneous determination of metolazone and valsartan in beagle dog plasma.Methods The chromatographic separation was achieved on an Agilent Poroshell 120(2.1 mm ×30 mm × 2.7 μm)analytical column.The multiple reaction monitoring mode operating in positive ion was adopted in MS detection, and precursors to the product ion transitions of m/z 366.2/259, 436.2/291 and 423.4/207 were used to measure metola-zone, valsartan and internal standard ( losartan potassium) .Results The method was linear over the concentration range of 0.5 ng/ml-100 ng/ml for metolazone and 5-5000 ng/ml for valsartan, with the correlation coefficients ( r2 ) of 0.9937 and 0.9939, respectively.The average intra-day precision values ( RSD) were 2.09% -8.85% for metolazone and 2.36%-13.12%for valsartan.The matrix effect values were 87.73%-98.62%for metolazone and 99.03%-137.35%for valsartan.The average recovery was 75.74%-81.82%for metolazone and 83.89%-95.64%for valsartan.Conclu-sion This analytical method for metolazone and valsartan is simple, accurate and sensitive, so it can be used for pharma-cokinetic research of metolazone and valsartan immediate release tablets in beagle dogs.

Bioavailability study of self-microemulsifying drug delivery system of a novel anti-stroke compound TID-101 in rats / 国际药学研究杂志

Objective To establish and validate a LC-MS/MS method for quantitative analysis of a new anti-stroke compound TID-101 in rat plasma and to study the pharmacokinetics and bioavailability of TID-101 self-(micro)emulsified drug delivery system (SMEDDS). Methods The plasma samples were treated with methanol for precipitating protein. The chromatographic separation was achieved with a acetonitrile-water mobile phase. Detection of TID-101 and the internal standard (IS) dexamethasone acetate was achieved by electrospray ionization(ESI)source in the negative ion mode at m/z 353.4→323.2 and m/z 433.4→353.4. The method was applied for pharmacokinetics study of TID-101 between SMEDDS in rats. Results The method was linear over TID-101 concen?tration range from 10-95 000 ng/ml with the correlation coefficients(r)of 0.9998. The intra-run and inter-run relative standard devia?tions(RSD)were less than 15%and the average absolute recovery values were 83.4-87.0%. The validated method was applied to a pharmacokinetic study in rats after intravenous administration of TID-101 fat emulsion injection and oral administration of TID-101 suspension and SMEDDS. The bioavailability of TID-101 API and SMEDDS was 2.8% and 14.9%,respectively. Conclusion The analysis method is simple,accurate,and sensitive for assaying the in vivo pharmacokinetic study of TID-101 in rats. SMEDDS could effectively enhance the oral bioavailability of TID-101.

Construction and evaluation of non-specific targeting cationic polymer lipid liposomes / 药学学报

A new class of dendrimer polylysine poly(ethylene glycol)-lipid was designed and synthesized. The cationic polymer liposomes were prepared by the lipid film-extrusion and post-insertion two methods with these dendrimer polylysine poly(ethylene glycol)-lipid and other lipids. The structural properties of obtained cationic polymer liposomes were studied by laser light scattering and fluorescence spectrometer. It was demonstrated that the nano sized liposomes with different density of surface cationic charges can be prepared by either lipid film-extrusion or post-insertion methods, but post-insertion process did not affect drug loading, did not influence drug loading capacity and did not induce liposomal morphology and particle size. The density of positive charge does not affect the size and distribution of different liposomes size and distribution. It was the better choice for manufacture because post-insertion method did not cause early release of drug and size changes. Cell binding experiments show that cationic polymer liposomes, especially dendrimer polymer liposomes had higher local charge density, and therefore have dramatic non specific cell targeting ability.

Study of pharmacological effects and mechanism of ethyl ferulate / 中国临床药理学与治疗学

AIM: To investigate the pharmacological effects and mechanism of ethyl ferulate (EF). METHODS: The platelet congregate rate was observed by congregater TYXN-91 and the platelet intracellular calcium oscillation was observed by laser scanning. The acute liver injury model of mice was made by using the CCl 4 156 mg?kg -1, ip. Then the levels of ALT and AST were determined in serum and the levels of MDA and SOD in the liver. RESULTS: The inhibition rate of the platelet congregate were 26.3%? 3.3%, 33.4%? 2.4%, 73.4%? 3.1%, and 94.9%? 2.7% (n=8) in different concentration( 0.1, 0.5, 1.5, and 3.0 mmol?L -1)of ethyl ferulate,respectively. It was higher than those in the same concentrations of ferulic acid. The change of the fluctuation of calcium (?FI 4.6? 1.7) in EF group was much lower than the rest level ( 10.3? 2.6) (n=8,P

Gender-based differences in genistein metabolism in rat liver microsomes / 中国药理学通报

Aim To study the gender-based difference in genistein metabolism in rat liver microsomes in vitro.Methods Liver microsomes was obtained from male and female rats.The optimized system of enzyme catalytic reaction of genistein in rat liver microsomes was set up.The reaction velocity of genistein in female and male rat liver microsomes was assessed by incubating genistein with CYP1A2 antibody or specific CYP1A2 inhibitor furafylline,and the percentage of the relative metabolism of genistein of CYP1A2 was derivated by using the data of the reaction velocity.Results The metabolism of genistein by microsomes was inhibited by CYP1A2 antibody(1 ∶400)after incubation for 30 min.The percentage of the control metabolism of genistein of microsomes in male and female rat were 20.95%?2.13% and 13.73%?1.26%respectively(P

Exogenous or endogenous nitric oxide pretreatment induced delayed protection of cardiomyocytes / 中华麻醉学杂志

Objective Ischemia preconditioning provides early and delayed protection against ischetnic injury. It has been shown that nitric oxide(NO) exerts protective effects on cardiovascular system. The purpose of this study was to determine if exogenous or endogenous NO pretreatment could provide delayed protection of neonatal rat cardiomyocytes. Methods Neonatal SD rats (1-3 days) were used in this study. Cardiomyocytes obtained from beating heart were cultured and incubated for 72 h. The study was composed of ten groups: (1) no medicine was added to the cell medium and the cardiomyocytes were subjected to no hypoxia/reoxygenation (control group);(2) NO donor, S-nitroso-N-acetylpenicillamine (SNAP) 500 ?mol.L-1 was added to cell medium 24 h before H/R( hypoxia 6 h followed by 3 h reoxygenatiori) (SNAP group); (3 )MO precusor, L-arginine 1 mmoL L-1 was added to cell medium 24 h before H/R (L-Arg group); (4) nitric oxide synthase(INOS) antagonist, L-NAME 1 mmol.L-1 and L-arginine 1 mmol.L-1 were added to cell medium 24 h before H/R (L-NAME + L-Arg group); (5) hypoxia preconditioning HP group) in which cultured cells were subjected to 60 min hypoxia followed by 30 min reoxygenation 24 h before H/R; (6) L-NAME 1 mmol.L was added to cell medium during hypoxia preconditioning 24 h before H/R ( L-NAME + HP group) ; (7) cGMP antagonist methylerie blue(MB) 50 ?mol ? L-1 was added to cell medium and one hour later SNAP 500 ?mol?L-1 was added , after being incubated for 24 h the cells were subjected to 6 h hypoxia and 3 h reoxygenation ( MB + SNAP group) ; (8) MB 50 ?mol ? L-1 and L-arginine 1 mmol.L-1 were added to cell medium at 1 h interval 24 h before H/R (MB + L-Arg group); (9) MB 50 ?mol ? L -1 was added to cell medium during hypoxia preconditioning 24 h before H/R (MB + HP group) ; (10) cardiorayocytes underwent 6 h hypoxia and 3 h reoxygenation without any pretreatment (H/R group) . After H/R cardiomyocytes was examined for lactate dehydrogenase ( LDH) activity and cell viability.Results SNAP pretreatment protected cardiomyocytes from H/R injury as shown by reduced LDH activity and improvement in cell viability ( P

Nitric oxide preconditioning induced early protection of cardiomyocytes / 中国药理学通报

AIM To study whether nitric oxide preconditioning induce early protection of neonatal rat cardiomyocytes. METHODS Cultured neonatal rat cardiomyocytes were divided into 6 groups. ①Normal group;②NO group: SNAP(500 ?mol?L -1 ) was added to cell medium 1 h before lethal hypoxia/reoxygenation (HR) injury (6 h hypoxia and 3 h reoxygenation); ③HP group: Cells were cultured for 60min hypoxia followed by 30 min reoxygenation to form hypoxia preconditioning before lethal HR injury;④ L NAME+HP group: Nitric oxide synthase antagonist L NAME was added during HP stage;⑤ L Arg group: L arginine was added to cell medium 1h before lethal HR injury;⑥ L NAME+ L Arg group: Both L NAME and L Arg were added to cell medium 1 h before lethal HR injury;⑦H/R group: Cells underwent lethal HR injury without any treatment. Cardiomyocytes injury was detected by lactate dehydrogenase(LDH) activity and cell viability. RESULTS Nitric oxide preconditioning can protect cardiomyocytes by reducing LDH activity and improving cell viability ( P

Inhibitory effect of hypoxia preconditioning on hypoxia/ reoxygenation-induced apoptosis in cardiomyocytes / 中国病理生理杂志

AIM: To study the role of hypoxia precondit io ning (HP) in hypoxia-reoxygenation (HR)-induced apoptosis in neonatal rat cardio myocytes and the possible mechanisms. METHODS: Cultured neonatal rat cardiomyocytes were divided into three groups: normal group, HP+H/R group and H/R group. Acridine orange (AO) sta ining was performed to detect morphological changes of apoptotic cells. Apoptosi s rates of cardiomyocytes were detected by flow cytometry. Colorimetric assay wa s used to detect caspase-3 activity. Expression of Bcl-2 protein was detected by immunohistochemistry combined with computer image analysis. RESULTS: Apoptotic cells were detected by AO staining after hypo xia of 6 h followed by 3 h-reoxygenation. The hypodiploid apoptotic peak was det ected by flow cytometry with the apoptotic rates of (29.7?5.4)%. A significan tly reduced apoptotic rates of (7.8?1.3)% was detected in HP group(P