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SARS-CoV-2 Seroprevalence in a Cohort of Asymptomatic, RT-PCR Negative Croatian First League Football Players 一组无症状、RT-PCR阴性的克罗地亚足球甲级联赛球员的SARS-CoV-2血清阳性率
Pub Date : 2020-11-04 DOI: 10.1101/2020.10.30.20223230
A. Vince, R. Zadro, Z. Šostar, S. L. Sternak, J. Vraneš, V. Škaro, Petar Projić, Vilim Molnar, V. Matišić, B. Baršić, G. Lauc, Zvjezdana Lovrić-Makarić, Z. Bahtijarević, T. Vlahovic, Sandra Šikić, O. Polašek, D. Primorac
Background: During the COVID-19 pandemic the Croatian Football Federation has launched a new model of pre-season systematic examination of football players, emphasizing the diagnosis of asymptomatic SARS-CoV-2 infection and preventing further spread among the players. Objectives: The aim of this study was to assess the prevalence and dynamics of SARS-CoV-2 IgA and IgG antibodies in the cohort of asymptomatic and SARS-CoV-2 PCR negative professional football players in the Croatian First Football League by using a commercial ELISA antibody assay in the paired serum samples taken 2 months apart. Methods: Serology testing was performed from May till July 2020 in a cohort of 305 asymptomatic football players and club staff members. RT-PCR for detection of SARS-CoV-2 from nasopharyngeal swabs was performed on three occasions, and Euroimmun ELISA for detection of IgA and IgG (S1 and NCP) antibodies was tested in paired serum samples in May and July. Results: All RT-PCR results were negative. Sixty-one (20%) participants were reactive in one or two classes of antibodies at baseline and/or follow-up serology testing. IgA reactivity was found in 41 (13.4% [95% CI=10.7-17.7]) baseline sera and 42 (13.8% [95% CI=10.3-18.9]) follow-up sera. IgG to S1 protein was found in 6 (2% [95% CI=0.9-4.2]) participants at baseline and 1 (0.33% [95% CI=0.0006-1.83]) at follow-up. IgG to NCP was found in 2 (0.7% [95% CI=0.2-2.4]) participants at baseline and 8 (2.6% (95% CI=1.3-5.1]) participants at follow-up. Noticeable dynamics in the paired sera was observed in 18 (5.9%) participants (excluding borderline IgA results) or 32 (10.5%) (including IgA borderline results). Conclusion: Various patterns of IgA and IgG reactivity were found in the paired serum samples. Based on serology dynamics we estimate that in 5.9%-10.5% of PCR negative football players asymptomatic exposure to SARS-CoV-2 during pandemics could not be excluded.
背景:在2019冠状病毒病大流行期间,克罗地亚足协启动了对足球运动员进行季前系统检查的新模式,强调诊断无症状的SARS-CoV-2感染并防止在球员中进一步传播。目的:本研究的目的是通过对相隔2个月的配对血清样本进行商用ELISA抗体测定,评估克罗地亚第一足球联赛无症状和SARS-CoV-2 PCR阴性职业足球运动员中SARS-CoV-2 IgA和IgG抗体的流行率和动态。方法:于2020年5月至7月对305名无症状足球运动员和俱乐部工作人员进行血清学检测。5月和7月分别进行了3次鼻咽拭子中SARS-CoV-2的RT-PCR检测和配对血清中IgA和IgG (S1和NCP)抗体的euroimmune ELISA检测。结果:所有RT-PCR结果均为阴性。61名(20%)参与者在基线和/或随访血清学检测中有一种或两种抗体反应。41例基线血清(13.4% [95% CI=10.7-17.7])和42例随访血清(13.8% [95% CI=10.3-18.9])出现IgA反应。基线时有6名(2% [95% CI=0.9-4.2])参与者检测到IgG - S1蛋白,随访时有1名(0.33% [95% CI=0.0006-1.83])参与者检测到IgG - S1蛋白。基线时2名(0.7% [95% CI=0.2-2.4])参与者和随访时8名(2.6% (95% CI=1.3-5.1])参与者中发现了NCP IgG。18名(5.9%)参与者(不包括IgA边缘结果)或32名(10.5%)参与者(包括IgA边缘结果)在配对血清中观察到明显的动态。结论:配对血清中IgA和IgG的反应模式不同。根据血清学动态,我们估计在5.9%-10.5%的PCR阴性足球运动员中,不能排除在大流行期间无症状暴露于SARS-CoV-2的可能性。
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引用次数: 4
Trends of per-patient healthcare cost and resource utilization of opioid use disorder among privately insured individuals in the United States from 2005-2014 2005-2014年美国私人保险个体阿片类药物使用障碍的人均医疗成本和资源利用趋势
Pub Date : 2020-06-05 DOI: 10.1101/2020.06.03.20121228
B. Jiang, Li Wang, D. Leslie
Background: Little are known about how per-patient healthcare cost and resource utilization of Opioid Use Disorder (OUD) have changed over time when governments continue to reduce availability and utilization barrier of OUD treatment. Objectives: Investigate trends of per-patient healthcare cost and utilization of outpatient, inpatient and emergency department services among privately insured individuals with OUD from 2005 to 2014. Methods: The MarketScan Commercial Claims and Encounters database was used to analyze healthcare cost and resource utilization of opioid used disorder from 2005 to 2014. A matched case-control design was employed to estimate the impact of OUD on healthcare cost and service utilization over this period. Main findings: Excess annual per-patient healthcare cost of OUD stayed relatively stable with an average of $14,586 between 2005 and 2014. However, excess outpatient cost increased while excess inpatient cost decreased over time. Among OUD patients, the increase of OUD related outpatient care utilization rate and average number of visits coincided with the decrease of inpatient and ED service utilization rates and average number of ED visits. Conclusions: Among OUD patients, the increasing per-patient utilization of OUD related outpatient care, together with the decline in per-patient utilization of more urgent care including inpatient and emergency department care might indicate increased awareness and diagnosis of OUD and a better control of the disease among existing patients with private insurance.
背景:当政府继续降低阿片类药物使用障碍治疗的可获得性和利用障碍时,对阿片类药物使用障碍(OUD)的每位患者医疗保健成本和资源利用如何随时间变化知之甚少。目的:调查2005年至2014年私人保险OUD患者的人均医疗保健费用和门诊、住院和急诊服务的使用趋势。方法:采用MarketScan商业索赔和遭遇数据库,分析2005 - 2014年阿片类药物使用障碍的医疗成本和资源利用情况。采用匹配的病例对照设计来估计OUD在此期间对医疗保健成本和服务利用率的影响。主要发现:2005年至2014年间,OUD患者每年额外医疗保健费用相对稳定,平均为14,586美元。然而,随着时间的推移,超额门诊费用增加而超额住院费用减少。在OUD患者中,与OUD相关的门诊服务使用率和平均就诊次数的增加与住院和ED服务使用率和平均就诊次数的下降相一致。结论:在OUD患者中,与OUD相关门诊的人均使用率增加,而包括住院和急诊在内的急诊的人均使用率下降,可能表明现有私人保险患者对OUD的认识和诊断有所提高,对疾病的控制也有所改善。
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引用次数: 0
Quercetin Inhibits the Formation of Atherosclerosis Plaque by Protecting Vascular Endothelial Cells 槲皮素通过保护血管内皮细胞抑制动脉粥样硬化斑块形成
Pub Date : 2019-01-01 DOI: 10.26502/jppr.0025
Ying Zhang, Fangfang Dou
Background: Quercetin and its derivatives are the most widely distributed flavonoids, which have many pharmacological activities, such as anti-oxidation, anti-aging and anti-inflammatory, Quercetin inhibits the occurrence of atherosclerosis (AS) due to its antioxidant activity, but the mechanism is unknown. Results: Our research found that quercetin plays a role in reducing the formation of atherosclerotic plaque by protecting vascular endothelial cell injury. In an atherosclerotic mouse model, quercetin inhibited the formation of atherosclerotic plaques and downregulated the level of endothelial cell protein C receptors (EPCR), thrombomodulin (TM), von willabrand factor (vWF) and intercellular cell adhesion molecule-1(ICAM-1) in peripheral blood of AS mouse, because of increasing the number of vascular endothelial cells at the atherosclerotic plaque. In vitro model of human vascular endothelial cells (HUVECs) injury by H2O2, we found that quercetin significantly reduced endothelial cell apoptosis, and it can prevent vascular endothelial cell injury by inhibiting the secretion of chemokines (CXCL1 and CXCL8) and inflammatory (TNF-α, IL-β, IL-6 and IL-12) factors and reducing macrophage infiltration, at the same time, quercetin promotes the secretion of pro-angiogenic chemokines (CXCL4 and CXCL10) from vascular endothelial cells. Real-time PCR and western-blot assay found that the quercetin protects vascular endothelial cells by inhibiting apoptotic signaling pathway proteins (Bax and Bcl-2) and inflammatory regulatory pathway proteins (IκBα and p65). Conclusion: Consequently, we concluded that the role of quercetin in the protection of vascular endothelial cells against atherosclerotic plaques may be through the inhibition of vascular endothelial cell apoptosis.
背景:槲皮素及其衍生物是分布最广泛的黄酮类化合物,具有抗氧化、抗衰老、抗炎等多种药理活性,槲皮素因其抗氧化活性而抑制动脉粥样硬化(as)的发生,但其作用机制尚不清楚。结果:我们的研究发现槲皮素通过保护血管内皮细胞损伤来减少动脉粥样硬化斑块的形成。在动脉粥样硬化小鼠模型中,槲皮素通过增加动脉粥样硬化斑块处血管内皮细胞的数量,抑制动脉粥样硬化斑块的形成,下调AS小鼠外周血内皮细胞蛋白C受体(EPCR)、血栓调节蛋白(TM)、血管性血管瘤因子(vWF)和细胞间细胞粘附分子-1(ICAM-1)的水平。在H2O2损伤人血管内皮细胞(HUVECs)的体外模型中,我们发现槲皮素可显著减少内皮细胞凋亡,通过抑制趋化因子(CXCL1、CXCL8)和炎症因子(TNF-α、IL-β、IL-6、IL-12)的分泌和减少巨噬细胞的浸润来预防血管内皮细胞损伤,同时槲皮素可促进血管内皮细胞分泌促血管生成趋化因子(CXCL4、CXCL10)。Real-time PCR和western-blot检测发现槲皮素通过抑制凋亡信号通路蛋白(Bax和Bcl-2)和炎症调节通路蛋白(i - κ b α和p65)保护血管内皮细胞。结论:槲皮素对血管内皮细胞抗动脉粥样硬化斑块的保护作用可能是通过抑制血管内皮细胞凋亡来实现的。
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引用次数: 2
Synergistic Growth Inhibitory Effects of Lycium barbarum (Goji berry) Extract with Doxorubicin against Human Breast Cancer Cells 枸杞提取物与阿霉素对人乳腺癌细胞的协同生长抑制作用
Pub Date : 2019-01-01 DOI: 10.26502/jppr.0020
K. Georgiev, Iliya J Slavov, I. Iliev
Lycium barbarum L. known as Goji berry is a plant with wide variety of medicinal properties, including anticancer. The present study aimed to explore the cytotoxic effect of Lycium barbarum fruit extract (LBE), and its combination with doxorubicin on MCF-7 and MDA-MB-231 breast cancer cells. The result of MTT assay showed that the single treatment of doxorubicin performed significant cytotoxic effect on MCF-7 and MDA-MB-231 cell lines. The combination of LBE and doxorubicin on MCF-7 and MDA-MB-231 cells showed synergistic cytotoxic effect based on the fractional effect analysis (FA) and the calculated combination index (CI). Increasing the anticancer effects on the one hand and preventing the dose-limiting effect, like cardiotoxicity on the other hand, of the anthracycline antibiotics indicate L. barbarum fruits as chemosensitizing and chemoprotective at the same time.
枸杞是一种具有多种药用特性的植物,包括抗癌。本研究旨在探讨枸杞提取物(Lycium barbarum fruit extract, LBE)及其联合阿霉素对MCF-7和MDA-MB-231乳腺癌细胞的细胞毒作用。MTT试验结果显示,阿霉素单次处理对MCF-7和MDA-MB-231细胞株有显著的细胞毒作用。根据分级效应分析(FA)和计算的联合指数(CI), LBE和阿霉素联合对MCF-7和MDA-MB-231细胞显示协同细胞毒作用。一方面增加了蒽环类抗生素的抗癌作用,另一方面防止了剂量限制作用,如心脏毒性,表明枸杞果同时具有化学增敏和化学保护作用。
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引用次数: 7
Development and Validation of Stability Indicating HPLC Method for Benzalkonium Chloride in Betaxolol (0.5%) Opthalmic Solution 倍他洛尔(0.5%)眼液中苯扎氯铵稳定性指示高效液相色谱法的建立与验证
Pub Date : 2019-01-01 DOI: 10.26502/JPPR.0017
Liena Alagib H Edress, D. Elhag
Background: Preservative assay in eye drops require the development of a suitable validated method for the assay. Objective: This study was conducted to develop and validate stability indicating High Performance Liquid Chromatography (HPLC) method for assay of benzalonium chloride in betaxolol 0.5% ophthalmic solution. Method: Method was developed validated according to International conference on harmonization (ICH) guideline. Chromatographic condition used was: L10 CN column (250 cm × 4.6 mm × 10 μm); flow rate 2.0 ml per minute; detection wavelength 245 nm; column oven 30°C; mobile phase: (0.1M sodium acetate, acetonitrile) (55:45 v/v) and injection volume 100 μL. Results: The method was found fulfilling the ICH requirement with R2 of 0.9995 for drug, Limit of detection (LOD) of 4.53 μg/ml, and Limit of quantification (LOQ) of 13.75 for benzalkonium chloride. The mean of overall recovery % was found to be 99.96% and the repeatability results was found to be: 99.95% for benzalkonium chloride. The overall intermediate precision results were found to be 100.77%. The method proved to be accurate, precise and specific. Conclusion: The developed method was found to be simple, sensitive and can be used for routine quality control analysis of benzalkonium chloride in betaxolol (0.5%) ophthalmic solutions.
背景:眼药水中的防腐剂检测需要开发一种合适的验证方法。目的:建立高效液相色谱法测定0.5%倍他洛尔眼液中苯扎氯铵含量的方法,并对其稳定性进行验证。方法:根据国际协调会议(ICH)指南制定方法并进行验证。色谱条件:L10 CN柱(250 cm × 4.6 mm × 10 μm);流速2.0 ml / min;检测波长245nm;柱式烘箱30℃;流动相:0.1M醋酸钠-乙腈(55:45 v/v),进样量100 μL。结果:该方法符合ICH要求,药物的检测限(LOD)为4.53 μg/ml,苯扎氯铵的定量限(LOQ)为13.75。苯扎氯铵的总回收率平均值为99.96%,重复性为99.95%。总体中间精度结果为100.77%。结果表明,该方法准确、精确、专属性强。结论:该方法简便、灵敏,可用于倍他洛尔(0.5%)眼液中苯扎氯铵的常规质量控制分析。
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引用次数: 1
Acknowledgement to Authors, Reviewers and Editors of Journal of Pharmacy and Pharmacology Research in 2017 and 2018. 感谢2017年和2018年《药学与药理学研究杂志》的作者、审稿人和编辑。
Pub Date : 2019-01-01 DOI: 10.26502/jppr.0015
Smith ,, M. ,
Rigorous peer-review is the main part in building the corner-stone of high-quality academic publishing. The editorial team greatly appreciates the authors, reviewers who contributed their knowledge and expertise to the journal’s editorial process over the past 12 months. In 2017, a total of 4 articles and in 2018 a total of 10 articles were published in the journal with a median time to first decision of 15 days and a median time to publication of 20 days. The editorial office would like to express their sincere gratitude to the following authors, reviewers and editors for their cooperation and dedication in 2017 and 2018:
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引用次数: 0
A Clinical Benefit of Training Asthmatic Patients on How to Use Metered Dose Inhalers by using the 2Tone Trainer In Libya 在利比亚使用2Tone训练器训练哮喘患者如何使用计量吸入器的临床效益
Pub Date : 2019-01-01 DOI: 10.26502/JPPR.0018
W. Tarsin, Nabila A. Hshad, Ishraq Elshamli, Fathi Mohamed Sherif
Bronchial asthma is a serious chronic inflammatory disease of the respiratory system. Aerosol inhalation as a route of drug delivery has become well-known in therapy of asthma. This study was designed to evaluate if the use of 2Tone helps patients maintain the correct inhalation technique after training and can improve the clinical benefit. 125 Libyan adult asthmatic patients were recruited. At the first clinical visit; 38, 44 and 43 patients were included as C, VT and 2T groups, respectively. Their inhalation flow rate through an MDI was measured using an In-Check Dial. Patients in 2T group were trained on how to use the 2Tone Trainer according to its PIL and practiced inhaling through this training aid to familiarize themselves with the different sounds according to the inhalation rates. At the second clinic visit for all the patients was held six weeks later, each patient was assessed in the same manner as on the first visit. Results show no significant difference in the change of FEV1 and PEFR between all the groups. Lung function measurements, percent predicted FEV1 and PEFR showed significant low correlation with all AQLQ domains, except for AQLQ environment which found no correlation with lung function measurement. Significant correlations between percent predicted FEV1 and PEFR with all AQLQ domains. Patients in the 2T group showed reduced IFR of about double that in VT group, whereas in the C group, there was no difference in IFR. Comparison of IFR between VT vs. 2T groups at visit one showed no statistical significant difference. However, at visit two, comparison between all the groups showed a highly significant difference. Thus, this study shows that 100% and 29% of the patients in the C and VT groups were inhaling at a high IFR while the 2T group shows only one patient (3%) was inhaling at the high flow rate while the rest of the patients managed to obtain the optimum IFR needed for the MDIs. Thus, the present findings show the importance of the use of the 2T device to train the patients to slow their IFR.
支气管哮喘是一种严重的呼吸系统慢性炎症性疾病。气雾剂吸入作为一种给药途径,在哮喘治疗中已得到广泛应用。本研究旨在评估使用2Tone是否有助于患者在训练后保持正确的吸入技术,并提高临床效益。招募了125名利比亚成年哮喘患者。第一次就诊时;C组38例,VT组44例,2T组43例。他们通过MDI的吸入流速使用In-Check Dial测量。2T组患者根据2Tone Trainer的PIL对其进行使用训练,并通过该训练辅助工具进行吸气练习,根据吸气速率熟悉不同的声音。在六周后对所有患者进行的第二次门诊访问中,以与第一次访问相同的方式对每位患者进行评估。结果显示,各组间FEV1、PEFR变化无显著性差异。除AQLQ环境与肺功能测量无相关性外,肺功能测量、预测FEV1百分比和PEFR与所有AQLQ结构域均呈显著低相关性。预测FEV1和PEFR与所有AQLQ域之间存在显著相关性。2T组患者IFR降低约为VT组的两倍,而C组IFR无差异。VT组与2T组在第一次就诊时IFR比较无统计学意义。然而,在第二次访问时,所有组之间的比较显示出高度显著的差异。因此,本研究显示,C组和VT组中100%和29%的患者以高IFR吸入,而2T组显示只有1名患者(3%)以高流速吸入,而其余患者设法获得mdi所需的最佳IFR。因此,目前的研究结果显示了使用2T设备来训练患者减缓IFR的重要性。
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引用次数: 1
Antioxidant, Antimicrobial and Anti-Inflammatory Activities of Edible Rhus Tripartita (Ucria) Hydromethanolic Extracts 食用三边草(Ucria)氢甲醇提取物的抗氧化、抗菌和抗炎活性
Pub Date : 2019-01-01 DOI: 10.26502/jppr.0022
Zaineb Ben Barka, K. Lahbib, C. Aouadhi, Mohamed H. Ladjimi, Hanène Ben Miled, K. Rhouma, M. Sakly, A. Maaroufi, Y. Schneider, O. Tebourbi
Background: Rhus tripartita (Anacardiacae) is a plant which is traditionally used for the treatment of ulcer and diarrhea in Tunisia. The core aim of this study is to evaluate the antioxidant, antimicrobial and anti-inflammatory activities of Rhus tripartita (leaf (RLE), stem (RSE) and root (RRE)) extracts. Results: RLE extract exhibited high total phenolic, flavonoids and condensed tannins. The in vitro antioxidant activity of the tested extracts (RLE, RSE and RRE) showed significant potent total antioxidant capacity (TAC), DPPH and ABTS radical scavenging activity, ferrous ions chelating and ferric reducing ions activities, H2O2 and OH scavenging capacities. The extracts showed great antimicrobial effects with an important inhibition zones (IZs). The minimum inhibitory concentration (MIC) and the lowest minimum bactericidal concentration (MBC) were recorded. The RRE showed the most significant protective anti-inflammatory effects compared to Indomethacin in carrageenan inflammation paw edema test. Conclusion: This work highlights the importance of Rhus tripartita as dietary source of natural antioxidants and might be appropriate for the development of reliable biotechnologic methods to identify and extract the antimicrobial and anti-inflammatory biomolecules.
背景:在突尼斯,蒺藜是一种传统上用于治疗溃疡和腹泻的植物。本研究的核心目的是评价三棱草(RLE)叶(RSE)、茎(RSE)和根(RRE)提取物的抗氧化、抗菌和抗炎活性。结果:RLE提取物具有较高的总酚、总黄酮和缩合单宁含量。三种提取物(RLE、RSE和RRE)的体外抗氧化活性均表现出显著的总抗氧化能力(TAC)、DPPH和ABTS自由基清除能力、铁离子螯合和铁还原离子清除能力、H2O2和OH清除能力。提取物具有良好的抑菌作用,具有重要的抑菌带。记录了最低抑菌浓度(MIC)和最低杀菌浓度(MBC)。与吲哚美辛相比,RRE在角叉菜胶炎症足跖水肿试验中表现出最显著的保护性抗炎作用。结论:本研究强调了三叶蛇属植物作为天然抗氧化剂的重要来源,可能适合开发可靠的生物技术方法来鉴定和提取其抗菌和抗炎生物分子。
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引用次数: 5
Comparative Studies on Safety of Glimepiride and Glipizide on Renal Microarchitecture and Oxidative Stress Markers of Pregnant Streptozotocin-Induced Diabetic Wistar Rats 格列美脲与格列吡嗪对妊娠链脲佐菌素诱导的糖尿病Wistar大鼠肾脏微结构及氧化应激标志物安全性的比较研究
Pub Date : 2019-01-01 DOI: 10.26502/jppr.0016
Esubi Ju, Olojede So, Lawal Sk, Medubi Lj, Adekoya Aj, Dauda Ff, Olus Ap, A. Osinubi
Introduction: A relatively decreased insulin secretion and impaired response of the body to insulin are the common attributes of gestational diabetes mellitus (GDM) and Type 2 diabetes mellitus. The oral hypoglycemic agents are less invasive, improve patients’ compliance, which can be effective in maintaining the blood sugar level during pregnancy. Aim: The overall aim of this research was to ascertain the comparative evaluation of the glimepiride and glipizide on the kidney and some maternal parameters of pregnant streptozotocin (STZ)-induced diabetic rats. Methodology: Thirty-five (35) female Sprague-Dawley rats weighing between 120-160 g were divided into 5 groups. Groups 2-5 were induced with diabetes mellitus by intraperitoneal injection of streptozotocin (STZ). Group 1: (Control given distilled water), Group 2: (Diabetic treated with Glimepiride), Group 3: (Diabetic treated with Insulin), Group 4: (Diabetic treated with Glipizide), Group 5: (Diabetic given citrate buffer). Results: Glimepiride and Glipizide treated groups showed statistically significant (p=0.05) improvement in oxidative stress markers, blood glucose level, body weight, hematological parameters and lipid profile when compared with diabetic and insulin groups. There was statistically significant (p=0.05) improvement on the oxidative stress marker, body weight and the restorative effect on renal histology in the group treated glimepiride when compared with glipizide and diabetic groups. Conclusion: This work has demonstrated that the two oral hypoglycaemic agents were effective in controlling glucose intolerance during pregnancy, renal oxidative stress as well as cytoarchitectonic properties of the kidney comparable with insulin. Therefore, because of its ameliorative and restorative effects on renal oxidative stress and micro-architectonic properties of the kidney, glimepiride could be tempting alternative drug of choice for adequate control of glucose intolerance during pregnancy.
妊娠期糖尿病(GDM)和2型糖尿病的共同特征是胰岛素分泌相对减少和机体对胰岛素的反应受损。口服降糖药侵入性小,提高患者依从性,可有效维持妊娠期血糖水平。目的:研究格列美脲和格列吡嗪对链脲佐菌素(STZ)诱导的妊娠糖尿病大鼠肾脏及母体某些指标的影响。方法:35只体重120 ~ 160 g的雌性Sprague-Dawley大鼠分为5组。2 ~ 5组腹腔注射链脲佐菌素(STZ)诱导糖尿病。1组(对照组给予蒸馏水),2组(糖尿病患者给予格列美脲),3组(糖尿病患者给予胰岛素),4组(糖尿病患者给予格列吡嗪),5组(糖尿病患者给予柠檬酸缓冲液)。结果:格列美脲和格列吡嗪治疗组与糖尿病组和胰岛素组相比,氧化应激指标、血糖水平、体重、血液学指标和血脂均有显著改善(p=0.05)。与格列吡嗪组和糖尿病组相比,格列美脲组氧化应激指标、体重及肾组织恢复效果均有统计学意义(p=0.05)。结论:这两种口服降糖药可有效控制妊娠期葡萄糖耐受不良、肾脏氧化应激以及与胰岛素相当的肾脏细胞结构特性。因此,由于其对肾脏氧化应激和肾脏微结构特性的改善和恢复作用,格列美脲可能是妊娠期间充分控制葡萄糖耐受不良的诱人替代药物选择。
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引用次数: 2
Simvastatin Modulates Extracellular Matrix Assembly by Displaying an Antifibrotic Activity in Vitro 辛伐他汀通过在体外显示抗纤维化活性来调节细胞外基质组装
Pub Date : 2019-01-01 DOI: 10.26502/jppr.0021
Annele Sainio, A. Laiho, H. Järveläinen
Statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, are known to possess properties beyond their cholesterol-lowering effect including anti-inflammatory, antiproliferative and anti-immunomodulatory effects. We examined the effect of simvastatin on extracellular matrix (ECM) assembly by human skin fibroblasts (HSFs) in vitro. Using collagen gel contraction (CGC) assay we showed that simvastatin inhibits contraction of type I collagen-rich gels in a dose-dependent manner. This effect of simvastatin could be overcome by co-incubating the cells with mevalonate. Actin staining revealed that inhibition of CGC by simvastatin is associated with diminished ability of the cells to form aggregates. Using whole human genome Illumina microarray we sought to search for new candidate genes whose expression is regulated by simvastatin during CGC and focused specifically on the genes related to ECM synthesis and remodeling. We found that simvastatin profoundly downregulated gene expression of 27 ECM molecules including proteoglycans decorin and versican, both of which are known to be essential constituents of proper ECM. Expression of these two molecules was further verified by Northern blot analysis. Finally, when simvastatin treated HSFs were activated with TGF-β1, the cell-mediated contraction of collagen gel was restored. Our results indicate that simvastatin markedly alters ECM assembly in vitro possessing an antifibrotic activity.
他汀类药物是3-羟基-3-甲基戊二酰辅酶A还原酶的竞争性抑制剂,已知除了具有降低胆固醇的作用外,还具有抗炎、抗增殖和抗免疫调节作用。我们研究了辛伐他汀对体外人皮肤成纤维细胞(hsf)细胞外基质(ECM)组装的影响。通过胶原凝胶收缩(CGC)实验,我们发现辛伐他汀以剂量依赖的方式抑制I型富胶原凝胶的收缩。辛伐他汀的这种作用可以通过与甲羟戊酸共孵育来克服。肌动蛋白染色显示辛伐他汀对CGC的抑制作用与细胞形成聚集体的能力减弱有关。利用全人类基因组Illumina微阵列,我们寻找新的候选基因,这些基因的表达在CGC过程中受到辛伐他汀的调控,并特别关注与ECM合成和重塑相关的基因。我们发现辛伐他汀显著下调27种ECM分子的基因表达,包括蛋白聚糖decorin和versican,这两种蛋白聚糖都是正常ECM的必需成分。Northern blot分析进一步验证了这两个分子的表达。最后,用TGF-β1激活辛伐他汀处理的hsf,恢复细胞介导的胶原凝胶收缩。我们的结果表明辛伐他汀在体外显著改变具有抗纤维化活性的ECM组装。
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Journal of pharmacy and pharmacology research
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