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Front & Back Matter 正面和背面
IF 3.1 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-01 DOI: 10.1159/000530999
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引用次数: 0
Front & Back Matter 正面和背面事项
IF 3.1 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-03-01 DOI: 10.1159/000529987
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引用次数: 0
Melatonin Supports the Survival of Cholinergic Neurons in Organotypic Brain Slices of the Basal Nucleus of Meynert. 褪黑素支持Meynert基底核器官型脑切片中胆碱能神经元的存活。
IF 3.1 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.1159/000527887
Grazia Ilaria Caruso, Dhwani S Korde, Christian Humpel

The nucleus basalis of Meynert (nBM) is the major source of cholinergic neurons in the basal forebrain, which require nerve growth factor (NGF) for their survival. Melatonin, a pleiotropic hormone, has been shown to exert neuroprotection in several experimental models, but its effect on nBM neurons is not well known. Thus, the aim of this study is to evaluate the effect of melatonin in organotypic brain slices of the nBM. Organotypic nBM slices were incubated for 2 weeks without (control) or with 100 ng/mL NGF, 1 μM melatonin, or a combination of both. Cholinergic neurons were immunohistochemically stained for choline acetyltransferase (ChAT) and subjected to a co-localization study with silent information regulator 1 (SIRT1) and melatonin receptor 1A (MT1A), both potentially involved in melatonin neuroprotection. Counting of ChAT-positive neurons in nBM slices showed that melatonin and NGF significantly increased the number of ChAT-positive neurons compared to the control in a dose-dependent manner (1-10 μM). In co-treatment with NGF, melatonin did not potentiate the maximal NGF-mediated effect. Immunohistochemical analysis proved that cholinergic nBM neurons co-localized with SIRT1 and MT1A receptor. Our data show that melatonin improves the survival of cholinergic nBM neurons and confirm that they express SIRT1 and MT1A.

Meynert基底核(nBM)是基底前脑胆碱能神经元的主要来源,这些神经元的生存需要神经生长因子(NGF)。褪黑素是一种多效性激素,已在多个实验模型中显示出神经保护作用,但其对nBM神经元的作用尚不清楚。因此,本研究的目的是评估褪黑素在脑基底细胞器官型脑切片中的作用。无(对照)、100 ng/mL NGF、1 μM褪黑素或两者联合孵育2周。对胆碱能神经元进行胆碱乙酰转移酶(ChAT)免疫组织化学染色,并与沉默信息调节因子1 (SIRT1)和褪黑激素受体1A (MT1A)进行共定位研究,两者都可能参与褪黑激素神经保护。nBM切片中chat -阳性神经元计数显示,与对照组相比,褪黑激素和NGF显著增加了chat -阳性神经元的数量,且呈剂量依赖性(1-10 μM)。在与NGF联合治疗时,褪黑素并没有增强最大的NGF介导效应。免疫组织化学分析证实胆碱能神经元与SIRT1和MT1A受体共定位。我们的数据表明,褪黑激素提高了胆碱能神经元的存活率,并证实了它们表达SIRT1和MT1A。
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引用次数: 1
Oral Administration of Artemisia argyi Polysaccharide Increases Estrogen Level and Maintains Blood Lipid Homeostasis in Ovariectomized Rats. 口服艾叶多糖可提高去卵巢大鼠雌激素水平及维持血脂稳态。
IF 3.1 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.1159/000527465
Pengfei Zhang, Huimin Sun, Dexin Yang, Yuanyuan Wang, Jiejuan Cheng, Changchun Zeng

Introduction: Artemisia argyi polysaccharide (AAP) has a beneficial effect on menstruation-related symptoms and the potential regulation of lipid metabolism. It is expected to be a safe and effective ingredient for estrogen deficiency and lipid metabolic disorders. Here, we investigate the effect of AAP on body weight gain, estrogen level, and blood lipid changes in ovariectomized (OVX) rats.

Methods: Thirty-six female Wistar rats were randomly divided into six treatment groups, including a sham-operated (Sham) group, OVX group, estrogen replacement (OVX + E2) group, and AAP treatment (OVX + 125, 250, 500 mg/kg AAP) group. The body weight and feed intake were recorded every week. The level of estrogen and blood lipid was determined. The gene expressions and protein expressions of estrogen receptors (ERs), fatty acid synthetase (FAS), acetyl CoA carboxylase 2 (ACC2), and 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) were determined.

Results: AAP treatment significantly decreased the body weight gain and average daily food intake of rats in the OVX group. Treatment with AAP significantly increased the relative weight of the uterus, plasma estrogen level, and the gene expression and protein expression of ER-α in the uterus. For blood lipids, plasma levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol were significantly reduced by AAP treatment in OVX rats. AAP treatment decreased the expression of FAS and HMGR in the liver of OVX rats. Furthermore, AAP treatment significantly increased the gene expression of ACC2, the protein expression of P-ACC2, and the ratio of P-ACC2/ACC2.

Conclusion: In summary, AAP treatment exerts beneficial effects on body weight gain and lipid metabolism disorder induced by ovariectomy through increasing estrogen levels, inhibiting FAS, and promoting fatty acid oxidation.

简介:艾叶多糖(AAP)对月经相关症状有有益作用,并可能调节脂质代谢。有望成为治疗雌激素缺乏和脂质代谢紊乱的安全有效的成分。在此,我们研究了AAP对去卵巢大鼠体重增加、雌激素水平和血脂变化的影响。方法:36只雌性Wistar大鼠随机分为6个治疗组,分别为假手术(Sham)组、OVX组、雌激素替代(OVX + E2)组和AAP治疗(OVX + 125、250、500 mg/kg AAP)组。每周记录体重和采食量。测定各组小鼠雌激素和血脂水平。测定雌激素受体(er)、脂肪酸合成酶(FAS)、乙酰辅酶A羧化酶2 (ACC2)、3-羟基-3-甲基戊二酰辅酶A还原酶(HMGR)的基因表达和蛋白表达。结果:AAP治疗显著降低OVX组大鼠增重和平均日摄食量。AAP治疗可显著提高子宫相对重量、血浆雌激素水平及子宫ER-α基因表达和蛋白表达。在血脂方面,AAP治疗显著降低了OVX大鼠的血浆甘油三酯、总胆固醇和低密度脂蛋白胆固醇水平。AAP可降低OVX大鼠肝脏中FAS和HMGR的表达。此外,AAP处理显著提高了ACC2基因表达、P-ACC2蛋白表达以及P-ACC2/ACC2比值。结论:综上所述,AAP治疗通过提高雌激素水平、抑制FAS、促进脂肪酸氧化,对卵巢切除术后体重增加和脂质代谢紊乱有有益作用。
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引用次数: 0
Lafutidine Ameliorates Indomethacin-Induced Small Intestinal Damage in Rats by Modifying the Intestinal Mucosal Barrier, Inflammation, and Microbiota. 拉福丁通过改变肠黏膜屏障、炎症和微生物群改善吲哚美辛诱导的大鼠小肠损伤。
IF 3.1 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.1159/000529879
Lanping Zhu, Junyi Guo, Qinlingfei Liu, Yang Luo, Jing Zhao, Weilong Zhong, Siyuan Sun, Xiuxiu Xu, Huixi Liang, Chenxi Lou, Chongfei Song, Jihua Chen, Jingwen Zhao, Bangmao Wang, Xin Chen

Introduction: Nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage is a serious and escalating clinical problem without effective treatment. Lafutidine (LAF) is a novel histamine H2 receptor antagonist with a mucosal protective action. This study aimed to investigate the protective effect of LAF on indomethacin (IND)-induced enteropathy in rats.

Methods: Rats were treated with LAF for 10 days with concomitant IND treatment on the final 5 days. Changes in metabolism and hematological and biochemical parameters were measured, and intestinal damage was blindly scored. Intestinal mucosal tissue and luminal contents were collected for transcriptome and microbiota sequencing. Intestinal inflammation and barrier function were also evaluated.

Results: LAF treatment prevented anorexia and weight loss in rats and ameliorated reductions in hemoglobin, hematocrit, total protein, and albumin levels. LAF reduced the severity of IND-induced intestinal damage including macroscopic and histopathological damage score. Transcriptome sequencing results indicated that LAF might have positive effects on intestinal inflammation and the intestinal mucosal barrier. Further research revealed that LAF decreased neutrophil infiltration, and IL-1β and TNF-α expression in intestinal tissue. Besides, the treatment increased mucus secretion, MUC2, Occludin, and ZO-1 expression, and decreased serum D-lactate levels. LAF treatment also ameliorates microbial dysbiosis in small intestine induced by IND and increased the abundance of Lactobacillus acidophilus.

Conclusion: LAF may protect against NSAID enteropathy via enhancing the intestinal mucosal barrier, inhibiting inflammation, and regulating microbiota.

简介:非甾体抗炎药(NSAID)引起的小肠损伤是一个严重且不断升级的临床问题,没有有效的治疗。拉富丁是一种具有黏膜保护作用的新型组胺H2受体拮抗剂。本研究旨在探讨LAF对吲哚美辛(IND)诱导的大鼠肠病的保护作用。方法:大鼠用LAF治疗10 d,最后用IND治疗5 d。测量代谢、血液学和生化参数的变化,并对肠道损伤进行盲目评分。收集肠道黏膜组织和肠道内容物进行转录组和微生物群测序。肠道炎症和屏障功能也进行了评估。结果:LAF治疗预防了大鼠的厌食症和体重减轻,改善了血红蛋白、红细胞压积、总蛋白和白蛋白水平的降低。LAF降低了ind诱导的肠道损伤的严重程度,包括宏观和组织病理学损伤评分。转录组测序结果表明,LAF可能对肠道炎症和肠黏膜屏障具有积极作用。进一步研究发现,LAF可降低肠组织中性粒细胞的浸润,降低IL-1β和TNF-α的表达。此外,治疗增加了粘液分泌、MUC2、Occludin和ZO-1的表达,降低了血清d -乳酸水平。LAF处理也改善了IND引起的小肠微生物生态失调,增加了嗜酸乳杆菌的丰度。结论:LAF可能通过增强肠黏膜屏障、抑制炎症和调节微生物群来预防非甾体抗炎药肠炎。
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引用次数: 0
High On-Treatment Platelet Reactivity: Aspirin versus Clopidogrel. 高治疗期血小板反应性:阿司匹林与氯吡格雷。
IF 3.1 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.1159/000527816
René M'Pembele, Samantha Ahlbrecht, Carolin Helten, Philipp Mourikis, David Naguib, Saif Zako, Kajetan Trojovsky, Ragnar Huhn, Tobias Petzold, Thomas Hohlfeld, Tobias Zeus, Malte Kelm, Lisa Dannenberg, Amin Polzin

Background: Antithrombotic regimen in patients on oral anticoagulation (OAC) post-percutaneous coronary intervention (PCI) is challenging. At least, one antiplatelet agent in combination with OAC is recommended after PCI for 6-12 months. Clopidogrel is used most frequently in this setting. However, data comparing P2Y12 inhibition with clopidogrel versus cyclooxygenase inhibition by acetylsalicylic acid (ASA, aspirin) is missing. It is well known that the antiplatelet effects of ASA and clopidogrel are frequently impaired (high on-treatment platelet reactivity [HTPR]). In this pilot investigation, we compared the antiplatelet effects of clopidogrel versus ASA.

Methods: In this retrospective single-center database analysis, we investigated platelet reactivity by light transmission aggregometry in patients under different antiplatelet regimes. Results were presented as maximum of aggregation (MoA). HTPR to ASA and to clopidogrel were assessed.

Results: 755 patients were enrolled. 677 were on ASA, 521 were on clopidogrel, and 198 had OAC. Overall mean age was 73 ± 13.4 years, and 458 (60.7%) were male. HTPR to ASA occurred in 94/677 patients (13.9%), and mean arachidonic acid-induced MoA was 14.15 ± 19.04%. HTPR to clopidogrel occurred in 241/521 patients (46.3%), and mean adenosine diphosphate-induced MoA was 50.06 ± 20.42%. HTPR to clopidogrel was significantly more frequent than HTPR to ASA; single antiplatelet therapy (SAPT)-mono ASA: 27/199 (13.6%) versus mono clopidogrel: 6/18 (33.3%); p = 0.037; SAPT with OAC-OAC with ASA: 8/35 (22.9%) versus OAC with clopidogrel: 27/60 (45%); p = 0.046. Same difference in HTPR contingency could be shown in subgroups of dual antiplatelet therapy and ASA + clopidogrel + OAC therapy.

Conclusion: Impaired pharmacodynamic response to clopidogrel was more frequent as HTPR to ASA. Hence, ASA should be tested in combination with OAC post-PCI.

背景:经皮冠状动脉介入治疗(PCI)后口服抗凝(OAC)患者的抗血栓治疗方案具有挑战性。PCI术后6-12个月,至少推荐一种抗血小板药物联合OAC。氯吡格雷在这种情况下最常用。然而,比较氯吡格雷抑制P2Y12与乙酰水杨酸(ASA,阿司匹林)抑制环氧化酶的数据缺失。众所周知,ASA和氯吡格雷的抗血小板作用经常受损(治疗时血小板反应性高[HTPR])。在这项初步研究中,我们比较了氯吡格雷和ASA的抗血小板作用。方法:在回顾性单中心数据库分析中,我们通过光透射聚集法研究了不同抗血小板方案患者的血小板反应性。结果以聚合最大值(MoA)表示。对ASA和氯吡格雷进行HTPR评估。结果:755例患者入组。677人服用ASA, 521人服用氯吡格雷,198人服用OAC。总体平均年龄73±13.4岁,男性458例(60.7%)。677例患者中有94例(13.9%)发生HTPR到ASA,花生四烯酸诱导的MoA平均为14.15±19.04%。521例患者中有241例(46.3%)发生对氯吡格雷的HTPR,二磷酸腺苷诱导的MoA平均为50.06±20.42%。HTPR对氯吡格雷的发生率明显高于HTPR对ASA的发生率;单抗血小板治疗(SAPT)-单抗ASA: 27/199 (13.6%) vs单抗氯吡格雷:6/18 (33.3%);P = 0.037;SAPT + OAC-OAC + ASA: 8/35 (22.9%) vs + OAC +氯吡格雷:27/60 (45%);P = 0.046。在双重抗血小板治疗和ASA +氯吡格雷+ OAC治疗的亚组中,HTPR意外发生率也有相同的差异。结论:氯吡格雷对ASA的药效学影响较HTPR更为常见。因此,ASA应与pci后OAC联合检测。
{"title":"High On-Treatment Platelet Reactivity: Aspirin versus Clopidogrel.","authors":"René M'Pembele,&nbsp;Samantha Ahlbrecht,&nbsp;Carolin Helten,&nbsp;Philipp Mourikis,&nbsp;David Naguib,&nbsp;Saif Zako,&nbsp;Kajetan Trojovsky,&nbsp;Ragnar Huhn,&nbsp;Tobias Petzold,&nbsp;Thomas Hohlfeld,&nbsp;Tobias Zeus,&nbsp;Malte Kelm,&nbsp;Lisa Dannenberg,&nbsp;Amin Polzin","doi":"10.1159/000527816","DOIUrl":"https://doi.org/10.1159/000527816","url":null,"abstract":"<p><strong>Background: </strong>Antithrombotic regimen in patients on oral anticoagulation (OAC) post-percutaneous coronary intervention (PCI) is challenging. At least, one antiplatelet agent in combination with OAC is recommended after PCI for 6-12 months. Clopidogrel is used most frequently in this setting. However, data comparing P2Y12 inhibition with clopidogrel versus cyclooxygenase inhibition by acetylsalicylic acid (ASA, aspirin) is missing. It is well known that the antiplatelet effects of ASA and clopidogrel are frequently impaired (high on-treatment platelet reactivity [HTPR]). In this pilot investigation, we compared the antiplatelet effects of clopidogrel versus ASA.</p><p><strong>Methods: </strong>In this retrospective single-center database analysis, we investigated platelet reactivity by light transmission aggregometry in patients under different antiplatelet regimes. Results were presented as maximum of aggregation (MoA). HTPR to ASA and to clopidogrel were assessed.</p><p><strong>Results: </strong>755 patients were enrolled. 677 were on ASA, 521 were on clopidogrel, and 198 had OAC. Overall mean age was 73 ± 13.4 years, and 458 (60.7%) were male. HTPR to ASA occurred in 94/677 patients (13.9%), and mean arachidonic acid-induced MoA was 14.15 ± 19.04%. HTPR to clopidogrel occurred in 241/521 patients (46.3%), and mean adenosine diphosphate-induced MoA was 50.06 ± 20.42%. HTPR to clopidogrel was significantly more frequent than HTPR to ASA; single antiplatelet therapy (SAPT)-mono ASA: 27/199 (13.6%) versus mono clopidogrel: 6/18 (33.3%); p = 0.037; SAPT with OAC-OAC with ASA: 8/35 (22.9%) versus OAC with clopidogrel: 27/60 (45%); p = 0.046. Same difference in HTPR contingency could be shown in subgroups of dual antiplatelet therapy and ASA + clopidogrel + OAC therapy.</p><p><strong>Conclusion: </strong>Impaired pharmacodynamic response to clopidogrel was more frequent as HTPR to ASA. Hence, ASA should be tested in combination with OAC post-PCI.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10488441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of Normal and Overweight Pregnancy in GLUT4 and Glucose-Dependent Vascular Contractility. 正常和超重妊娠对GLUT4和葡萄糖依赖性血管收缩性的影响。
IF 3.1 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 Epub Date: 2023-09-06 DOI: 10.1159/000533344
Esther Juarez Cortés, Gustavo López Y López, Eduardo I Perez Muñoz, Betzabel Rodriguez Reyes, Damian A Madrigal-Aguilar, Rosa A Bobadilla-Lugo

Introduction: Obesity during pregnancy can contribute to hypertensive complications through changes in glucose utilization. We investigated the impact of vascular glucose uptake, GLUT4 density, and endothelium on agonist-induced vasoconstriction in the aortas of overweight pregnant rats.

Methods: Isolated aortic rings with or without endothelium from pregnant or nonpregnant rats fed a standard (SD) or hypercaloric diet (HD) were contracted with phenylephrine or serotonin (10-9 to 10-4M) using standard (11 mm) or without (0 mm) glucose Krebs solution. GLUT4 density in the aortas was measured using the en face method.

Results: Aortas from overweight pregnant animals (PHD) showed increased Phe-induced vasoconstriction (p < 0.05 vs. pregnant standard diet [PSD]), which was endothelium-independent. The contraction decreased significantly in the absence of glucose. In contrast, vessels from pregnant SD rats maintained their contraction in glucose-free Krebs solution. 5-HT increases PHD aortic contraction only in the absence of glucose. The fetal aortas from PHD mothers showed blunted vasoconstriction. Overweight significantly reduced GLUT4 expression in maternal and fetal aortas (p < 0.05 vs. PSD).

Conclusions: Aortic contractility is independent of glucose uptake during healthy pregnancy. In contrast, overweight pregnancy increases contractility. This increase depends directly on smooth muscle glucose uptake and inversely on GLUT-4 density. The increased contraction observed in the vasculature of overweight mothers was inverted in the fetal aortas.

妊娠期肥胖可通过改变葡萄糖利用导致高血压并发症。我们研究了超重妊娠大鼠血管葡萄糖摄取、GLUT4密度和内皮对激动剂诱导的血管收缩的影响。方法:用标准(SD)或高热量饮食(HD)喂养的怀孕或非怀孕大鼠分离的带内皮或不带内皮的主动脉环,用标准(11 mm)或不含(0 mm)葡萄糖Krebs溶液注射苯肾上腺素或5 -羟色胺(10-9至10-4M)。采用面法测定主动脉内GLUT4密度。结果:超重妊娠动物(PHD)的主动脉显示出phe诱导的血管收缩增加(p <0.05 vs.妊娠标准饮食[PSD]),内皮不依赖性。在没有葡萄糖的情况下,收缩明显减弱。妊娠SD大鼠血管在无糖Krebs溶液中保持收缩。5-HT仅在没有葡萄糖的情况下增加PHD主动脉收缩。来自博士母亲的胎儿主动脉显示钝性血管收缩。超重显著降低了母体和胎儿主动脉中GLUT4的表达(p <0.05 vs. PSD)。结论:健康妊娠期间主动脉收缩力与葡萄糖摄取无关。相反,超重妊娠会增加收缩力。这种增加直接取决于平滑肌葡萄糖摄取,而与GLUT-4密度成反比。在超重母亲的血管系统中观察到的增加的收缩在胎儿主动脉中是相反的。
{"title":"Impact of Normal and Overweight Pregnancy in GLUT4 and Glucose-Dependent Vascular Contractility.","authors":"Esther Juarez Cortés, Gustavo López Y López, Eduardo I Perez Muñoz, Betzabel Rodriguez Reyes, Damian A Madrigal-Aguilar, Rosa A Bobadilla-Lugo","doi":"10.1159/000533344","DOIUrl":"10.1159/000533344","url":null,"abstract":"<p><strong>Introduction: </strong>Obesity during pregnancy can contribute to hypertensive complications through changes in glucose utilization. We investigated the impact of vascular glucose uptake, GLUT4 density, and endothelium on agonist-induced vasoconstriction in the aortas of overweight pregnant rats.</p><p><strong>Methods: </strong>Isolated aortic rings with or without endothelium from pregnant or nonpregnant rats fed a standard (SD) or hypercaloric diet (HD) were contracted with phenylephrine or serotonin (10-9 to 10-4<sc>M</sc>) using standard (11 m<sc>m</sc>) or without (0 m<sc>m</sc>) glucose Krebs solution. GLUT4 density in the aortas was measured using the en face method.</p><p><strong>Results: </strong>Aortas from overweight pregnant animals (PHD) showed increased Phe-induced vasoconstriction (p &lt; 0.05 vs. pregnant standard diet [PSD]), which was endothelium-independent. The contraction decreased significantly in the absence of glucose. In contrast, vessels from pregnant SD rats maintained their contraction in glucose-free Krebs solution. 5-HT increases PHD aortic contraction only in the absence of glucose. The fetal aortas from PHD mothers showed blunted vasoconstriction. Overweight significantly reduced GLUT4 expression in maternal and fetal aortas (p &lt; 0.05 vs. PSD).</p><p><strong>Conclusions: </strong>Aortic contractility is independent of glucose uptake during healthy pregnancy. In contrast, overweight pregnancy increases contractility. This increase depends directly on smooth muscle glucose uptake and inversely on GLUT-4 density. The increased contraction observed in the vasculature of overweight mothers was inverted in the fetal aortas.</p>","PeriodicalId":20209,"journal":{"name":"Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10169381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Safety of Tigecycline in Patients on Antithrombotic Therapy: A Single-Center Retrospective Study. 替加环素在抗血栓治疗患者中的安全性:一项单中心回顾性研究。
IF 3.1 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 Epub Date: 2023-09-26 DOI: 10.1159/000532001
Chuwen Lin, Miaoqin Tan, Dongmei Wang, Chunping Gu, Yongming Wu, Shengnan Wang

Introduction: The aims of the study were to investigate the risk factors of tigecycline-induced hypofibrinogenemia and to evaluate the safety of tigecycline with concomitant antithrombotic drugs.

Methods: We performed a retrospective analysis of patients who received tigecycline for more than 3 days between January 2015 and June 2019. Clinical and laboratory data were collected including fibrinogen concertation, tigecycline dose, duration of treatment, disease severity, complete blood count, indicators of infection, liver and renal function. Risk factors of hypofibrinogenemia were analyzed by univariate and multivariate analysis. To evaluate the safety of tigecycline and concomitant antithrombotic drugs, bleeding events were assessed by comparing the decline in hemoglobin and the amount of red blood cell transfusion in patients with antithrombotic drugs and those without.

Results: This study included a total of 68 cases, 20 of which experienced hypofibrinogenemia while receiving tigecycline treatment. Duration of treatment, cefoperazone/sulbactam combination therapy, and fibrinogen levels prior to initiation of tigecycline were risk factors associated with tigecycline-induced hypofibrinogenemia. There were 26 recorded bleeding incidents, 25 of which happened before the start of tigecycline. Antithrombotic and non-antithrombotic patients did not differ in their hemoglobin decline or need for red blood cell transfusions while taking tigecycline.

Conclusion: A longer treatment duration, cefoperazone/sulbactam combination therapy, and a lower level of fibrinogen before tigecycline were associated with an increased risk of tigecycline-induced hypofibrinogenemia. A combination of antithrombotic drugs and tigecycline did not aggravate the bleeding events during tigecycline treatment.

引言:本研究的目的是调查替加环素诱导的低纤维蛋白原血症的危险因素,并评估替加环肽联合抗血栓药物的安全性。方法:我们对2015年1月至2019年6月期间接受替加环素治疗超过3天的患者进行了回顾性分析。收集临床和实验室数据,包括纤维蛋白原浓度、替加环素剂量、治疗时间、疾病严重程度、全血细胞计数、感染指标、肝肾功能。采用单因素和多因素分析法分析低纤维蛋白原血症的危险因素。为了评估替加环素和联合抗血栓药物的安全性,通过比较服用抗血栓药物和未服用抗血栓药的患者血红蛋白和红细胞输注量的下降来评估出血事件。结果:本研究共纳入68例患者,其中20例在接受替加环素治疗时出现低纤维蛋白原血症。治疗持续时间、头孢哌酮/舒巴坦联合治疗和替加环素治疗前纤维蛋白原水平是与替加环肽诱导的低纤维蛋白原血症相关的危险因素。记录在案的出血事件有26起,其中25起发生在替加环素治疗开始前。抗血栓患者和非抗血栓患者在服用替加环素时血红蛋白下降或需要输注红细胞方面没有差异。结论:在替加环素治疗前,较长的治疗时间、头孢哌酮/舒巴坦联合治疗和较低的纤维蛋白原水平与替加环肽诱导的低纤维蛋白原血症的风险增加有关。在替加环素治疗期间,抗血栓药物和替加环肽的联合用药不会加重出血事件。
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引用次数: 0
The Effects of Novel Triazolopyrimidine Derivatives on H2S Production in Lung and Vascular Tonus in Aorta. 新型三唑嘧啶衍生物对肺和主动脉血管张力产生H2S的影响。
IF 3.1 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 Epub Date: 2023-09-11 DOI: 10.1159/000533419
Emine Nur Ozbek, Huseyin Istanbullu, Umran Kızrak, Elif Alan Albayrak, Gülnur Sevin, Gunay Yetik-Anacak

Introduction: Hydrogen sulfide (H2S), known as a third gasotransmitter, is a signaling molecule that plays a regulatory role in physiological and pathophysiological processes. Decreased H2S levels were reported in inflammatory respiratory diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary hypertension. H2S donors or drugs that increase H2S have emerged as novel treatments for inflammatory respiratory diseases. We previously showed that resveratrol (RVT) causes vascular relaxation and antioxidant effects by inducing H2S production. In the current study, we synthesized a new molecule Cpd2, as an RVT analog. We examined the effect of Cpd2 and its precursor chalcone compound (Cpd1) on H2S formation under both healthy and oxidative stress conditions in the lung, as well as vascular relaxation in the aorta.

Methods: Cpd2 synthesized from Cpd1 with microwaved in basic conditions. H2S formation was measured by H2S biosensor in the mice lungs under both healthy and pyrogallol-induced oxidative stress conditions in the presence/absence of H2S synthesis inhibitor aminooxyacetic acid (AOAA). The effect of compounds on vascular tonus is investigated in mice aorta by DMT myograph.

Results: RVT and Cpd2 significantly increased l-cysteine (l-cys) induced-H2S formation in the lung homogenates of healthy mice, but Cpd1 did not. Superoxide anion generator pyrogallol caused a decrease in H2S levels in mice lungs and Cpd2 restored it. Inhibition of Cpd2-induced H2S formation by AOAA confirmed that Cpd2 increases endogenous H2S formation in both healthy and oxidative stress conditions. Furthermore, we found that both Cpd1 and Cpd2 (10-8-10-4 M) caused vascular relaxation in mice aorta.

Discussion and conclusion: We found that Cpd2, a newly synthesized RVT analog, is an H2S-inducing molecule and vasorelaxant similar to RVT. Since H2S has antioxidant and anti-inflammatory effects, Cpd2 has a potential for the treatment of respiratory diseases where oxidative stress and decreased H2S levels are present.

硫化氢(H2S)是一种信号分子,在生理和病理生理过程中起调节作用,被称为第三气体传递素。据报道,炎症性呼吸系统疾病如哮喘、慢性阻塞性肺病和肺动脉高压中H2S水平降低。H2S供体或增加H2S的药物已成为治疗炎症性呼吸道疾病的新方法。我们之前的研究表明,白藜芦醇(RVT)通过诱导H2S的产生而引起血管松弛和抗氧化作用。在目前的研究中,我们合成了一个新的分子Cpd2,作为RVT的类似物。我们研究了Cpd2及其前体查尔酮化合物(Cpd1)在健康和氧化应激条件下对肺部H2S形成以及主动脉血管松弛的影响。方法:以Cpd1为原料,在基本条件下微波合成Cpd2。采用H2S生物传感器测量健康和邻苯三酚诱导的氧化应激条件下小鼠肺中H2S的形成情况,以及H2S合成抑制剂氨基乙酸(AOAA)的存在和不存在。采用DMT肌图研究了化合物对小鼠主动脉血管张力的影响。结果:RVT和Cpd2显著增加健康小鼠肺匀浆中l-半胱氨酸(l-cys)诱导的h2s的形成,而Cpd1没有。超氧阴离子产生物邻苯三酚引起小鼠肺中H2S水平下降,Cpd2使其恢复。AOAA对Cpd2诱导的H2S形成的抑制证实了Cpd2在健康和氧化应激条件下增加内源性H2S的形成。此外,我们发现Cpd1和Cpd2 (10-8-10-4 M)均引起小鼠主动脉血管松弛。讨论与结论:我们发现新合成的RVT类似物Cpd2是一种类似于RVT的h2s诱导分子和血管松弛剂。由于H2S具有抗氧化和抗炎作用,Cpd2具有治疗氧化应激和H2S水平降低的呼吸系统疾病的潜力。
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引用次数: 0
Research Progress on the Anticancer Molecular Mechanism of Targets Regulating Cell Autophagy. 调控细胞自噬的抗癌靶点分子机制研究进展。
IF 3.1 4区 医学 Q2 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-01-01 DOI: 10.1159/000529279
Ting Zhang, Jia Yu, Sha Cheng, Ya Zhang, Chang-Hua Zhou, Juan Qin, Heng Luo

Background: Autophagy is a lysosome-mediated catabolic process that maintains cell homeostasis and survival. It occurs not only in normal cells such as cardiac muscle cells, neurons, and pancreatic acinar cells but also in various benign and malignant tumors. The abnormal level of intracellular autophagy is closely related to multiple pathophysiological processes, including aging, neurodegeneration, infectious diseases, immune disorders, and cancer. Autophagy mainly plays a dual role in life and death by regulating cell survival, proliferation, and death, thus being involved in the occurrence, development, and treatment of cancer. It is also involved in chemotherapy resistance by a dual role, since it not only promotes the occurrence of drug resistance but also reverses it. Previous findings suggest that the regulation of autophagy can be used as an effective strategy in tumor therapy.

Summary: Recent studies found that small molecules from natural products and their derivatives exert anticancer activity by regulating the level of autophagy in tumor cells.

Key messages: Therefore, this review article describes the mechanism of autophagy, the role of autophagy in normal cells and tumor cells, and the research progress on the anticancer molecular mechanism of targets regulating cell autophagy. The aim is to provide a theoretical basis for developing autophagy inhibitors or activators to improve anticancer efficacy.

背景:自噬是一种溶酶体介导的分解代谢过程,维持细胞稳态和存活。它不仅存在于心肌细胞、神经元、胰腺腺泡细胞等正常细胞中,也存在于各种良恶性肿瘤中。细胞内自噬水平异常与多种病理生理过程密切相关,包括衰老、神经退行性疾病、传染病、免疫紊乱、癌症等。自噬主要通过调节细胞的存活、增殖和死亡,在生命和死亡中起着双重作用,参与了癌症的发生、发展和治疗。它还以双重作用参与化疗耐药,既能促进耐药的发生,又能逆转耐药。以往的研究结果表明,调节自噬可以作为一种有效的肿瘤治疗策略。摘要:近年来的研究发现,天然产物及其衍生物中的小分子通过调节肿瘤细胞的自噬水平来发挥抗癌作用。因此,本文综述了自噬的发生机制,自噬在正常细胞和肿瘤细胞中的作用,以及调控细胞自噬的靶点抗癌分子机制的研究进展。目的是为开发自噬抑制剂或激活剂以提高抗癌效果提供理论依据。
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引用次数: 3
期刊
Pharmacology
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