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Impact of COVID-19 on clinical trials protocol amendments 新冠肺炎对临床试验方案修订的影响
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-04-27 DOI: 10.18413/rrpharmacology.9.10021
A. Eleskina, O. Filippova, Nathalia V. Pyatigorskaya
Introduction: The COVID-19 pandemic situation had a great impact on all spheres of people’s lives. It also affected clinical trials as Sponsors, sites and investigators faced a number of problems, such as systematic IMP taking, adherence to protocol visits, efficacy evaluations, laboratory procedures, and analyses.Materials and Methods: The amendments issued in 2020 were compared with the amendments issued in the previous three years 2017-2019. The literature about COVID-19 and its impact on clinical trials were analyzed. Clinical trial protocol amendments published in 2020 were studied to evaluate pandemic influence on ongoing clinical studies. Statistical processing of the results was carried out using the correlation analysis.Results:  The highest quantity of amendments was released in 2020 –14 (36%). Fewer amendments came out in 2019 – 13 (33%), in 2018 – 9 (23%), and the fewest amendments were issued in 2017 – 3 (8%). Conclusion: The existing system of clinical trial protocol creation is dependable and adequate. It allows reacting flexibly to unexpected challenges, like COVID-19, fully complying with the prescribed procedures and carefully observing participants’ safety and well-being. That is why the current pandemic did not affect the number of protocol amendments.Graphical Abstract
简介:新冠肺炎疫情对人们生活的各个领域都产生了巨大影响。它还影响了临床试验,因为申办方、研究地点和研究人员面临着许多问题,如系统性IMP服用、方案访问的依从性、疗效评估、实验室程序和分析。材料和方法:将2020年发布的修正案与2017-2019年前三年发布的修订案进行了比较。分析了有关新冠肺炎的文献及其对临床试验的影响。研究了2020年发布的临床试验方案修正案,以评估疫情对正在进行的临床研究的影响。使用相关分析对结果进行统计处理。结果:2020-2014年发布的修正案数量最高(36%)。2019-13年(33%)、2018-9年(23%)发布的修正案较少,2017-3年(8%)发布的修订案最少。结论:现有的临床试验方案创建系统是可靠和充分的。它允许灵活应对意外挑战,如新冠肺炎,完全遵守规定的程序,并仔细观察参与者的安全和健康状况。这就是为什么当前的疫情没有影响议定书修正案的数量。图形摘要
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引用次数: 0
Pathomorphological analysis of the gum tissues in the application of the combination of Soderm®-Forte gel with Cytoflavin® in experimental periodontitis in rats Soderm®-Forte凝胶与Cytoflavin®联合应用于实验性牙周炎大鼠牙龈组织的病理形态学分析
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-04-19 DOI: 10.18413/rrpharmacology.9.10017
P. Galenko-Yaroshevsky, A. Slavinskiy, Mark A. Zadorozhniy, V. K. Leontev, Artur V. Kheigetyan, V. Popkov, A. Zelenskaya, Lyudmila M. Chuprinenko, A. A. Verevkin, Izabella G. Lomsadze, Mariya Yu. Materenchuk, S. Lebedeva
Introduction: Periodontitis is one of the most urgent problems of modern dentistry. The development of new paradigms and regimens of combination therapy of patients with periodontitis is a strategic task for pharmacologists and dentists. In view of this, pathomorphological examination is of high importance, since it allow us to conclude about the therapeutic effectiveness of the administered drugs with high objectivity.Aim of the study: to evaluate the effect of the composition of Soderm®-Forte and Cytoflavin® on the pathomorphological pattern of gum tissues of rats with experimental periodontitis (EP).Materials and Methods: EP was simulated in rats by ligature method. Study design: animals with intact periodontium; animals with untreated EP; animals with EP treated with traditional drug therapy (TDT); animals with EP treated with the combination of TDT and Soderm®-Forte gel; and animals with EP treated with the combination of TDT, Soderm®-Forte and Cytoflavin®. For pathomorphological examination, biopsy specimen was taken from the gingival margin of the lower incisors. Slides were stained with hematoxylin and eosin, as well as by Masson. Computer morphometry was performed using the ImageJ software.Results: In EP, TDT has a moderate positive effect on pathomorphological changes in the gum. The combination of TDT and Soderm®-Forte and, to a greater degree, the combination of TDT, Soderm®-Forte and Cytoflavin® have high therapeutic efficacy, characterized by rapid regeneration of the gum tissues. Conclusion: The combination of TDT, Soderm®-Forte and Cytoflavin® in EP has a more pronounced therapeutic effect, manifested by early regression of pathological changes and acceleration of tissue regeneration in the gum.Graphical Abstract
前言:牙周炎是现代牙科最紧迫的问题之一。开发新的牙周炎患者联合治疗模式和方案是药理学家和牙医的一项战略任务。鉴于此,病理形态学检查具有高度重要性,因为它使我们能够以高度客观性得出所给药物的治疗效果的结论。研究目的:评价Soderm®-Fote和Cytoflain®的组成对实验性牙周炎(EP)大鼠牙龈组织病理形态学模式的影响。材料和方法:采用结扎法模拟EP。研究设计:具有完整牙周组织的动物;患有未经治疗的EP的动物;用传统药物治疗(TDT)治疗EP的动物;用TDT和Soderm®-Fote凝胶组合治疗EP的动物;以及用TDT、Soderm®-Fote和细胞黄素®联合治疗的EP动物。为了进行病理形态学检查,活检标本取自下切牙的牙龈边缘。载玻片用苏木精和伊红以及Masson染色。使用ImageJ软件进行计算机形态测量。结果:在EP中,TDT对牙龈的病理形态学变化具有中等的积极作用。TDT和Soderm®-Fote的组合,以及在更大程度上,TDT、Soderm™-Fote和细胞黄素®的组合具有很高的治疗效果,其特征是牙龈组织的快速再生。结论:TDT、Soderm®-Fote和细胞黄素®联合治疗EP具有更显著的治疗效果,表现为早期病变消退和加速牙龈组织再生。图形摘要
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引用次数: 1
Analysis of the frequency of detection of hypercholesterolemia, carotid atherosclerosis and lipid-lowering therapy prescription in young adults under 45 years old according to the Duplex registry database 根据Duplex注册数据库分析45岁以下年轻人高胆固醇血症、颈动脉粥样硬化的检测频率和降脂治疗处方
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-03-31 DOI: 10.18413/rrpharmacology.9.10007
O. Gaisenok
Aim of the study to analyze the detection of hypercholesterolemia (HCHL) and carotid atherosclerosis (CAS), verified by duplex scanning of the carotid arteries (DSCA) in young adults (YA), and to evaluate the lipid-lowering therapy (LLT) prescription among them according to the local registry database. Material and Methods: The Duplex registry database was used for this study (n=2548). YA up to 45 years old were selected for the final analysis (n=351). Results: HCHL (> 5 mmol/L) was detected in 68.9% of patients (n=241), and only 9.5% of them received LLT (n=23). CAS was detected in 12.8% (n=45), only 17.8% of them had received LLT (n=8). Men and women differed 1.5 times by the incidence of CAS in this age range: 15.7% (30 out of 191) vs 9.4% (15 out of 160), p=0.05. Men also generally have a higher prevalence of other risk factors/diseases: HCHL (78.0% (n=149) vs 58.1% (n=93) in women, p=0.00004), hypertension (AH) (15.7% (n=30) vs 9.4% (n=15) in women, p=0,05), history of myocardial infarction (MI) (1,6% (n=3) vs 0% (n=0) in women, ns). Signs that had a significant impact on LLT intake were the following: CAS (OR 2.8 [1.09;6.6] p=0.036); AH (OR 3.1 [1.32; 7.16] p=0.009); HCHL (> 5 mmol/L) (OR 4.2 [1.12; 26.83] p=0.06); HCHL (ICD-10 code E78) (OR 5.4 [2.04; 13.7] p=0.0003); MI history (OR 22.3 [1.65;675.5] p=0.009). Conclusion: The insufficient LLT prescription in young adults with HCHL and CAS was ascertained in the present study. The use of imaging methods to clarify the degree of cardiovascular risk is advisable for low and intermediate risk patients, which include young adults. DSСA is the main method for subclinical atherosclerosis verification. LLT should be prescribed to all YA patients with CAS (in the absence of contraindications). Graphical Abstract
本研究旨在分析年轻人(YA)颈动脉双重扫描(DSCA)检测的高胆固醇血症(HCHL)和颈动脉粥样硬化(CAS)的检测结果,并根据当地注册数据库评估他们的降脂疗法(LLT)处方。材料和方法:Duplex注册数据库用于本研究(n=2548)。选择45岁以下的YA进行最终分析(n=351)。结果:68.9%的患者(n=241)检测到六氯环己烷(>5mmol/L),其中只有9.5%的患者接受了LLT(n=23)。CAS检出率为12.8%(n=45),其中接受LLT者仅17.8%(n=8)。在这一年龄段,男性和女性CAS的发病率相差1.5倍:15.7%(191人中有30人)和9.4%(160人中有15人),p=0.05。男性通常也有更高的其他危险因素/疾病的患病率:六氯环己烷(女性为78.0%(n=149)vs 58.1%(n=93),p=0.0004)、高血压(AH)(女性为15.7%(n=30)vs 9.4%(n=15),p=0.005)、心肌梗死史(女性为1.6%(n=3)vs 0%(n=0),ns)。对LLT摄入有显著影响的迹象如下:CAS(OR 2.8[1.09;6.6]p=0.036);AH(OR 3.1[1.32;7.16]p=0.009);六氯环己烷(>5 mmol/L)(OR 4.2[1.12;26.83]p=0.06);六氯环己烷(ICD-10代码E78)(OR 5.4[2.04;13.7]p=0.0003);MI病史(OR 22.3[1.65;675.5]p=0.009)。对于包括年轻人在内的中低风险患者,宜使用成像方法来明确心血管风险的程度。DSСA是亚临床动脉粥样硬化验证的主要方法。所有患有CAS的YA患者应开具LLT处方(在没有禁忌症的情况下)。图形摘要
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引用次数: 0
Thrombopoietin receptor agonists in pharmacotherapy of pediatric immune thrombocytopenia 血小板生成素受体激动剂在儿童免疫性血小板减少症药物治疗中的作用
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-03-31 DOI: 10.18413/rrpharmacology.9.10011
O. S. Levchenkova, V. V. Vorobieva, V. Novikov, T. I. Legonkova, Elena N. Volkova
Introduction: Thrombopoietin receptor agonists are commonly second-line drugs in immune thrombocytopenia (ITP) pharmacotherapy in children and prescribed for chronic ITP refractory to first-line therapy. Standard ITP pharmacotherapy in children: includes prescribing glucocorticoids or intravenous immunoglobulins. Thrombopoietin receptor agonists: Currently Romiplostim and Eltrombopag are used in the Russian Federation pediatrics. Their pharmacodynamic features in comparison with other drugs used in ITP are presented in the paper. Increased thrombocytopoiesis is the dominant, but not the only component of Romiplostim and Eltrombopag mechanism of action. It is relevant to study their effect on immune tolerance in ITP, which may be associated with a persistent platelet response in some patients after drug discontinuation. Conclusion: The issue of thrombopoietin receptor agonist efficacy and safety as well as the mode of their use in ITP children treatment continues to be studied. The high cost of drugs continues to be a limiting factor to their earlier prescription. Generic drugs – Romiplostim and Eltrombopag partly solve the problem, promote their earlier prescription in ITP, but require additional study of their bioequivalence and therapeutic equivalence in comparison with the original drugs. Graphical Abstract    
简介:血小板生成素受体激动剂是儿童免疫性血小板减少症(ITP)药物治疗中常用的二线药物,用于一线治疗难治的慢性ITP。儿童ITP的标准药物治疗:包括开糖皮质激素或静脉注射免疫球蛋白。血小板生成素受体激动剂:目前俄罗斯联邦儿科使用Romiplostim和Eltrombopag。本文介绍了它们与ITP中使用的其他药物的药效学特征。血小板生成增加是Romiplostim和Eltrombopag作用机制的主要组成部分,但不是唯一的组成部分。研究它们对ITP免疫耐受的影响是相关的,这可能与一些患者停药后持续的血小板反应有关。结论:血小板生成素受体激动剂的有效性、安全性及其在ITP儿童治疗中的使用模式仍有待研究。高昂的药物成本仍然是他们早期处方的一个限制因素。仿制药——Romiplostim和Eltrombopag在一定程度上解决了这个问题,促进了他们在ITP中的早期处方,但与原始药物相比,需要对他们的生物等效性和治疗等效性进行额外的研究。图形摘要
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引用次数: 1
Correlation analysis between inflammatory biomarkers and significant clinical phenotypes of chronic obstructive pulmonary disease 慢性阻塞性肺疾病炎症生物标志物与重要临床表型的相关性分析
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-03-31 DOI: 10.18413/rrpharmacology.9.10004
E. Orlova, B. Kuzmichev, M. A. Orlov, I. Dorfman
Introduction: Chronic obstructive pulmonary disease (COPD) is the leading cause of mortality. Using the evidence obtained about various clinical phenotypes of patients with the same disease allowed us to expand our understanding of the treatment of COPD. Nowadays the only option for solving the problem will be the definition of the clinical phenotype of COPD, and the receipt of expanded data on its correlation with respiratory and other significant biomarkers.Materials and methods: We analyzed the correlations between FKN, CRP and TBA-active lipid peroxidation products in 373 patients with various COPD phenotypes and 60 healthy volunteers. Enzyme immunoassay was used to study the levels of inflammatory biomarkers.Results: We have identified a statistically significant increase in the levels of inflammatory biomarkers in patients with COPD compared with the control. The FKN level in the group of patients with COPD was 1.3 ng/ml, which was higher (p<0.001) than in the control (FKN level of 0.3 ng/ml, p<0.001). The CRP level in patients with COPD was 27.8 mg/L, whereas in control the CRP level was 1.2 mg/L (p<0.001). The TBA-active lipid peroxidation products level in patients with COPD was 14.5 mmol/L, which was higher when compared to the control (p<0.001).Discussion: The correlation analysis revealed very strong relationships between the levels of all the biomarkers studied. The highest values of the Kendall rank correlation coefficient (τ) were determined between the levels of all the inflammatory biomarkers in subgroups of patients with chronic bronchitis and mixed COPD phenotypes.Conclusion: Detection of the COPD phenotype will help actively monitor the therapy of COPD exacerbations.Graphical Abstract
慢性阻塞性肺疾病(COPD)是导致死亡的主要原因。利用获得的关于同一疾病患者不同临床表型的证据,使我们扩大了对COPD治疗的理解。目前,解决这一问题的唯一选择将是对COPD临床表型的定义,以及对其与呼吸和其他重要生物标志物相关性的扩展数据的接收。材料和方法:我们分析了373名不同COPD表型患者和60名健康志愿者的FKN、CRP和tba活性脂质过氧化产物的相关性。采用酶免疫分析法研究炎症生物标志物水平。结果:我们发现,与对照组相比,COPD患者的炎症生物标志物水平有统计学意义上的显著增加。COPD患者FKN水平为1.3 ng/ml,高于对照组(0.3 ng/ml, p<0.001)。COPD患者CRP水平为27.8 mg/L,而对照组CRP水平为1.2 mg/L (p<0.001)。COPD患者tba活性脂质过氧化产物水平为14.5 mmol/L,高于对照组(p<0.001)。讨论:相关分析显示,所研究的所有生物标志物水平之间存在很强的相关性。在慢性支气管炎和混合型COPD患者亚组中,所有炎症生物标志物的水平之间确定了肯德尔等级相关系数(τ)的最高值。结论:COPD表型的检测有助于积极监测COPD急性加重的治疗。图形抽象
{"title":"Correlation analysis between inflammatory biomarkers and significant clinical phenotypes of chronic obstructive pulmonary disease","authors":"E. Orlova, B. Kuzmichev, M. A. Orlov, I. Dorfman","doi":"10.18413/rrpharmacology.9.10004","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10004","url":null,"abstract":"Introduction: Chronic obstructive pulmonary disease (COPD) is the leading cause of mortality. Using the evidence obtained about various clinical phenotypes of patients with the same disease allowed us to expand our understanding of the treatment of COPD. Nowadays the only option for solving the problem will be the definition of the clinical phenotype of COPD, and the receipt of expanded data on its correlation with respiratory and other significant biomarkers.\u0000Materials and methods: We analyzed the correlations between FKN, CRP and TBA-active lipid peroxidation products in 373 patients with various COPD phenotypes and 60 healthy volunteers. Enzyme immunoassay was used to study the levels of inflammatory biomarkers.\u0000Results: We have identified a statistically significant increase in the levels of inflammatory biomarkers in patients with COPD compared with the control. The FKN level in the group of patients with COPD was 1.3 ng/ml, which was higher (p<0.001) than in the control (FKN level of 0.3 ng/ml, p<0.001). The CRP level in patients with COPD was 27.8 mg/L, whereas in control the CRP level was 1.2 mg/L (p<0.001). The TBA-active lipid peroxidation products level in patients with COPD was 14.5 mmol/L, which was higher when compared to the control (p<0.001).\u0000Discussion: The correlation analysis revealed very strong relationships between the levels of all the biomarkers studied. The highest values of the Kendall rank correlation coefficient (τ) were determined between the levels of all the inflammatory biomarkers in subgroups of patients with chronic bronchitis and mixed COPD phenotypes.\u0000Conclusion: Detection of the COPD phenotype will help actively monitor the therapy of COPD exacerbations.\u0000Graphical Abstract\u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45718829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Investigation of antiparkinsonian activity of new imidazole-4,5-dicarboxylic acid derivatives on the experimental model of catalepsy 新型咪唑-4,5-二羧酸衍生物在催化实验模型上抗帕金森病活性的研究
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-03-31 DOI: 10.18413/rrpharmacology.9.10006
Vladimir D. Dergachev, E. E. Yakovleva, M. A. Brusina, E. Bychkov, L. B. Piotrovskiy, P. Shabanov
Introduction: To study the antiparkinsonian activity of new ligands of the glutamate NMDA receptor complex – 1,2–substituted imidazole-4,5-dicarboxylic acids – on an experimental model of catalepsy caused by haloperidolintraabdominal injections in rats.Materials and methods: The experiments were performed on Wistar rats weighing 300-350 g, obtained from the Rappolovo nursery of the Russian Academy of Medical Sciences (Leningrad Region). The animals were kept in standard plastic cages in vivarium conditions with free access to water and food at a temperature of 22±2 °C and in the experiment were divided into several groups (6 animals each). All the experiments were carried out in the autumn-winter period. The animals were kept in accordance with the rules of laboratory practice (GLP), regulatory documents ”Sanitary Rules for the Device, Equipment and Maintenance of Vivarium” and the Order of the Ministry of Health and Social Development of the Russian Federation dated 23.08.2010 No. 708n “On Approval of the Rules of Laboratory Practice”. Imidazole-dicarboxylic acid derivatives (IEM-2295, IEM-2296) were injected intraperitoneally at doses from 5 mg/kg to 40 mg/kg simultaneously with haloperidol at a dose of 1 mg/kg, after which the duration and severity of catalepsy were evaluated after 30, 60, 120 minutes from 0 to 6 points according to the Morpurgo method.Results: The severity of catalepsy with the injection of IEM-2295 decreased on average to 3 points, while in the control group it remained at the level of 6 points throughout the observation. However, the severity of catalepsy with the introduction of IEM-2296 decreased to an average of 4 points, but the effect itself lasted longer than with the introduction of IEM-2295. Thus, it was noted that by the 120th minute of observation, the severity of catalepsy in rats receiving the IEM-2295 compound averaged 5 points, whereas in animals receiving IEM-2296 – 3 points.Discussion: Basing on the results of our work and similar experiments, we can conclude that the studied compounds, which are not channel blockers, have an active effect on dopaminergic neurotransmission, because of which the symptoms of catalepsy that occur when haloperidol is injected to rats were stopped to one degree or another.Conclusion: The studied substances exhibit antiparkinsonian activity on an experimental haloperidol model of catalepsy in rats and are promising for development as potential therapies for neurodegenerative diseases. Further study of these compounds and other ligands from the NMDA-blocker group in a wider sample on the catalepsy model, as well as on other models of Parkinsonism, is required.Graphical Abstract
前言:研究谷氨酸NMDA受体复合物的新配体- 1,2 -取代咪唑-4,5-二羧酸对氟哌啶酮腹腔注射致大鼠猝倒的抗帕金森活性。材料和方法:实验用Wistar大鼠,体重300-350 g,来自俄罗斯医学科学院(列宁格勒地区)Rappolovo托儿所。实验动物饲养在标准塑料笼内,在22±2℃的条件下自由饮水和进食。实验动物分为几组,每组6只。所有实验均在秋冬季节进行。这些动物是按照实验室操作规则(GLP)、规范性文件“试管设备、设备和维护卫生规则”以及俄罗斯联邦卫生和社会发展部2010年8月23日第708n号“关于批准实验室操作规则”的命令饲养的。将咪唑-二羧酸衍生物(IEM-2295、IEM-2296)以5 ~ 40 mg/kg的剂量与氟哌啶醇1 mg/kg的剂量同时腹腔注射,分别于0 ~ 6点30、60、120分钟后,根据Morpurgo法评价其持续时间和严重程度。结果:注射IEM-2295后,患者的麻痹程度平均降低至3分,而对照组在整个观察过程中保持在6分水平。然而,引入IEM-2296后,麻痹的严重程度下降到平均4分,但效果本身持续的时间比引入IEM-2295时更长。因此,我们注意到,在观察第120分钟时,接受IEM-2295化合物的大鼠的麻痹严重程度平均为5分,而接受IEM-2296 - 3分的动物。讨论:根据我们的工作和类似的实验结果,我们可以得出结论,所研究的化合物,不是通道阻滞剂,对多巴胺能神经传递有积极的影响,因为氟哌啶醇注射给大鼠时发生的猝厥症状在某种程度上停止了。结论:所研究的物质在氟哌啶醇猝倒大鼠实验模型中表现出抗帕金森活性,有望成为神经退行性疾病的潜在治疗药物。这些化合物和来自nmda阻断剂组的其他配体在更广泛的样本中对猝睡模型以及其他帕金森模型进行进一步的研究是必要的。图形抽象
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引用次数: 1
Molecular mechanisms of wound healing: the role of zinc as an essential microelement 伤口愈合的分子机制:锌作为一种必需微量元素的作用
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-03-31 DOI: 10.18413/rrpharmacology.9.10003
S. Lebedeva, P. A. Galenko-Yaroshevsky (Jr.), M. Samsonov, Arkadiy B. Erlich, A. Zelenskaya, Arus G. Margaryan, M. Materenchuk, I. R. Arshinov, Yuriy V. Zharov, O. V. Shelemekh, Isabella Yu. Lomsadze, T. Demura
Introduction: In the course of evolution, humans developed a number of complex multi-step wound healing mechanisms which limit the infectious agents access to the bloodstream, protect the organism from blood loss, and restore skin integrity. The process of skin wound healing includes the following stages: haemostasis, inflammation, proliferation, and remodeling. These processes are possible because of modulators, growth factors, cytokines, matrix metalloproteinases and cellular receptors, as well as some trace elements like zinc.Materials and Methods: The presented data was analyzed and compiled using all relevant articles describing the role of zinc in blood coagulation, proliferation, damaged tissues regeneration and angiogenesis.Results and Discussion: There are some on-going studies about zinc effects on blood coagulation, proliferation, damaged tissues regeneration and angiogenesis. However, molecular mechanisms of these processes are not yet fully understood and require further study.  The analysis of scientific efforts to investigate the role of zinc in wound healing molecular mechanisms is especially relevant to the understanding of treatment of skin wound injuries.Conclusion: Wound healing is a complex multi-phase process consisting of several phases. Each stage involves metal ions, primarily zinc, which stimulates re-epithelialization, decreases inflammation and bacterial growth. The use of known zinc-based drugs is accompanied by side effects and low efficacy due to low skin absorption. These factors significantly limit use of such drugs and highlight the urgency of finding new, more effective and safe treatment. The emerging field of nanobiotechnology may provide an alternative platform to develop new therapeutic agents for the wound healing process.Graphical Abstract
导论:在进化过程中,人类发展了许多复杂的多步骤伤口愈合机制,这些机制限制了传染性病原体进入血液,保护生物体免受失血,并恢复皮肤完整性。皮肤伤口愈合的过程包括以下几个阶段:止血、炎症、增殖和重塑。这些过程是可能的,因为调节剂,生长因子,细胞因子,基质金属蛋白酶和细胞受体,以及一些微量元素,如锌。材料和方法:利用所有描述锌在血液凝固、增殖、受损组织再生和血管生成中的作用的相关文章对所提供的数据进行分析和汇编。结果与讨论:锌对血液凝固、增殖、损伤组织再生和血管生成的影响正在进行研究。然而,这些过程的分子机制尚不完全清楚,需要进一步研究。分析研究锌在创面愈合分子机制中的作用的科学努力对理解皮肤创面损伤的治疗尤其重要。结论:伤口愈合是一个复杂的多阶段过程。每个阶段都涉及金属离子,主要是锌离子,它刺激上皮再生,减少炎症和细菌生长。使用已知的锌基药物,由于皮肤吸收低,伴随着副作用和低疗效。这些因素极大地限制了这类药物的使用,并突出了寻找新的、更有效和安全的治疗方法的紧迫性。纳米生物技术的新兴领域可能为开发用于伤口愈合过程的新治疗剂提供另一种平台。图形抽象
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引用次数: 2
Pharmacotherapy of small cell lung cancer: Current state-of-the-art 小细胞肺癌的药物治疗:最新进展
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-03-31 DOI: 10.18413/rrpharmacology.9.10001
T. Berezhnova, Yelena A. Lunyova, Kseniya S. Dyadina, V. Borisov
Introduction: Lung carcinoma is the leading cause of death in men and is closely related to smoking. The article focuses on the current statistics of this pathology in the world. Materials and methods: The literature review was carried out using PubMed database and included articles published from 2006 to 2021. The current schemes of chemotherapy and diagnostic options of small cell lung cancer were analyzed. The mechanisms of drug action on tumor cells were considered. An analysis of the publication activity in PubMed database related to pharmacotherapy of small cell lung cancer allows reporting a twofold increase in the number of publications over the period from 2007 to 2017. Results and discussion: A systematic review presenting staging of small cell lung cancer (SCLC) and its radiation diagnostics has been conducted. As demonstrated, there are no current methods with proven effectiveness to early detect this pathology. However, it has been found that annual low-dose CT screenings helped detect a significant number of lung cancer cases at the early stage, although, the proportion of small cell carcinoma is still very high. Analyses of clinical outcomes of small cell lung cancer have showed that cisplatin/etoposide (EP) or carboplatin/etoposide (EC) appear to be the key combinations with high treatment efficacy. The article also discusses chemotherapy for small cell lung cancer, namely and the principle of its effect on tumor cells. However, this chemotherapy remains very toxic and causes a number of life-threatening side effects. It is necessary to assess the effectiveness of chemotherapy immediately after the start of treatment in order to balance benefits and risks. Conclusion: The search is currently under way for less toxic but effective compounds, this fact being a crucial issue of healthcare in providing high-quality medical and pharmaceutical care for cancer patients. Chemotherapy of the pathology under study requires high costs; therefore, a pharmacoeconomical assessment of the prescription of chemotherapy for small cell lung cancer is necessary to compare the costs of treatment and its effectiveness Graphical Abstract
引言:肺癌是男性死亡的主要原因,与吸烟密切相关。这篇文章的重点是目前世界上对这种病理学的统计。材料和方法:使用PubMed数据库进行文献综述,包括2006年至2021年发表的文章。分析了癌症小细胞肺癌的化疗方案和诊断方案。探讨了药物对肿瘤细胞的作用机制。对PubMed数据库中与小细胞肺癌癌症药物治疗相关的出版活动进行分析,可以报告2007年至2017年期间出版数量增加了两倍。结果与讨论:对癌症小细胞肺癌(SCLC)的分期及其放射诊断进行了系统综述。正如所证明的,目前还没有被证明有效的方法来早期检测这种病理。然而,人们发现,每年低剂量CT筛查有助于在早期发现大量癌症病例,尽管小细胞癌的比例仍然很高。小细胞肺癌癌症的临床结果分析表明,顺铂/依托泊苷(EP)或卡铂/依托泊苷(EC)似乎是具有高治疗效果的关键组合。本文还讨论了小细胞肺癌癌症的化学治疗,即对肿瘤细胞的作用原理。然而,这种化疗仍然毒性很大,并会导致一些危及生命的副作用。有必要在治疗开始后立即评估化疗的有效性,以平衡益处和风险。结论:目前正在寻找毒性较低但有效的化合物,这是为癌症患者提供高质量医疗和药物护理的医疗保健关键问题。所研究的病理学的化疗需要高成本;因此,有必要对癌症小细胞化疗的处方进行药物经济学评估,以比较其治疗成本和疗效
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引用次数: 0
The endogenic neurosteroid system and its role in the pathogenesis and therapy of mental disorders 内源性神经鞘瘤系统及其在精神障碍发病机制和治疗中的作用
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-03-31 DOI: 10.18413/rrpharmacology.9.10015
S. P. Bairamova, D. Petelin, R. Akhapkin, N. Kudryashov, O. Sorokina, S. A. Semin, Veronika Panfilova, B. A. Volel
Introduction: Although neurosteroids have been relatively recently discovered, their significant role in the neurochemical processes and pathogenesis of a number of psychiatric and neurological disorders is now quite clear. First of all, it seems important to clarify the definition of the endogenous neurosteroids as a class of steroids, taking into account the variability of approaches to their description. Currently, neurosteroids include endogenous steroids synthesized in the central nervous system, gonads, or adrenal glands and interacting with GABAA, NMDA, and sigma-1 receptors. Neurosteroid biosynthesis: Biosynthesis of neurosteroids begins with rate-limiting reaction of TSPO binding cholesterol and transporting it into the mitochondria, where pregnenolone is synthesized following the cytochrome P450scc (CYP11A1) impact. Interaction with GABAА, NMDA and sigma-1 receptors: According to the experimental data, neurosteroids act as the most highly potent endogenous allosteric modulators of the GABA receptor; some types of neurosteroids (ALLO, DHEA, etc.) can produce a rapid anxiolytic and anticonvulsant effect. There is some experimental evidence for antipsychotic effects of some neurosteroids realized through NMDA receptors: intracerebral administration of ALLO to laboratory animals can prevent further appearance of motor agitation and other equivalents of psychosis after administration of high doses of amphetamines. It has also been proven in several studies on animal models that neurosteroids exhibit anxiolytic effects through sigma-1 receptors. Conclusion: The article describes the process of neurosteroidogenesis and the effect of neurosteroids on listed receptorsin accordance with already available scientific data. In addition, this paper describes the specific role of various neurosteroids in the development of mental illnesses, including anxiety disorders, depression, and schizophrenia Graphical Abstract
引言:尽管神经甾体是最近才发现的,但它们在许多精神和神经疾病的神经化学过程和发病机制中的重要作用现在已经很清楚了。首先,考虑到描述方法的可变性,澄清内源性神经类固醇作为一类类固醇的定义似乎很重要。目前,神经类固醇包括在中枢神经系统、性腺或肾上腺合成的内源性类固醇,并与GABAA、NMDA和sigma-1受体相互作用。神经类固醇生物合成:神经类固醇的生物合成始于TSPO结合胆固醇的限速反应,并将其运输到线粒体中,在线粒体中,孕烯醇酮是在细胞色素P450scc(CYP11A1)影响下合成的。与GABAА、NMDA和sigma-1受体的相互作用:根据实验数据,神经类固醇是GABA受体最高效的内源性变构调节剂;某些类型的神经类固醇(ALLO、DHEA等)可以产生快速的抗焦虑和抗惊厥作用。有一些实验证据表明,一些神经类固醇通过NMDA受体实现了抗精神病作用:对实验动物脑内给予ALLO可以防止在给予高剂量的安非他命后进一步出现运动激动和其他类似的精神病。在几项关于动物模型的研究中也证明,神经类固醇通过sigma-1受体表现出抗焦虑作用。结论:根据已有的科学数据,本文描述了神经甾体发生的过程以及神经甾体对所列受体的影响。此外,本文还描述了各种神经类固醇在精神疾病发展中的具体作用,包括焦虑症、抑郁症和精神分裂症
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引用次数: 2
Endothelial dysfunction: developmental mechanisms and therapeutic strategies Endothelial功能障碍:发育机制和治疗策略
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2022-12-22 DOI: 10.3897/rrpharmacology.8.80376
Dmitry V. Shcheblykin, Anton A. Bolgov, M. Pokrovskii, Julia V. Stepenko, Julia M. Tsuverkalova, Olesya V. Shcheblykina, P. A. Golubinskaya, L. Korokina
Introduction: Every year the importance of the normal functioning of the endothelial layer of the vascular wall in maintaining the health of the body becomes more and more obvious. The physiological role of the endothelium: The endothelium is a metabolically active organ actively involved in the regulation of hemostasis, modulation of inflammation, maintenance of hemovascular homeostasis, regulation of angiogenesis, vascular tone, and permeability. Risk factors for the development of endothelial dysfunction: Currently, insufficient bioavailability of nitric oxide is considered the most significant risk factor for endothelial dysfunction. Mechanisms of development of endothelial dysfunction: The genesis of endothelial dysfunction is a multifactorial process. Among various complex mechanisms, this review examines oxidative stress, inflammation, hyperglycemia, vitamin D deficiency, dyslipidemia, excess visceral fat, hyperhomocysteinemia, hyperuricemia, as well as primary genetic defect of endotheliocytes, as the most common causes in the population underlying the development of endothelial dysfunction. Markers of endothelial dysfunction in various diseases: This article discusses the main biomarkers of endothelial dysfunction currently used, as well as promising biomarkers in the future for laboratory diagnosis of this pathology. Therapeutic strategies: Therapeutic approaches to the endothelium in order to prevent or reduce a degree of damage to the vascular wall are briefly described. Conclusion: Endothelial dysfunction is a typical pathological process involved in the pathogenesis of many diseases. Thus, pharmacological agents with endothelioprotective properties can provide more therapeutic benefits than a drug without such an effect.
引言:血管壁内皮层的正常功能在维持身体健康方面的重要性每年都变得越来越明显。内皮的生理作用:内皮是一种代谢活跃的器官,积极参与止血、炎症调节、血管稳态维持、血管生成、血管张力和通透性的调节。内皮功能障碍的危险因素:目前,一氧化氮的生物利用度不足被认为是内皮功能障碍的最重要危险因素。内皮功能障碍的发展机制:内皮功能障碍的发生是一个多因素的过程。在各种复杂的机制中,这篇综述探讨了氧化应激、炎症、高血糖、维生素D缺乏、血脂异常、内脏脂肪过多、高同型半胱氨酸血症、高尿酸血症以及内皮细胞的原发性遗传缺陷,这些是内皮功能障碍发展的最常见原因。各种疾病中内皮功能障碍的标志物:本文讨论了目前使用的内皮功能障碍的主要标志物,以及未来用于该病理学实验室诊断的有前景的标志物。治疗策略:为了预防或减少一定程度的血管壁损伤,对内皮细胞的治疗方法进行了简要描述。结论:内皮功能障碍是一个典型的病理过程,参与了多种疾病的发病机制。因此,与没有内皮保护作用的药物相比,具有内皮保护特性的药物可以提供更多的治疗益处。
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引用次数: 1
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Research Results in Pharmacology
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