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Исследование влияния полипренолов пихты сибирской на обучаемость и память мышей с экспериментальной моделью болезни Альцгеймера 研究西伯利亚冷杉多酚对阿尔茨海默病实验模型小鼠学习和记忆的影响
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-08-08 DOI: 10.18413/rrpharmacology.10.489
Николай Иннокентьевич Суслов, Юлия С. Федорова, Максим Л. Коробов
Введение. Болезнь Альцгеймера все чаще становится причиной ранней инвалидизацией и смерти. Попытки создания фармакотерапевтического средства, дающего эффективный результат в лечении этой патологии, до сегодняшнего дня не увенчались успехом. В данной статье приведены результаты экспериментальных исследований, ставящие целью создание более эффективного средства лечения данного заболевания.Материалы и методы. Объектом исследования явились полипренолы, выделенные из пихты сибирской (Abiessibirica Ledeb.). Эксперименты выполнены на 108 аутбредных половозрелых мышах-самцах стока СDI массой тела 28 – 30г (в возрасте 5 недель). Эффект суммы полипренолов на обучаемость и память исследовался в интервале доз – 5, 20, 50, 100, 200 и 500 мг/кг массы тела мыши. В качестве препарата сравнения использовали глиатилин в дозе 90 мг/кг. Экспериментальная модель нарушения когнитивных функций создавалась хроническим (в течение 20 дней) внутрибрюшинным введением скополамина в дозе 2 мг/кг. Нарушение когнитивных функций оценивались по изменениям показателей выработки и воспроизведения условного рефлекса пассивного избегания (УРПИ).Результаты и их обсуждение. Результаты проведенных экспериментов показали, что хроническое введение скополамина вызвало выраженное снижение воспроизводимости УРПИ. Одновременно с этим изучаемая субстанция в дозах 20 и 50 мг/кг. Глиатилин оказывал близкое по характеру действие. Авторы полагают что в развитии антиамнестического эффекта участвуют холинергические рецепторы.Заключение. Приведенное доклиническое исследование показывает, что найдено новое средство с антиамнестическим действием на основе суммы полипренолов Пихты сибирской (Abies sibirica Ledeb.), семейство Сосновые (fam. Pinaceae). Данное средство может быть использовано для лечения заболеваний нейродегенеративных патологических процессов, в частности болезни Альцгеймера.
导 言阿尔茨海默病正日益成为导致早期残疾和死亡的原因。迄今为止,试图研制出一种能有效治疗这种病症的药物治疗剂的努力尚未取得成功。本文介绍了实验研究的结果,旨在创造一种更有效的方法来治疗这种疾病。研究对象是从西伯利亚冷杉(Abiessibirica Ledeb.)中分离出的多酚。实验对象是 108 只体重为 28 - 30 克(5 周龄)的 SDI 种群外交性成熟雄性小鼠。在 5、20、50、100、200 和 500 毫克/千克小鼠体重的剂量间隔内,研究了多酚总和对学习和记忆的影响。将剂量为 90 毫克/千克的 Gliatilin 作为对比药物。通过长期(20 天)腹腔注射 2 毫克/千克剂量的东莨菪碱,建立了认知功能障碍的实验模型。实验结果和讨论。实验结果表明,长期服用东莨菪碱会导致PDMA的再现性明显下降。同时,所研究物质的剂量为 20 和 50 毫克/千克。Gliatilin 也有类似的效果。作者认为,胆碱能受体参与了抗镇静作用的形成。上述临床前研究表明,我们发现了一种具有抗失眠作用的新药,其成分是松科植物西伯利亚冷杉(Abies sibirica Ledeb.)的多酚总和。这种疗法可用于治疗神经退行性病理过程疾病,尤其是阿尔茨海默氏症。
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引用次数: 0
Chemoproteomic analysis of the promising candidate molecule of the indole derivative with lab code SV-1010 and other non-steroidal anti-inflammatory drugs 对实验室代号为 SV-1010 的吲哚衍生物和其他非甾体抗炎药的候选分子进行化学蛋白组学分析
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-07-19 DOI: 10.18413/rrpharmacology.10.497
P. Galenko-Yaroshevsky, I. Torshin, A. N. Gromov, I. A. Reyer, O. Gromova, Tereza R. Glechyan, Konstantin F. Suzdalev, Andrey V. Zadorozhniy, A. Zelenskaya
Introduction: For effective and safe pharmacotherapy of pain, it is important to evaluate the mechanisms and spectrum of action of non-steroidal anti-inflammatory drugs (NSAIDs), including their effect on the proteom, central effect, as well as pain relieving and anti-inflammatory effects. The aim of the study was to evaluate the complex of differences between the promising candidate-molecule of indole derivative SV-1010 and the well-known NSAIDs.Materials and Methods: Chemoproteomic moduling of pharmacological effects of SV-1010 and NSAID diclofenac, nimesulide and ketorolac on the rat proteom by means of topological analysis of chemographs.Results: The significant differences in the effects of the studied molecules were found for 820 proteins of the rat proteom. SV-1010, to a lesser degree than the other molecules, can inhibit dopamine D1- and D2-type receptors and, at the same time, stimulate the release of dopamine in the neostriatum (EC50 = 27 nM). SV-1010, to a greater extent than the other molecules, can inhibit the GABA conveyor (EC50 = 65 nM) and the NMDA receptors Grin1/Grin2b (IC50 175 nM). SV-1010 can activate Cannabinoid CB2 receptors, inhibit enzymes of leukotriene biosynthesis, CC receptors of pro-inflammatory chemokines and leukotrienes.Conclusion: The chemoreactomic and chemoproteomic profiling of SV-1010 indicated its potential central effect through dopaminergic and GABA-neurotransmission and additional anti-inflammatory mechanisms, which can help increase pain-relieving effects.
导言:为了对疼痛进行有效而安全的药物治疗,必须评估非甾体抗炎药(NSAIDs)的作用机制和作用范围,包括其对蛋白体的影响、中枢效应以及止痛和抗炎作用。该研究的目的是评估吲哚衍生物 SV-1010 这一有希望的候选分子与知名非甾体抗炎药之间的复杂差异:通过化学图谱拓扑分析,对 SV-1010 和非甾体抗炎药双氯芬酸、尼美舒利和酮咯酸对大鼠蛋白质组的药理作用进行化学蛋白质组学调制:结果发现,所研究分子对大鼠蛋白质组中 820 种蛋白质的影响存在明显差异。SV-1010 能抑制多巴胺 D1 和 D2 型受体,同时刺激新纹状体中多巴胺的释放(EC50 = 27 nM),但抑制程度低于其他分子。与其他分子相比,SV-1010 能在更大程度上抑制 GABA 传达子(EC50 = 65 nM)和 NMDA 受体 Grin1/Grin2b(IC50 175 nM)。SV-1010 能激活大麻素 CB2 受体,抑制白三烯生物合成酶、促炎趋化因子和白三烯的 CC 受体:SV-1010的化学反应组学和化学蛋白组学分析表明,它可以通过多巴胺能和GABA神经传递以及其他抗炎机制发挥潜在的中枢效应,这有助于增强镇痛效果。
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引用次数: 0
An effective way for targeting EGFR-mediated carcinogenesis: an in vitro study 针对表皮生长因子受体介导的癌变的有效方法:体外研究
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-06-12 DOI: 10.18413/rrpharmacology.10.453
Viktoria A. Pakina, Evgeniya Z. Iksanova, Evgeniya V. Shih, O. Tumutolova, Karen K. Arutiunian, I V Kargina, K. Blinov, Fedor P. Pilgaev, A. Epishkina, D. Blinov, E. V. Grebenkin, E. Blinova
Introduction: EGFR-activating overexpression or somatic mutations are common in different human cancers. In this regard, the search for promising ways to control the carcinogenic transformation of tumor cells and the progression of malignant tumors expressing EGFR seems to be one of the most promising and developing areas of modern molecular pathology and pharmacology.Material and Methods: An antitumor activity of a novel compound, a pyridine carboxylic acid derivative LHT-17-19, was studied. The molecule was developed and synthesized at the Department of Chemistry, Drug Design and Technology of All-Russian Research Center for Biological Active Compounds Safety (Russia). The study was carried out in cell cultures of stomach cancer (Hs746T, AGS and MKN1) and patient-derived organoid (PDO) model of breast cancer (BC) expressing wild-type EGFR.Results: It was shown that LHT-17-19 induced concentration-dependent cytotoxicity of EGFR-expressing gastric cancer cells of all the aforementioned cultures. Pathomorphological, immunohistochemical and molecular validation of BC organoids derived from ductal breast carcinoma cells of a 68-year-old patient was done. PDOs were established as ER-negative, PR-negative, Her2/neu-negative, EGFR-positive with 35% of the Ki-67 expression index. In addition, the tumor cells translocation was resulted in a loss of ER expression and PDOs molecular pattern conversion towards a more aggressive triple negative type. PDOs incubation with 0.5-60.0 µM LHT-17-19 was accompanied not only by inhibition of their growth and proliferation, but also by significant cytoreduction.Conclusion: Thus, in two-dimensional and three-dimensional tumor cell cultures, the possibility of controlling the oncogenic expression of EGFR with the acridone compound 9-ammonium-3,3-dimethyl-3,4-dihydroacridine-1(2H)-OH L-2-hydroxybutanedivacate (LHT-17-19) was shown.
导言:表皮生长因子受体(EGFR)激活过表达或体细胞突变在不同的人类癌症中很常见。因此,寻找有希望的方法来控制肿瘤细胞的癌变和表达表皮生长因子受体的恶性肿瘤的进展,似乎是现代分子病理学和药理学最有希望和最有发展前景的领域之一:研究了一种新型化合物--吡啶甲酸衍生物 LHT-17-19 的抗肿瘤活性。该分子由全俄生物活性化合物安全研究中心(俄罗斯)化学、药物设计和技术部开发合成。研究在胃癌(Hs746T、AGS和MKN1)细胞培养物和表达野生型表皮生长因子受体(EGFR)的乳腺癌(BC)患者衍生有机体(PDO)模型中进行:结果表明,LHT-17-19能诱导上述所有培养物中表达表皮生长因子受体的胃癌细胞产生浓度依赖性细胞毒性。对从一名 68 岁患者的乳腺导管癌细胞中提取的 BC 有机体进行了病理形态学、免疫组化和分子验证。PDOs被确定为ER阴性、PR阴性、Her2/neu阴性、表皮生长因子受体(EGFR)阳性,Ki-67表达指数为35%。此外,肿瘤细胞易位导致ER表达丧失,PDOs分子模式向更具侵袭性的三阴型转化。用 0.5-60.0 µM LHT-17-19 培养 PDOs 不仅能抑制其生长和增殖,还能显著减少细胞减少:因此,在二维和三维肿瘤细胞培养中,吖啶酮化合物 9-铵-3,3-二甲基-3,4-二氢吖啶-1(2H)-OH L-2-hydroxybutanedivacate (LHT-17-19) 可以控制表皮生长因子受体的致癌表达。
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引用次数: 0
Protective effects of thymogen analogues, modified by D-alanine, in hydrazine liver damage 经 D-丙氨酸修饰的胸腺肽类似物对肼类肝损伤的保护作用
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-06-07 DOI: 10.18413/rrpharmacology.10.458
A. A. Chulanova, A. M. Smakhtina, Galina S. Mal, I. Bobyntsev, E. Mishina, M. Y. Smakhtin, Pavel M. Kopeykin, Elena G. Bogomolova
Introduction: It is known that the insertion of D-amino acids into the structure of a peptide molecule can increase its half-life. The pharmacological drug Thymogen was modified with D-alanine from the N- and C-terminus of the molecule. The aim of the investigation was to study the reparative and antioxidant activity of structural analogues of thymogen in toxic liver damage by hydrazine in rats.Materials and Methods: The investigation was conducted on 40 Wistar rats. Acute toxic liver damage was simulated with a single intraperitoneal injection of hydrazine hydrochloride at a dose of 50 mg/kg. Thymogen and its modified D-Ala analogues were administered intraperitoneally in equimolar doses for 5 days after intoxication. The animals were removed from the experiment 12 hours after the final administration of the peptides.Results and Discussion: It has been established the reparative and antioxidant activities of thymogen structural analogues increased in conditions of liver damage with hydrazine. Peptides with the insertion of D-Ala reduced the level of free radical reactions more significantly in comparison with thymogen. All peptides comparably increased catalase activity in blood plasma and liver homogenate.Conclusion: Thymogen analogues modified with D-Ala from the N- and C-terminus of the molecule can be considered as promising pharmacological substances for the development of new hepatoprotective drugs.
简介众所周知,在肽分子结构中加入 D-氨基酸可延长其半衰期。药用药物 Thymogen 在分子的 N 端和 C 端加入了 D-丙氨酸。调查的目的是研究胸腺肽原结构类似物对大鼠肼中毒性肝损伤的修复和抗氧化活性:研究对象为 40 只 Wistar 大鼠。通过腹腔注射 50 毫克/千克剂量的盐酸肼来模拟急性中毒性肝损伤。在中毒后的 5 天内,以等摩尔剂量腹腔注射胸腺肽原及其改良的 D-Ala 类似物。最后一次给药 12 小时后,将动物从实验中移出:已证实胸腺肽结构类似物的修复和抗氧化活性在肼损伤肝脏的情况下会增加。与胸腺肽相比,插入 D-Ala 的肽能更显著地降低自由基反应的水平。所有肽都能显著提高血浆和肝匀浆中过氧化氢酶的活性:结论:在胸腺肽分子的 N 端和 C 端加入 D-Ala 修饰的胸腺肽类似物可被视为具有开发新型保肝药物前景的药理物质。
{"title":"Protective effects of thymogen analogues, modified by D-alanine, in hydrazine liver damage","authors":"A. A. Chulanova, A. M. Smakhtina, Galina S. Mal, I. Bobyntsev, E. Mishina, M. Y. Smakhtin, Pavel M. Kopeykin, Elena G. Bogomolova","doi":"10.18413/rrpharmacology.10.458","DOIUrl":"https://doi.org/10.18413/rrpharmacology.10.458","url":null,"abstract":"Introduction: It is known that the insertion of D-amino acids into the structure of a peptide molecule can increase its half-life. The pharmacological drug Thymogen was modified with D-alanine from the N- and C-terminus of the molecule. The aim of the investigation was to study the reparative and antioxidant activity of structural analogues of thymogen in toxic liver damage by hydrazine in rats.\u0000Materials and Methods: The investigation was conducted on 40 Wistar rats. Acute toxic liver damage was simulated with a single intraperitoneal injection of hydrazine hydrochloride at a dose of 50 mg/kg. Thymogen and its modified D-Ala analogues were administered intraperitoneally in equimolar doses for 5 days after intoxication. The animals were removed from the experiment 12 hours after the final administration of the peptides.\u0000Results and Discussion: It has been established the reparative and antioxidant activities of thymogen structural analogues increased in conditions of liver damage with hydrazine. Peptides with the insertion of D-Ala reduced the level of free radical reactions more significantly in comparison with thymogen. All peptides comparably increased catalase activity in blood plasma and liver homogenate.\u0000Conclusion: Thymogen analogues modified with D-Ala from the N- and C-terminus of the molecule can be considered as promising pharmacological substances for the development of new hepatoprotective drugs.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141373958","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
Assessment of VEGF and TNF-alpha levels in patients with an unexpectedly poor and suboptimal response during the treatment of infertility using ART methods 评估使用抗逆转录病毒疗法治疗不孕症期间意外反应不佳和不理想患者的血管内皮生长因子和 TNF-α 水平
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-04-18 DOI: 10.18413/rrpharmacology.10.437
V. N. Perfilova, E. A. Muzyko, K. Y. Tikhaeva, M. V. Kustova, Anna V. Mukhina, Anna Yu. Fokina, Evgeniya I. Zhuravleva, Tatyana D. Lenskaya
Introduction: The problem of infertility treatment currently has medical, socio-demographic and economic significance. Progress in the field of reproductive technologies has improved the situation, but the issue has not yet been completely resolved. Infertility is diagnosed in 8-12% of couples of reproductive age; in Russia this figure exceeds 15%, and, according to WHO, it is a critical level. It is known that immunological factors can disrupt the reproductive process at the stages of folliculogenesis, ovulation, and implantation. These include vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α) and others. The aim of this study: to assess the levels of VEGF and TNF-α in women with different outcomes of hormonal stimulation of the ovaries during the treatment of infertility using ART methods.Materials and methods: Based on voluntary informed consent, a simple open comparative randomized study was conducted with the participation of 71 women in the Volgograd region undergoing infertility treatment using ART methods. Inclusion criteria were the age up to 42 years inclusive and the anti-Mullerian hormone level over 1.2 ng/mL. Before ovulation stimulation with gonadotropins, data on ovarian reserve parameters were collected. Based on the results of stimulation, women were divided into 3 groups: Group 1 – with high and normal ovarian response – 10 or more oocytes were obtained (control group); Group 2 – with suboptimal ovarian response – 5-9 oocytes received; Group 3 – with a poor response – 4 or less oocytes were received. After venipuncture, which was performed in preparation for standard anesthesia, VEGF and TNF-α were quantitatively determined in the blood plasma using an enzyme-linked immunosorbent assay.Results: The study results showed a statistically significant difference in VEGF levels in follicular fluid and serum between the groups of women with high/normal, suboptimal and poor ovarian response to gonadotropin stimulation. A higher level of this marker was observed in the serum of patients with high/normal and poor response – 48.15±4.23 and 41.29±8.26 pg/mL, respectively, while in women with a suboptimal response a lower VEGF level was determined –29.19±3.41 pg/mL. The levels of VEGF in the follicular fluid of women included in the high/normal, suboptimal and poor response groups were 35.95±3.20; 27.42±2.53 and 41.22±3.23 pg/mL, respectively (Table 1). As for TNF-α, its serum level in women with a high and normal response was lower than in the patients with a suboptimal response. In the follicular fluid of patients of group 3, there was a higher level of TNF-α, compared to groups 1 and 2, where the indicator was almost the same. However, the difference was not statistically significant.Conclusions: Thus, VEGF is directly involved in the mechanisms of regulation of oocyte maturation and can be not only a marker of poor ovarian response, but also a predictor of unsatisfactory results of ovarian stimulation in t
导言目前,不孕症治疗问题在医学、社会人口和经济方面都具有重要意义。生殖技术领域的进步改善了这一状况,但这一问题尚未完全解决。8%-12%的育龄夫妇被诊断出患有不孕症;在俄罗斯,这一数字超过了 15%,世界卫生组织认为这是一个临界水平。众所周知,免疫因素会在卵泡生成、排卵和着床阶段干扰生殖过程。这些因素包括血管内皮生长因子(VEGF)、肿瘤坏死因子-α(TNF-α)等。本研究的目的是:在使用 ART 方法治疗不孕症期间,评估不同激素刺激卵巢结果的妇女体内血管内皮生长因子和 TNF-α 的水平:在自愿知情同意的基础上,对伏尔加格勒地区 71 名接受抗逆转录病毒疗法治疗的不孕症妇女进行了简单的开放式随机比较研究。纳入标准为年龄不超过 42 岁(含 42 岁),抗穆勒氏管激素水平超过 1.2 纳克/毫升。在使用促性腺激素刺激排卵前,收集了卵巢储备参数数据。根据刺激结果,妇女被分为 3 组:第 1 组--卵巢反应高且正常--获得 10 个或更多卵细胞(对照组);第 2 组--卵巢反应欠佳--获得 5-9 个卵细胞;第 3 组--反应欠佳--获得 4 个或更少卵细胞。在准备标准麻醉的情况下进行静脉穿刺后,使用酶联免疫吸附试验定量测定血浆中的 VEGF 和 TNF-α:研究结果显示,卵泡液和血清中的 VEGF 水平在促性腺激素刺激下卵巢反应高/正常组、卵巢反应不佳组和卵巢反应差组之间存在显著统计学差异。在卵巢反应高/正常和反应差的患者血清中,该标记物的水平较高,分别为(48.15±4.23)和(41.29±8.26)pg/mL,而在反应次佳的妇女中,VEGF 水平较低(29.19±3.41)pg/mL。高/正常组、次优组和不良反应组妇女卵泡液中的VEGF水平分别为(35.95±3.20)、(27.42±2.53)和(41.22±3.23)pg/mL(表1)。至于 TNF-α,高反应和正常反应妇女的血清水平低于反应不佳的患者。在第 3 组患者的卵泡液中,TNF-α 的水平较高,而在第 1 组和第 2 组中,该指标几乎相同。然而,差异并无统计学意义:因此,血管内皮生长因子直接参与卵母细胞成熟的调节机制,它不仅可以作为卵巢反应不良的标志物,还可以作为使用 ART 方法治疗不孕症时卵巢刺激效果不理想的预测因子。在使用辅助生殖技术治疗不孕症的过程中,卵泡液中的α-TNF对卵泡发育没有统计学意义上的影响。
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引用次数: 0
Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of N-isopropenylimidazole zinc complex derivative 研究 N-异丙烯酰咪唑锌络合物衍生物的抗炎、镇痛、致溃疡和抗溃疡活性
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-02-13 DOI: 10.18413/rrpharmacology.10.443
P. Galenko-Yaroshevsky, O. V. Shelemekh, V. Popkov, Andrey V. Zadorozhniy, Irina B. Nektarevskaya, Natalia D. Bunyatyan, Roman A. Murashko, S. Lebedeva, A. Zelenskaya, Aleksandr V. Uvarov, O. N. Gulevskaya, Lusine O. Alukhanyan, Tereza R. Glechyan, Alina V. Sergeeva, Alina V. Kornetskaya, Nikolay E. Korovaykin
Introduction: Although nonsteroidal anti-inflammatory drugs (NSAIDs) have a clear therapeutic benefit, they can also have serious side effects. The most serious of these is the ulcerogenic effect, which can result in a decline in the quality of life or even death. This calls for the search for and creation of novel compounds with potent anti-inflammatory properties that do not have adverse effects on the digestive system. The aim of the study was to investigate the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activities of N-isopropenylimidazole zinc complex derivative.Materials and Methods: Experiments in rats and mice were used to determine the median lethal dose LD50 for N-isopropenylimidazole zinc complex derivative (laboratory name Pilim-1). Experimental models of acute exudative inflammation and chronic proliferative inflammation were used. In the first case, the inflammation was induced by sub-plantar injection of carrageenan and a complete Freund’s adjuvant into the hind paw of rats. In the second case, the inflammation was induced by the implantation of a sterile cotton pellet (“cotton pellet–induced granuloma”) under the skin of rats. Acute and tonic pain, visceral, and somatic deep pain were simulated using the formalin test in rats and the acetic acid-induced writhing test in mice, respectively. The ulcerogenic and anti-ulcerogenic effects of Pilim-1 were studied in rat experiments. Pilim-1 and the reference drugs diclofenac, indomethacin and famotidine were administered intragastrically.Results and Discussion: Pilim-1 showed marked anti-inflammatory and analgesic effects, demonstrated less toxicity than diclofenac and indomethacin, while its activity is comparable to diclofenac and superior to indomethacin. Its therapeutic index is higher than that of indomethacin and diclofenac and, in contrast, it essentially has no ulcerogenic effect and exhibits stronger anti-ulcerogenic activity than famotidine. It appears that the anti-inflammatory, analgesic, and gastroprotective properties of Pilim-1 are largely due to its antioxidant and antihypoxic properties, its inhibitory effects on cyclooxygenase and 5-lipoxygenase, and the presence of imidazole and zinc in its structure, both of which have a wide range of biological activity.Conclusion: Pilim-1 can be recommended for further preclinical studies due to its relatively low (practically absent) ulcerative activity, strong anti-inflammatory, analgesic, and anti-ulcerative effects, greater therapeutic index, and less acute toxicity in comparison with diclofenac and indomethacin.
导言:尽管非甾体抗炎药(NSAIDs)具有明显的治疗效果,但它们也会产生严重的副作用。其中最严重的副作用是致溃疡,可导致生活质量下降甚至死亡。这就需要寻找和创造具有强效抗炎特性,但不会对消化系统产生不良影响的新型化合物。本研究旨在探讨 N-异丙烯基咪唑锌络合物衍生物的抗炎、镇痛、致溃疡和抗溃疡活性:大鼠和小鼠实验用于确定 N-异丙烯酰亚胺唑锌络合物衍生物(实验室名称 Pilim-1)的中位致死剂量 LD50。实验中使用了急性渗出性炎症和慢性增殖性炎症模型。在第一种情况下,向大鼠的后爪注射角叉菜胶和完全弗氏佐剂,诱发炎症。第二种情况是在大鼠皮下植入无菌棉球("棉球诱发肉芽肿")诱发炎症。大鼠的急性和强直性疼痛、内脏疼痛和躯体深部疼痛分别通过福尔马林试验和醋酸诱导的小鼠蠕动试验进行模拟。在大鼠实验中研究了 Pilim-1 的致溃疡作用和抗溃疡作用。结果和讨论:Pilim-1 具有明显的抗炎和镇痛作用,毒性低于双氯芬酸和吲哚美辛,其活性与双氯芬酸相当,优于吲哚美辛。它的治疗指数高于吲哚美辛和双氯芬酸,相反,它基本上没有致溃疡作用,而且比法莫替丁具有更强的抗溃疡活性。由此看来,Pilim-1 的抗炎、镇痛和胃保护特性主要是由于其抗氧化和抗缺氧特性、对环氧化酶和 5-脂氧合酶的抑制作用,以及其结构中含有咪唑和锌,而这两种物质都具有广泛的生物活性:结论:与双氯芬酸和吲哚美辛相比,Pilim-1 的溃疡活性相对较低(几乎没有),具有较强的抗炎、镇痛和抗溃疡作用,治疗指数较高,急性毒性较小,因此可推荐用于进一步的临床前研究。
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引用次数: 0
Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of N-isopropenylimidazole zinc complex derivative 研究 N-异丙烯酰咪唑锌络合物衍生物的抗炎、镇痛、致溃疡和抗溃疡活性
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-02-13 DOI: 10.18413/rrpharmacology.10.443
P. Galenko-Yaroshevsky, O. V. Shelemekh, V. Popkov, Andrey V. Zadorozhniy, Irina B. Nektarevskaya, Natalia D. Bunyatyan, Roman A. Murashko, S. Lebedeva, A. Zelenskaya, Aleksandr V. Uvarov, O. N. Gulevskaya, Lusine O. Alukhanyan, Tereza R. Glechyan, Alina V. Sergeeva, Alina V. Kornetskaya, Nikolay E. Korovaykin
Introduction: Although nonsteroidal anti-inflammatory drugs (NSAIDs) have a clear therapeutic benefit, they can also have serious side effects. The most serious of these is the ulcerogenic effect, which can result in a decline in the quality of life or even death. This calls for the search for and creation of novel compounds with potent anti-inflammatory properties that do not have adverse effects on the digestive system. The aim of the study was to investigate the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activities of N-isopropenylimidazole zinc complex derivative.Materials and Methods: Experiments in rats and mice were used to determine the median lethal dose LD50 for N-isopropenylimidazole zinc complex derivative (laboratory name Pilim-1). Experimental models of acute exudative inflammation and chronic proliferative inflammation were used. In the first case, the inflammation was induced by sub-plantar injection of carrageenan and a complete Freund’s adjuvant into the hind paw of rats. In the second case, the inflammation was induced by the implantation of a sterile cotton pellet (“cotton pellet–induced granuloma”) under the skin of rats. Acute and tonic pain, visceral, and somatic deep pain were simulated using the formalin test in rats and the acetic acid-induced writhing test in mice, respectively. The ulcerogenic and anti-ulcerogenic effects of Pilim-1 were studied in rat experiments. Pilim-1 and the reference drugs diclofenac, indomethacin and famotidine were administered intragastrically.Results and Discussion: Pilim-1 showed marked anti-inflammatory and analgesic effects, demonstrated less toxicity than diclofenac and indomethacin, while its activity is comparable to diclofenac and superior to indomethacin. Its therapeutic index is higher than that of indomethacin and diclofenac and, in contrast, it essentially has no ulcerogenic effect and exhibits stronger anti-ulcerogenic activity than famotidine. It appears that the anti-inflammatory, analgesic, and gastroprotective properties of Pilim-1 are largely due to its antioxidant and antihypoxic properties, its inhibitory effects on cyclooxygenase and 5-lipoxygenase, and the presence of imidazole and zinc in its structure, both of which have a wide range of biological activity.Conclusion: Pilim-1 can be recommended for further preclinical studies due to its relatively low (practically absent) ulcerative activity, strong anti-inflammatory, analgesic, and anti-ulcerative effects, greater therapeutic index, and less acute toxicity in comparison with diclofenac and indomethacin.
导言:尽管非甾体抗炎药(NSAIDs)具有明显的治疗效果,但它们也会产生严重的副作用。其中最严重的副作用是致溃疡,可导致生活质量下降甚至死亡。这就需要寻找和创造具有强效抗炎特性,但不会对消化系统产生不良影响的新型化合物。本研究旨在探讨 N-异丙烯基咪唑锌络合物衍生物的抗炎、镇痛、致溃疡和抗溃疡活性:大鼠和小鼠实验用于确定 N-异丙烯酰亚胺唑锌络合物衍生物(实验室名称 Pilim-1)的中位致死剂量 LD50。实验中使用了急性渗出性炎症和慢性增殖性炎症模型。在第一种情况下,向大鼠的后爪注射角叉菜胶和完全弗氏佐剂,诱发炎症。第二种情况是在大鼠皮下植入无菌棉球("棉球诱发肉芽肿")诱发炎症。大鼠的急性和强直性疼痛、内脏疼痛和躯体深部疼痛分别通过福尔马林试验和醋酸诱导的小鼠蠕动试验进行模拟。在大鼠实验中研究了 Pilim-1 的致溃疡作用和抗溃疡作用。结果和讨论:Pilim-1 具有明显的抗炎和镇痛作用,毒性低于双氯芬酸和吲哚美辛,其活性与双氯芬酸相当,优于吲哚美辛。它的治疗指数高于吲哚美辛和双氯芬酸,相反,它基本上没有致溃疡作用,而且比法莫替丁具有更强的抗溃疡活性。由此看来,Pilim-1 的抗炎、镇痛和胃保护特性主要是由于其抗氧化和抗缺氧特性、对环氧化酶和 5-脂氧合酶的抑制作用,以及其结构中含有咪唑和锌,而这两种物质都具有广泛的生物活性:结论:与双氯芬酸和吲哚美辛相比,Pilim-1 的溃疡活性相对较低(几乎没有),具有较强的抗炎、镇痛和抗溃疡作用,治疗指数较高,急性毒性较小,因此可推荐用于进一步的临床前研究。
{"title":"Study of the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activity of N-isopropenylimidazole zinc complex derivative","authors":"P. Galenko-Yaroshevsky, O. V. Shelemekh, V. Popkov, Andrey V. Zadorozhniy, Irina B. Nektarevskaya, Natalia D. Bunyatyan, Roman A. Murashko, S. Lebedeva, A. Zelenskaya, Aleksandr V. Uvarov, O. N. Gulevskaya, Lusine O. Alukhanyan, Tereza R. Glechyan, Alina V. Sergeeva, Alina V. Kornetskaya, Nikolay E. Korovaykin","doi":"10.18413/rrpharmacology.10.443","DOIUrl":"https://doi.org/10.18413/rrpharmacology.10.443","url":null,"abstract":"Introduction: Although nonsteroidal anti-inflammatory drugs (NSAIDs) have a clear therapeutic benefit, they can also have serious side effects. The most serious of these is the ulcerogenic effect, which can result in a decline in the quality of life or even death. This calls for the search for and creation of novel compounds with potent anti-inflammatory properties that do not have adverse effects on the digestive system. The aim of the study was to investigate the anti-inflammatory, analgesic, ulcerogenic and anti-ulcerogenic activities of N-isopropenylimidazole zinc complex derivative.\u0000Materials and Methods: Experiments in rats and mice were used to determine the median lethal dose LD50 for N-isopropenylimidazole zinc complex derivative (laboratory name Pilim-1). Experimental models of acute exudative inflammation and chronic proliferative inflammation were used. In the first case, the inflammation was induced by sub-plantar injection of carrageenan and a complete Freund’s adjuvant into the hind paw of rats. In the second case, the inflammation was induced by the implantation of a sterile cotton pellet (“cotton pellet–induced granuloma”) under the skin of rats. Acute and tonic pain, visceral, and somatic deep pain were simulated using the formalin test in rats and the acetic acid-induced writhing test in mice, respectively. The ulcerogenic and anti-ulcerogenic effects of Pilim-1 were studied in rat experiments. Pilim-1 and the reference drugs diclofenac, indomethacin and famotidine were administered intragastrically.\u0000Results and Discussion: Pilim-1 showed marked anti-inflammatory and analgesic effects, demonstrated less toxicity than diclofenac and indomethacin, while its activity is comparable to diclofenac and superior to indomethacin. Its therapeutic index is higher than that of indomethacin and diclofenac and, in contrast, it essentially has no ulcerogenic effect and exhibits stronger anti-ulcerogenic activity than famotidine. It appears that the anti-inflammatory, analgesic, and gastroprotective properties of Pilim-1 are largely due to its antioxidant and antihypoxic properties, its inhibitory effects on cyclooxygenase and 5-lipoxygenase, and the presence of imidazole and zinc in its structure, both of which have a wide range of biological activity.\u0000Conclusion: Pilim-1 can be recommended for further preclinical studies due to its relatively low (practically absent) ulcerative activity, strong anti-inflammatory, analgesic, and anti-ulcerative effects, greater therapeutic index, and less acute toxicity in comparison with diclofenac and indomethacin.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":"395 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139841485","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
Antibiotic resistance of infectious agents associated with prior hospitalization 与之前住院治疗相关的感染病原体的抗生素耐药性
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-02-09 DOI: 10.18413/rrpharmacology.10.436
D. Y. Perfileva, Alexander G. Miroshnichenko, E. S. Kulikov, V. Y. Perfilev, V. Boykov, S. Nesterovich
Introduction: One of the frequent causes of re-hospitalization is infectious complications due to previous colonization of patient loci by microorganisms circulating in the hospital environment. In the conditions of real clinical practice among hospital-acquired infections (HAI), it is advisable to distinguish a special group of diseases – infections associated with previous hospitalization (IPAH). Of particular scientific interest is the study of the antibiotic resistance profile of IPAH pathogens in order to determine the further strategy of empirical antibiotic therapy.Materials and Methods: A two-center descriptive study was conducted in Tomsk region. We analyzed 170 cases of IPAH according to the medical records of patients receiving medical care in inpatient settings (form N 003/u) in the period from 2019 to 2023. Identification of microorganisms was carried out by classical bacteriological method. Results and Discussion: Gram-negative bacteria (95.3%) predominated in the etiology of pneumonia associated with prior hospitalization. Among Gram-negative microorganisms, the most frequent were K. pneumoniae, P. aeroginosa and K. oxytoca. Representatives of the families Enterobacteriaceae (48.2%), Staphylococcaceae (28.9%) and Enterococcaceae (10.8%) predominated in the etiology of surgical infection associated with previous hospitalization. In the species structure, the key pathogens were K. pneumoniae, S. aureus and E. coli. IPAH pathogens were characterized by an unfavorable resistance profile. Conclusion: Despite the fact that the etiological structure and antibiotic resistance profile of IPAH are similar to those of classical nosocomial infections, IPAH has important features that should certainly be taken into account when organizing medical care for this cohort of patients.
简介再次住院的常见原因之一是由于医院环境中的微生物在病人体内定植而引起的感染性并发症。在医院获得性感染(HAI)的实际临床实践中,最好区分一组特殊的疾病--与既往住院相关的感染(IPAH)。研究 IPAH 病原体的抗生素耐药性情况,以确定经验性抗生素治疗的进一步策略,具有特殊的科学意义:在托木斯克地区开展了一项双中心描述性研究。我们根据 2019 年至 2023 年期间住院病人的医疗记录(表 N 003/u)分析了 170 例 IPAH 病例。微生物的鉴定采用经典细菌学方法进行。结果与讨论:革兰氏阴性菌(95.3%)在与之前住院相关的肺炎病因中占主导地位。在革兰氏阴性微生物中,最常见的是肺炎克氏菌、气单胞菌和氧单胞菌。肠杆菌科(48.2%)、葡萄球菌科(28.9%)和肠球菌科(10.8%)的代表菌在与既往住院相关的外科感染病因中占主导地位。在物种结构中,主要病原体为肺炎双球菌、金黄色葡萄球菌和大肠杆菌。IPAH病原体的特点是耐药性差。结论尽管 IPAH 的病原学结构和抗生素耐药性特征与传统的院内感染相似,但 IPAH 具有一些重要特征,在为这类患者组织医疗护理时一定要加以考虑。
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引用次数: 0
Antibiotic resistance of infectious agents associated with prior hospitalization 与之前住院治疗相关的感染病原体的抗生素耐药性
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-02-09 DOI: 10.18413/rrpharmacology.10.436
D. Y. Perfileva, Alexander G. Miroshnichenko, E. S. Kulikov, V. Y. Perfilev, V. Boykov, S. Nesterovich
Introduction: One of the frequent causes of re-hospitalization is infectious complications due to previous colonization of patient loci by microorganisms circulating in the hospital environment. In the conditions of real clinical practice among hospital-acquired infections (HAI), it is advisable to distinguish a special group of diseases – infections associated with previous hospitalization (IPAH). Of particular scientific interest is the study of the antibiotic resistance profile of IPAH pathogens in order to determine the further strategy of empirical antibiotic therapy.Materials and Methods: A two-center descriptive study was conducted in Tomsk region. We analyzed 170 cases of IPAH according to the medical records of patients receiving medical care in inpatient settings (form N 003/u) in the period from 2019 to 2023. Identification of microorganisms was carried out by classical bacteriological method. Results and Discussion: Gram-negative bacteria (95.3%) predominated in the etiology of pneumonia associated with prior hospitalization. Among Gram-negative microorganisms, the most frequent were K. pneumoniae, P. aeroginosa and K. oxytoca. Representatives of the families Enterobacteriaceae (48.2%), Staphylococcaceae (28.9%) and Enterococcaceae (10.8%) predominated in the etiology of surgical infection associated with previous hospitalization. In the species structure, the key pathogens were K. pneumoniae, S. aureus and E. coli. IPAH pathogens were characterized by an unfavorable resistance profile. Conclusion: Despite the fact that the etiological structure and antibiotic resistance profile of IPAH are similar to those of classical nosocomial infections, IPAH has important features that should certainly be taken into account when organizing medical care for this cohort of patients.
简介再次住院的常见原因之一是由于医院环境中的微生物在病人体内定植而引起的感染性并发症。在医院获得性感染(HAI)的实际临床实践中,最好区分一组特殊的疾病--与既往住院相关的感染(IPAH)。研究 IPAH 病原体的抗生素耐药性情况,以确定经验性抗生素治疗的进一步策略,具有特殊的科学意义:在托木斯克地区开展了一项双中心描述性研究。我们根据 2019 年至 2023 年期间住院病人的医疗记录(表 N 003/u)分析了 170 例 IPAH 病例。微生物的鉴定采用经典细菌学方法进行。结果与讨论:革兰氏阴性菌(95.3%)在与之前住院相关的肺炎病因中占主导地位。在革兰氏阴性微生物中,最常见的是肺炎克氏菌、气单胞菌和氧单胞菌。肠杆菌科(48.2%)、葡萄球菌科(28.9%)和肠球菌科(10.8%)的代表菌在与既往住院相关的外科感染病因中占主导地位。在物种结构中,主要病原体为肺炎双球菌、金黄色葡萄球菌和大肠杆菌。IPAH病原体的特点是耐药性差。结论尽管 IPAH 的病原学结构和抗生素耐药性特征与传统的院内感染相似,但 IPAH 具有一些重要特征,在为这类患者组织医疗护理时一定要加以考虑。
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引用次数: 0
Modern doctors' view on the problem of diagnostics and treatment of asthenic syndrome in different regions of the Russian Federation 现代医生对俄罗斯联邦不同地区衰弱综合征诊断和治疗问题的看法
Q3 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2024-01-30 DOI: 10.18413/rrpharmacology.10.398
Y. Belousova, A. M. Tynterova, V. Rafalskiy
Introduction: The problem of asthenic disorders is determined by their high prevalence, the lack of diagnostic criteria and recommendations for therapy, and the absence of unified principles of coding in ICD-10. The aim of the study was to evaluate the current practice of neurologists and physicians of the Russian Federation (RF) in the diagnosis and pharmacotherapy of asthenic syndrome (AS).Materials and Methods: An anonymous author-developed questionnaire survey of physicians on the issues of diagnostics and treatment of asthenia was conducted on the Google forms platform.Results: Total 238 specialists from 23 regions of the RF, 62.5% of neurologists and 37.5% of physicians, took part in the survey. Women suffer from AS more often than men. AS is most frequently verified at the age of 40-60 (65.5%) and under 40 (39.6%). Doctors use the codes G90.8 – other disorders of the autonomic nervous system – and I67.8 – other specified cerebral vascular lesions. The main causes of AS are affective disorders in 67.2% of patients and infectious diseases in 70% of patients. Almost 67% of doctors use anxiety and depression assessment scale, and only 13% of respondents use MFI-20 scale. The choice of therapy depended on the psychopathologic syndrome in 73.9% of cases. Most doctors favored nootropic drugs, metabolic action drugs, and B vitamins.Conclusion: The current medical practice of diagnosing and treating AS was studied and informative data were obtained with regard to understanding the clinical-typological structure and nosological affiliation of AS. The results demonstrate the expediency of developing a unified algorithm for the management of patients with various manifestations of AS.
导言:气喘病的问题在于其发病率高、缺乏诊断标准和治疗建议,以及 ICD-10 缺乏统一的编码原则。本研究的目的是评估俄罗斯联邦(RF)神经科医生和内科医生目前在气喘综合征(AS)诊断和药物治疗方面的实践情况:在谷歌表格平台上对医生进行了匿名问卷调查:来自俄罗斯联邦 23 个地区的 238 名专家参加了调查,其中 62.5%为神经科医生,37.5%为内科医生。女性比男性更易患强直性脊柱炎。强直性脊柱炎的高发年龄为 40-60 岁(65.5%)和 40 岁以下(39.6%)。医生使用的代码是 G90.8 - 其他自律神经系统疾病和 I67.8 - 其他特定脑血管病变。导致强直性脊柱炎的主要原因是情感障碍(占 67.2%)和感染性疾病(占 70%)。近 67% 的医生使用焦虑和抑郁评估量表,只有 13% 的受访者使用 MFI-20 量表。在 73.9% 的病例中,治疗方法的选择取决于精神病理综合征。大多数医生倾向于使用促智药物、代谢作用药物和 B 族维生素:对目前诊断和治疗强直性脊柱炎的医疗实践进行了研究,并获得了有关了解强直性脊柱炎的临床类型学结构和疾病分类的信息数据。研究结果表明,为治疗有各种表现的强直性脊柱炎患者制定统一的算法是很有必要的。
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引用次数: 0
期刊
Research Results in Pharmacology
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