Pub Date : 2023-10-11DOI: 10.18413/rrpharmacology.9.10043
Vladimir N. Fedorov, Mikhail K. Korsakov, Vladimir P. Vdovichenko, Salavat S. Suleimanov, Alena N. Tyushina, Anastasiya A. Popova
Introduction: In vivo screening studies, in which the efficacy of dozens of drugs is tested to select several applicants for further study of their safety in humans, are the main stage in the study of the pharmacodynamics of promising antiglaucoma drugs. This imposes a number of specific requirements both on experimental models of glaucoma and on laboratory animals used in the experiment.
Materials and Methods: 32 male rabbits of the Soviet Сhinchilla breed, 6 male albino rabbits weighing 3-3.5 kg, and 20 outbred white rats weighing 220-250 g were used in total in experiments to reproduce the glaucoma process. All manipulations on the rabbit eye were performed by an ophthalmologist under general anesthesia with telazol. Triamcinolone (vitreous injection) was used to simulate glaucoma in rabbits, lauromacrogol 400 or fine kaolin (anterior chamber injection) was used to simulate glaucoma in rabbits; adrenaline hydrochloride (intraperitoneal administration) was used to simulate glaucoma in rats.
Results and Discussion: Double intravitreal administration of a suspension of triamcinolone at a dose of 4 mg was the most attractive model in terms of the technique of reproducing the pathology and the results obtained in modeling glaucoma in rabbits. However, this model did not produce a stable increase in intraocular pressure (IOP). Doubling the dose of triamcinolone and replacing chinchilla rabbits with albinos did not lead to a positive result. The introduction of the venous sclerosing drug lauromacrogol 400 into the anterior chamber of the eye proved to be ineffective either. The introduction of finely dispersed kaolin into the anterior chamber of the eye of rabbits led to a persistent increase in IOP. The intraperitoneal administration of epinephrine hydrochloride to rats according to the described method gave no stable results. The increase in IOP became stable only after a significant increase in the dose of adrenaline.
Conclusion: The conducted studies of four models of glaucoma and their three modifications in animals made it possible to select two of them, which contributed to a stable and fairly long-term increase in IOP in rabbits (introduction of finely dispersed kaolin into the anterior chamber of the eye) and rats (adrenaline-induced model).
{"title":"Modeling experimental glaucoma for screening studies of antiglaucomatous activity","authors":"Vladimir N. Fedorov, Mikhail K. Korsakov, Vladimir P. Vdovichenko, Salavat S. Suleimanov, Alena N. Tyushina, Anastasiya A. Popova","doi":"10.18413/rrpharmacology.9.10043","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10043","url":null,"abstract":"Introduction: In vivo screening studies, in which the efficacy of dozens of drugs is tested to select several applicants for further study of their safety in humans, are the main stage in the study of the pharmacodynamics of promising antiglaucoma drugs. This imposes a number of specific requirements both on experimental models of glaucoma and on laboratory animals used in the experiment.
 Materials and Methods: 32 male rabbits of the Soviet Сhinchilla breed, 6 male albino rabbits weighing 3-3.5 kg, and 20 outbred white rats weighing 220-250 g were used in total in experiments to reproduce the glaucoma process. All manipulations on the rabbit eye were performed by an ophthalmologist under general anesthesia with telazol. Triamcinolone (vitreous injection) was used to simulate glaucoma in rabbits, lauromacrogol 400 or fine kaolin (anterior chamber injection) was used to simulate glaucoma in rabbits; adrenaline hydrochloride (intraperitoneal administration) was used to simulate glaucoma in rats.
 Results and Discussion: Double intravitreal administration of a suspension of triamcinolone at a dose of 4 mg was the most attractive model in terms of the technique of reproducing the pathology and the results obtained in modeling glaucoma in rabbits. However, this model did not produce a stable increase in intraocular pressure (IOP). Doubling the dose of triamcinolone and replacing chinchilla rabbits with albinos did not lead to a positive result. The introduction of the venous sclerosing drug lauromacrogol 400 into the anterior chamber of the eye proved to be ineffective either. The introduction of finely dispersed kaolin into the anterior chamber of the eye of rabbits led to a persistent increase in IOP. The intraperitoneal administration of epinephrine hydrochloride to rats according to the described method gave no stable results. The increase in IOP became stable only after a significant increase in the dose of adrenaline.
 Conclusion: The conducted studies of four models of glaucoma and their three modifications in animals made it possible to select two of them, which contributed to a stable and fairly long-term increase in IOP in rabbits (introduction of finely dispersed kaolin into the anterior chamber of the eye) and rats (adrenaline-induced model).","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":"164 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136252523","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}
Pub Date : 2023-10-04DOI: 10.18413/rrpharmacology.9.10040
Pavel A. Galenko-Yaroshevsky, Aleksandr А. Slavinskiy, Sergey S. Todorov, Viktor L. Popkov, Olga V. Shelemekh, Svetlana A. Lebedeva, Andrey V. Zadorozhniy, Anait V. Zelenskaya, Lusine O. Alukhanyan, Irina B. Nektarevskaya, Natalia D. Bunyatyan, Aleksandr А. Verevkin
Introduction: Combined inflammatory and destructive processes affecting the dental pulp and tissues of the periodontal complex are among the most problem diseases of the dental system. Current therapy with use of available pharmacological agents does not always allow achieving the expected positive result. In addition, often the lack of information about morphological processes in the tissues of the dental system, in particular the gums, with endodontic-periodontal lesion (EPL) limits the ability of dentists to carry out targeted pharmacotherapy with both traditional and, in particular, new medications. The aim of the study was to evaluate the morphological characteristics of gum tissues in a therapeutic context of N-isopropenylimidazole zinc complex derivative in experimental endodontic-periodontal lesion in rats. Materials and Methods: A simulation of EPL in rats was performed in two ways: simultaneous induction of acute periodontitis and parodontitis by pulp extraction and natural infection of the pulp cavity, as well as by ligation of the necks of lower incisors. The research protocols included 5 groups of animals: 1st – intact group (control-1); 2nd – animals with simulated EPL (control-2); 3rd – animals with simulated EPL and treated with Metrogyl Denta® gel (M-D); 4th – animals with simulated EPL and treated with N–isopropenylimidazole zinc complex derivative gel under the laboratory code Pilim-1; and 5th – animals with simulated EPL and treated with the combination of M-D + Pilim-1. The gum of the lower incisors was taken for morphological studies. Slides were stained with hematoxylin and eosin. Computer morphometry was performed using the ImageJ software. Results and Discussion: The substances M-D, Pilim-1 and, especially, the combination of M-D+Pilim-1 (against the background of chlorhexidine bigluconate used as oral rinse) for 14 days in rats with simulated EPL cause a significant improvement of the morphological structure of the gum with minimal residual dystrophy and sclerosis. The combination M-D + Pilim-1 led to a 1.3-time increase in epithelial thickness, and a 1.5-time decrease in acanthosis depth in comparison with M-D, while the number of capillaries and their diameter had no significant differences. Compared with Pilim-1, the epithelial thickness increased 1.5 times, and the acanthosis depth and the number of capillaries decreased 1.6 and 1.4 times, respectively, whereas the diameter of the capillaries did not change significantly. The pronounced protective effect of the combination M-D + Pilim-1 on the morphological structure of the gingival mucosa of rats with simulated EPL may be associated with antimicrobial, anti-inflammatory, regenerating, angioprotective and antioxidant properties of both M-D and Pilim-1 separately, and, possibly to a greater extent, of the combination M-D + Pilim-1. Conclusion: The substances M-D, Pilim-1 and, especially, the combination M-D + Pilim-1 (against the background of chlorhexidine bigluconat
{"title":"The effect of zinc complex of N-isopropenylimidazole on the morphological characteristics of gum tissues in experimental endodontic-periodontal lesions in rats","authors":"Pavel A. Galenko-Yaroshevsky, Aleksandr А. Slavinskiy, Sergey S. Todorov, Viktor L. Popkov, Olga V. Shelemekh, Svetlana A. Lebedeva, Andrey V. Zadorozhniy, Anait V. Zelenskaya, Lusine O. Alukhanyan, Irina B. Nektarevskaya, Natalia D. Bunyatyan, Aleksandr А. Verevkin","doi":"10.18413/rrpharmacology.9.10040","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10040","url":null,"abstract":"Introduction: Combined inflammatory and destructive processes affecting the dental pulp and tissues of the periodontal complex are among the most problem diseases of the dental system. Current therapy with use of available pharmacological agents does not always allow achieving the expected positive result. In addition, often the lack of information about morphological processes in the tissues of the dental system, in particular the gums, with endodontic-periodontal lesion (EPL) limits the ability of dentists to carry out targeted pharmacotherapy with both traditional and, in particular, new medications. The aim of the study was to evaluate the morphological characteristics of gum tissues in a therapeutic context of N-isopropenylimidazole zinc complex derivative in experimental endodontic-periodontal lesion in rats. Materials and Methods: A simulation of EPL in rats was performed in two ways: simultaneous induction of acute periodontitis and parodontitis by pulp extraction and natural infection of the pulp cavity, as well as by ligation of the necks of lower incisors. The research protocols included 5 groups of animals: 1st – intact group (control-1); 2nd – animals with simulated EPL (control-2); 3rd – animals with simulated EPL and treated with Metrogyl Denta® gel (M-D); 4th – animals with simulated EPL and treated with N–isopropenylimidazole zinc complex derivative gel under the laboratory code Pilim-1; and 5th – animals with simulated EPL and treated with the combination of M-D + Pilim-1. The gum of the lower incisors was taken for morphological studies. Slides were stained with hematoxylin and eosin. Computer morphometry was performed using the ImageJ software. Results and Discussion: The substances M-D, Pilim-1 and, especially, the combination of M-D+Pilim-1 (against the background of chlorhexidine bigluconate used as oral rinse) for 14 days in rats with simulated EPL cause a significant improvement of the morphological structure of the gum with minimal residual dystrophy and sclerosis. The combination M-D + Pilim-1 led to a 1.3-time increase in epithelial thickness, and a 1.5-time decrease in acanthosis depth in comparison with M-D, while the number of capillaries and their diameter had no significant differences. Compared with Pilim-1, the epithelial thickness increased 1.5 times, and the acanthosis depth and the number of capillaries decreased 1.6 and 1.4 times, respectively, whereas the diameter of the capillaries did not change significantly. The pronounced protective effect of the combination M-D + Pilim-1 on the morphological structure of the gingival mucosa of rats with simulated EPL may be associated with antimicrobial, anti-inflammatory, regenerating, angioprotective and antioxidant properties of both M-D and Pilim-1 separately, and, possibly to a greater extent, of the combination M-D + Pilim-1. Conclusion: The substances M-D, Pilim-1 and, especially, the combination M-D + Pilim-1 (against the background of chlorhexidine bigluconat","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":"178 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135646358","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}
Pub Date : 2023-09-30DOI: 10.18413/rrpharmacology.9.10044
Veronika A. Zemskova, Yuliya A. Trubchanina, Tatyana A. Berezhnova, Andrey M. Zemskov, Vladimir A. Borisov, Nadezhda Yu. Kuzmenko, Kseniya S. Dyadina
Introduction: Patients with purulent-inflammatory diseases (PID), especially those with allergization, manifest chronicity, low treatment efficiency, and the risk of relapses; the above actualizes the search for innovative treatment technologies.
The aim of the study: The aim of the study was to specify pharmacological (body-wide) and specific (immunotropic) effects of the immunomodulator galavit additionally prescribed in the context of basic treatment for patients with deep pyoderma, chronic pyelonephritis, adnexitis, purulent infection of soft tissues, complicated by atopic dermatitis.
Materials and Methods: The study included 331 patients with PID and 30 healthy volunteers of the same age and gender who were examined prior and following the basic treatment of each nosoform. The diverse clinical and laboratory examination options were applied to investigate 17 clinical, 7 hematological, 16 immunological, 13 metabolic parameters that were grouped into clinical, hematological, immunological and metabolic syndromes, and divided into links – cellular, humoral, phagocytic, cytokine, metabolic and antioxidant. The results were statistically processed using variational parametric and nonparametric techniques; this allowed calculating the coefficient of diagnostic value, diagnostic formulas of disorders and targets of galavit under various conditions.
Results and Discussion: Targeted pharmacological therapy with galavit reliably eliminates clinical, hemato-immuno-metabolic disorders in patients with PID, though dependently on the nosoform of the disease.
Conclusion: It was demonstrated that the correction of clinical and laboratory disorders depend on PID pathogenesis and allergization; the laboratory mechanism of therapeutic effects was specified.
{"title":"Pharmacological body-wide and immunotropic effects of galavit in the treatment of patients with purulent-inflammatory diseases of various origins and allergization","authors":"Veronika A. Zemskova, Yuliya A. Trubchanina, Tatyana A. Berezhnova, Andrey M. Zemskov, Vladimir A. Borisov, Nadezhda Yu. Kuzmenko, Kseniya S. Dyadina","doi":"10.18413/rrpharmacology.9.10044","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10044","url":null,"abstract":"Introduction: Patients with purulent-inflammatory diseases (PID), especially those with allergization, manifest chronicity, low treatment efficiency, and the risk of relapses; the above actualizes the search for innovative treatment technologies.
 The aim of the study: The aim of the study was to specify pharmacological (body-wide) and specific (immunotropic) effects of the immunomodulator galavit additionally prescribed in the context of basic treatment for patients with deep pyoderma, chronic pyelonephritis, adnexitis, purulent infection of soft tissues, complicated by atopic dermatitis.
 Materials and Methods: The study included 331 patients with PID and 30 healthy volunteers of the same age and gender who were examined prior and following the basic treatment of each nosoform. The diverse clinical and laboratory examination options were applied to investigate 17 clinical, 7 hematological, 16 immunological, 13 metabolic parameters that were grouped into clinical, hematological, immunological and metabolic syndromes, and divided into links – cellular, humoral, phagocytic, cytokine, metabolic and antioxidant. The results were statistically processed using variational parametric and nonparametric techniques; this allowed calculating the coefficient of diagnostic value, diagnostic formulas of disorders and targets of galavit under various conditions.
 Results and Discussion: Targeted pharmacological therapy with galavit reliably eliminates clinical, hemato-immuno-metabolic disorders in patients with PID, though dependently on the nosoform of the disease.
 Conclusion: It was demonstrated that the correction of clinical and laboratory disorders depend on PID pathogenesis and allergization; the laboratory mechanism of therapeutic effects was specified.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":"51 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136343036","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}
Pub Date : 2023-09-30DOI: 10.18413/rrpharmacology.9.10045
Dina V. Yunina, Valentin P. Ageev, Andrey V. Zaborovskiy, Larisa A. Tararina, Sergei V. Tsaregorodtsev, Alexander V. Kokorev, Dmitry N. Andreev, Aleksandra E. Pyanzina, Vasilisa I. Shlyapkina, Nikolay A. Pyataev, Oleg A. Kulikov
Introduction: The study of the pharmacokinetics of glucocorticosteroids is often required to solve fundamental and applied tasks of pharmacology. HPLC methods based on ultraviolet detection are attractive due to their availability, but their sensitivity is low enough to study in vivo kinetics. In this study, we propose a method for the determination of dexamethasone in biological objects, based on the use of HPLC with UV detection and having sufficient sensitivity to determine the drug in biological media (blood and periarticular tissues). Materials and methods: Extraction of dexamethasone from biosamples was carried out by liquid-liquid extraction with acetone in an acidic medium using atenolol as an internal standard. The analysis was carried out on a Kromasil-100 C18 column. A mixture of methanol with phosphate buffer in the ratio 50÷50, pH=5.6 was used as the mobile phase. Detector - UV, wavelength - 254 nm. The LLOQ of the method was 50 ng/mL; the calibration curve demonstrated linearity in the con-centration range of 50-1000 ng/mL.The method was used to detect the medicinal product in peri-synovial tissues of rats with an autoimmune arthritis model. Results: This study demonstrated that intraarticular injection of the liposomal form of dexamethasone, compared with its water-soluble form, allows maintaining the active concentration of the product in the joint and periarticular tissues for a longer time, which creates prerequisites for enhancing its therapeutic effect. Conclusion: The proposed method provides a sensitive and specific approach for measuring dexamethasone in biological samples, such as blood and periarticular tissues. Preliminary findings indicate that the liposomal form of dexamethasone may exhibit better pharmacokinetic properties than the water-soluble form, which could lead to improved therapeutic outcomes.
{"title":"Method of detection of dexamethasone in biological tissues and its application to assess the local kinetics of this drug","authors":"Dina V. Yunina, Valentin P. Ageev, Andrey V. Zaborovskiy, Larisa A. Tararina, Sergei V. Tsaregorodtsev, Alexander V. Kokorev, Dmitry N. Andreev, Aleksandra E. Pyanzina, Vasilisa I. Shlyapkina, Nikolay A. Pyataev, Oleg A. Kulikov","doi":"10.18413/rrpharmacology.9.10045","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10045","url":null,"abstract":"Introduction: The study of the pharmacokinetics of glucocorticosteroids is often required to solve fundamental and applied tasks of pharmacology. HPLC methods based on ultraviolet detection are attractive due to their availability, but their sensitivity is low enough to study in vivo kinetics. In this study, we propose a method for the determination of dexamethasone in biological objects, based on the use of HPLC with UV detection and having sufficient sensitivity to determine the drug in biological media (blood and periarticular tissues). Materials and methods: Extraction of dexamethasone from biosamples was carried out by liquid-liquid extraction with acetone in an acidic medium using atenolol as an internal standard. The analysis was carried out on a Kromasil-100 C18 column. A mixture of methanol with phosphate buffer in the ratio 50÷50, pH=5.6 was used as the mobile phase. Detector - UV, wavelength - 254 nm. The LLOQ of the method was 50 ng/mL; the calibration curve demonstrated linearity in the con-centration range of 50-1000 ng/mL.The method was used to detect the medicinal product in peri-synovial tissues of rats with an autoimmune arthritis model. Results: This study demonstrated that intraarticular injection of the liposomal form of dexamethasone, compared with its water-soluble form, allows maintaining the active concentration of the product in the joint and periarticular tissues for a longer time, which creates prerequisites for enhancing its therapeutic effect. Conclusion: The proposed method provides a sensitive and specific approach for measuring dexamethasone in biological samples, such as blood and periarticular tissues. Preliminary findings indicate that the liposomal form of dexamethasone may exhibit better pharmacokinetic properties than the water-soluble form, which could lead to improved therapeutic outcomes.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136342772","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}
Pub Date : 2023-09-30DOI: 10.18413/rrpharmacology.9.10042
Иван Н. Тюренков, Дмитрий А. Бакулин, Юлия И. Великородная, Александр В. Борисов, Елизавета А. Абросимова, Алексей В. Смирнов, Григорий Л. Снигур, Святослав С. Сурин, Дарья А. Кавалерова, Ольга С. Васильева
Введение: Гамма-аминомасляная кислота (ГАМК) и ГАМК-ергические соединения в последние годы рассматриваются как потенциальные средства для лечения сахарного диабета и его осложнений. Помимо основной тормозной функции в мозге, ГАМК также является сигнальной молекулой в островках поджелудочной железы (ПЖ), оказывая влияние на секрецию инсулина и глюкагона, а также апоптоз, выживаемость бета-клеток и их регенерацию. Цель: Сравнить защитное действие на β-клетки поджелудочной железы у ГАМК и ее новых производных у животных возрастом 18 месяцев с продолжительным стрептозотоцин-никотинамид-индуцированным сахарным диабетом. Материалы и методы: Сахарный диабет моделировали белым аутбредным крысам-самцам (12 месяцев) посредством введения комбинации стрептозотоцина (65 мг/кг) и никотинамида (230 мг/кг). В течение последующих 6 месяцев осуществлялся контроль уровня гликемии каждые 4 недели. Далее для исследования были отобраны животные с уровнем постпрандиальной гликемии между 11 и 18 ммоль/л. После формирования групп, в течение 1 месяца животные соответственно получали ГАМК и ГАМК-ергические соединения (композиция 2 и 3), контрольная группа получала физиологический раствор. После лечения был выполнен пероральный тест на толерантность к глюкозе. Далее был произведен забор образцов крови и тканей ПЖ (селезеночная часть) для иммуноферментного анализа (уровень ГПП-1, TNF-α в сыворотке и уровень NF-Κb,Nrf2, Клото в гомогенате ПЖ), иммуногистохимического анализа (экспрессия NF-Κb, Nrf2 и Клото в островках ПЖ) и иммунофлуоресцентного анализа (экспрессия инсулина и глюкагона в островках ПЖ). Результаты: Результаты исследования подтверждают выраженный гипогликемический эффект изученных производных ГАМК у животных возрастом 18 месяцев с продолжительной гипергликемией. Гипогликемическое действие исследуемых композиций сопровождалось увеличенной продукцией ГПП-1, улучшением функции и массы β-клеток ПЖ. Кроме того, повышенные уровни белка Клото и транскрипционного фактора Nrf2, а также подавление транскрипционного фактора NF-κB после лечения, могут играть ключевую роль в защитном действии исследуемых ГАМК-ергических соединений в отношении β-клеток. Заключение: Новые производные ГАМК обладают значительным защитным эффектом для β-клеток ПЖ. Эффекты могут быть обусловлены увеличенной на фоне их введения продукцией ГПП-1, белка Клото и транскрипционного фактора Nrf2, а также подавлением транскрипционного фактора NF-κB. Эти результаты подчеркивают потенциал ГАМК-ергических соединений в качестве средств для лечения сахарного диабета и его осложнений.
{"title":"Защитное действие новых производных ГАМК на β-клетки поджелудочной железы в условиях экспериментального сахарного диабета 2 типа","authors":"Иван Н. Тюренков, Дмитрий А. Бакулин, Юлия И. Великородная, Александр В. Борисов, Елизавета А. Абросимова, Алексей В. Смирнов, Григорий Л. Снигур, Святослав С. Сурин, Дарья А. Кавалерова, Ольга С. Васильева","doi":"10.18413/rrpharmacology.9.10042","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10042","url":null,"abstract":"Введение: Гамма-аминомасляная кислота (ГАМК) и ГАМК-ергические соединения в последние годы рассматриваются как потенциальные средства для лечения сахарного диабета и его осложнений. Помимо основной тормозной функции в мозге, ГАМК также является сигнальной молекулой в островках поджелудочной железы (ПЖ), оказывая влияние на секрецию инсулина и глюкагона, а также апоптоз, выживаемость бета-клеток и их регенерацию. Цель: Сравнить защитное действие на β-клетки поджелудочной железы у ГАМК и ее новых производных у животных возрастом 18 месяцев с продолжительным стрептозотоцин-никотинамид-индуцированным сахарным диабетом. Материалы и методы: Сахарный диабет моделировали белым аутбредным крысам-самцам (12 месяцев) посредством введения комбинации стрептозотоцина (65 мг/кг) и никотинамида (230 мг/кг). В течение последующих 6 месяцев осуществлялся контроль уровня гликемии каждые 4 недели. Далее для исследования были отобраны животные с уровнем постпрандиальной гликемии между 11 и 18 ммоль/л. После формирования групп, в течение 1 месяца животные соответственно получали ГАМК и ГАМК-ергические соединения (композиция 2 и 3), контрольная группа получала физиологический раствор. После лечения был выполнен пероральный тест на толерантность к глюкозе. Далее был произведен забор образцов крови и тканей ПЖ (селезеночная часть) для иммуноферментного анализа (уровень ГПП-1, TNF-α в сыворотке и уровень NF-Κb,Nrf2, Клото в гомогенате ПЖ), иммуногистохимического анализа (экспрессия NF-Κb, Nrf2 и Клото в островках ПЖ) и иммунофлуоресцентного анализа (экспрессия инсулина и глюкагона в островках ПЖ). Результаты: Результаты исследования подтверждают выраженный гипогликемический эффект изученных производных ГАМК у животных возрастом 18 месяцев с продолжительной гипергликемией. Гипогликемическое действие исследуемых композиций сопровождалось увеличенной продукцией ГПП-1, улучшением функции и массы β-клеток ПЖ. Кроме того, повышенные уровни белка Клото и транскрипционного фактора Nrf2, а также подавление транскрипционного фактора NF-κB после лечения, могут играть ключевую роль в защитном действии исследуемых ГАМК-ергических соединений в отношении β-клеток. Заключение: Новые производные ГАМК обладают значительным защитным эффектом для β-клеток ПЖ. Эффекты могут быть обусловлены увеличенной на фоне их введения продукцией ГПП-1, белка Клото и транскрипционного фактора Nrf2, а также подавлением транскрипционного фактора NF-κB. Эти результаты подчеркивают потенциал ГАМК-ергических соединений в качестве средств для лечения сахарного диабета и его осложнений.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":"45 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136343448","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}
Pub Date : 2023-09-20DOI: 10.18413/rrpharmacology.9.10047
Svetlana A. Lebedeva, Pavel A. Galenko-Yaroshevsky (Jr.), Tatiana V. Fateeva, Sergey S. Pashin, Nataliya R. Pashina, Irina B. Nektarevskaya, Andrey V. Zadorozhniy, Olga V. Shelemekh, Marina Yu. Ravaeva, Elena N. Chuyan, Lusine O. Alukhanyan, Tereza R. Glechyan, Kerim Mutig, Maria Yu. Materenchuk
Introduction: The therapeutic effect of commercially available domestic and foreign drugs for the treatment of various skin injuries is far from optimal. These drugs have no universal effects, but cause pronounced side reactions. There is a clear demand for development of innovative wound-healing drugs with antimicrobial properties, which increase the natural protective function of the skin. Pharmaceutical compounds with zinc nanoparticles have been increasingly recognized as a promising therapeutic direction. These drugs can easily penetrate into damaged tissues and stimulate metabolic processes. Zinc complexes with imidazole derivatives are of a particular interest. Imidazole acts as a structural fragment of many natural physiologically active compounds, thus providing targeted delivery of this essential trace element into the wound for inclusion in the multicascade mechanism of wound healing. The aim of the study: to provide experimental evidence for effects of recently developed zinc complexes with N-alkenylimidazole as wound healing agents. Materials and Methods: Wound-healing effects of six 1% gels containing distinct N-alkenylimidazole zinc complexe derivatives based on the Na-carboxymethylcellulose (Na-CMC) were comparatively studied in 128 outbred white rats of both genders. The Na-CMC-based Zinc Sulfate 1% gel, Methyluracil and Solcoseryl served as reference drugs. After performing the local tolerance study of zinc complexes, linear and planar sterile wounds of comparable size were inflicted in anesthetized animals. The degree of healing was evaluated on the day 8 and day 28 after the treatment start by wound sizes and histological examination of inflammatory response, epithelization, granulation tissue, angiogenesis, and necrosis. The skin microcirculation system was evaluated using the laser Doppler Flowmetry (LDF), whereby the blood flow indicators were recorded 30 and 60 minutes after intraperitoneal administration of the trial compound. The antimicrobial activity of the zinc compounds was determined in vitro by means of their minimum inhibitory concentration suppressing the bacteria and fungi growth using the double serial dilution method in liquid culture media. The statistical data processing was performed using the Statistica 12 software package. Results and Discussion: In the linear wound model, all animals treated with either of six experimental zinc compounds showed almost complete reduction in wound size (92-100%, p<0.05) on the day 8, significantly exceeding the wound healing in the control animals (reduction by 67-88 %, p<0.05) and effects of the reference drugs (reduction by 83-86%, p<0.05). In the planar wound model, the most significant wound healing effect was reached by using the gel containing N-isopropenylimidazole zinc diacetate (encoded as Pilim-1). The respective histological examination showed signs of complete epithelialization, absence of destructive changes in the epidermis, restoration of skin appendages and
{"title":"Effective wound healing agents based on N-alkenylimidazole zinc complexes derivatives: future prospects and opportunities","authors":"Svetlana A. Lebedeva, Pavel A. Galenko-Yaroshevsky (Jr.), Tatiana V. Fateeva, Sergey S. Pashin, Nataliya R. Pashina, Irina B. Nektarevskaya, Andrey V. Zadorozhniy, Olga V. Shelemekh, Marina Yu. Ravaeva, Elena N. Chuyan, Lusine O. Alukhanyan, Tereza R. Glechyan, Kerim Mutig, Maria Yu. Materenchuk","doi":"10.18413/rrpharmacology.9.10047","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10047","url":null,"abstract":"Introduction: The therapeutic effect of commercially available domestic and foreign drugs for the treatment of various skin injuries is far from optimal. These drugs have no universal effects, but cause pronounced side reactions. There is a clear demand for development of innovative wound-healing drugs with antimicrobial properties, which increase the natural protective function of the skin. Pharmaceutical compounds with zinc nanoparticles have been increasingly recognized as a promising therapeutic direction. These drugs can easily penetrate into damaged tissues and stimulate metabolic processes. Zinc complexes with imidazole derivatives are of a particular interest. Imidazole acts as a structural fragment of many natural physiologically active compounds, thus providing targeted delivery of this essential trace element into the wound for inclusion in the multicascade mechanism of wound healing. The aim of the study: to provide experimental evidence for effects of recently developed zinc complexes with N-alkenylimidazole as wound healing agents. Materials and Methods: Wound-healing effects of six 1% gels containing distinct N-alkenylimidazole zinc complexe derivatives based on the Na-carboxymethylcellulose (Na-CMC) were comparatively studied in 128 outbred white rats of both genders. The Na-CMC-based Zinc Sulfate 1% gel, Methyluracil and Solcoseryl served as reference drugs. After performing the local tolerance study of zinc complexes, linear and planar sterile wounds of comparable size were inflicted in anesthetized animals. The degree of healing was evaluated on the day 8 and day 28 after the treatment start by wound sizes and histological examination of inflammatory response, epithelization, granulation tissue, angiogenesis, and necrosis. The skin microcirculation system was evaluated using the laser Doppler Flowmetry (LDF), whereby the blood flow indicators were recorded 30 and 60 minutes after intraperitoneal administration of the trial compound. The antimicrobial activity of the zinc compounds was determined in vitro by means of their minimum inhibitory concentration suppressing the bacteria and fungi growth using the double serial dilution method in liquid culture media. The statistical data processing was performed using the Statistica 12 software package. Results and Discussion: In the linear wound model, all animals treated with either of six experimental zinc compounds showed almost complete reduction in wound size (92-100%, p<0.05) on the day 8, significantly exceeding the wound healing in the control animals (reduction by 67-88 %, p<0.05) and effects of the reference drugs (reduction by 83-86%, p<0.05). In the planar wound model, the most significant wound healing effect was reached by using the gel containing N-isopropenylimidazole zinc diacetate (encoded as Pilim-1). The respective histological examination showed signs of complete epithelialization, absence of destructive changes in the epidermis, restoration of skin appendages and","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136375804","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}
Pub Date : 2023-07-30DOI: 10.18413/rrpharmacology.9.10039
K. S. Trunov
Introduction: Currently, there are no safe and ideal medicines for the prevention and treatment of oophorectomy-induced osteoporosis. The development of an effective pharmacotherapy for hypoestrogen-induced osteoporosis is an important task of pharmacology. Materials and Methods: A new supramolecular complex (composition №1) was obtained on the basis of 3-hydroxypyridine derivatives: 2-ethyl-6-methyl-3-hydroxypyridinium 3-pyridinocarbonoate and 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate in a ratio of 1:3 by topochemical synthesis. The study of the osteoprotective activity of the supramolecular complex at a dose of 50 mg/kg was performed on 60 white female rats of the Wistar line on a model of hypoestrogen-induced osteoporosis. The effectiveness of the osteoprotective activity of the complex was evaluated on the 57th day of the experiment. Results and Discussion: The new supramolecular complex (composition №1) has osteoprotective activity, which is expressed in improving the indicators of X-ray and histomorphological samples. Oral administration of composition №1 at a dose of 50 mg/kg led to an increase in bone density to values of 2.55±0.02 g/cm3, which is 1.3 times higher than in the control group 1.92±0.01 g/cm3 (p≤0.05) and reduce bone resorption by improving cortical and trabecular bone structures. Conclusion: The obtained data characterize the prospects of studying composition №1 for the correction and prevention of hypoestrogen-induced osteoporosis. Graphical Abstract
导读:目前，还没有安全、理想的预防和治疗卵巢切除术所致骨质疏松症的药物。开发一种有效的药物治疗低雌激素性骨质疏松症是药理学的一项重要任务。材料与方法:以3-羟吡啶衍生物2-乙基-6-甲基-3-羟吡啶-3-吡啶碳酸酯和2-乙基-6-甲基-3-羟吡啶- n -乙酰-6-氨基己酸酯为原料，以1:3的拓扑化学比例合成了一种新的超分子配合物(组合物№1)。采用低雌激素致骨质疏松症Wistar系白种雌性大鼠60只，研究了50 mg/kg剂量下该超分子复合物的骨保护活性。在实验第57天评估复合物的骨保护活性的有效性。结果与讨论:新型超分子复合物(组合物№1)具有骨保护活性，其表现为改善x射线和组织形态学样品的指标。口服剂量为50 mg/kg的组合物№1导致骨密度增加至2.55±0.02 g/cm3，比对照组(1.92±0.01 g/cm3)高1.3倍(p≤0.05)，并通过改善骨皮质和骨小梁结构减少骨吸收。结论:所获得的数据表征了研究组合物№1用于纠正和预防低雌激素性骨质疏松症的前景。图形抽象
{"title":"Method for obtaining supramolecular complex based on 3-ohypyridine derivatives and its application for correction of osteoporosis","authors":"K. S. Trunov","doi":"10.18413/rrpharmacology.9.10039","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10039","url":null,"abstract":"Introduction: Currently, there are no safe and ideal medicines for the prevention and treatment of oophorectomy-induced osteoporosis. The development of an effective pharmacotherapy for hypoestrogen-induced osteoporosis is an important task of pharmacology.\u0000Materials and Methods: A new supramolecular complex (composition №1) was obtained on the basis of 3-hydroxypyridine derivatives: 2-ethyl-6-methyl-3-hydroxypyridinium 3-pyridinocarbonoate and 2-ethyl-6-methyl-3-hydroxypyridinium N-acetyl-6-aminohexanoate in a ratio of 1:3 by topochemical synthesis. The study of the osteoprotective activity of the supramolecular complex at a dose of 50 mg/kg was performed on 60 white female rats of the Wistar line on a model of hypoestrogen-induced osteoporosis. The effectiveness of the osteoprotective activity of the complex was evaluated on the 57th day of the experiment.\u0000Results and Discussion: The new supramolecular complex (composition №1) has osteoprotective activity, which is expressed in improving the indicators of X-ray and histomorphological samples. Oral administration of composition №1 at a dose of 50 mg/kg led to an increase in bone density to values of 2.55±0.02 g/cm3, which is 1.3 times higher than in the control group 1.92±0.01 g/cm3 (p≤0.05) and reduce bone resorption by improving cortical and trabecular bone structures.\u0000Conclusion: The obtained data characterize the prospects of studying composition №1 for the correction and prevention of hypoestrogen-induced osteoporosis.\u0000Graphical Abstract\u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43435010","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}
Pub Date : 2023-07-19DOI: 10.18413/rrpharmacology.9.10038
Павел А. Галенко-Ярошевский, Марина Ю. Раваева, Елена Н. Чуян, Марк А. Задорожний, Виктор Л. Попков, Анаит В. Зеленская, Артур В. Хейгетян, Лусине О. Алуханян, Елизавета В. Стаценко, Мария Ю. Матеренчук, Светлана Александровна Лебедева
Введение. Изменения в системе микроциркуляции (МЦ) отражают нарушения физиологических процессов в организме и служат диагностическим и прогностическим фактором многих патологических состояний, в том числе, воспалительных поражений тканей пародонта. Поскольку в патогенезе микроциркуляторных расстройств важную роль играют процессы свободно-радикального окисления, препараты, обладающие антиоксидантным действием, представляют определенный интерес с точки зрения фармакологической коррекции нарушений кровотока в пародонтальном комплексе. Представляло интерес провести сравнительную оценку влияния Содерм®-Форте, Цитофлавина® и их сочетания на МЦ в слизистой оболочке десны крыс. Цель исследования – выявить наличие способности Содерм®-Форте, Цитофлавина® и их сочетания повышать микроциркуляцию в слизистой оболочке десны крыс. Материалы и методы. Исследование МЦ в слизистой десны крыс проводили методом лазерной допплеровской флоуметрии. Было сформировано 4 группы крыс по 10 особей в каждой: 1 группа контрольная; 2-4 – подопытные, животным которых наносили гель Содерм®-Форте на слизистую десны нижних резцов, инъецировали Цитофлавин® (100 мг/кг внутрибрюшинно – в/бр) и наносили гель Содерм®-Форте на слизистую десны на фоне в/бр введения Цитофлавина® соответственно. Показатели кровотока регистрировали через 30 и 60 мин. Результаты и их обсуждение. Содерм®-Форте увеличивал МЦ слизистой десны за счет повышения базального уровня NO, активности прекапиллярных сфинктеров и метартериол, снижения активности адренергических вазомоторов. Цитофлавин® повышал активность прекапиллярных сфинктеров и метартериол, внесосудистых компонентов МЦ, не изменял перфузию слизистой десны. Сочетание Содерм®-Форте и Цитофлавина® повышало МЦ в меньшей степени, чем Содерм®-Форте, но более выраженно, чем Цитофлавин®. Заключение. По способности увеличивать кровоток в слизистой десны крыс исследованные вещества и их сочетание можно расположить в следующий ряд: Содерм®-Форте > Содерм®-Форте + Цитофлавин® > Цитофлавин®. Графическая аннотация
{"title":"Сравнительная оценка влияния Содерм®-Форте, Цитофлавина® и их сочетания на микроциркуляцию в слизистой десны крыс","authors":"Павел А. Галенко-Ярошевский, Марина Ю. Раваева, Елена Н. Чуян, Марк А. Задорожний, Виктор Л. Попков, Анаит В. Зеленская, Артур В. Хейгетян, Лусине О. Алуханян, Елизавета В. Стаценко, Мария Ю. Матеренчук, Светлана Александровна Лебедева","doi":"10.18413/rrpharmacology.9.10038","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10038","url":null,"abstract":"Введение. Изменения в системе микроциркуляции (МЦ) отражают нарушения физиологических процессов в организме и служат диагностическим и прогностическим фактором многих патологических состояний, в том числе, воспалительных поражений тканей пародонта. Поскольку в патогенезе микроциркуляторных расстройств важную роль играют процессы свободно-радикального окисления, препараты, обладающие антиоксидантным действием, представляют определенный интерес с точки зрения фармакологической коррекции нарушений кровотока в пародонтальном комплексе. Представляло интерес провести сравнительную оценку влияния Содерм®-Форте, Цитофлавина® и их сочетания на МЦ в слизистой оболочке десны крыс. Цель исследования – выявить наличие способности Содерм®-Форте, Цитофлавина® и их сочетания повышать микроциркуляцию в слизистой оболочке десны крыс.\u0000 Материалы и методы. Исследование МЦ в слизистой десны крыс проводили методом лазерной допплеровской флоуметрии. Было сформировано 4 группы крыс по 10 особей в каждой: 1 группа контрольная; 2-4 – подопытные, животным которых наносили гель Содерм®-Форте на слизистую десны нижних резцов, инъецировали Цитофлавин® (100 мг/кг внутрибрюшинно – в/бр) и наносили гель Содерм®-Форте на слизистую десны на фоне в/бр введения Цитофлавина® соответственно. Показатели кровотока регистрировали через 30 и 60 мин.\u0000Результаты и их обсуждение. Содерм®-Форте увеличивал МЦ слизистой десны за счет повышения базального уровня NO, активности прекапиллярных сфинктеров и метартериол, снижения активности адренергических вазомоторов. Цитофлавин® повышал активность прекапиллярных сфинктеров и метартериол, внесосудистых компонентов МЦ, не изменял перфузию слизистой десны. Сочетание Содерм®-Форте и Цитофлавина® повышало МЦ в меньшей степени, чем Содерм®-Форте, но более выраженно, чем Цитофлавин®.\u0000Заключение. По способности увеличивать кровоток в слизистой десны крыс исследованные вещества и их сочетание можно расположить в следующий ряд: Содерм®-Форте > Содерм®-Форте + Цитофлавин® > Цитофлавин®.\u0000Графическая аннотация","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48293708","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}
Pub Date : 2023-07-01DOI: 10.18413/rrpharmacology.9.10037
Елена А. Лунева
Введение. За последние десятилетия значительно продвинулся фармакоэкономический анализ множественных заболеваний: в частности, наиболее распространенным является анализ экономической эффективности. Химиотерапия остается ведущим и наиболее эффективным методом лечения мелкоклеточного рака легкого, на долю которого приходится более четверти всех других форм рака органов дыхания. Материалы и методы. Проведена оценка заболеваемости раком легкого и его вероятных причин. Основными методами, использованными в исследовании, были анализ «стоимости лечения», анализ ABC/VEN и анализ «затраты – эффективности». Оценивались также показатели выживаемости (количество лет или месяцев, интервал и среднее число лет/месяцев) и стоимость месяца жизни. Обсуждение. Результаты, полученные на основе анкетирования больных раком легкого, свидетельствуют о том, что ведущим фактором риска является курение – 24,9%. Автор выделил самые дорогие лекарственные препараты стоимостью 60-80% бюджета, то есть схема 2 «этопозид + карбоплатин», и наименее дорогие лекарственные препараты стоимостью 5-10% бюджета, являющиеся вспомогательными лекарственными препаратами. Согласно результатам исследования, пациенты, получающие лечение по схеме химиотерапии «этопозид + карбоплатин», имеют самую высокую выживаемость при наибольшей стоимости лечения по сравнению с пациентами, получающими наименее дорогостоящую схему химиотерапии «циклофосфамид + доксорубицин + винкристин». Заключение. Доказательная комплексная фармакоэкономическая модель оценки лекарственного обеспечения химиотерапии при мелкоклеточном раке легкого улучшает регистрацию анамнезных случаев и позволяет проводить фармакоэкономический анализ экономической эффективности с учетом особенностей каждого пациента. Графический абстракт
{"title":"Фармакоэкономическая оценка лекарственного обеспечения химиотерапии мелкоклеточного рака легкого","authors":"Елена А. Лунева","doi":"10.18413/rrpharmacology.9.10037","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10037","url":null,"abstract":"Введение. За последние десятилетия значительно продвинулся фармакоэкономический анализ множественных заболеваний: в частности, наиболее распространенным является анализ экономической эффективности. Химиотерапия остается ведущим и наиболее эффективным методом лечения мелкоклеточного рака легкого, на долю которого приходится более четверти всех других форм рака органов дыхания.\u0000Материалы и методы. Проведена оценка заболеваемости раком легкого и его вероятных причин. Основными методами, использованными в исследовании, были анализ «стоимости лечения», анализ ABC/VEN и анализ «затраты – эффективности». Оценивались также показатели выживаемости (количество лет или месяцев, интервал и среднее число лет/месяцев) и стоимость месяца жизни.\u0000Обсуждение. Результаты, полученные на основе анкетирования больных раком легкого, свидетельствуют о том, что ведущим фактором риска является курение – 24,9%. Автор выделил самые дорогие лекарственные препараты стоимостью 60-80% бюджета, то есть схема 2 «этопозид + карбоплатин», и наименее дорогие лекарственные препараты стоимостью 5-10% бюджета, являющиеся вспомогательными лекарственными препаратами. Согласно результатам исследования, пациенты, получающие лечение по схеме химиотерапии «этопозид + карбоплатин», имеют самую высокую выживаемость при наибольшей стоимости лечения по сравнению с пациентами, получающими наименее дорогостоящую схему химиотерапии «циклофосфамид + доксорубицин + винкристин».\u0000Заключение. Доказательная комплексная фармакоэкономическая модель оценки лекарственного обеспечения химиотерапии при мелкоклеточном раке легкого улучшает регистрацию анамнезных случаев и позволяет проводить фармакоэкономический анализ экономической эффективности с учетом особенностей каждого пациента.\u0000Графический абстракт\u0000","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46951826","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}
Pub Date : 2023-06-30DOI: 10.18413/rrpharmacology.9.10033
Abdullah AL-Dhuraibi, A. Alkhawaldeh, Wadah Mohammed Al-Dhuraibi, A. Peresypkina, V. Soldatov
Introduction: Immune thrombocytopenia (ITP) is a complex autoimmune syndrome associated with low platelet count. Eltrombopag is an oral thrombopoietin receptor agonist that used in the treatment of chronic ITP. The aim of the study: The present meta-analysis is to evaluate the safety and efficiency of Eltrombopag in theprevention and therapy of ITP. Materials and Methods: The analysis was performed according to the PRISMA guideline with use of Excerpta MedicaDatabase (EMBASE) as well as Web of Science and the Cochrane (CENTAL) databases. Results: Seven randomized controlled trials (N=766 patients) were included in the final analysis. Overall platelet response was significantly higher in the Eltrombopag group than in placebo (RR=3.90; 95%CI [2.89-5.25];P<0.00001) showing mild heterogeneity (I2=45%). Incidences of significant bleeding events in Eltrombopaggroup (World Health Organization [WHO] grades II-IV) (RR=0.63; 95% CI: [0.47-0.85]; P=0.003) showed lowerheterogeneity (I2=18%) in comparison to placebo group. Cases of use of rescue medications in Eltrombopag group compared to placebo group (RR=0.40; 95% CI: [0.29- 0.55]; P<0.00001) in all considered studies showed low heterogeneity (I2=41 %; P=0.16). Incidences of any bleeding in Eltrombopag group compared to placebo group(RR=0.77; 95% CI: [0.70-0.86]; P<0.00001; I2=65%) showed substantial heterogeneity. Finally, subgroup analysis of Eltrombopag efficiency revealed significant difference in frequency of bleeding cases between adults (RR=0.84)and children (RR=0.51); (P=0.005). Conclusion: This systematic review presents class one evidence suggesting Eltrombopag as safe and effective drug for therapy of both children and adult patients with ITP.
{"title":"Evaluation safety, efficacy and pharmacokinetic of Eltrombopag in patients with chronic immune thrombocytopenia: Meta-analysis of randomized controlled trials","authors":"Abdullah AL-Dhuraibi, A. Alkhawaldeh, Wadah Mohammed Al-Dhuraibi, A. Peresypkina, V. Soldatov","doi":"10.18413/rrpharmacology.9.10033","DOIUrl":"https://doi.org/10.18413/rrpharmacology.9.10033","url":null,"abstract":"Introduction: Immune thrombocytopenia (ITP) is a complex autoimmune syndrome associated with low platelet count. Eltrombopag is an oral thrombopoietin receptor agonist that used in the treatment of chronic ITP.\u0000The aim of the study: The present meta-analysis is to evaluate the safety and efficiency of Eltrombopag in theprevention and therapy of ITP.\u0000Materials and Methods: The analysis was performed according to the PRISMA guideline with use of Excerpta MedicaDatabase (EMBASE) as well as Web of Science and the Cochrane (CENTAL) databases.\u0000Results: Seven randomized controlled trials (N=766 patients) were included in the final analysis. Overall platelet response was significantly higher in the Eltrombopag group than in placebo (RR=3.90; 95%CI [2.89-5.25];P<0.00001) showing mild heterogeneity (I2=45%). Incidences of significant bleeding events in Eltrombopaggroup (World Health Organization [WHO] grades II-IV) (RR=0.63; 95% CI: [0.47-0.85]; P=0.003) showed lowerheterogeneity (I2=18%) in comparison to placebo group. Cases of use of rescue medications in Eltrombopag group compared to placebo group (RR=0.40; 95% CI: [0.29- 0.55]; P<0.00001) in all considered studies showed low heterogeneity (I2=41 %; P=0.16). Incidences of any bleeding in Eltrombopag group compared to placebo group(RR=0.77; 95% CI: [0.70-0.86]; P<0.00001; I2=65%) showed substantial heterogeneity. Finally, subgroup analysis of Eltrombopag efficiency revealed significant difference in frequency of bleeding cases between adults (RR=0.84)and children (RR=0.51); (P=0.005).\u0000Conclusion: This systematic review presents class one evidence suggesting Eltrombopag as safe and effective drug for therapy of both children and adult patients with ITP.","PeriodicalId":21030,"journal":{"name":"Research Results in Pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44203452","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}
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