Pub Date : 2023-07-20DOI: 10.15825/1995-1191-2023-3-31-37
M. Bekov, I. Pashkov, N. Mozheiko, R. Latypov, D. Oleshkevich, K. S. Smirnov, E. Shigaev, Y. S. Yakunin, S. Gautier
Bronchial complications, along with development and progression of chronic dysfunction on the background of chronic rejection, are factors that reduce the quality and life of lung and heart-lung recipients. They also increase the frequency of hospitalizations. Application of cryotechnology is based on the contact effect of extremely low temperatures on organs and tissues using a cryoprobe. This article demonstrates the experience of using cryotechnology in the diagnosis and treatment of complications in lung and heart-lung recipients.
{"title":"Cryotechnology in lung and heart-lung transplantation","authors":"M. Bekov, I. Pashkov, N. Mozheiko, R. Latypov, D. Oleshkevich, K. S. Smirnov, E. Shigaev, Y. S. Yakunin, S. Gautier","doi":"10.15825/1995-1191-2023-3-31-37","DOIUrl":"https://doi.org/10.15825/1995-1191-2023-3-31-37","url":null,"abstract":"Bronchial complications, along with development and progression of chronic dysfunction on the background of chronic rejection, are factors that reduce the quality and life of lung and heart-lung recipients. They also increase the frequency of hospitalizations. Application of cryotechnology is based on the contact effect of extremely low temperatures on organs and tissues using a cryoprobe. This article demonstrates the experience of using cryotechnology in the diagnosis and treatment of complications in lung and heart-lung recipients.","PeriodicalId":21400,"journal":{"name":"Russian Journal of Transplantology and Artificial Organs","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139357404","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 : 2023-07-17DOI: 10.15825/1995-1191-2023-3-122-128
M. Zhulkov, I. Zykov, A. G. Makaev, A. Protopopov, M. Murtazaliev, F. Kosimov, A. Tarkova, A. D. Limansky, Ya. M. Smirnov, H. Agaeva, O. Frykina, D. A. Sirota
Objective: to develop and approve the surgical technique for explantation of a functioning cardiopulmonary complex under normothermic autoperfusion.Materials and methods. Landrace pigs were used as the experimental model for a series of acute experiments (n = 10). During the experiment, invasive pressure in the cavities of the heart and main arteries, blood gas composition, and myocardial contractility were monitored. The functioning cardiopulmonary complex was explanted through a median sternotomy. The explanted complex was conditioned at 37–38 °C for 6 hours.Results. In the course of a series of experiments, it was shown that stable operation of the isolated heart-lung complex ex vivo for 6 hours was fundamentally possible provided that the parameters of the basic homeostasis constants are maintained. The technological solutions used made it possible to ensure safe hemodynamic and anatomical isolation of the working cardiopulmonary complex.Conclusion. The developed protocol for isolating a functioning cardiopulmonary complex allows to provide stable graft function for 6 hours under normothermic autoperfusion. Implementation of this concept in the development of transport systems would significantly facilitate their design and eliminate the use of expensive components. This would contribute to widespread introduction into clinical practice.
{"title":"Surgical technique for explantation of a functioning cardiopulmonary complex in an experiment","authors":"M. Zhulkov, I. Zykov, A. G. Makaev, A. Protopopov, M. Murtazaliev, F. Kosimov, A. Tarkova, A. D. Limansky, Ya. M. Smirnov, H. Agaeva, O. Frykina, D. A. Sirota","doi":"10.15825/1995-1191-2023-3-122-128","DOIUrl":"https://doi.org/10.15825/1995-1191-2023-3-122-128","url":null,"abstract":"Objective: to develop and approve the surgical technique for explantation of a functioning cardiopulmonary complex under normothermic autoperfusion.Materials and methods. Landrace pigs were used as the experimental model for a series of acute experiments (n = 10). During the experiment, invasive pressure in the cavities of the heart and main arteries, blood gas composition, and myocardial contractility were monitored. The functioning cardiopulmonary complex was explanted through a median sternotomy. The explanted complex was conditioned at 37–38 °C for 6 hours.Results. In the course of a series of experiments, it was shown that stable operation of the isolated heart-lung complex ex vivo for 6 hours was fundamentally possible provided that the parameters of the basic homeostasis constants are maintained. The technological solutions used made it possible to ensure safe hemodynamic and anatomical isolation of the working cardiopulmonary complex.Conclusion. The developed protocol for isolating a functioning cardiopulmonary complex allows to provide stable graft function for 6 hours under normothermic autoperfusion. Implementation of this concept in the development of transport systems would significantly facilitate their design and eliminate the use of expensive components. This would contribute to widespread introduction into clinical practice.","PeriodicalId":21400,"journal":{"name":"Russian Journal of Transplantology and Artificial Organs","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139358720","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 : 2023-07-17DOI: 10.15825/1995-1191-2023-3-87-96
E. A. Nemets, A. I. Khairullina, V. Y. Belov, V. A. Surguchenko, V. N. Vasilets, V. Sevastianov, E. Volkova, Y. Basok
High surgical porosity (SP) is one of the causes of significant blood loss, as well as hematoma formation. So, reducing the SP of small-diameter vascular grafts (VGs) is a crucial task.The objective of this work was to develop a technology for the formation of polycaprolactone (PCL)-based small-diameter VGs with a bioactive coating with reduced SP.Materials and methods. Porous VGs with an inner diameter of 3 mm were fabricated by electrospinning from 5% PCL solution with addition of 5–30% gelatin (PCL/G) on an NANON-01A unit (MECC CO, Japan). Bioactive coating was applied by sequential incubation of VGs in solutions of bovine serum albumin, heparin and platelet lysate with fixation in a glutaric aldehyde solution. The surface structure and mechanical properties of the samples were investigated. Functional properties of the bioactive VGs were evaluated in relation to their interaction with cell cultures in vitro.Results. It was found that introduction of gelatin into the working solution reduces SP from 30.4 ± 1.5 mL/(cm2 ·min) to 2.8 ± 0.5 ml/(cm2 ·min). It was shown that at a PCL/gelatin ratio of 9 : 1, the outer and inner sides of the bioactive VGs samples are characterized by surface uniformity (no defects), mechanical properties close to blood vessels of the same diameter (Young’s modulus 6.7 ± 2.1 MPa, tensile strength 26.7 ± 4.9 N and elongation to break 423 ± 80%) and ability to support adhesion and proliferation of human umbilical vein endothelial cell line, EA.hy926.Conclusion. Introduction of 10% gelatin content (by the polymer weight) into PCL solution reduces the SP of small-diameter VGs, leads to uniformity in their inner and outer surface, improvement in their mechanical properties without reducing their ability to support adhesion and proliferation of vascular endothelial cells.
{"title":"Technique for reducing the surgical porosity of small-diameter vascular grafts","authors":"E. A. Nemets, A. I. Khairullina, V. Y. Belov, V. A. Surguchenko, V. N. Vasilets, V. Sevastianov, E. Volkova, Y. Basok","doi":"10.15825/1995-1191-2023-3-87-96","DOIUrl":"https://doi.org/10.15825/1995-1191-2023-3-87-96","url":null,"abstract":"High surgical porosity (SP) is one of the causes of significant blood loss, as well as hematoma formation. So, reducing the SP of small-diameter vascular grafts (VGs) is a crucial task.The objective of this work was to develop a technology for the formation of polycaprolactone (PCL)-based small-diameter VGs with a bioactive coating with reduced SP.Materials and methods. Porous VGs with an inner diameter of 3 mm were fabricated by electrospinning from 5% PCL solution with addition of 5–30% gelatin (PCL/G) on an NANON-01A unit (MECC CO, Japan). Bioactive coating was applied by sequential incubation of VGs in solutions of bovine serum albumin, heparin and platelet lysate with fixation in a glutaric aldehyde solution. The surface structure and mechanical properties of the samples were investigated. Functional properties of the bioactive VGs were evaluated in relation to their interaction with cell cultures in vitro.Results. It was found that introduction of gelatin into the working solution reduces SP from 30.4 ± 1.5 mL/(cm2 ·min) to 2.8 ± 0.5 ml/(cm2 ·min). It was shown that at a PCL/gelatin ratio of 9 : 1, the outer and inner sides of the bioactive VGs samples are characterized by surface uniformity (no defects), mechanical properties close to blood vessels of the same diameter (Young’s modulus 6.7 ± 2.1 MPa, tensile strength 26.7 ± 4.9 N and elongation to break 423 ± 80%) and ability to support adhesion and proliferation of human umbilical vein endothelial cell line, EA.hy926.Conclusion. Introduction of 10% gelatin content (by the polymer weight) into PCL solution reduces the SP of small-diameter VGs, leads to uniformity in their inner and outer surface, improvement in their mechanical properties without reducing their ability to support adhesion and proliferation of vascular endothelial cells.","PeriodicalId":21400,"journal":{"name":"Russian Journal of Transplantology and Artificial Organs","volume":"212 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139358744","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 : 2023-07-17DOI: 10.15825/1995-1191-2023-3-38-49
S. Voskanyan, V. L. Korobka, V. Syutkin, A. R. Monakhov, A. Maltseva, E. Pak, R. V. Korobka, E. I. Kolodyazhny, S. Zubenko, Yu. V. Voskanyan, V. Y. Kotsiyaev
Graft-versus-host disease (GvHD) after liver transplantation (LT) occurs in 0.2–0.3% of liver transplant recipients. Each case is characterized by individual peculiarities of the clinical picture. There are no standards or clinical guidelines for the treatment of GvHD in solid organ recipients; mortality remains very high among these patients. We present two clinical cases of verified GvHD that developed early after LT, and we offer a brief review of the current state of the art in the study of this problem.
{"title":"Development of graft-versus-host disease in a liver recipient. Clinical observations and literature review","authors":"S. Voskanyan, V. L. Korobka, V. Syutkin, A. R. Monakhov, A. Maltseva, E. Pak, R. V. Korobka, E. I. Kolodyazhny, S. Zubenko, Yu. V. Voskanyan, V. Y. Kotsiyaev","doi":"10.15825/1995-1191-2023-3-38-49","DOIUrl":"https://doi.org/10.15825/1995-1191-2023-3-38-49","url":null,"abstract":"Graft-versus-host disease (GvHD) after liver transplantation (LT) occurs in 0.2–0.3% of liver transplant recipients. Each case is characterized by individual peculiarities of the clinical picture. There are no standards or clinical guidelines for the treatment of GvHD in solid organ recipients; mortality remains very high among these patients. We present two clinical cases of verified GvHD that developed early after LT, and we offer a brief review of the current state of the art in the study of this problem.","PeriodicalId":21400,"journal":{"name":"Russian Journal of Transplantology and Artificial Organs","volume":"74 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139358559","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 : 2023-07-16DOI: 10.15825/1995-1191-2023-2-158-166
I. Pashkov, S. Gautier, V. Bogdanov, D. Oleshkevich, D. M. Bondarenko, N. Mozheiko, N. S. Bunenkov, N. V. Grudinin
The continued unavailability of adequate organs for transplantation to meet the existing demand has resulted in a major challenge in transplantology. This is especially felt in lung transplantation (LTx). LTx is the only effective method of treatment for patients with end-stage lung diseases. Normothermic ex vivo lung perfusion (EVLP) has been proposed to increase the number of donor organs suitable for transplant – EVLP has proven itself in a number of clinical trials. The ability to restore suboptimal donor lungs, previously considered unsuitable for transplantation, can improve organ functionality, and thus increase the number of lung transplants. However, widespread implementation of ex vivo perfusion is associated with high financial costs for consumables and perfusate.Objective: to test the developed solution on an ex vivo lung perfusion model, followed by orthotopic LT under experimental conditions.Materials and methods. The experiment included lung explantation stages, static hypothermic storage, EVLP and orthotopic left LTx. Perfusion was performed in a closed perfusion system. We used our own made human albumin-based perfusion solution as perfusate. Perfusion lasted for 2 hours, and evaluation was carried out every 30 minutes. In all cases, static hypothermic storage after perfusion lasted for 4 hours. The orthotopic single-lung transplantation procedure was performed using assisted circulation, supplemented by membrane oxygenation. Postoperative follow-up was 2 hours, after which the experimental animal was euthanized.Results. Respiratory index before lung explantation was 310 ± 40 mmHg. The PaO2/FiO2 ratio had positive growth dynamics throughout the entire EVLP procedure. Oxygenation index was 437 ± 25 mm Hg after 120 minutes of perfusion. Throughout the entire EVLP procedure, there was a steady decrease in pulmonary vascular resistance (PVR). Initial PVR was 300 ± 100 dyn×s/cm5; throughout the EVLP, PVR tended to fall, reaching 38,5 ± 12 dyn×s/cm5 at the end of perfusion.Conclusion. A safe and effective EVLP using our perfusate is possible. The developed orthotopic left lung transplantation protocol under circulatory support conditions, supplemented by membrane oxygenation, showed it is efficient and reliable.
由于仍然没有足够的移植器官来满足现有的需求，这对移植学造成了重大挑战。这在肺移植(LTx)中尤其明显。LTx是终末期肺部疾病患者唯一有效的治疗方法。常温离体肺灌注(EVLP)已被提出用于增加适合移植的供体器官数量，EVLP已在许多临床试验中得到证明。先前被认为不适合移植的次优供体肺的恢复能力可以改善器官功能，从而增加肺移植的数量。然而，体外灌注的广泛实施与耗材和灌注液的高财务成本有关。目的:在离体肺灌注模型上验证所研制的溶液，并在实验条件下进行原位肝移植。材料和方法。实验包括肺移植阶段、静态低温储存、EVLP和原位左LTx。灌注在封闭的灌注系统中进行。我们用自己研制的人白蛋白基灌注液作为灌注液。灌注2小时，每30分钟评估一次。所有病例均在灌注后静置低温保存4小时。原位单肺移植手术采用辅助循环，辅以膜氧合。术后随访2小时，对实验动物实施安乐死。肺移植前呼吸指数为310±40 mmHg。在整个EVLP过程中，PaO2/FiO2比率呈正增长动态。灌注120 min后氧合指数为437±25 mm Hg。在整个EVLP过程中，肺血管阻力(PVR)稳步下降。初始PVR为300±100 dyn×s/cm5;在整个EVLP过程中，PVR呈下降趋势，灌注结束时PVR达到38.5±12 dyn×s/cm5。使用我们的灌注液进行安全有效的EVLP是可能的。在循环支持条件下发展的原位左肺移植方案，辅以膜氧合，证明是有效和可靠的。
{"title":"Normothermic ex vivo lung perfusion using a developed solution followed by orthotopic left lung transplantation (experimental study)","authors":"I. Pashkov, S. Gautier, V. Bogdanov, D. Oleshkevich, D. M. Bondarenko, N. Mozheiko, N. S. Bunenkov, N. V. Grudinin","doi":"10.15825/1995-1191-2023-2-158-166","DOIUrl":"https://doi.org/10.15825/1995-1191-2023-2-158-166","url":null,"abstract":"The continued unavailability of adequate organs for transplantation to meet the existing demand has resulted in a major challenge in transplantology. This is especially felt in lung transplantation (LTx). LTx is the only effective method of treatment for patients with end-stage lung diseases. Normothermic ex vivo lung perfusion (EVLP) has been proposed to increase the number of donor organs suitable for transplant – EVLP has proven itself in a number of clinical trials. The ability to restore suboptimal donor lungs, previously considered unsuitable for transplantation, can improve organ functionality, and thus increase the number of lung transplants. However, widespread implementation of ex vivo perfusion is associated with high financial costs for consumables and perfusate.Objective: to test the developed solution on an ex vivo lung perfusion model, followed by orthotopic LT under experimental conditions.Materials and methods. The experiment included lung explantation stages, static hypothermic storage, EVLP and orthotopic left LTx. Perfusion was performed in a closed perfusion system. We used our own made human albumin-based perfusion solution as perfusate. Perfusion lasted for 2 hours, and evaluation was carried out every 30 minutes. In all cases, static hypothermic storage after perfusion lasted for 4 hours. The orthotopic single-lung transplantation procedure was performed using assisted circulation, supplemented by membrane oxygenation. Postoperative follow-up was 2 hours, after which the experimental animal was euthanized.Results. Respiratory index before lung explantation was 310 ± 40 mmHg. The PaO2/FiO2 ratio had positive growth dynamics throughout the entire EVLP procedure. Oxygenation index was 437 ± 25 mm Hg after 120 minutes of perfusion. Throughout the entire EVLP procedure, there was a steady decrease in pulmonary vascular resistance (PVR). Initial PVR was 300 ± 100 dyn×s/cm5; throughout the EVLP, PVR tended to fall, reaching 38,5 ± 12 dyn×s/cm5 at the end of perfusion.Conclusion. A safe and effective EVLP using our perfusate is possible. The developed orthotopic left lung transplantation protocol under circulatory support conditions, supplemented by membrane oxygenation, showed it is efficient and reliable.","PeriodicalId":21400,"journal":{"name":"Russian Journal of Transplantology and Artificial Organs","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84378330","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 : 2023-07-16DOI: 10.15825/1995-1191-2023-2-167-169
D. A. Altman, O. Tsirulnikova, A. Poltorak, V. V. Pchelnikov, B. Sarsenbayev, А. S. Ryzhykh, I. Y. Bondarevsky, Е. G. Muravyeva
Objective: to analyze the possibility of using the liver of a donor undergoing hemodialysis as a transplant.Materials and methods. A case of successful liver transplantation (LT) from a 40-year-old deceased donor, who had been on hemodialysis for 10 years for chronic pyelonephritis and nephrosclerosis, is presented. Of the known hemodialysis complications of chronic kidney disease, the donor’s medical records showed anemia and grade 3 arterial hypertension.Results. The recipient’s post-LT period had no significant differences from the postoperative period of those that received liver from donors with standard criteria.Conclusion. Our first experience with the use of a liver transplant from a donor who was on hemodialysis, in the absence of other risk factors, suggests that the liver of this category of donors can be used for transplantation.
{"title":"Successful liver transplantation from a deceased donor who was on hemodialysis for 10 years","authors":"D. A. Altman, O. Tsirulnikova, A. Poltorak, V. V. Pchelnikov, B. Sarsenbayev, А. S. Ryzhykh, I. Y. Bondarevsky, Е. G. Muravyeva","doi":"10.15825/1995-1191-2023-2-167-169","DOIUrl":"https://doi.org/10.15825/1995-1191-2023-2-167-169","url":null,"abstract":"Objective: to analyze the possibility of using the liver of a donor undergoing hemodialysis as a transplant.Materials and methods. A case of successful liver transplantation (LT) from a 40-year-old deceased donor, who had been on hemodialysis for 10 years for chronic pyelonephritis and nephrosclerosis, is presented. Of the known hemodialysis complications of chronic kidney disease, the donor’s medical records showed anemia and grade 3 arterial hypertension.Results. The recipient’s post-LT period had no significant differences from the postoperative period of those that received liver from donors with standard criteria.Conclusion. Our first experience with the use of a liver transplant from a donor who was on hemodialysis, in the absence of other risk factors, suggests that the liver of this category of donors can be used for transplantation.","PeriodicalId":21400,"journal":{"name":"Russian Journal of Transplantology and Artificial Organs","volume":"462 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82989810","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 : 2023-07-16DOI: 10.15825/1995-1191-2023-2-170-177
V. A. Ryzhikova, E. G. Kuznetsova, O. M. Kuryleva, L. A. Salomatina, S. V. Kursakov, A. Nikolskaya, V. Sevastianov
In recent years, oxidative stress, characterized by excess free radicals in the body, has been called the cause of many diseases. There is an active search for drugs with antioxidant properties that are suitable for long-term maintenance therapy. Nicotinamide (NAM), an antioxidant, is used to treat a variety of diseases, usually in oral or injectable form. Given the peculiarities of the drug regimen (dose, prolonged administration), a new dosage form of NAM, a microemulsion-based transdermal patch (TP), containing 20 mg/10 cm2 of NAM, has been proposed.The objective of this work is to compare the pharmacokinetic parameters of intramuscular and transdermal NAM administration in animal experiments for 24 hours.Materials and methods. We used laboratory samples of nicotinamide TP based on a microemulsion-based transdermal delivery emulsion (TDS) with different content of sodium docusate transfer activator. The pharmacokinetics of transdermal and intramuscular injections were studied in male Chinchilla rabbits weighing 3.5–4.0 kg. Plasma NAM levels of the experimental animals were determined by high-performance liquid chromatography using a specially designed method on NUCLEODUR PFP columns (5 μm, 250 × 4.6 mm) using the mobile phase acetonitrile: deionized water. The samples were preliminarily purified by solid-phase extraction using Chromabond C18 Hydra cartridges.Results. When administered intramuscularly, the maximum blood NAM level was 13.3±1 μg/mL; when NAM transdermal forms were applied in the same dosage with different contents of the transfer activator, the levels did not differ significantly – 3.1 and 3.2 μg/mL. It was shown that in transdermal administration of NAM, concentration of the active substance remained at a constant level for ~6 hours. The bioavailability of NAM with transdermal administration was calculated relative to intramuscular administration: 1.43 for TP with 9.8% docusate sodium and 1.84 with 3.3% docusate sodium.Conclusion. NAM has a higher bioavailability when administered transdermally at 20 mg than when administered intramuscularly in the same dose. With transdermal administration, NAM concentration can be maintained at a constant level for a long time, without the jumps that are typical of intramuscular administration.
{"title":"Comparative analysis of the pharmacokinetic parameters of transdermal and injectable forms of nicotinamide","authors":"V. A. Ryzhikova, E. G. Kuznetsova, O. M. Kuryleva, L. A. Salomatina, S. V. Kursakov, A. Nikolskaya, V. Sevastianov","doi":"10.15825/1995-1191-2023-2-170-177","DOIUrl":"https://doi.org/10.15825/1995-1191-2023-2-170-177","url":null,"abstract":"In recent years, oxidative stress, characterized by excess free radicals in the body, has been called the cause of many diseases. There is an active search for drugs with antioxidant properties that are suitable for long-term maintenance therapy. Nicotinamide (NAM), an antioxidant, is used to treat a variety of diseases, usually in oral or injectable form. Given the peculiarities of the drug regimen (dose, prolonged administration), a new dosage form of NAM, a microemulsion-based transdermal patch (TP), containing 20 mg/10 cm2 of NAM, has been proposed.The objective of this work is to compare the pharmacokinetic parameters of intramuscular and transdermal NAM administration in animal experiments for 24 hours.Materials and methods. We used laboratory samples of nicotinamide TP based on a microemulsion-based transdermal delivery emulsion (TDS) with different content of sodium docusate transfer activator. The pharmacokinetics of transdermal and intramuscular injections were studied in male Chinchilla rabbits weighing 3.5–4.0 kg. Plasma NAM levels of the experimental animals were determined by high-performance liquid chromatography using a specially designed method on NUCLEODUR PFP columns (5 μm, 250 × 4.6 mm) using the mobile phase acetonitrile: deionized water. The samples were preliminarily purified by solid-phase extraction using Chromabond C18 Hydra cartridges.Results. When administered intramuscularly, the maximum blood NAM level was 13.3±1 μg/mL; when NAM transdermal forms were applied in the same dosage with different contents of the transfer activator, the levels did not differ significantly – 3.1 and 3.2 μg/mL. It was shown that in transdermal administration of NAM, concentration of the active substance remained at a constant level for ~6 hours. The bioavailability of NAM with transdermal administration was calculated relative to intramuscular administration: 1.43 for TP with 9.8% docusate sodium and 1.84 with 3.3% docusate sodium.Conclusion. NAM has a higher bioavailability when administered transdermally at 20 mg than when administered intramuscularly in the same dose. With transdermal administration, NAM concentration can be maintained at a constant level for a long time, without the jumps that are typical of intramuscular administration.","PeriodicalId":21400,"journal":{"name":"Russian Journal of Transplantology and Artificial Organs","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79270527","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 : 2023-07-16DOI: 10.15825/1995-1191-2023-2-148-157
S. Sharapchenko, A. Mamedova, O. Shevchenko
Federation Clinical outcomes of solid organ transplantation depend on many factors. One of the main factors is the risk of post-transplant complications, which affect allograft and recipient survival. Multifactorial organ damage in post-transplant complications and the search for diagnostic and prognostic indicators of the condition have contributed to the study and selection of a wide range of proteomic and molecular genetic biomarkers, which have shown to be effective in solid organ transplantation. The use of biomarkers opens up additional possibilities for assessing the risk of complications and their early diagnosis. This potentially reduces the frequency of invasive diagnostic procedures. Transforming growth factor beta 1 (TGF-β1) regulates many biological processes, has anti-inflammatory and immunosuppressive effects, participates in immune response, and plays a key role in extracellular matrix (ECM) protein synthesis. ECM dysregulation leads to fibroblast hyperproliferation and increased collagen synthesis and, consequently, tissue fibrosis. The variability of the diagnostic and prognostic potential of TGF-β1 has been demonstrated in studies on recipients of various solid organs. The objective of this review is to analyze recent evidence on the role of TGF-β1 in the development of post-transplant complications and to assess its prospects as a marker of graft pathology or as a target for therapy.
{"title":"Diagnostic and therapeutic potential of transforming growth factor beta 1 in solid organ transplantation: recent research findings","authors":"S. Sharapchenko, A. Mamedova, O. Shevchenko","doi":"10.15825/1995-1191-2023-2-148-157","DOIUrl":"https://doi.org/10.15825/1995-1191-2023-2-148-157","url":null,"abstract":"Federation Clinical outcomes of solid organ transplantation depend on many factors. One of the main factors is the risk of post-transplant complications, which affect allograft and recipient survival. Multifactorial organ damage in post-transplant complications and the search for diagnostic and prognostic indicators of the condition have contributed to the study and selection of a wide range of proteomic and molecular genetic biomarkers, which have shown to be effective in solid organ transplantation. The use of biomarkers opens up additional possibilities for assessing the risk of complications and their early diagnosis. This potentially reduces the frequency of invasive diagnostic procedures. Transforming growth factor beta 1 (TGF-β1) regulates many biological processes, has anti-inflammatory and immunosuppressive effects, participates in immune response, and plays a key role in extracellular matrix (ECM) protein synthesis. ECM dysregulation leads to fibroblast hyperproliferation and increased collagen synthesis and, consequently, tissue fibrosis. The variability of the diagnostic and prognostic potential of TGF-β1 has been demonstrated in studies on recipients of various solid organs. The objective of this review is to analyze recent evidence on the role of TGF-β1 in the development of post-transplant complications and to assess its prospects as a marker of graft pathology or as a target for therapy.","PeriodicalId":21400,"journal":{"name":"Russian Journal of Transplantology and Artificial Organs","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81485723","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 : 2023-07-15DOI: 10.15825/1995-1191-2023-2-82-98
Y. Basok, A. A. Kondratenko, L. Kalyuzhnaya, E. Volkova, K. Vorobyov, V. Sevastianov
Despite great progress in the field of biomaterials for tissue engineering and regenerative medicine, the high requirements placed on artificial matrices (matrices, carriers, scaffolds) are the reason for the ongoing search for natural or synthetic extracellular matrix mimetics. Among such materials, decellularized umbilical cord (UC) stroma appears to be very attractive – it has a high content of hyaluronic acid, cytokines, and growth factors, and there are no ethical restrictions for its production. Decellularized UC stroma has been found to promote cartilage, liver tissue and nerve tissue repair, as well as wound healing. The review critically analyzes and summarizes published data on the ability of decellularized UC stroma to maintain the necessary conditions for adhesion, migration, differentiation and functional activity of adherent cells, thus stimulating the internal (physiological) regenerative potential of tissues. Literature was searched for in the following electronic databases: Medline/PubMed (www/ncbi. nlm.nih.gov/pubmed), Cochrane library (https://www.cochrane.org), and eLIBRARY/Russian Science Citation Index (https://www.elibrary.ru). Inclusion criteria were the presence of biomaterials obtained from decellularized human UC stroma. Exclusion criteria for papers included research objects as decellularized umbilical cord vessels (veins and arteries) and umbilical cord cell cultures. Twenty-five original articles in English and Russian were selected for analysis of the products obtained, their applications, decellularization methods and research results. The review also discusses the prospects for decellularized umbilical cord in medicine.
尽管用于组织工程和再生医学的生物材料领域取得了很大进展，但对人工基质(基质、载体、支架)的高要求是不断寻找天然或合成细胞外基质模拟物的原因。在这些材料中，脱细胞脐带(UC)基质似乎非常有吸引力-它具有高含量的透明质酸，细胞因子和生长因子，并且对其生产没有伦理限制。脱细胞UC基质已被发现促进软骨、肝组织和神经组织修复，以及伤口愈合。这篇综述批判性地分析和总结了关于脱细胞UC间质维持贴壁细胞粘附、迁移、分化和功能活性的必要条件，从而刺激组织内部(生理)再生潜力的已发表数据。在以下电子数据库中检索文献:Medline/PubMed (www.ncbi)。nlm.nih.gov/pubmed)、Cochrane图书馆(https://www.cochrane.org)和eLIBRARY/Russian Science Citation Index (https://www.elibrary.ru)。纳入标准是存在从脱细胞人UC基质中获得的生物材料。论文的排除标准包括研究对象为脱细胞脐带血管(静脉和动脉)和脐带细胞培养物。选取25篇英文和俄文的原创文章，对所获得的产品、应用、脱细胞方法和研究结果进行分析。并对脱细胞脐带在医学上的应用前景进行了展望。
{"title":"Decellularized umbilical cord stroma in tissue engineering and regenerative medicine: a systematic review","authors":"Y. Basok, A. A. Kondratenko, L. Kalyuzhnaya, E. Volkova, K. Vorobyov, V. Sevastianov","doi":"10.15825/1995-1191-2023-2-82-98","DOIUrl":"https://doi.org/10.15825/1995-1191-2023-2-82-98","url":null,"abstract":"Despite great progress in the field of biomaterials for tissue engineering and regenerative medicine, the high requirements placed on artificial matrices (matrices, carriers, scaffolds) are the reason for the ongoing search for natural or synthetic extracellular matrix mimetics. Among such materials, decellularized umbilical cord (UC) stroma appears to be very attractive – it has a high content of hyaluronic acid, cytokines, and growth factors, and there are no ethical restrictions for its production. Decellularized UC stroma has been found to promote cartilage, liver tissue and nerve tissue repair, as well as wound healing. The review critically analyzes and summarizes published data on the ability of decellularized UC stroma to maintain the necessary conditions for adhesion, migration, differentiation and functional activity of adherent cells, thus stimulating the internal (physiological) regenerative potential of tissues. Literature was searched for in the following electronic databases: Medline/PubMed (www/ncbi. nlm.nih.gov/pubmed), Cochrane library (https://www.cochrane.org), and eLIBRARY/Russian Science Citation Index (https://www.elibrary.ru). Inclusion criteria were the presence of biomaterials obtained from decellularized human UC stroma. Exclusion criteria for papers included research objects as decellularized umbilical cord vessels (veins and arteries) and umbilical cord cell cultures. Twenty-five original articles in English and Russian were selected for analysis of the products obtained, their applications, decellularization methods and research results. The review also discusses the prospects for decellularized umbilical cord in medicine.","PeriodicalId":21400,"journal":{"name":"Russian Journal of Transplantology and Artificial Organs","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85519308","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 : 2023-07-15DOI: 10.15825/1995-1191-2023-2-26-37
A. Shabunin, P. Drozdov, D. A. Makeev, I. Nesterenko, O. S. Zhuravel, S. А. Astapovich, E. Lidjieva
Objective: to evaluate the effectiveness of a new device for second warm ischemia (SWI) elimination in kidney transplantation (KT).Materials and methods. The study included clinical and experimental stages. The clinical stage included 63 patients out of 219 who underwent KT at Botkin Moscow City Clinical Hospital between July 2018 and August 2022. The inclusion criteria were kidneys from donation after brain death (DBD) donors with expanded criteria or kidneys from donation after circulatory death (DCD) donors, and an SWI time greater than 45 minutes. The first group consisted of 24 recipients operated on using the new SWI elimination device. The second retrospective control group consisted of 39 patients where sterile ice bags were used at the implantation stage. The groups had no statistically significant differences in the main recipient and donor characteristics, as well as in perioperative parameters. Also, from November 2021 to April 2022, 23 kidney autotransplantation experiments in female Landrace pigs were performed. The animals were cared for in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, 18 March 1986). Efficiency of different SWI elimination techniques was compared on two experimental models: standard donor (group 1, n = 12) and asystolic donor (group 2, n = 11).Results. In the clinical trial group, mean graft temperature (tm) before reperfusion was statistically significantly lower in group 1 using the special SWI elimination device: 6.4 ± 1.7 °C (95% CI 3.2–8.5) versus 22.1 ± 2.3 °C (18.1–24.6), р < 0.001. The risk of delayed graft function (DGF) was 3.86 times higher (95% CI 1.11–13.43) with the standard SWI elimination technique. In the experimental group, in the subgroups using the new device (n = 12), graft tm before reperfusion was 5.1 ± 0.4 °C (95% CI 4.5–5.8), whereas in the ice bag subgroups (n = 11), tm was 29.3 ± 1.3 °C (95% CI 27.7–30.8), which was significantly higher (p < 0.001). The overall 1-week survival of the experimental animals was significantly higher in the SWI elimination device subgroup (logrank p = 0.036).Conclusion. The developed device is effective in eliminating SWI of renal graft.
目的:评价一种新型肾移植第二次热缺血消除装置的效果。材料和方法。该研究包括临床和实验阶段。临床阶段包括2018年7月至2022年8月在莫斯科博特金市临床医院接受KT治疗的219名患者中的63名。纳入标准为扩展标准的脑死亡(DBD)供者捐赠肾脏或循环死亡(DCD)供者捐赠肾脏，SWI时间大于45分钟。第一组24例采用新型SWI消除器。第二个回顾性对照组由39例,无菌冰包在植入阶段使用。两组在主要受体和供体特征以及围手术期参数方面无统计学差异。此外，从2021年11月至2022年4月，在雌性长白猪身上进行了23次肾脏自体移植实验。这些动物是按照《欧洲保护用于实验和其他科学目的的脊椎动物公约》(1986年3月18日，斯特拉斯堡)照料的。比较不同SWI消除技术在标准供体(1组，n = 12)和无收缩供体(2组，n = 11)两种实验模型上的效率。在临床试验组中，使用特殊SWI消除装置的1组再灌注前的平均移植物温度(tm)有统计学意义显著降低:6.4±1.7°C (95% CI 3.2-8.5)与22.1±2.3°C (18.1-24.6)， χ 2 < 0.001。采用标准SWI消除技术，移植延迟功能(DGF)的风险是前者的3.86倍(95% CI 1.11-13.43)。在实验组中，在使用新装置的亚组(n = 12)中，再灌注前移植物tm为5.1±0.4°C (95% CI 4.5-5.8)，而在冰袋亚组(n = 11)中，tm为29.3±1.3°C (95% CI 27.7-30.8)，差异有统计学意义(p < 0.001)。SWI消除装置亚组实验动物的总1周生存率显著高于对照组(logrank p = 0.036)。该装置可有效消除移植肾的SWI。
{"title":"Effect of second warm ischemia elimination on kidney graft function: an experiment and clinical study","authors":"A. Shabunin, P. Drozdov, D. A. Makeev, I. Nesterenko, O. S. Zhuravel, S. А. Astapovich, E. Lidjieva","doi":"10.15825/1995-1191-2023-2-26-37","DOIUrl":"https://doi.org/10.15825/1995-1191-2023-2-26-37","url":null,"abstract":"Objective: to evaluate the effectiveness of a new device for second warm ischemia (SWI) elimination in kidney transplantation (KT).Materials and methods. The study included clinical and experimental stages. The clinical stage included 63 patients out of 219 who underwent KT at Botkin Moscow City Clinical Hospital between July 2018 and August 2022. The inclusion criteria were kidneys from donation after brain death (DBD) donors with expanded criteria or kidneys from donation after circulatory death (DCD) donors, and an SWI time greater than 45 minutes. The first group consisted of 24 recipients operated on using the new SWI elimination device. The second retrospective control group consisted of 39 patients where sterile ice bags were used at the implantation stage. The groups had no statistically significant differences in the main recipient and donor characteristics, as well as in perioperative parameters. Also, from November 2021 to April 2022, 23 kidney autotransplantation experiments in female Landrace pigs were performed. The animals were cared for in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, 18 March 1986). Efficiency of different SWI elimination techniques was compared on two experimental models: standard donor (group 1, n = 12) and asystolic donor (group 2, n = 11).Results. In the clinical trial group, mean graft temperature (tm) before reperfusion was statistically significantly lower in group 1 using the special SWI elimination device: 6.4 ± 1.7 °C (95% CI 3.2–8.5) versus 22.1 ± 2.3 °C (18.1–24.6), р < 0.001. The risk of delayed graft function (DGF) was 3.86 times higher (95% CI 1.11–13.43) with the standard SWI elimination technique. In the experimental group, in the subgroups using the new device (n = 12), graft tm before reperfusion was 5.1 ± 0.4 °C (95% CI 4.5–5.8), whereas in the ice bag subgroups (n = 11), tm was 29.3 ± 1.3 °C (95% CI 27.7–30.8), which was significantly higher (p < 0.001). The overall 1-week survival of the experimental animals was significantly higher in the SWI elimination device subgroup (logrank p = 0.036).Conclusion. The developed device is effective in eliminating SWI of renal graft.","PeriodicalId":21400,"journal":{"name":"Russian Journal of Transplantology and Artificial Organs","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91370358","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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