Recovery of the contractile function of the heart and the regeneration of the myocardium after ischemic injury are contemporary issues in regenerative medicine and cell biology. This study aimed to analyze early transcriptional events in cardiac tissue after infarction and to explore the cell population that can be isolated from myocardial tissue. We induced myocardial infarction in Wistar rats by permanent ligation of the left coronary artery and showed a change in the expression pattern of Notch-associated genes and Bmp2/Runx2 in post-MI tissues using RNA sequencing and RT-PCR. We obtained primary cardiac mesenchymal cell (CMC) cultures from postinfarction myocardium by enzymatic dissociation of tissues, which retained part of the activation stimulus and had a pronounced proliferative potential, assessed using a “xCELLigence” real-time system. Hypoxia in vitro also causes healthy CMCs to overexpress Notch-associated genes and Bmp2/Runx2. Exogenous activation of the Notch signaling pathway by lentiviral transduction of healthy CMCs resulted in a dose-dependent activation of the Runx2 transcription factor but did not affect the activity of the Bmp2 factor. Thus, the results of this study showed that acute hypoxic stress could cause short-term activation of the embryonic signaling pathways Notch and Bmp in CMCs, and this interaction is closely related to the processes of early myocardial remodeling after a heart attack. The ability to correctly modulate and control the corresponding signals in the heart can help increase the regenerative capacity of the myocardium before the formation of fibrotic conditions.
26 December 2022 in Traumatology and Orthopedics of Russia
This review article focuses on issues of economic analysis in providing care to patients requiring total hip arthroplasty. A large number of factors affecting the final financial result force us to look at economic research in the field of arthroplasty with a certain degree of criticality. At the same time, the existing financing systems cannot fully take into account all the possible costs arising from total hip arthroplasty. For this reason, studies concerning revision total hip arthroplasty are of particular interest, where treatment costs can vary significantly depending on the etiology and complexity of the case. These differences are reflected in the works of authors from France, Germany and Great Britain, who compared the treatment costs of patients with septic and aseptic revisions. Very different data both between countries and within the same country well demonstrate the need for a critical approach to the results of cost-effectiveness studies, QALYs based on Markov and other models, as the quality of the original data can be highly variable and reproduce the error of the initially incorrect price structure. At the same time, the rapidly increasing number of operations of primary and revision hip arthroplasty and, accordingly, the increasing economic costs of these operations require clear and effective economic criteria for their evaluation. The formation and application of these criteria will be the purpose of further research.
Background. The formation of a pseudarthrosis is one of the most severe complications of bone fractures. Pseudarthrosis occurs as a result of a disorder in the fracture union, has a poor prognosis and requires long-term treatment and repeated surgeries. A small number of representative pseudarthrosis models makes it difficult to conduct preclinical studies of promising pharmacological substances, bone replacement materials and surgical methods of treatment.The aim. To develop and to validate an experimental model of normotrophic pseudarthrosis of a rabbit’s tibia by creating diastasis between bone fragments, forming local vascularization disturbance and using unstable fixation.Materials and methods. The study was carried out on Soviet Chinchilla rabbits. The animals were divided into 2 groups: in experimental group, we formed tibial pseudarthrosis; in control group, we made a simple transverse tibial fracture. The pseudarthrosis was formed by segmental resection (5 mm) of the middle third of the tibia, bone fragments dilatation for 5 mm, removal of periosteum and bone marrow within 5 mm followed by daily destabilization of a fracture in an external fixation device. The duration of the experiment was 6 weeks. X-ray examination of the fracture area was carried out weekly, multi-layer spiral computed tomography (MSCT) and histological examinations were carried out at the end of the experiment.Results. The survival value in the experiment was 100 %. According to weekly X-ray examination, fracture union was registered only in the control group and occurred on average on the 22,8 ± 5,1 day, while the formation of pseudarthrosis was observed only in the experimental group, and radiographic signs of a pseudarthrosis were noted on average on the 33,6 ± 3,5 day. The formation of a pseudarthrosis by the end of the experiment was confirmed by MSCT and histological studies.Conclusions. The developed model of the normotrophic pseudarthrosis of a rabbit’s tibia can be used for experimental tests of various factors for stimulating reparative regeneration and methods for treatment of the pseudarthrosis.