Replacement of the large joints osteochondral defects

Rationale. Injuries and diseases of large joints occupy a leading place in the list of urgent problems in orthopedics. Various methods of treatment for this pathology are regularly offered in the literature, but most of them do not allow restoring a full-fledged hyaline cartilage.Background. To improve the results of organ-preserving treatment in patients with osteo-chondral defects of large joints.Material and methods. А prospective study was conducted on 30 large animals (60 knee joints) aged 1.5 to 3 years. We divided the animals into 3 groups of 10 individuals (20 joints) in each, based on the method of replacement of the osteo-chondral defect. In all cases, a full-layer defect formed from the hyaline cartilage by a mill with a diameter of 4.5 mm, depth of 7 mm with the capture of the subchondral bone in the medial condyle of the right thigh. Artificial defects were restored by one of the following methods. The left joint was considered a control joint and the defect formed by the same technique was not filled.Results. The result was evaluated in 1 month, 3 months and 6 months viewing the nature and degree of defect filling. Specific volumes of such tissues as chondrocytes, cartilage matrix and the average depth of the defect from the thickness of the native cartilage were better in group 3, and connective tissue was less in group 3.Conclusion. In the group without defect replacement, the  obtained data are comparable with the studies of other authors, according to which bone and cartilaginous defects practically do not regenerate on their own. Our proposed method with the use of extracellular collagen matrix, autocartilage and plate rich plasma is less aggressive in comparison with autochondroplasty and the result can be more stable compared to microfracturing or tunnelization

Method of replacement osteochondral defects of the large joints (remote results of experimental research)

Aim: Injuries and diseases of large joints occupy a leading place in the list of urgent problems of orthopedics. Various methods of treatment of such pathology offered in the literature. Objective: to Improve the results of treatment of patients with hyaline cartilage damage. Materials and methods: we conducted a prospective study on small cattle for individuals, the age of the animals ranged from 1.5 to 3 years, weight 20 to 30 kg. All the animals divided into 3 groups depending on the method of replacement of the defect The results evaluated using an evaluation scale. Also performed morphometric study of the regenerate with the assessment of the specific volume of chondrocytes, cartilage matrix, connective tissue and the average depth of the defect. Results: evaluated 6 months after surgery. The best results were obtained in-group 3. According to the analysis, the specific volume of cartilage matrix in all groups is significantly higher than in the control group. In addition, the volume of cartilage matrix in-group 3 is significantly higher than in groups 1 and 2. Discussion: in the group without defect replacement, the data obtained are comparable with studies by other authors, according to which bone and cartilage defects practically do not regenerate on their own. Our proposed method with the use of extracellular collagen matrix, autocartilage and plate rich plasma is less aggressive in comparison with autochondroplasty, and regenerate more stable compared to microfracturing or tunnelization.Актуальность: Травмы и заболевания крупных суставов занимают лидирующее место в списке актуальных проблем ортопедии. В литературе регулярно предлагаются различные методы лечения такой патологии. Цель: Улучшить результаты лечения пациентов с повреждением гиалинового хряща Материалы и методы: Проведено проспективное исследование на мелком рогатом скоте в количестве 30 особей, возраст животных составил от 1.5 до 3 лет, вес от 20 до 30 кг. Все животные были разделены на 3 группы в зависимости от метода замещения дефекта Оценку результатов осуществляли при помощи оценочной шкалы. Так же выполнялась морфометрическое исследование регенерата с оценкой удельного объёма хондроцитов, хрящевого матрикса, соединительной ткани и средней глубины дефекта Результаты: Результат оценивали через б месяцев после операции. Лучшие результаты были получены в группе №3. Согласно проведенному анализу удельный объём хрящевого матрикса во всех группах статистически значимо выше чем в контрольной группе. Кроме того, объём хрящевого матрикса в 3 группе статистически значимо выше чем в 1 и 2 группах Дискуссия: в группе без замещения дефекта полученные данные сопоставимы с исследованиями других авторов, согласно которым костно-хрящевые дефекты практически не регенерируют самостоятельно. Предложенная нами методика с применением внеклеточного коллагенового матрикса, аутохряща и плазмы обогащенной тромбоцитами, является менее агрессивной в сравнении с аутохондропластикой, а образованный регенерат более стабильный по сравнению с микрофрактурированием или туннелизацией

Unraveling the impact of cysteine-to-serine mutations on the structural and functional properties of Cu(I)-binding proteins

Appropriate maintenance of Cu(I) homeostasis is an essential requirement for proper cell function because its misregulation induces the onset of major human diseases and mortality. For this reason, several research efforts have been devoted to dissecting the inner working mechanism of Cu(I)-binding proteins and transporters. A commonly adopted strategy relies on mutations of cysteine residues, for which Cu(I) has an exquisite complementarity, to serines. Nevertheless, in spite of the similarity between these two amino acids, the structural and functional impact of serine mutations on Cu(I)-binding biomolecules remains unclear. Here, we applied various biochemical and biophysical methods, together with all-atom simulations, to investigate the effect of these mutations on the stability, structure, and aggregation propensity of Cu(I)-binding proteins, as well as their interaction with specific partner proteins. Among Cu(I)-binding biomolecules, we focused on the eukaryotic Atox1-ATP7B system, and the prokaryotic CueR metalloregulator. Our results reveal that proteins containing cysteine-to-serine mutations can still bind Cu(I) ions; however, this alters their stability and aggregation propensity. These results contribute to deciphering the critical biological principles underlying the regulatory mechanism of the in-cell Cu(I) concentration, and provide a basis for interpreting future studies that will take advantage of cysteine-to-serine mutations in Cu(I)-binding systems

Bone marrow edema in terms of joint pathology

New possibilities of modern medical science open up prospects for instrumental and laboratory diagnostics of many pathological conditions, unknown or not previously diagnosed in the practice of an orthopedist. These include bone marrow edema. Not only orthopedic traumatologists, but also rheumatologists, neurosurgeons, general practitioners, rehabilitation therapists, morphologists, and many others today face this concept in a variety of definitions, concepts of etiology, pathogenesis, and clinical recommendations for treatment.The authors performed a systematic review by using four open resources: electronic scientific library (elibrary), PubMed, SciVerse (Science Direct), and Scopus.The complexity of pathology lies in the fact that in each specific case, the development of treatment tactics requires a personal interpretation of the entire variety of data obtained and a case by case approach

The current state of the problem of soft tissue defects replacement in the lower extremities in conditions of chronic osteomyelitis

Based on the data of scientific literature, the current state of the problem of soft tissue defects replacement in the lower extremities in conditions of chronic osteomyelitis has been analyzed. Taking into account certain requirements for the replacement of defects of this nature, the following reconstructive tasks have been indicated. First of all, for adequate restoration of the skin with simultaneous relief of the purulent-necrotic process, it is necessary to use blood-supplied tissue complexes, which, if possible, should be formed from tissues similar to those surrounding the defect. The predominant use of technically and economically beneficial interventions is of great importance. The most suitable are loco-regional flaps with axial blood supply, among which the most promising are perforant flaps. It is necessary to develop an algorithm for defects reconstruction using loco-regional perforant flaps, depending on the defect area. It is also necessary to conduct a comparative analysis of the anatomical advantages and effectiveness of using various perforant and insular flaps on the vascular pedicle. A one-stage orthoplastic approach will allow the most effective use of the achievements of reconstructive plastic surgery in orthopedics to restore limb function, which will improve the results of treatment of patients

Cu(I) Controls Conformational States in Human Atox1 Metallochaperone: An EPR and Multiscale Simulation Study

Atox1 is a human copper metallochaperone that is responsible for transferring copper ions from the main human copper transporter, hCtr1, to ATP7A/B in the Golgi apparatus. Atox1 interacts with the Ctr1 C-terminal domain as a dimer, although it transfers the copper ions to ATP7A/B in a monomeric form. The copper binding site in the Atox1 dimer involves Cys12 and Cys15, while Lys60 was also suggested to play a role in the copper binding. We recently showed that Atox1 can adopt various conformational states, depending on the interacting protein. In the current study, we apply EPR experiments together with hybrid quantum mechanics-molecular mechanics molecular dynamics simulations using a recently developed semiempirical density functional theory approach, to better understand the effect of Atox1's conformational states on copper coordination. We propose that the flexibility of Atox1 occurs owing to protonation of one or more of the cysteine residues, and that Cys15 is an important residue for Atox1 dimerization, while Cys12 is a critical residue for Cu(I) binding. We also show that Lys60 electrostatically stabilizes the Cu(I)-Atox1 dimer

Electron Emission from Ferroelectric/Antiferroelectric Cathodes Excited by Short High-Voltage Pulses

Un-prepoled Lead Zirconate Titanate Lanthanum doped-PLZT ferroelectric cathodes have emitted intense current pulses under the action of a high voltage pulse of typically 8 kV/cm for PLZT of 8/65/35 composition and 25 kV/cm for PLZT of 4/95/5 composition. In the experiments described in this paper, the exciting electric field applied to the sample is directed from the rear surface towards the emitting surface. The resulting emission is due to an initial field emission from the metal of the grid deposited over the emitting surface with the consequent plasma formation and the switching of ferroelectric domains. These electrons may be emitted directly form the crystal or from the plasma. This emission requires the material in ferroelectric phase. In fact, PLZT cathodes of the 8/65/35 type, that is with high Titanium content, showing ferroelectric-paraelectric phase sequence, emit at room temperature, while PLZT cathodes of the 4/95/5 type, that is with low Titanium content, having antiferro-ferro-paraelectric phase sequence, emit strongly at a temperature higher than 130°C

Expression of Toll-like receptors in emotiogenic structures of rat brain is changed under longterm alcohol consumption and ethanol withdrawal

Recent studies have provided strong evidence that long-term ethanol consumption leads to activation the mechanisms of neuroimmune signaling. Recently, much attention has been focused on the study of toll-like receptors (Toll-like receptors, TLRs), which play one of the key roles in the mechanisms of activation of the innate immune system in brain structures subsequently ethanol consumption. It is known that the activation of TLRs leads to the release of many proinflammatory cytokines with the resulting neuroinflammatory process. There are suggestions that TLRs may also be involved in the modulation of neurotransmitter systems of the brain, thereby contributing to the formation of pathological dependence on ethanol. The goal of our work was to study the level of expression the genes of TLRs (TLR3, TLR4, TLR7) and pro-inflammatory cytokine genes (IL-1β, CCL2) in the rat brain (amygdala, hippocampus, medial entorhinal cortex, striatum) under conditions of prolonged alcoholization and on different periods of alcohol withdrawal, which was previously not studied by researchers. Prolonged alcoholization of rats with ethanol did not lead to changes in levels mRNA of TLRs in the studied structures of the rat brain, with the exception of a small increase in the level of TLR3 mRNA in the hippocampus of prolonged alcoholized rats and a slight increase in the level of TLR3 mRNA in mEC. However, gene expression of TLRs undergoes changes in all the structures of the rat brain studied by us at different periods of alcohol withdrawal. The increased level of expression of both TLRs and proinflammatory genes in the period of alcohol withdrawal in the rat brain hippocampus deserves special attention, which indicates the presence of a persistent neuroinflammatory process in this brain structure in the period of alcohol withdrawal, which is probably supported with the participation of TLR-dependent signaling. The study of the mechanisms of inflammatory process activation by TLR-dependent signaling in different brain structures can open new targets for drug exposure. Such drugs can be used in the treatment of alcoholism

Therapeutic potential of platelet-rich plasma in diseases and injuries of the large joints

Numerous non-surgical and surgical procedures have been proposed to treat injuries and diseases of the large joints. Any small bone and cartilage defect can progress quite quickly and cause osteoarthritis to develop in many joints without proper treatment. Surgical procedures include tunnelization, microfracturing, mosaic autochondroplasty, etc. The joint condition can be improved by using exogenous growth factors. Platelet-rich plasma (PRP) is one of the remedies that contain regeneration-stimulating factors. The article discusses the positive effects of PRP not only on chondrogenesis in the area of hyaline cartilage defects, but also on osteoarthritis. There is a need to further clarify the mechanism of action of plasma and the exact concentration of the preparation