Resorption Phase Research Articles

Flavonols do not affect aphid load in green or senescing birch leaves but coincide with a decrease in Photosystem II functionality.

Instead of red anthocyanins, birches synthesise colourless (to human eye), UV-absorbing flavonols during autumn senescence. To test if flavonols protect against insects, and if leaves with high or low amounts of flavonols differ in their photosynthetic functions, aphid-free and aphid-infested green and senescing birch leaves were collected from outdoor-grown trees and analysed. Photosynthetic parameters were greatly affected by the leaf chlorophyll content (i.e. the phase of senescence). Photochemical quenching and the amount of functional Photosystem I decreased linearly with chlorophyll content, while FV/FM (Photosystem II functionality) decreased strongly only at the end of senescence. Non-photochemical quenching of excitation energy (NPQ) increased towards the end of senescence. However, no significant differences in the total flavonol amounts, nor in individual flavonol species, were found between aphid-free and aphid-infested leaves, suggesting that flavonols play no role in defence against aphid herbivory. Interestingly, both green and senescing leaves with a high flavonol content showed low FV/FM values. High flavonol content slowed down PSII photoinhibition and improved recovery, but only in green leaves. Previously, we proposed that anthocyanins provide an additional sink for photosynthates at the nitrogen resorption phase during autumn senescence, and the present data may suggest that flavonol synthesis plays a similar role.

Radiometry in a comprehensive assessment of the effectiveness of extracorporeal shock wave therapy of calcifying tendinobursopathy of the shoulder

Introduction. Uncomfortable working conditions and excessive professional loads on the shoulder joints cause a high prevalence of degenerative-dystrophic changes in the periarticular tissues. Calcifying tendinitis and bursitis occupy a special place, characterized by multifocal accumulation of calcium phosphate crystals in tendons, mucous bags and muscles. The study is devoted to solving the problem of optimizing the X-ray diagnostics of the evolution of calcifying tendinobursopathy of the shoulder (CTS) in the dynamic assessment of the effectiveness of extracorporeal shock wave therapy.
 The aims of the study to optimize the X–ray diagnosis of calcifying tendinobursopathy of the shoulder in people working under the influence of adverse production factors.
 Materials and methods. The authors conducted a comparative retrospective analysis of the results of a comprehensive dynamic clinical and X-ray examination of 155 able-bodied men aged 35-57 years with an average work experience of 14.5±2.7 years (miners, loaders, bricklayers) examined for pain syndrome and dysfunction in the shoulder joint. The main group (65 people) are patients with CTS clinic, the presence of calcifications in the periaricular tissues of the rotator cuff and in the biceps muscle of the shoulder, evaluated in dynamics after shock wave therapy (SWT) of the shoulder in the phases of rest, resorption and recovery. The comparison group (90 people) consisted of patients with the absence of instrumentally detectable signs of multifocal accumulation of calcium phosphate crystals in the periarticular tissues of the shoulder. The study included patients whose routine conservative treatment proved ineffective. The following criteria for the effectiveness of therapy were identified: pain at rest, measured using a visual analog scale (VAS); dimensions (calcification area (in mm2)); optical density and calcification density gradient. Specialists evaluated the data at the initial stage of the study before the use of therapy, immediately after treatment and 12 months after the final SWT session.
 Results. In patients of the main group with the presence of CTS, the main manifestations of shoulder-scapular periarthritis (SSP) both in the main group and in the comparison group were moderately pronounced, however, the frequency of detection of the main SSP syndromes, primarily rotator cuff lesion, as well as background pathology (arthrosis of the shoulder joint) and acromioclavicular joint) were significantly higher in the main group. The effectiveness of SWT was demonstrated by regression of pain syndrome and positive dynamics of density characteristics of periarticular tissues of shoulder joints in areas of interest (in anatomotopographic projections of localization of tendons, mucous bags and muscles). In all patients of the main group, the decalcification process was characterized by both a visually perceptible pattern of disintegration and a decrease in its area, and a decrease in optical density immediately after the end of treatment. In 36.9% of patients, 12 months after the start of SWT, the X-ray and X-ray densitometric picture confirmed the prolongation of the decalcification process up to complete lysis of foci and calcification sites.
 Conclusions. In a comprehensive assessment of the effectiveness of CTS therapy, along with traditional X-ray diagnostics, special methodological techniques of radiometry (X-ray diffraction and X-ray densitometry in areas of interest) can be used, allowing for more accurate and more objective reflection of the direction of the dynamics of changes.
 The use of X-ray calcifications in the arsenal of methodological techniques, such as area, optical density and optical density gradient, can significantly improve the quality of diagnosis and avoid the use of computed tomography and an increase in radiation exposure to the patient.
 High-energy extracorporeal shockwave therapy is largely able to solve the problem of treating resistant forms of calcifying tendinobursopathy of the shoulder.

Clinical and radiographic features of external cervical resorption - An observational study.

To determine the prevalence of symptoms, clinical signs and radiographic presentation of external cervical resorption (ECR). This study involved 215 ECR lesions in 194 patients referred to the Endodontic postgraduate Unit at King's College London or Specialist Endodontic practice (London, UK). The clinical and radiographic findings (periapical [PA] and cone beam computed tomography [CBCT]) were readily accessible for evaluation. A checklist was used for data collection. Inferential analysis was carried out to determine if there was any potential association between type and location of tooth in the jaw as well as sex, age of the patient and ECR presentation and radiographic feature. Eighty-eight patients (94 teeth) were female and 106 patients were male (121 teeth), the mean age (±SD) was 41.5 (±17.7) years. Fifteen patients (7.7%) had more than one ECR lesion. The most affected teeth were maxillary central incisors (21.4% [46 teeth]) and mandibular first molars (10.2% [22 teeth]). ECR was most commonly detected as an incidental radiographic finding in 58.1% [125 teeth] of the cases. ECR presented with symptoms of pulpal/periapical disease in 23.3% [n = 50] and clinical signs (e.g. pink spot, cavitation) in 16.7% [36 teeth] of the cases. Clinical signs such as cavitation (14%), pink spot (5.1%) and discolouration (2.8%) were uncommon, but their incidence increased up to 24.7% when combined with other clinical findings. ECR was detected in the resorptive and reparative phases in 70.2% and 29.8% of the cases respectively. ECR appears to be quiescent in nature, the majority being asymptomatic and diagnosed incidentally from PA or CBCT. When assessed with the Patel classification, most lesions were minimal to moderate in relation to their height (1 or 2) and circumferential spread (A or B). However, the majority of ECRs were in (close) proximity to the pulp. Symptoms and clinical signs were associated with (probable) pulp involvement rather than the height and circumferential spread of the lesion. Clinical signs were more frequently associated when ECR affected multiple surfaces.

Osteocyte RANKL Drives Bone Resorption in Mouse Ligature-Induced Periodontitis.

Mouse ligature-induced periodontitis (LIP) has been used to study bone loss in periodontitis. However, the role of osteocytes in LIP remains unclear. Furthermore, there is no consensus on the choice of alveolar bone parameters and time points to evaluate LIP. Here, we investigated the dynamics of changes in osteoclastogenesis and bone volume (BV) loss in LIP over 14 days. Time-course analysis revealed that osteoclast induction peaked on days 3 and 5, followed by the peak of BV loss on day 7. Notably, BV was restored by day 14. The bone formation phase after the bone resorption phase was suggested to be responsible for the recovery of bone loss. Electron microscopy identified bacteria in the osteocyte lacunar space beyond the periodontal ligament (PDL) tissue. We investigated how osteocytes affect bone resorption of LIP and found that mice lacking receptor activator of NF-κB ligand (RANKL), predominantly in osteocytes, protected against bone loss in LIP, whereas recombination activating 1 (RAG1)-deficient mice failed to resist it. These results indicate that T/B cells are dispensable for osteoclast induction in LIP and that RANKL from osteocytes and mature osteoblasts regulates bone resorption by LIP. Remarkably, mice lacking the myeloid differentiation primary response gene 88 (MYD88) did not show protection against LIP-induced bone loss. Instead, osteocytic cells expressed nucleotide-binding oligomerization domain containing 1 (NOD1), and primary osteocytes induced significantly higher Rankl than primary osteoblasts when stimulated with a NOD1 agonist. Taken together, LIP induced both bone resorption and bone formation in a stage-dependent manner, suggesting that the selection of time points is critical for quantifying bone loss in mouse LIP. Pathogenetically, the current study suggests that bacterial activation of osteocytes via NOD1 is involved in the mechanism of osteoclastogenesis in LIP. The NOD1-RANKL axis in osteocytes may be a therapeutic target for bone resorption in periodontitis. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Clinical and Radiographic Outcomes of Nitinol Compression Staples for Midfoot and Chopart Arthrodesis

Category: Midfoot/Forefoot; Hindfoot Introduction/Purpose: Continuous compression implant (nitinol staples) use in orthopaedic surgery has increased in recent years. There are several advantages of nitinol staples, including a lower profile when compared to traditional fixation methods. They are easy to apply and take up a smaller footprint than most plating techniques, thus decreasing surgical time and dissection. Additionally, continuous compression across the fusion site is maintained during the resorptive phase of bone healing. Biomechanical studies provide useful data supporting the use of nitinol staples in the foot and ankle; however, clinical data is limited. This study’s purpose is to determine the efficacy of nitinol staples to achieve stable, bony healing in midfoot and Chopart joint arthrodesis, and examine their clinical outcomes, complications, and pain scores. Methods: A retrospective chart review was performed on 127 midfoot/Chopart joints (71 patients) that underwent arthrodesis using nitinol staples in isolation over a five-year period (January 2017 – February 2022). The primary outcome variable was radiographic evidence of healing. Radiographs were blinded, randomized, and independently reviewed by three board certified foot and ankle surgeons. Each investigator reviewed digital radiographs independently and recorded their radiographic finding responses. Fusions were deemed healed if greater than 50% of the arthrodesis site contained bridging bone. A partially healed arthrodesis was defined as some bridging bone, but less than 50% of the overall arthrodesis site, and a nonunion was defined as no healing seen radiographically or loss of reduction. There were no cases of complete inter-surgeon radiographic disagreement in this study. Pain scores and clinical outcomes were also collected. Smokers and diabetics represented 27% (n = 19) and 13% (n=9) of the patient population, respectively. Results: Complete/partial union was seen in 89% of all joints (113/127) and 93% of midfoot joints (98/106). Chopart joints had a significantly lower healing rate (15/21; 71%) compared to midfoot joints (p = 0.013) and TMT joints in isolation (86/91; 95%) (p = 0.006). Neuropathy and smoking had no effect on healing but diabetes did (p = 0.004). Joints requiring bone grafting had a worse healing rate (38/49; 76%) (p = 0.002). For all joints, post-operative VAS scores were significantly lower than pre-operative (p < 0.00001). Midfoot and Chopart pre-operative pain scores did not differ (p= 0.30), but differed post-operatively (p = 0.003). Midfoot joints had significantly lower pain scores post-operatively than pre-operatively (p < 0.00001). No such significance existed in Chopart joints (p = 0.070). Conclusion: Isolated nitinol staples are a viable option for midfoot arthrodesis, especially TMT joints, and offer significant pain improvement. Staples are lower profile, decreasing hardware irritation and potential secondary surgeries, and ease of use makes insertion efficient and reproducible. They offer the benefit of continuous compression of the fusion site, and are rigid enough to maintain reduction. Chopart joints, however, may require a more rigid fixation than nitinol staples can provide, given the lower healing rate. Caution should be exercised in diabetics and joints that may require bone grafting.

A Novel Achilles Tendon Repair Technique Utilizing a Bio-Composite Scaffold for a Sub-Acute Tear.

Achilles tendon ruptures are prevalent musculoskeletal injuries accounting for 20% of all large tendon ruptures with a re-rupture rate of 2.1-8.8%. Ineffectual management of these injuries can lead to a significant loss in push-off strength and overall ankle function. The field of orthopedic surgery has shown an increasing interest in biologic augmentation. Encouraged by its success in various other applications, this approach holds promise for potentially enhancing outcomes in Achilles tendon repairs, especially in poor tendon tissue. The BioBrace® (ConMed, New Haven, Connecticut) is a biocomposite scaffold made of highly porous type I collagen and bioresorbable poly (L-Lactide) (PLLA) microfilaments. It can be applied in conjunction with Achilles tendon repair or reconstruction. It provides immediate strength to the augmented repair upon implantation and simultaneously promotes new, organized tissue growth throughout its resorptive phase. Here, we outline a technique to effectively augment an acute Achilles tendon repair utilizing the BioBrace® reinforced bio-inductive implant.

Prospective Evaluation of Magnetic Resonance Imaging Features of Magnesium-Based Alloy Screw Resorption in Pediatric Fractures.

The resorption of magnesium-based alloy bioabsorbable screws results in the release of hydrogen gas, which can mimic infection and enter the growth plate. The screw itself and the released gas may also affect image quality. The evaluation of magnetic resonance imaging (MRI) findings during the most active phase of screw resorption is the objective, with particular focus on the growth plate and to assess for the presence of metal-induced artifacts. In total, 30 prospectively acquired MRIs from 17 pediatric patients with fractures treated with magnesium screws were assessed for the presence and distribution of intraosseous, extraosseous, and intra-articular gas; gas within the growth plate; osteolysis along the screw; joint effusion; bone marrow edema; periosteal reaction; soft tissue edema; and metal-induced artifacts. Gas locules were found in the bone and soft tissues in 100% of the examinations, intra-articular in 40%, and in 37% of unfused growth plates. Osteolysis and the periosteal reaction were present in 87%, bone marrow edema in 100%, soft tissue edema in 100%, and joint effusion in 50% of examinations. Pile-up artifacts were present in 100%, and geometric distortion in 0% of examinations. Fat suppression was not significantly impaired in any examination. Gas and edema in the bone and soft tissues are normal findings during the resorption of magnesium screws and should not be misinterpreted as infection. Gas can also be detected within growth plates. MRI examinations can be performed without metal artifact reduction sequences. Standard fat suppression techniques are not significantly affected.

Zero echo time MRI in shoulder MRI protocols for the diagnosis of rotator cuff calcific tendinopathy improves identification of calcific deposits compared to conventional MR sequences but remains sub-optimal compared to radiographs.

To compare the diagnostic performance of standard MRI and standard MRI + ZTE images for the detection of rotator cuff calcific tendinopathy (RCCT) and to describe the artifacts encountered with ZTE images, using computed radiography (CR) as a reference. In a retrospective study, patients with suspicion of rotator cuff tendinopathy who underwent standard MRI + ZTE images after radiography were enrolled between June 2021 and June 2022. Images were independently analyzed for calcific deposit presence and ZTE images artifacts, by two radiologists. Diagnostic performance was calculated individually with MRI + CR as the reference standard. A total of 46 RCCT subjects (27 women; mean age, 55.3years ± 12.4) and 51 control subjects (27 men; mean age, 45.5 ± 12.9) were evaluated. For both readers, there was an increase in the sensitivity for the identification of calcific deposits of MRI + ZTE compared to MRI (77% (95% CI: 64.5-86.8) and 75.4% (95% CI: 62.7-85.5) versus 57.4% (95% IC: 44.1-70) and 47.5% (95% IC: 34.6-60.7), for R1 and R2, respectively). Specificity was quite similar for both readers and both imaging techniques and ranged from 96.6% (95% IC: 93.3-98.5) to 98.7% (95% IC: 96.3-99.7). Hyperintense joint fluid (62.8% of patients), long head of the biceps tendon (in 60.8%), and subacromial bursa (in 27.8%) on ZTE were considered artifactual. The addition of ZTE images to a standard MRI protocol improved MRI diagnostic performance of RCCT, but with a suboptimal detection rate and a relatively high frequency of artifactual soft tissue signal hyperintensity. • Adding ZTE images to standard shoulder MRI improves the MR-based detection of rotator cuff calcific tendinopathy, but half of the calcification unseen with standard MRI remained unseen with ZTE MRI. On ZTE images, joint fluid and long head biceps tendon were hyperintense in about 60% of the shoulders, as well as the subacromial bursa in about 30%, without calcific deposit on conventional radiographs. • The detection rate of calcific deposits using ZTE images was dependent on the disease phase. In the calcific stage, it reached 100% in this study but remained at a maximum of 80.7% in the resorptive phase.

Spatio-temporal simulations of bone remodelling using a bone cell population model based on cell availability.

Here we developed a spatio-temporal bone remodeling model to simulate the action of Basic Multicelluar Units (BMUs). This model is based on two major extensions of a temporal-only bone cell population model (BCPM). First, the differentiation into mature resorbing osteoclasts and mature forming osteoblasts from their respective precursor cells was modelled as an intermittent process based on precursor cells availability. Second, the interaction between neighbouring BMUs was considered based on a "metabolic cost" argument which warrants that no new BMU will be activated in the neighbourhood of an existing BMU. With the proposed model we have simulated the phases of the remodelling process obtaining average periods similar to those found in the literature: resorption ( days)-reversal (∼8days)-formation (∼65days)-quiescence (560-600days) and an average BMU activation frequency of ∼1.6BMUs/year/mm3. We further show here that the resorption and formation phases of the BMU become coordinated only by the presence of TGF-β (transforming growth factor β), i.e., a major coupling factor stored in the bone matrix. TGF-β is released through resorption so upregulating osteoclast apoptosis and accumulation of osteoblast precursors, i.e., facilitating the transition from the resorption to the formation phase at a given remodelling site. Finally, we demonstrate that this model can explain targeted bone remodelling as the BMUs are steered towards damaged bone areas in order to commence bone matrix repair.

A Novel Distal Biceps Rupture Repair Technique Utilizing a Biocomposite Scaffold.

Distal biceps tendon ruptures are uncommon injuries that have a re-rupture rate of 1.2% - 6%. In severe traumatic injuries or chronic injuries, a distal biceps tendon repair may require augmentation due to insufficient tissue quality. Unsuccessful treatment of these injuries can result in the loss of approximately 40% of supination strength and 30% of elbow flexion strength. There has been a growing interest in biologic augmentation in orthopedic surgery, and its incorporation into distal biceps tendon repairs has increased as well. Established bio-inductive implants and dermal allografts have been shown to be of benefit; however, these biologics have drawbacks such as failure to incorporate at time of implantation, lack of structural strength, and technical difficulty of implantation. The BioBrace® (ConMed, New Haven, CT) is a bio-inductive, biocomposite scaffold that is composed of highly porous type I collagen and bio-resorbable poly (L-Lactide) (PLLA) microfilaments. It can be used in conjunction with distal biceps tendon repair or reconstruction. It has the advantage of providing strength to the augmented repair at time zero of implantation, while also demonstrating the ability to induce new organized tissue growth throughout its resorptive phase. We describe a technique to successfully augment a distal biceps tendon repair using the BioBrace®.

Conservative Otosclerosis Treatment With Sodium Fluoride and Other Modern Formulations: A Systematic Review.

Otosclerosis, also known as otospongiosis, is a primary osteodystrophy of the otic capsule of the inner ear and one of the leading causes of deafness in adults. The rationale for medical therapy for otospongiosis is to slow down and eventually stop the phase of bone resorption. Conservative treatments includesodium fluoride (NaF), bisphosphonates, and other modern medicines. A systematic review of the existing and published articles and books until April 2021 has been conducted in Medscape, Google Scholar, PubMed, and other databasesusing appropriate terms.According to the results of the research, the administration of NaF for a period of at least six months stabilizes hearing thresholds (HTs), improves vestibular symptoms, and delays the worsening of tinnitus. The administration of bisphosphonates for a period of at least six months showed significant percentage differences in the improvement of hearing loss, dizziness, and tinnitus remission.In the already existing double-blind studies that were evaluated, groups of patients treated with bisphosphonates for at least 24 months showed greater stabilization of the mean air and bone conduction thresholds than groups of patients treated with a placebo. The new modern medications have not yet been widely administered clinically to draw useful conclusions, although the test results of some of their use are quite encouraging.

The “Mellanby effect” in alcoholised e-scooter drivers

PurposeSeveral studies tried to discuss and clarify the so-called Mellanby effect: Similar blood alcohol concentrations (BACs) supposedly lead to more signs of impairment in the phase of alcohol resorption than elimination. To assess this effect for alcoholised e-scooter driving, results of a real-driving fitness study were subanalysed.MethodsSixteen subjects (9 females; 7 males) who completed runs at comparable BACs in the phases of alcohol resorption and elimination were chosen to assess a possible “Mellanby effect”. The data of the subjects was taken from a prior e-scooter study by Zube et al., which included 63 subjects in total.ResultsIn the phase of alcohol resorption, the relative driving performance was approx. 92% of the phase of elimination (p value 0.21).Statistically significant more demerits were allocated to the obstacle “narrowing track” in the phase of resorption than elimination.Subjects also needed significantly more time to pass the obstacles “narrowing track”, “driving in circles counterclockwise” and “thresholds” in the phase of resorption than elimination.DiscussionThe most relevant obstacle to discriminate between the two different states of alcoholisation was the narrowing track. Insofar, measurements of the standard deviation of the lateral position (SDLP) might also be a sensitive component for the detection of central nervous driving impairment during shorter trips with an e-scooter.Additionally, driving slower during the phase of alcohol resorption seems to be the attempt to compensate alcohol-related deficits.ConclusionThe results of the study suggest a slight Mellanby effect in e-scooter drivers.

Quantitative analyses of matrices, osteoblasts, and osteoclasts during bone remodeling using an in vitro system.

Bone remodeling plays a central role in the maintenance of bone homeostasis. Our group has established an in vitro system by which the cellular events during bone remodeling can be observed longitudinally. This study used this system to quantitatively analyze osteoblasts, osteoclasts, and matrices to elucidate their temporal changes and correlations. Osteoblasts from EGFP mice were cultured to form calcified nodules, followed by co-culture with bone marrow macrophages from Tnfrsf11aCre/+ x Ai14 mice for 3weeks (resorption phase). Then cells were cultured with osteoblast differentiation medium for 3weeks (formation phase). The same sites were observed weekly using 2-photon microscopy. Matrices were detected using second harmonic generation. Parameters related to matrices, osteoblasts, and osteoclasts were quantified and statistically analyzed. Resorption and replenishment of the matrix were observed at the same sites by 2photon microscopy. Gross quantification revealed that matrix and osteoblast parameters decreased in the resorption phase and increased in the formation phase, while osteoclast parameters showed the opposite pattern. When one field of view was divided into 16 regions of interest (ROIs) and correlations between parameters were analyzed in each ROI, decreased and increased matrix volumes were moderately correlated. Parameters of matricesand osteoblasts, and those of matrices andosteoclasts exhibited moderate correlations, while those of osteoblasts and osteoclasts were only weakly correlated. Several correlations between cells and matrix during remodeling were demonstrated quantitatively. This system may be a powerful tool for the research of bone remodeling.

Biopsies from the Distal Radius after Implantation of Calcium Phosphate Cement

Background: Calcium Phosphate (CaP) bone cement is gradually replaced by new bone when used as a gap-filler. Details of the re-modelling process are still unclear. Uncertainty is also present as to the possible release of cement particles during the resorption phase causing local soft tissue reactions. The objective of this study was to perform a comprehensive histological investigation of the injectable CaP bone cement used as a void filler in corrective radius osteotomies and adjacent tissue reactions. Methods: Fourteen patients, median age 56 years (18-72), 4 men/10 women, underwent removal of distal radius plates (11 dorsal/3 volar) due to tenosynovitis-like symptoms. Eleven study patients went through corrective osteotomies with CaP bone cement and three were control patients. Previous surgery in three controls consisted in (1) corrective osteotomy with bone graft (dorsal plate), and (2) plated distal radius fractures (1 dorsal/1 volar plate). Biopsies were taken of bone-cement-bone junctions (11), bone-bone graft-bone junctions (1), bone (2) and juxtaposing soft tissue (14). The interval from corrective CaP cement surgery to biopsy was median 1.1 (0.6-2.3) years. Results: Biopsies of bone-cement junctions showed the different stages of new bone formation from CaP to immature bone and later mature well-organised bone. The cement showed signs of osteoclast-mediated resorption. Cement particles, macrophages, multinucleated giant cells (MNGC) and plasma cells were observed in most soft tissue biopsies. MNGC with internalised particles were seen. Macrophages were found along and/or within tendon sheaths in all patients in both groups, but rarely containing cement particles. Conclusions: Gradual re-modelling of the cement into well-organised bone was observed confirming osteoclast-osteoblast coupling. There was no indication that cement particles were the cause of the tenosynovitis-like symptoms.

THE LYMPHATIC SYSTEM – A NEW LOOK AT OLD PROBLEMS

The lack of adequate methods for the simultaneous detection of lymphatic and blood microvessels in hollow organs does not make it possible to determine the morphological basis of lymph formation and lymph dynamics. In the relevant scientific literature, information about of the structural organization of the lymphatic system, obtained using transmission and scanning electron microscopy, does not provide exhaustive answers to the currently controversial and unresolved issues of the structural organization of the lymphatic microcirculatory bed. The purpose of the study is to presenting data on the organization of the initial lymphatic channel, obtained on the basis of the use of original impregnation methods. Studies were conducted on cats (n=17) and dogs (n=11). The microvascular bed of the intestine and epicardium was identified along with the surrounding tissues by impregnation. On histological preparations, endothelial trabeculae were identified in the lumen of non-muscular lymphatic microvessels of different diameters in the muscular layer and in the submucosa of the intestine. In the muscular layer of the intestinal wall, numerous interstitial channels were found that communicated with open lymphatic capillaries. In the submucosa of the intestinal wall of experimental animals, in addition to the classic capillaries that begin closedly, previously unknown structures were identified - open perivasal lymphatic microvessels and open lymphatic capillaries flowing into them. In the lumen of the perivasal lymphatics are arterioles or arteries. Lymphatic capillaries were in various functional states, which indicates their active peristalsis and suction capacity, which characterize them as utilizers of «biological debris». As a result of the conducted studies, new objective data on the structural organization of the initial lymphatic bed in hollow organs were obtained. The authors showed that the vasomotor activity of the initial lymphatics can serve as a morphological basis for the hypothesis of the initial lymphatic cycle, which consists of a resorption phase and an expulsion phase. The hydrostatic pressure drops in the lumen arising from such a two-phase vasomotor activity of the lymphatics indicate their important role in the process of lymph formation and lymph circulation.

GsαR201C and estrogen reveal different subsets of bone marrow adiponectin expressing osteogenic cells

The Gsα/cAMP signaling pathway mediates the effect of a variety of hormones and factors that regulate the homeostasis of the post-natal skeleton. Hence, the dysregulated activity of Gsα due to gain-of-function mutations (R201C/R201H) results in severe architectural and functional derangements of the entire bone/bone marrow organ. While the consequences of gain-of-function mutations of Gsα have been extensively investigated in osteoblasts and in bone marrow osteoprogenitor cells at various differentiation stages, their effect in adipogenically-committed bone marrow stromal cells has remained unaddressed. We generated a mouse model with expression of GsαR201C driven by the Adiponectin (Adq) promoter. Adq-GsαR201C mice developed a complex combination of metaphyseal, diaphyseal and cortical bone changes. In the metaphysis, GsαR201C caused an early phase of bone resorption followed by bone deposition. Metaphyseal bone formation was sustained by cells that were traced by Adq-Cre and eventually resulted in a high trabecular bone mass phenotype. In the diaphysis, GsαR201C, in combination with estrogen, triggered the osteogenic activity of Adq-Cre-targeted perivascular bone marrow stromal cells leading to intramedullary bone formation. Finally, consistent with the previously unnoticed presence of Adq-Cre-marked pericytes in intraosseous blood vessels, GsαR201C caused the development of a lytic phenotype that affected both cortical (increased porosity) and trabecular (tunneling resorption) bone. These results provide the first evidence that the Adq-cell network in the skeleton not only regulates bone resorption but also contributes to bone formation, and that the Gsα/cAMP pathway is a major modulator of both functions.

Calcific Shoulder Tendinopathy (CT): Influence of the Biochemical Process of Hydrolysis of HA (Hydroxyapatite) on the Choice of Ultrasound-Guided Percutaneous Treatment (with the Three-Needle Technique)

Calcific shoulder tendinopathy (CT) is a common condition involving the central part or insertion of the rotator cuff tendons (RC) or the subacromial-subdeltoid bursa (SASD). The calcific deposits consist of poorly crystallized calcium hydroxyapatite but the mechanism of their formation still remains unclear. CT can be divided into three distinct stages, as reported by Uthhoff et al. Clinically, this condition varies with the extent of the calcification and the phase of the condition. In particular, the disorder is asymptomatic or may cause mild discomfort during the deposition of calcium, while it becomes acutely painful during the resorptive phase. US-PICT (ultrasound-guided percutaneous irrigation of calcific tendinopathy) is indicated in the acute phase (resorptive phase) of CT with significant pain relief and a very low rate of minor complications. The aim of this manuscript is to define the rationale of the ultrasound-guided percutaneous irrigation of calcific tendinopathy, correlating it with the sequence of biochemical processes that lead to the hydrolysis of hydroxyapatite. Furthermore, we will explain the reasons why we prefer using the three-needle technique for the dissolution of calcifications.

Aspects of intercellular communication in bone and implications in therapy.

Communication processes among the cells of bone are essential for the structure and function of the organ. After it was proposed that communication from the osteoblast lineage to hemopoietic cells initiated osteoclastogenesis, the molecular controls were identified to be the tumour necrosis factor ligand and receptor families. This was followed by revelation of very many signalling processes among the cells of bone that regulate the three phases of bone remodelling, the resorption, reversal and formation phases. In many instances the ways in which these mechanisms operate can determine how drugs act on bone, whether they be inhibitors of resorption or promoters of formation.

Dynamics of hematological parameters in rabbits for osteosubstitution by hydroxyapatite ceramics doped with germanium and in complex with blood coagulation activator

Bone tissue has powerful regenerative properties, thanks to which, with stable fixation, quite large amounts of skeletal bone damage can be successfully repaired. However, in the case of fragmentary fractures, the use of osteosynthesis methods alone does not always ensure the optimal course of reparative regeneration, as its regenerative potential is lost. Therefore, there is a need to replace post-traumatic bone defects and stimulate reparative osteogenesis. For this purpose, doped or doped with various elements (Ge, Si, Zn, Ag, Cu) composite materials. The aim of the study was to investigate the dynamics of hematological parameters in rabbits for osteosubstitution by hydroxyapatite ceramics doped with germanium and in combination with a blood clotting activator. Model defects were formed in the radial diaphysis and femur metaphysis in rabbits with a 3 mm and 4.2 mm diameter drill bit, respectively. Anesthesia included acepromazine, thiopenate, and lidocaine infiltration anesthesia. Animals of the first experimental group (n = 12) were replaced by defects with granules of hydroxyapatite ceramics doped with germanium (HTGe), the second (n = 12) – hydroxyapatite ceramics doped with germanium with blood coagulation activator (HTGe + a), the third – (n = 12). hydroxyapatite α + β with active (α + β + a), and control – granules of undoped ceramics (HT). On day 7, animals of all groups had minor post-traumatic erythrocytopenia and oligochromemia. There was also a gradual increase in the content of leukocytes in the blood with a peak on the 14th day, which in the group HTGe + a lasted until the 30th day. The increase in the number of leukocytes and their peak values occurred within the physiological norm and only approached its upper limit. In most groups there was a pronounced thrombocytosis during the first 14 days with normalization to the 30th day, but in the 2nd experimental group the number of platelets returned to normal only on the 60th day. Changes in most integral hematological indices, which reflect the relationship between blood cell populations, are characteristic of the inflammatory-resorptive phase of reparative osteogenesis. The dynamics of hematological parameters indicates the absence of a pronounced reaction of the body to the implantation of hydroxyapatite composite doped with germanium. The combination of hydroxyapatite ceramics doped with germanium with coagulation activator eliminates post-traumatic oligochromemia and erythrocytopenia and significantly increases the level of hematological integral indices, which indicates a more intensive course of inflammatory-resorptive clinical resorptive aparation phase.

Effect of implants of hydroxyapatite with tricalcium phosphates alloyed with Si on histomorphological and biochemical parameters in cases of bone defects of rabbits

Complex comminuted fractures are accompanied by development of bone defects and loss of reparative potential of the bone tissue in the region of the trauma. This brings the necessity of using implants with optimum osteoconductive and osteointegration properties. The objective of the study was determining the condition of biochemical bone markers and peculiarities of histomorphological changes under the influence of ceramic hydroxyapatite (HA) implants with various physical-chemical properties in the conditions of diaphyseal bone defects in rabbits. We composed control and experimental groups of rabbits with 10 individuals in each with diaphyseal bone defects (3 mm) of the radial bones formed under general anesthesia. In one experimental group, they were filled with granules of hydroxyapatite with α-tricalcium phosphate, and in the second group – with β-tricalcium phosphate, alloyed with Si. In the control rabbits, the defects healed under a blood clot. Blood was analyzed on the 3rd, 7th, 14th, 21st and 42nd days, and as reference we used biochemical parameters of blood of clinically healthy rabbits (n = 10). Bone biopsied materials were taken on days 21–42 under general anesthesia. When using hydroxyapatite with β-tricalcium phosphate, alloyed with Si, we determined early intensification of the levels of nitrogen oxide, angiogenesis and development of bone regenerate in conditions of shortening of inflammatory resorption phase, which was verified according to the level of tartrate-resistant acid phosphatase. According to the level of bone isoenzyme of alkaline phosphatase in the blood serum of animals of the control group, the reparative osteogenesis developed slowly and peaked on day 42, whereas in animals implanted with α-tricalcium phosphate, its development peaked peaked on days 14–42, and when using Si-alloy – on days 7–14. Histomorphologically, on the 21st day, in the case of replacement of bone defect with hydroxyapatite with α-tricalcium phosphate, coarse-fibered type of bone regenerate developed with no dense contact with the elements of the regenerate, while spongy bone trabeculae occurred when hydroxyapatite was applied with β-tricalcium phosphate alloyed with Si, and the control rabbits were observed to be in the stage of cartilaginous callus. On the 42nd day, under the influence of implants of hydroxyapatite with α-tricalcium phosphate, the spongy bone tissue transformed into compact tissue with further mineralization. With implants alloyed with Si, there occurred compact bone tissue, and bone regenerates of the control animals were regions of coarse-fibered and spongy bone tissue without dense contact with the parent bone. This study revealed that hydroxyapatite with β-tricalcium phosphate alloyed with Si had notable osteoinductive and osteointegrating properties, as indicated by early angiogenesis and osteoblast reaction, positive dynamics of the marker biochemical parameters with faster and better development of bone regenerate as spongy bone trabeculae.