The Role of Cytokines in the Metastasis of Solid Tumors to the Spine: Systematic Review.

Although many studies have investigated the role of cytokines in bone metastases, our knowledge of their function in spine metastasis is limited. Therefore, we performed a systematic review to map the available evidence on the involvement of cytokines in spine metastasis in solid tumors. A PubMed search identified 211 articles demonstrating a functional link between cytokines/cytokine receptors and bone metastases, including six articles confirming the role of cytokines/cytokine receptors in spine metastases. A total of 68 cytokines/cytokine receptors were identified to mediate bone metastases; 9 (mostly chemokines) played a role in spine metastases: CXC motif chemokine ligand (CXCL) 5, CXCL12, CXC motif chemokine receptor (CXCR) 4, CXCR6, interleukin (IL) 10 in prostate cancer, CX3C motif chemokine ligand (CX3CL) 1 and CX3C motif chemokine receptor (CX3CR) 1 in liver cancer, CC motif chemokine ligand (CCL) 2 in breast cancer, and transforming growth factor (TGF) ß in skin cancer. Except for CXCR6, all cytokines/cytokine receptors were shown to operate in the spine, with CX3CL1, CX3CR1, IL10, CCL2, CXCL12, and CXCR4 mediating bone marrow colonization, CXCL5 and TGFß promoting tumor cell proliferation, and TGFß additionally driving bone remodeling. The number of cytokines/cytokine receptors confirmed to mediate spinal metastasis is low compared with the vast spectrum of cytokines/cytokine receptors participating in other parts of the skeleton. Therefore, further research is needed, including validation of the role of cytokines mediating metastases to other bones, to precisely address the unmet clinical need associated with spine metastases.

The Increased Mortality Rate with Lower Incidence of Traumatic Brain Injury during the COVID-19 Pandemic: A National Study.

BACKGROUND: the COVID-19 pandemic with the following lockdown strategies have affected virtually all aspects of everyday life. Health services all over the world faced the crisis on an unprecedented scale, hampering timely care delivery. The present study was designed to assess the impact of the COVID-19 outbreak on the incidence and treatment of traumatic brain injuries in Poland. METHODS: the data on hospital admissions with traumatic brain injuries as the primary diagnosis were extracted from the National Health Fund of Poland. For the purpose of this study, the search was limited to four relevant diagnosis-related groups. The overall in-house mortality was calculated. RESULTS: there were 115,200 hospitalizations due to traumatic brain injury identified in the database. Overall, in comparison with the average of six prior years, in 2020 the volume of patients with traumatic brain injury dropped by 24.68% while the in-house mortality rate was increased by 26.75%. CONCLUSIONS: the COVID-19 pandemic with the resulting lockdown caused a radical reduction in human mobility. It had a profound impact on the incidence of traumatic brain injury, which dropped significantly. At the same time, the mortality rate increased drastically.

Factors Influencing Treatment Outcome and Proprioception after Electrocoagulation of the Femoral Insertion of the Anterior Cruciate Ligament.

(1) Background: Studies have established that exercises shaping the sense of deep sensation are an important element of medical rehabilitation of patients after vaporization of the femoral insertion of the anterior cruciate ligament and affect the restoration of correct movement patterns, thus reducing the risk of injuries. The aim of this study was to determine the factors influencing the treatment outcome and deep-feeling function after applying a specific rehabilitation scheme 12 weeks after anterior cruciate ligament electrocoagulation surgery. (2) Methods: The study group consisted of 41 patients after partial rupture of the anterior cruciate ligament, who underwent electrocoagulation of the femoral cruciate ligament attachment and microfracture of the femoral attachment area. All patients were operated on by the same surgeon and then rehabilitated according to the same medical rehabilitation protocol. The anthropometric and clinical data were collected through an anterior drawer test, Lachman test, assessment of the range of movements in the knee joint, muscle strength test, Unterberger test and Lysholm questionnaire. The assessment was performed before the surgery, and then on days 7-10, after 6 and 12 weeks of rehabilitation treatment. (3) Results: Statistical improvement of the parameters was demonstrated by strength of the quadriceps and hamstrings muscle, the Unterberger test, and the Lysholm scale after surgery. A negative correlation was found between the Unterberger test and Lysholm scale at the end of the research period and it differed depending on the gender and the dominant limb. The Lysholm scale and muscle strength were independent of sex, dominant extremity and associated damage of the meniscus and cartilage. The Lysholm scale 6 weeks after surgery negatively correlated with BMI. (4) Conclusions: Stability of the knee joint and improvement of proprioception were demonstrated 12 weeks after treatment with an ACL electrocoagulation and rehabilitation regimen. The factors contributing to a better treatment outcome were greater muscle strength, less thigh asymmetry, better sense of depth, younger age and lower body weight.

Sex- and Age-Related Dynamic Changes of the Macroelements Content in the Femoral Bone with Hip Osteoarthritis.

BACKGROUND: The content of macroelements in bones varies with age and depends on sex. The aim of the study was to evaluate the content of macroelements and its correlation with age and sex in the femoral bone obtained during total hip arthroplasty. METHODS: In the 86 patients, the content of macroelements (Ca, P, Mg, and Na) in the femoral head and neck (cancellous and cortical bone) was assessed by means of the inductively coupled plasma optical emission spectrometry analytical technique (ICP-OES). RESULTS: There was a decrease in the content of macroelements in the cortical bone with age in the women in the 51-60 years (statistically significant: -0.59 for Ca, -0.65 for P) and over 70 years age groups (correlation not statistically significant: -0.29 for Ca, -0.38 for P). A significant decrease in the content of macroelements in the cortical bone was found in men over 70 years of age. CONCLUSIONS: Patterns of increased loss of macronutrients (Ca, P, and Mg) in the femoral neck (cortical bone) were demonstrated in the following patients with osteoarthritis: women aged 51-60 years and patients of both sexes over 70 years of age.

Avascular Necrosis Bone Complication after Active COVID-19 Infection: Preliminary Results.

Background and objectives: The course of SARS-CoV-2 (COVID-19) is still under analysis. The majority of complications arising from the infection are related to the respiratory system. The adverse effect of the viral infection on bone and joint tissue has also been observed. Materials and Methods: We present a group of 10 patients with degeneration of large joints and adjacent epiphyses of long bones and the spine, with a background of bone infarctions and avascular necrosis (AVN) immediately after infection with the COVID-19 virus. In MR imaging, changes in the characteristics of AVN were documented. Results: Observation of this group showed a clear correlation among the history of COVID-19 disease in the patients, moderately severe symptoms, high levels of IgG antibodies, and the time of occurrence of joint changes. No other clinically significant complications were observed following COVID-19 infection in the study group. No other risk factors for AVN or autoimmune or degenerative diseases were found in the study group. The group of patients responded well to empirical treatment with steroids, which normalized acute inflammatory symptoms and pain in the joints. Conclusions: During coronavirus (COVID-19) infection, there are complications in the locomotor system, such as microembolism and the formation of AVN; hence, more research is needed.

Retracted: Atomic Absorption Spectrometry Analysis of Trace Elements in Degenerated Intervertebral Disc Tissue.

Medical Science Monitor is retracting the following publication on the basis of duplicated published content. 1) Kubaszewski L, Ziola-Frankowska A, Frankowski M, Rogala P, Gasik Z, Kaczmarczyk J, Nowakowski A, Dabrowski M, Labedz W, Miekisiak G, Gasik R. Comparison of trace element concentration in bone and intervertebral disc tissue by atomic absorption spectrometry techniques. J Orthop Surg Res. 2014 Oct 25;9: 99. doi: 10.1186/s13018-014-0099-y. PMID: 25342441; PMCID: PMC4220064. 2) Kubaszewski L, Ziola-Frankowska A, Frankowski M, Nowakowski A, Czabak-Garbacz R, Kaczmarczyk J, Gasik R. Atomic absorption spectrometry analysis of trace elements in degenerated intervertebral disc tissue. Med Sci Monit. 2014 Nov 4;20: 2157-64. doi: 10.12659/MSM.890654. PMID: 25366266; PMCID: PMC4301216. 3) Nowakowski A, Kubaszewski L, Frankowski M, Wilk-Franczuk M, Ziola-Frankowska A, Czabak-Garbacz R, Kaczmarczyk J, Gasik R. Analysis of trace element in intervertebral disc by Atomic Absorption Spectrometry techniques in degenerative disc disease in the Polish population. Ann Agric Environ Med. 2015;22(2): 362-7. doi: 10.5604/12321966.1152096. PMID: 26094540. We have reviewed the content of all three similar publications. We note that Medical Science Monitor was the second to publish this study, in November 2014. At that time, the Corresponding Author gave no declaration of submitting this study to any other journal, nor of previously publishing this study. Reference: Lukasz Kubaszewski, Anetta Ziola-Frankowska, Marcin Frankowski, Andrzej Nowakowski, Róza Czabak-Garbacz, Jacek Kaczmarczyk, Robert Gasik. Atomic Absorption Spectrometry Analysis of Trace Elements in Degenerated Intervertebral Disc Tissue. Med Sci Monit, 2014; 20: 2157-2164. DOI: 10.12659/MSM.890654.

Impact of the oxidative and enzymatic metals in degenerated intervertebral disc disease.

INTRODUCTION: The degenerative process of the intervertebral disc is a heterogeneous process that may exist in two forms, and involves dominant degenerative changes within the nucleus pulposus and the annulus fibrosus. In degenerative disc disease, the oxidative stress factor can play an important role. OBJECTIVE: The aim of research was to present a new approach to understanding the role of the analyzed elements in the process of degeneration of the intervertebral disc. MATERIAL AND METHODS: Selected elements from oxidative groups (Fe, Zn, Mo, As, Se), associated with enzymatic processes (Fe, Mo, Se, Zn, Ag, As, Bi), metals (Fe, Zn, Mo, Li) and metalloids (As, Bi) and their content was analyzed depending on the changes in the radiological images of the intervertebral disc. Elemental content analysis was performed by Inductively Coupled Plasma Mass Spectrometry analytical technique. RESULTS: The similarity between Fe and Se has been demonstrated during different stages of the analysis of groups of patients with degenerative disc disease. There was a negative correlation between Li and degenerative disc disease. The results also suggest that Fe and Ag are involved in degenerative changes within the intervertebral disc. A potential relationship between As/Bi and Fe/Mo in the degeneration of the intervertebral disc was demonstrated. CONCLUSIONS: Only some of the correlations can be explained by the metabolism of morphological elements of the intervertebral disc. The relationships indicate new directions for further studies on the degeneration process of the intervertebral disc. The presented study may reflect metabolic changes in the intervertebral disc and adjacent structures in response to the progressive degenerative process.

Addition of Popular Exogenous Antioxidant Agent, PBN, to Culture Media May Be an Important Step to Optimization of Myogenic Stem/Progenitor Cell Preparation Protocol.

The aim of the study was to modify human skeletal muscle-derived stem/progenitor cells (SkMDS/PCs) and demonstrate the optimal cell preparation protocol for application in post-infarction hearts. We used conditioned SkMDS/PC culture medium with α-phenyl-N-tert-butyl nitrone (PBN). SkMDS/PCs were cultured under hypoxic conditions and the results were compared to the standard ones. We observed a significant increase of CD-56 positive phenotypic marker the ability to form functional myotubes, increase in the proportion of young cells in cell primary suspensions, and a decrease in the percentage of apoptotic cells among PBN-conditioned cells in normoxia an hypoxia. We also observed significantly higher levels of SOD3 expression; maintained expression of SOD1, SOD2, and CAT; a higher level of BCL2 gene expression; and a rather significant decrease in Hsp70 gene expression in PBN-conditioned SkMDS/PCs compared to the WT population under hypoxic conditions. In addition, significant increase of myogenic genes expression was observed after PBN addition to culture medium, compared to WT population under hypoxia. Interestingly, PBN addition significantly increased the lengths of telomeres under hypoxia. Based on the data obtained, we can postulate that PBN conditioning of human SkMDS/PCs could be a promising step in improving myogenic cell preparation protocol for pro-regenerative treatment of post-infarction hearts.

Comparison of Bone Tissue Trace Element Content in the Different Radiological Stages of Hip Osteoarthritis.

Bone metabolism and the trace element content associated with it change at each stage of degenerative disease. The aim of this study was to find out about the role of the analyzed elements in different stages of hip osteoarthritis. Elements associated with oxidative and enzymatic processes were analyzed depending on the changes in the radiological images of the hip joint. Element content analysis was performed by the inductively coupled plasma mass spectrometry analytical technique. The femoral head in severely osteoarthritic hips (KL3-4) compared to mild grade osteoarthritis (KL2) had a greater content of Cu (median 1.04 vs. 0.04), Sr (median 38.71 vs. 29.59), and Zn (median 75.12 vs. 63.21). There were no significant differences in the content of Mo, Cr, and Fe in the femoral head and neck between the groups. The Cu/Fe correlation was negative in the KL2 group (-0.47) and positive in the KL3-4 groups (0.45). Changes in the content and correlation of trace elements in the hip joint explain the changes in metabolism dependent on the severity of degenerative changes.

Diffuse Idiopathic Skeletal Hyperostosis of Cervical Spine with Dysphagia-Molecular and Clinical Aspects.

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by the calcification and ossification of the ligaments of the cervical spine; in some cases, it may result in dysphagia. The condition is more common in men over 50 years of age with metabolic disorders, and it is often asymptomatic and not a major issue for patients. The etiology of DISH is poorly understood, and known genetic factors indicate multiple signal pathways and multigene inheritance. In this review, we discuss the epidemiological, clinical, and etiological aspects of DISH with a special focus on dysphagia.

Transient and Stable Overexpression of Extracellular Superoxide Dismutase Is Positively Associated with the Myogenic Function of Human Skeletal Muscle-Derived Stem/Progenitor Cells.

In the present study, the genetic modification of human skeletal muscle-derived stem/progenitor cells (SkMDS/PCs) was investigated to identify the optimal protocol for myogenic cell preparation for use in post-infarction heart therapy. We used two types of modifications: GFP-transfection (using electroporation) and SOD3 transduction (using a lentiviral vector). SkMDS/PCs were cultured under different in vitro conditions, including standard (21% oxygen) and hypoxic (3% oxygen), the latter of which corresponded to the prevailing conditions in the post-infarction heart. Transfection/transduction efficacy, skeletal myogenic cell marker expression (CD56), cellular senescence, and apoptosis, as well as the expression of antioxidant (SOD1, SOD2, and SOD3), anti-aging (SIRT1 and FOXO), anti-apoptotic (BCL2), and myogenic (MyoD and MyoG) genes, were evaluated. The percentage of GFP-positive SkMDS/PCs was determined as an indicator of the efficacy of transfection, which reached 55%, while transduction showed better efficiency, reaching approximately 85% as estimated by fluorescence microscopy. The CD56-positive SkMDS/PCs were present in approximately 77% of the tested cells after transient transfection and approximately 96% after transduction. Under standard in vitro culture conditions, the ability of the differentiated, transfected SkMDS/PCs to form myotubes was greater than that of the wild type (WT) cell population (p < 0.001), while the cells transduced with the SOD3 gene exhibited an increase in cell fusion under both standard (p < 0.05) and hypoxic conditions (p < 0.001). In transduced SkMDS/PCs, we observed a positive influence of SOD3 overexpression on cell ageing and apoptosis. We observed an increase in the percentage of young cells under standard (p < 0.05) and hypoxic (p < 0.001) in vitro culture conditions, with a notable decrease in the percentage of senescent and advanced senescent cells in the SOD3-overexpressing cell population detected compared to that observed for the untransduced muscle-derived cells. A lower percentage of apoptotic cells was observed for transduced SkMDS/PCs than that for WT cells under hypoxic in vitro culture conditions. In transiently transfected SkMDS/PCs, we observed significantly higher gene expression levels of SOD2 (almost 40-fold) (p < 0.001) and FOXO (p < 0.05) (approximately 3-fold) under both normoxic and hypoxic culture conditions and of BCL2 under hypoxia compared to those observed in untreated cells (WT). In addition, myogenic genes showed a significant increase in MyoD (almost 18-fold) expression under standard culture conditions (p < 0.0001) and decreased MyoG expression (approximately 2-fold) after transfection (p < 0.05) compared with that detected in the WT skeletal muscle-derived cell control. Taken together, these results demonstrate that SOD3-tranduced skeletal muscle-derived cells may have potential for use in the regenerative treatment of the post-infarction heart.

Surgical treatment of diffuse idiopathic skeletal hyperostosis of cervical spine with dysphagia - Case report.

INTRODUCTION: Diffuse idiopathic skeletal hyperostosis of cervical spine can lead to dysphagia. PRESENTATION OF CASE: A 73-year-old male weighing 110 kg and diagnosed with diffuse idiopathic skeletal hyperostosis in cervical spine with dysphagia. Patient manifested local pain of neck, a gradual limitation of spinal mobility. The surgery decision was based on swallowing problems, not pain in the spine. Before surgery radiographs, magnetic resonance images, computed tomography of the cervical spine and gastroscopy were obtained. Osteophytes were removed from the anterior approach with present otolaryngologist by surgery. DISCUSSION: In this case used gastroscopy, CT and MRI for diagnostics. During the procedure we had support otolaryngologist. The patient has not been found a stenosis spinal canal and neurological symptoms. We were removed the ostheophytes. Interbody implants have not been applied. CONCLUSION: Disc degeneration disease itself can be asymptomatic or not a dominant problem for the DISH patients. Clinical signs may pharyngoesophageal and tracheal compression, causing dysphagia, shortness of breath and stridor. In this case, the cervical spine was stability and not demonstrated a stenosis in the spinal canal. Isolate removing of the osteophytes without implants in DISH of cervical spine can be enough solution.

Tissue-specific promoter-based reporter system for monitoring cell differentiation from iPSCs to cardiomyocytes.

The possibility of using stem cell-derived cardiomyocytes opens a new platform for modeling cardiac cell differentiation and disease or the development of new drugs. Progress in this field can be accelerated by high-throughput screening (HTS) technology combined with promoter reporter system. The goal of the study was to create and evaluate a responsive promoter reporter system that allows monitoring of iPSC differentiation towards cardiomyocytes. The lentiviral promoter reporter system was based on troponin 2 (TNNT2) and alpha cardiac actin (ACTC) with firefly luciferase and mCherry, respectively. The system was evaluated in two in vitro models. First, system followed the differentiation of TNNT2-luc-T2A-Puro-mCMV-GFP and hACTC-mcherry-WPRE-EF1-Neo from transduced iPSC line towards cardiomyocytes and revealed the significant decrease in both inserts copy number during the prolonged in vitro cell culture (confirmed by I-FISH, ddPCR, qPCR). Second, differentiated and contracting control cardiomyocytes (obtained from control non-reporter transduced iPSCs) were subsequently transduced with TNNT2-luc-T2A-Puro-CMV-GFP and hACTC-mcherry-WPRE-EF1-Neo lentiviruses to observe the functionality of obtained cardiomyocytes. Our results indicated that the reporter modified cell lines can be used for HTS applications, but it is essential to monitor the stability of the reporter sequence during extended cell in vitro culture.

The change of volume of the lumbar vertebrae along with aging in asymptomatic population: a preliminary analysis.

INTRODUCTION: Previous studies have demonstrated that the length of the lumbar spine is decreasing with age. Despite considerable research based on sagittal measurements, little is known about the changes in the volume of vertebrae. The objective of this study was to evaluate the changes in the volume of either column of the spine with age. MATERIALS AND METHODS: Computed tomography scans of 62 asymptomatic subjects, performed for thoracolumbar trauma evaluation were used to create virtual 3D models. At least 10 patients were assigned to every decade of life from third to eight. We used a novel technique to measure the volume of anterior column (AC) and posterior column (PC) per each segment (a total of 310 segments). Midline sagittal images were used to measure disc height (DH) and vertebral body height (VH). RESULTS: With age, both DH increases, whereas the VH decreases. The overall length of lumbar segment of the spine decreases with age. The volumetric measurements performed on same subjects showed that volume of both AC and PC does not change with age in females. In males, there is a weak but statistically significant correlation between AC volume and age and no change in the volume of PC. The ratio of PC:AC volume does not change with age in women, although it decreases slightly but significantly (in favor of AC) with age in males. CONCLUSIONS: The overall length of lumbar spine decreases with age. This process is not a result of mere changes in the volume of either AC or PC.

Urban and rural area differences in the interaction between oxidative process elements in human femoral bone.

Elements in the human body come from contaminated food, water, and air from the living area. Bones are a marker of long-term exposure to elements and show a relationship between them. The aim of the study was to analyze the correlation between the contents of Zn, Cu, Fe, Mo, Cr, Ni, Ba, Sr, and Pb in the proximal femoral head (cancellous bone) and femoral neck (cortical bone) in rural and urban populations. The study included 96 patients who were operated on for total hip replacement (THR), acquired in a surgical procedure with atomic absorption spectrometry, and the content of Zn, Cu, Fe, Mo, Cr, Ni, Ba, Sr, and Pb was evaluated. In rural areas, significant negative correlations were observed for Mo/Cr, Mo/Cu, and Ni/Fe, and positive correlations were observed for Fe/Zn and Pb/Zn. In urban areas, a negative correlation was found for Pb/Mo. Pb and Ni increased with age only in villagers, and Zn and Sr decreased with age in urban citizens. Ba decreased with age in people from rural areas. The correlation showed variances mainly in molybdenum, nickel, and oxidative elements between rural and urban populations.

The impact of in vitro cell culture duration on the maturation of human cardiomyocytes derived from induced pluripotent stem cells of myogenic origin.

Ischemic heart disease, also known as coronary artery disease (CAD), poses a challenge for regenerative medicine. iPSC technology might lead to a breakthrough due to the possibility of directed cell differentiation delivering a new powerful source of human autologous cardiomyocytes. One of the factors supporting proper cell maturation is in vitro culture duration. In this study, primary human skeletal muscle myoblasts were selected as a myogenic cell type reservoir for genetic iPSC reprogramming. Skeletal muscle myoblasts have similar ontogeny embryogenetic pathways (myoblasts vs. cardiomyocytes), and thus, a greater chance of myocardial development might be expected, with maintenance of acquired myogenic cardiac cell characteristics, from the differentiation process when iPSCs of myoblastoid origin are obtained. Analyses of cell morphological and structural changes, gene expression (cardiac markers), and functional tests (intracellular calcium transients) performed at two in vitro culture time points spanning the early stages of cardiac development (day 20 versus 40 of cell in vitro culture) confirmed the ability of the obtained myogenic cells to acquire adult features of differentiated cardiomyocytes. Prolonged 40-day iPSC-derived cardiomyocytes (iPSC-CMs) revealed progressive cellular hypertrophy; a better-developed contractile apparatus; expression of marker genes similar to human myocardial ventricular cells, including a statistically significant CX43 increase, an MHC isoform switch, and a troponin I isoform transition; more efficient intercellular calcium handling; and a stronger response to ß-adrenergic stimulation.

Biomechanical analysis of the durability of a modified S1 vertebrae transpedicular screws insertion technique.

BACKGROUND: One of the most important elements of the transpedicular screw implantation technique, which enables a strong screw-bone interface, is the precise choice of the site of screw insertion and the screw's trajectory. Due to the complex biomechanics of the lumbosacral interface and different shape of the sacrum, fixation of this segment remains a challenge for surgeons. Because of this, Kubaszewski et al. proposed a modified technique in which the entry point for screw insertion in the S1 vertebra is changed. METHODS: Six human cadaver specimens of the S1 vertebrae were examined. Two transpedicular screws were inserted into the body of each examined vertebra using two implantation methods with different screw entry points and trajectories. The screws were subjected to cyclic preloading, followed by the pull-out test. The ultimate pull-out force, displacement, stiffness, and failure energy were measured. FINDINGS: The average pull-out force obtained for the standard method of implantation was 498 N (SD 201), whereas for the modified technique, it was 1308 N (SD 581). Displacement of the inserted screws in the new method was 36% higher than in the case of the standard method. This method is also characterized by the greater stiffness of the obtained interface and greater failure energy than the normally used technique. INTERPRETATION: The obtained results demonstrate that the use of the new technique of implantation significantly increases the strength of the obtained screw-bone interface. It should also increase the success rate of the performed fixations and increase the safety of such fixations in clinical practice.

Cytokines in the pathogenesis of hemophilic arthropathy.

Hemophilic arthropathy (HA) is one of the most common and typical manifestation in the course of recurrent bleeding episodes in patients with hemophilia. Clinical and subclinical joint bleeding episodes gradually lead to irreversible changes manifesting themselves as pain, progressing ankylosis, marked limitation of the range of motion, muscle atrophy and osteoporosis commonly concomitant with joint deformity resulting from chronic proliferative synovitis and both cartilage and bone degeneration leading to the final functional impairment of the joint. In spite of numerous studies, the pathophysiology of HA has not been fully elucidated, especially as regards immunopathological mechanisms which are associated with the subclinical and early stage of the disease and to be more precise, with chronic joint inflammation. It needs to be emphasized that the pathophysiological processes occurring in a joint with HA are most probably highly mediated by interactions within the cytokine network and other inflammatory mediators present in the tissues of affected joint. Among numerous compounds participating in the induction of an inflammatory process in the pathogenesis of HA, cytokines seem to play a leading role. The most important group controlling the disease seems to be well known inflammatory cytokines, including IL-1ß, TNFα and IL-6. The second group with antagonistic effect is formed by anti-inflammatory cytokines such as IL-4 and IL-10. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of HA with respect to cellular and intracellular signaling pathways is still under investigation. This review, summarizes and discusses the current knowledge about cytokine network in the pathogenesis of HA, indicating possible molecular and cellular mechanisms that may provide potential new therapeutic directions.

Chemometric evaluation of concentrations of trace elements in intervertebral disc tissue in patient with degenerative disc disease.

BACKGROUND: The work is designed to uncover the pattern of mutual relation among trace elements and epidemiological data in the degenerated intervertebral disk tissue in humans. Hitherto the reason of the degenerative process is not fully understood. Trace elements are the basic components of the biological compound related both its metabolism as well as environmental exposure. The relation pattern among elements occurs gives new perspective in solving the cause of the disease. MATERIAL AND METHODS: We have analysed trace elements content in the 30 intervertebral disc from 22 patients with degenerative disc disease. The concentrations of Al, Cu, Cd, Mo, Ni and Pb were determined with Atomic Absorption Spectrometry. To analyse the multidimentional relation between trace element concentration and epidemiological data the chemometric analysis was applied. RESULTS: The similarity have been shown in occurrence of following pairs: Cd-Mo as well as Mg-Zn. The second pair was correlated with Pb concentration. Pb levels are observed to be competitive to Cu concentration. Cd concentration was related to Zn and Mg deficiency. No single but rather cluster of epidemiological data show observable influence on the TE tissue variance. Zn and Cu was related to the male sex. Operation with orthopedic implants were related to combined Al, Mo and Zn concentration. CONCLUSIONS: This is the first chemometric analysis of trace elements in disk tissue. It shows multidimentional relations that are missed by the classical statistic. The analysis shows significant relation. The nature of the relations is the basis for further metabolic and environmental research.

Interrelationship between silicon, aluminum, and elements associated with tissue metabolism and degenerative processes in degenerated human intervertebral disc tissue.

There is a growing body of evidence concerning the significant role of silicon in development and composition of both connective and bone tissue. Bio-essential silicon shows strong chemical and biological affinity to aluminum, which is toxic and biologically inessential element. The presence of silicon was confirmed in a variety of tissues; however, it has never been examined in intervertebral disc tissue, neither in healthy nor in degenerated one. In this paper, for the first time in the literature, we present the content of silicon in the degenerated intervertebral disc tissue. We also compared the results of silicon analysis with aluminum values in degenerated intervertebral disc tissue in humans. We used chemometric methods to find correlations and similarities between silicon, aluminum, and elements associated with tissue metabolism (Mg) and degenerative processes (Zn and Cu). The presence of silicon was confirmed in all 30 samples harvested from 22 patients operated on due to degenerative changes. Its concentration was within the range of 5.37-12.8 µg g-1 d.w., with the mean concentration of 7.82 µg g-1 d.w. The analysis showed significant correlation between Si and both Al and Mg and weak or negative correlation with Zn and Cu, where the latter was probably the result of degenerative processes. Although silicon is considered essential in glycosaminoglycan and collagen synthesis in connective tissue, it did not show any correlation nor similarities with elements reflecting changes associated with the degenerative process of the intervertebral disc. Silicon showed significant correlation with aluminum, similar to those observed in other human tissues.