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Arthritis of major joints, especially osteoarthritis of the knee is a very frequent disease of human beings mainly in the developed countries. The pathology of osteoarthritis has been subject of many publications before, using a wide spectrum of different methods to evaluate degenerative changes of hyaline cartilage. The authors examined osteoarthritic human knee joint hyaline cartilage with differential scanning calorimetry. The different stages of cartilage degeneration have been verified by histological examinations. The research group demonstrated thermal differences between various stages of osteoarthritis. Besides explaining possible causes for experienced thermodynamic effects, the authors reflect upon future research ways and the possibilities of applying the method in practice. [ABSTRACT FROM AUTHOR]

Aims: The incidence, bone marrow morphology and genetic features of bcr+ essential thrombocythaemia were investigated. Methods and results: Sixty-four consecutive patients meeting the criteria of essential thrombocythaemia have been investigated for bcr-abl rearrangement and chimera mRNA expression. Reverse transcriptase-polymerase chain reaction indicated bcr-abl expression in six patients, in two of whom large fraction of the blood and bone marrow cells proved to be positive for Philadelphia chromosome (Ph) by fluorescent in-situ hybridization (FISH) and conventional cytogenetic analysis. In the remaining four patients FISH analysis could not detect Ph+ cells among the blood cells, but in one of these four patients conventional cytogenetic analysis indicated a very small fraction (2%) of Ph+ mitoses in the bone marrow (bcr+ essential thrombocythaemia patients). In three of these four patients, X-chromosome-linked clonality assay showed that the disease is of uncommitted stem cell origin. During an average of 57 month long follow-up no transformation to chronic myeloid leukaemia type of disease or acceleration/blastic crisis could be observed in the four bcr+ essential thrombocythaemia patients. They did not differ significantly from typical essential thrombocythaemia patients in quantitative indices of bone marrow cellularity or the size of megakaryocytes. In these two parameters as well as in the total nucleolus organizer region area per nucleus, however, significant differences could be detected between these four as well as typical chronic myeloid leukaemia patients. Statistical analysis of the morphometric data obtained from all six Ph+ and bcr+ essential thrombocythaemia patients combined indicated a shift of the bone marrow morphology towards the chronic myeloid leukaemia type of myeloproliferation. Conclusions: These investigations indicate that bcr+ essential thrombocythaemia is infrequent among essential thrombocythaemia patients, and this condition... [ABSTRACT FROM AUTHOR]

Abstract: The Achilles tendon rupture is a common injury of the foot in middle age and physically active population in Europe. The aetiology of the degenerative changes in the collagen structures of the tendon which could be disposed for the rupture is still not clear. Our hypothesis was that before the injury there is a clear pathological abnormality in the tissue elements building up the Achilles tendon, which is responsible for the disease, and could be monitored besides the classical histological methods by differential scanning calorimetry. The thermal denaturation of human samples was monitored by a SETARAM Micro DSC-II calorimeter. All the experiments were performed between 0 and 100°C. The heating rate was 0.3K/min. DSC scans clearly demonstrated significant differences between the control and ruptured samples (control: T m =59.7°C, T 1/2 =1.4°C and ΔH cal =8.54J/g; ruptured: T m =62.75°C, T 1/2 =2.6°C and ΔH cal =1.54J/g). These observations could be explained with the structural alterations caused by the biochemical and structural processes. With our investigations we could demonstrate that DSC is a useful and well applicable method for the investigation of collagen tissue of the human Achilles tendon. We can prove with this method, that the earlier series of microtraumas which result a scar formation in the tendon tissue increases the thermal stability of collagen in ruptured tendon. [Copyright &y& Elsevier]

Shoulder pain is a common presentation of the dysfunction of the glenohumeral joint. The long head of the biceps tendon has been proposed as a source of pain in rotator cuff pathologies. The rotator cuff is a dynamic stabilizer of the glenohumeral joint, and its tear can create different shoulder dysfunctions. The long head of the biceps has a special intraarticular localisation, so the arthricular destruction affects its tendon too. In the process of the rotator cuff degeneration and tear the structure of the biceps tendon pathological transforms. With foregoing studies authors have demonstrated the feasibility of DSC in the investigation of the musculoskeletal system. The aim of this study was to establish the curves and the histological properties of the tendon of the long head of the biceps in different magnitudes of the rotator cuff tear on cadavers. The DSC results clearly proved that definitive differences are present between the structural state of the tendons in different magnitudes of the rotator cuff tears, which have also been demonstrated by the histological examination. [ABSTRACT FROM AUTHOR]

Cruciate ligaments of the knee joint are important structures very often affected by the degenerative process in case of osteoarthritis. One of the most controversial issues in knee arthroplasty practice nowadays is the role of the posterior cruciate ligament. With foregoing studies authors have demonstrated the feasibility of DSC in the investigation of the musculoskeletal system. With current study authors established the thermal behaviour of healthy cruciate ligaments and detected the alterations in case of osteoarthritis. By establishing the DSC scans of the normal ligaments authors demonstrated clear differences between the posterior and anterior ligament. In addition alterations between normal and arthritic samples could be detected both in terms of changes in total enthalpy and heat capacity. Calorimetric findings have been verified by histological examinations as well. [ABSTRACT FROM AUTHOR]

Analysis of lineage involvement was performed in 17 Philadelphia chromosome-positive acute lymphoblastic leukemia patients with no history of chronic myeloproliferative disorder. The percentage of blastic cells as defined by flow cytometry matched that of the Ph-positive cells in 14 out of 17 patients. The bcr-abl rearrangement was investigated by fluorescent in situ hybridization in morphologically identified blastic cells, myeloid elements, lymphocytes and erythroblasts using a combined light and fluorescent microscopical imaging. Lymphoid lineage restriction could be determined in all but three of the patients. These 14 patients exhibited heterogeneity in terms of m-bcr and M-bcr types of translocation as revealed by reverse transcription polymerase chain reaction. The three patients with multilineage involvement and M-bcr type of translocation reverted to chronic phase and the percentage of Ph-positive cells remained high. Thus, we could identify an uncommitted stem cell origin among Ph-positive ALLs only in those patients whose disease subsequently proved to be a lymphoid blastic crisis with clinically silent chronic phase. [ABSTRACT FROM AUTHOR]

During revision hip surgeries, a soft pseudo-capsule is formed around the artificial joint. The roles of the pseudo-capsule are to protect and to stabilize the joint. Based on intraoperative observation, we have found that different types of pseudo-capsules have different thickness and elasticity, compared to the primary joint capsule. The purpose of the study was to evaluate and identify the different types of pseudo-capsules, based on thermal characteristics and histological examinations. The pseudo-capsule samples were collected during aseptic hip revision (n = 3), septic hip revision (n = 2) and during revision surgery after antibiotic-impregnated spacer implantation (n = 3). The thermal characteristics (maximal denaturation temperature, Tm, and calorimetric enthalpy change, ΔHcal) were determined from the measurements made by SETARAM Micro DSC-II calorimeter between 37° and 90°C with 0.3 K min−1 heating rate. The denaturation scans of different pseudo-capsule samples have clearly demonstrated specific, representative changes, comparing samples with aseptic and septic origins. These changes were confirmed by histological evaluations; therefore, DSC could be a useful tool in the evaluation of hip pseudo-capsules with different origins, providing further help in the differential diagnostics of septic conditions. [ABSTRACT FROM AUTHOR]

Sporadic clinical reports suggested that marijuana smoking induces spontaneous pneumothorax, but no animal models were available to validate these observations and to study the underlying mechanisms. Therefore, we performed a systematic study in CD1 mice as a predictive animal model and assessed the pathophysiological alterations in response to 4-mo-long whole body marijuana smoke with integrative methodologies in comparison with tobacco smoke. Bronchial responsiveness was measured with unrestrained whole body plethysmography, cell profile in the bronchoalveolar lavage fluid with flow cytometry, myeloperoxidase activity with spectrophotometry, inflammatory cytokines with ELISA, and histopathological alterations with light microscopy. Daily marijuana inhalation evoked severe bronchial hyperreactivity after a week. Characteristic perivascular/peribronchial edema, atelectasis, apical emphysema, and neutrophil and macrophage infiltration developed after 1 mo of marijuana smoking; lymphocyte accumulation after 2 mo; macrophage-like giant cells, irregular or destroyed bronchial mucosa, goblet cell hyperplasia after 3 mo; and severe atelectasis, emphysema, obstructed or damaged bronchioles, and endothelial proliferation at 4 mo. Myeloperoxidase activity, inflammatory cell, and cytokine profile correlated with these changes. Airway hyperresponsiveness and inflammation were not altered in mice lacking the CB1 cannabinoid receptor. In comparison, tobacco smoke induced hyperresponsiveness after 2 mo and significantly later caused inflammatory cell infiltration/activation with only mild emphysema. We provide the first systematic and comparative experimental evidence that marijuana causes severe airway hyperresponsiveness, inflammation, tissue destruction, and emphysema, which are not mediated by the CB1 receptor. [ABSTRACT FROM AUTHOR]

Highlights: [•] We summarize our experiences with use of DSC for the diagnosis and prognostic grading of human musculoskeletal diseases. [•] We found a recognizable pattern in comparison of the thermal characteristics of the studied human tissue samples. [•] Utilization of DSC scans would provide help to select the most sufficient treatment for musculoskeletal diseases. [ABSTRACT FROM AUTHOR]

The compartment syndrome—conditions of elevated intramuscular pressure—is one of the most serious complications of the injuries of the lower extremities. Early diagnosis is important, as delayed treatment leads to significant complications. The diagnosis of compartment syndrome is most commonly made by clinical examination and direct measurement of the intra-compartmental pressure. Our hypothesis was that in different stages of compartment syndrome there is a clear pathological abnormality in the tissue elements of the affected muscles, which is responsible for seriousness of the disease, and could be monitored besides the classical histological methods by differential scanning calorimetry. The thermal denaturation of different parts of human samples was monitored by a SETARAM Micro DSC-II calorimeter. All the experiments were performed between 0 and 100 °C. The heating rate was 0.3 K/min. DSC scans clearly demonstrated significant differences between the different types and conditions of samples (control: Tm = 55.5; 59.9 °C and ΔHcal = 0.52 J/g, Gr. I.: Tm = 58.1; 62.2 °C and ΔHcal = 0.28 J/g, Gr. II.: Tm = 57.45; 61.5 °C and ΔHcal = 0.24 J/g, Volkmann’s ischemic contracture Tm = 57.75; 61.8; 65.8 °C and ΔHcal = 0.74 J/g). These observations could be explained with the structural alterations caused by the biochemical processes. The heat capacity change between native and denatured states of muscle samples was significant, indicating significant water loosing during denaturation, but independent from the structural alterations. [ABSTRACT FROM AUTHOR]

The Dupuytren contracture - degenerative shortening of the palmar aponeurosis - is a common disease of the hand in Europe. The aetiology of the degenerative changes in the collagen structures is still not clear. To describe the clinical manifestation of the disease we use an international classification according to Iselin. Our hypothesis was that in Dupuytren disease there is a clear pathological abnormality in the tissue elements building up the palmar aponeurosis, which is responsible for the disease, and could be monitored besides the classical histological methods by differential scanning calorimetry. The thermal denaturation of different parts of human samples was monitored by a SETARAM Micro DSC-II calorimeter. All the experiments were performed between 0 and 100°C. The heating rate was 0.3 K min−1. DSC scans clearly demonstrated significant differences between the different types and conditions of samples (control: Tm=63°C and Δ Hcal=4.1 J g−1, stage I.: Tm= 63°C and Δ Hcal=5.1 J g−1, stage II.: Tm=64°C and Δ Hcal=5.2 J g−1, stage III.: Tm=60°C and Δ Hcal=5.2 J g−1, stage IV.: Tm=60.2°C and Δ Hcal=5.3 J g−1). The heat capacity change between native and denatured states of aponeurosis samples increased with the degree of structural alterations indicating significant water loosing. These observations could be explained with the structural alterations caused by the biochemical processes. With our investigations we could demonstrate that DSC is a useful and well applicable method for the investigation of collagen tissue of the human aponeurosis. Our results may be of clinical relevance in the future i.e. in the choice of the optimal time of surgical therapy of different clinical level Dupuytren contractures. [ABSTRACT FROM AUTHOR]

The carpal tunnel syndrome - compression of the median nerve by the transverse ligament of the wrist - is a serious disease of the human hand. The electrophysiological changes in the median nerve can be easily followed by electroneurography (ENG). The degenerative changes in the collagen structures of the carpal ligament cause shrinking of the ligament and compression of the nerve. According to the present study we could demonstrate that DSC is a useful and well applicable method for the investigation of collagen tissue of the human carpal transverse ligament. DSC scans clearly demonstrated significant differences between the different types and conditions of samples (control: Tm=61.3°C and Δ Hcal=4.04 J g−1, mild: Tm=62°C and Δ Hcal=4.3 J g−1, middle: Tm=61.5°C and ΔHcal=5.17 J g−1 as well as severe: Tm=61.85°C and Δ Hcal=8.44 J g−1). After these investigations we can choose the optimal time of surgical therapy of different clinical level carpal tunnel syndrome too. [ABSTRACT FROM AUTHOR]

Abstract: The shoulder is the most frequently dislocated joint of the human body. The instability of the joint can be caused by ligamentous capsular redundancy. When non-operative management fails for this patient, quality of life is significantly impaired and surgical treatment is required to tighten the ligaments and the joint capsule. Radiofrequency (RF) energy of electrothermal arthroscopic capsulorrhaphy (ETC) represents a relatively non-invasive method to stabilize joints with excessive laxity by thermally shrinking redundant joint capsular tissue. Due to the thermal treatment of joint capsular tissue collagen fibers the capsule shrinks, so the stability of the joint rises. RF energy induces shrinkage, but also significant decline in the structural properties of the collagenous capsular tissue, which is thought to abate the final results of the treatment. The indication of the ETC treatment, the optimal device settings and shrinkage rate are still not clarified. Differential scanning calorimetric (DSC) examination is a validly efficient method for the demonstration of structural changes in biological systems. The purpose of this study was to establish the feasibility of DSC in the field of monitoring the structural alteration of the ETC treated collagenous capsular tissue. We used cadaver tissue samples to establish the thermograms of the thermal treated and the intact capsular joint tissue. Our preliminary findings show that the untreated tissue has a much cooperated transition with about T 1/2 of 1.5°C. In case of treated sample this was about 8°C of course with two superimposed transitions. The lower melting transition stands for the heat-treated part of collagen. This proves, that in the heat-treated part, the collagen transformed into a random coil conformation with less thermal stability and suggest that DSC can be a viable method by monitoring the structural effects of ETC. [Copyright &y& Elsevier]

Background and purpose:Substance P (SP) and calcitonin gene-related peptide (CGRP) released from capsaicin-sensitive sensory nerves induce local neurogenic inflammation; somatostatin exerts systemic anti-inflammatory actions presumably via sst4/sst1 receptors. This study investigates the effects of a high affinity, sst4-selective, synthetic agonist, J-2156, on sensory neuropeptide release in vitro and inflammatory processes in vivo.Experimental approach:Electrically-induced SP, CGRP and somatostatin release from isolated rat tracheae was measured with radioimmunoassay. Mustard oil-induced neurogenic inflammation in rat hindpaw skin was determined by Evans blue leakage and in the mouse ear with micrometry. Dextran-, carrageenan- or bradykinin-induced non-neurogenic inflammation was examined with plethysmometry or Evans blue, respectively. Adjuvant-induced chronic arthritis was assessed by plethysmometry and histological scoring. Granulocyte accumulation was determined with myeloperoxidase assay and IL-1β with ELISA.Key results:J-2156 (10–2000 nM) diminished electrically-evoked neuropeptide release in a concentration-dependent manner. EC50 for the inhibition of substance P, CGRP and somatostatin release were 11.6 nM, 14.3 nM and 110.7 nM, respectively. J-2156 (1–100 μg kg−1 i.p.) significantly, but not dose-dependently, inhibited neurogenic and non-neurogenic acute inflammatory processes and adjuvant-induced chronic oedema and arthritic changes. Endotoxin-evoked myeloperoxidase activity and IL-1β production in the lung, but not IL-1β- or zymosan-induced leukocyte accumulation in the skin were significantly diminished by J-2156.Conclusions and implications:J-2156 acting on sst4 receptors inhibits neuropeptide release, vascular components of acute inflammatory processes, endotoxin-induced granulocyte accumulation and IL-1β synthesis in the lung and synovial and inflammatory cells in chronic arthritis. Therefore it might be a promising lead for the development of novel anti-inflammatory drugs.British Journal of Pharmacology (2006) 149, 405–415. doi:10.1038/sj.bjp.0706876; published online 4 September 2006 [ABSTRACT FROM AUTHOR]

Abstract: Rotator cuff tear is a common musculoskeletal disorder with pathological changes occurring in the structure of the rotator cuff musculature (fatty infiltration). Severe fatty infiltration, observed on MRI or CT scan, negatively influences the result of rotator cuff reconstruction in human beings. The basic histological and biochemical alterations in fatty infiltration of the rotator cuff muscle with torn tendon are still not clear. Differential scanning calorimetric (DSC) examination is a well-established method for the demonstration of thermal consequences of local and global conformational changes in biological systems. With foregoing studies, authors have demonstrated the feasibility of DSC in the investigation of the musculoskeletal system. The aim of this study was to establish the thermograms of the rotator cuff muscles with normal and torn tendons, experimentally induced in rabbits. The DSC results clearly proved that definitive differences are present between the muscles with normal and torn tendons, which have also been demonstrated by MRI and CT scans. [Copyright &y& Elsevier]