Gabriel Dischereit

Infliximab improves bone metabolism and bone mineral density in rheumatoid arthritis and ankylosing spondylitis: a prospective 2-year study

Based on the systemic inflammatory processes, severe alterations in bone turnover are more frequent in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) [1]. A large body of evidence indicates that the inflammatory diseases themselves initiate and perpetuate mechanisms of bone loss, especially by inducing the synthesis of resorptive factors [2], subsequently followed by osteopenia and osteoporosis. Furthermore, it has long been known that the frequently required treatment with corticosteroids also causes a substantial decrease of bone mass [3]. The results are often fractures after falling, pain, loss of independence, and an overall reduction in quality of life. Therefore, understanding and preventing osteoporosis in patients with RA or AS will not only have a great impact on the individual patient’s wellbeing but also on health-care economy. Conversely, recent studies have shown, over a short-term period, that anti-tumor necrosis factor alpha (TNF-α) therapy is an effective agent to halt this process and increase bone mineral density (BMD) in patients with RA and AS [4, 5]. It has been shown that the proinflammatory cytokine TNF-α mediates bone resorption both in systemic postmenopausal osteoporosis and in periarticular or periprosthetic bone erosions [6]. Therefore, we performed an open-label prospective pilot study to evaluate changes in BMD of patients with RA and AS receiving long-term anti-TNF-α therapy. To address this goal, infliximab was used due to its successful long-term use in the treatment of RA and AS [7]. Bone metabolism was analyzed based on biochemical markers of bone formation and resorption, and the relationships between BMD, markers of bone turnover, and response to treatment were examined. Changes in disease activity and response to treatment were monitored by the established activity scores disease activity score of 28 joints (DAS28), Bath ankylosing spondylitis disease activity index (BASDAI), visual analog scale (VAS), and health assessment questionnaire (HAQ).

Time course of cigarette smoke-induced changes of systemic inflammation and muscle structure

It has become more evident that long-term cigarette smoking (LTCS) has an important extrapulmonary toxicity. The aim of the study was to investigate the time-dependent effects of cigarette smoke exposure on exercise capacity, markers of systemic inflammation, and skeletal muscle structure. c57bl/6j-mice were either exposed to mainstream cigarette smoke for 6 h/day, 5 days/wk [smoke-exposed (SE) group] or assigned to the control, unexposed group (Con group). SE group mice were exposed for 8, 16, 24, and 32 wk to smoke and unexposed Con mice were used as age-matched controls. Exercise capacity was investigated by spiroergometry. Systemic inflammatory status was analyzed by flow cytometry and multiplexed fluorescent immunoassay. For analysis of muscle tissue, histological techniques and microarray analysis were used. Mice of the SE group exhibited a lower increase of body mass and a decrease of V̇o2 max (P < 0.05). An increase of lymphocyte CD62, ICAM, and VCAM expression was found in SE mice (P < 0.05). A biphasic trend of protein up- and downregulation was observed in markers of systemic inflammation, tissue deterioration, and allergic reactions such as C-reactive protein (CRP), eotaxin, haptoglobin, macrophage colony-stimulating factor-1 (M-CSF-1), and macrophage inflammatory protein-1γ (MIP-1γ). Thereby, the expression of several chemotactic proteins in plasma correlated with their expression in muscle. A time-dependent decrease of muscle mass, oxidative type-I fibers, and muscle cross-sectional area was found (P < 0.05). Microarray analysis revealed a SE-induced upregulation of several pathways of metabolic processes and tissue degradation. Taken together it was found that the loss of exercise capacity and systemic inflammation are early events of SE, which might induce muscular atrophy and loss of oxidative muscle capacity.

Osteoimmunological Aspects on Inflammation and Bone Metabolism

Bone remodelling is characterized by a balance between bone resorption and bone formation. The osteoblasts are responsible for bone synthesis and the osteoclasts for bone resorption. A finely adjusted interaction between molecular mechanisms results, via cytokines, hormones and growth factors, in homeostasis of bone metabolism. Here, the RANK/RANKL/OPG-system is actively involved in the differentiation and function of osteoclasts and is known to play a central role in the majority of pathophysiological mechanisms. Also the Wnt and BMP signalling pathways play a major role in osteoblast differentiation and bone remodeling. An increased osteoclast activity contributes to inflammatory and destructive osteocatabolic manifestations and/or osteoporosis whereas an increased osteoblast activity can result in osteopetrosis. This overview describes the known relevant pathophysiological metabolic pathways in this remodelling process, especially the effect of inflammation on bone metabolism, and outlines the links from bench to bedside.

Molekulare Wirkungen physikalischer Therapiemaßnahmen

Modern molecular medicine offers the possibility to investigate the potential influences of different methods of physical therapy on pivotal mechanisms and mediators of the inflammatory processes of rheumatic diseases and interactions between cells of the immune system and bone. Based on recent studies, it could be shown that modulation of these regulatory systems can be achieved by various physiotherapeutics.ZusammenfassungMittels Methoden der molekularen Medizin ist es inzwischen bei entzündlich rheumatischen Erkrankungen möglich, den Einfluss von unterschiedlichen Physiotherapeutika auf zentrale Botenstoffe des Entzündungsprozesses sowie Interaktionen zwischen Zellen des Immunsystems und des Knochens zu analysieren. Anhand aktueller Studien wird der Eingriff in diese Regulationssysteme durch diverse Physiotherapeutika vorgestellt.AbstractModern molecular medicine offers the possibility to investigate the potential influences of different methods of physical therapy on pivotal mechanisms and mediators of the inflammatory processes of rheumatic diseases and interactions between cells of the immune system and bone. Based on recent studies, it could be shown that modulation of these regulatory systems can be achieved by various physiotherapeutics.

Severe osteoarthritic manifestations of ochronosis

The congenital form of ochronosis is a result of the rare autosomal recessive inherited metabolic disease alkaptonuria. The disruption of tyrosine metabolism based on a genetic defect in the enzyme homogentisate dioxygenase results in accumulation of homogentisic acid (HA) which is excreted in the urine and leads to a dark discoloration after a certain incubation time at room temperature. Furthermore, HA polymerizes forming a pigment that is deposited in connective tissues such as tendons, cartilage, bones, intervertebral discs, sclerae, ossicles, cardiac valves and coronary arteries and leads to dark brown discoloration and degeneration. The case of a 74-year-old female patient with ochronosis and classical manifestations is described and in addition a current overview of this rare disease is provided.

Schwerste arthrotische Veränderungen durch eine Ochronose

The congenital form of ochronosis is a result of the rare autosomal recessive inherited metabolic disease alkaptonuria. The disruption of tyrosine metabolism based on a genetic defect in the enzyme homogentisate dioxygenase results in accumulation of homogentisic acid (HA) which is excreted in the urine and leads to a dark discoloration after a certain incubation time at room temperature. Furthermore, HA polymerizes forming a pigment that is deposited in connective tissues such as tendons, cartilage, bones, intervertebral discs, sclerae, ossicles, cardiac valves and coronary arteries and leads to dark brown discoloration and degeneration. The case of a 74-year-old female patient with ochronosis and classical manifestations is described and in addition a current overview of this rare disease is provided.

Evidenzbasierte physikalische Therapie bei rheumatoider Arthritis

Die rheumatoide Arthritis als entzündlich-rheumatische Erkrankung geht aufgrund ihres progredienten Verlaufs oft mit Einschränkungen der funktionellen und funktionalen Gesundheit einher. Gerade hierdurch ergibt sich eine elementare Indikation für den Einsatz von Physiotherapie und physikalischen Maßnahmen. Die vorliegende Arbeit fokussiert auf den Stellenwert und die Bedeutung physikalischer Therapieoptionen und gibt einen Überblick über die Versorgungsrealität und die vorhandene Evidenz.

Molekulare Wirkungen physikalischer Therapiemaßnahmen@@@Molecular effects of physical therapy: Was gibt es Neues?@@@What’s new?

Modern molecular medicine offers the possibility to investigate the potential influences of different methods of physical therapy on pivotal mechanisms and mediators of the inflammatory processes of rheumatic diseases and interactions between cells of the immune system and bone. Based on recent studies, it could be shown that modulation of these regulatory systems can be achieved by various physiotherapeutics.ZusammenfassungMittels Methoden der molekularen Medizin ist es inzwischen bei entzündlich rheumatischen Erkrankungen möglich, den Einfluss von unterschiedlichen Physiotherapeutika auf zentrale Botenstoffe des Entzündungsprozesses sowie Interaktionen zwischen Zellen des Immunsystems und des Knochens zu analysieren. Anhand aktueller Studien wird der Eingriff in diese Regulationssysteme durch diverse Physiotherapeutika vorgestellt.AbstractModern molecular medicine offers the possibility to investigate the potential influences of different methods of physical therapy on pivotal mechanisms and mediators of the inflammatory processes of rheumatic diseases and interactions between cells of the immune system and bone. Based on recent studies, it could be shown that modulation of these regulatory systems can be achieved by various physiotherapeutics.

Molekulare Wirkungen physikalischer TherapiemaßnahmenMolecular effects of physical therapy

Modern molecular medicine offers the possibility to investigate the potential influences of different methods of physical therapy on pivotal mechanisms and mediators of the inflammatory processes of rheumatic diseases and interactions between cells of the immune system and bone. Based on recent studies, it could be shown that modulation of these regulatory systems can be achieved by various physiotherapeutics.ZusammenfassungMittels Methoden der molekularen Medizin ist es inzwischen bei entzündlich rheumatischen Erkrankungen möglich, den Einfluss von unterschiedlichen Physiotherapeutika auf zentrale Botenstoffe des Entzündungsprozesses sowie Interaktionen zwischen Zellen des Immunsystems und des Knochens zu analysieren. Anhand aktueller Studien wird der Eingriff in diese Regulationssysteme durch diverse Physiotherapeutika vorgestellt.AbstractModern molecular medicine offers the possibility to investigate the potential influences of different methods of physical therapy on pivotal mechanisms and mediators of the inflammatory processes of rheumatic diseases and interactions between cells of the immune system and bone. Based on recent studies, it could be shown that modulation of these regulatory systems can be achieved by various physiotherapeutics.

[Molecular effects of physical therapy. What's new?].

Modern molecular medicine offers the possibility to investigate the potential influences of different methods of physical therapy on pivotal mechanisms and mediators of the inflammatory processes of rheumatic diseases and interactions between cells of the immune system and bone. Based on recent studies, it could be shown that modulation of these regulatory systems can be achieved by various physiotherapeutics.ZusammenfassungMittels Methoden der molekularen Medizin ist es inzwischen bei entzündlich rheumatischen Erkrankungen möglich, den Einfluss von unterschiedlichen Physiotherapeutika auf zentrale Botenstoffe des Entzündungsprozesses sowie Interaktionen zwischen Zellen des Immunsystems und des Knochens zu analysieren. Anhand aktueller Studien wird der Eingriff in diese Regulationssysteme durch diverse Physiotherapeutika vorgestellt.AbstractModern molecular medicine offers the possibility to investigate the potential influences of different methods of physical therapy on pivotal mechanisms and mediators of the inflammatory processes of rheumatic diseases and interactions between cells of the immune system and bone. Based on recent studies, it could be shown that modulation of these regulatory systems can be achieved by various physiotherapeutics.