Tendon Cell Behavior and Matrix Remodeling in Degenerative Tendinopathy

Tendon injuries are common in human athletes [1-4]. Furthermore, such injuries are also prevalent in the ageing sedentary population [5-7]. In recent decades, the incidence of tendon injuries has risen due to both an increase in an elderly population and a rise in participation in recreational and competitive sporting activities. In the general population the lifetime cumulative incidence of Achilles tendinopathy is 5.9 % among sedentary people and 50 % among elite endurance athletes [2]. Despite the high frequency, there are still many unsolved questions and differences of opinion concerning pathology, etiology, and even terminology. Until several years ago the most often used word for tendon disease in the clinical practice of orthopaedic and sports medicine was ’tendonitis/ tendinitis’, literally meaning tendon inflammation, reflecting the general idea that overuse tendinopathies were due to inflammation. However, this common wisdom was challenged by that time, as the histopathological feature usually described in tendinopathies was a degenerative process and inflammation was not typically seen [8-11]. Therefore Nicola Maffulli suggested to use the term ‘tendinopathy’ as a general descriptor of the clinical conditions in and around tendons arising from overuse [12, 13]. In addition the term ‘tendinosis’, literally meaning tendon degeneration, should be used after histopathological examination. This nomenclature is gradually being integrated now in research communication and clinicial practice. The clinical presentation of tendinopathy is characterized by a combination of pain, swelling, and impaired performance. A variety of tendons in humans may be affected including the supraspinatus tendon in the shoulder, the forearm extensor and flexor muscle tendons in the elbow, and the Achilles tendon and the patellar tendon in the lower limb. The respons of tendinopathy to the currently available treatment options is often unsatisfactory requiring lengthy periods of rehabilitation or even surgical intervention [14, 15]

In search for the etiology of the complex regional pain syndrome

The complex regional pain syndrome is poorly elucidated. In line with this its diagnosis and clinical management have remained suboptimal. The multifaceted nature makes it a fascinating study topic for scientists with varying interests, but unraveling the etiology has been proven a laborious mission. The first notification of what could have been (what is currently named) complex regional pain syndrome (CRPS) stems from 1634, when the surgeon Ambroise Pare described that King Charles IX suffered from persistent pain and contractures of his arm following a bloodletting procedure.1 The next remarks came from the military physician Scott Mitchell and date from the American Civil War: “…Long after the trace of the effect of a wound has gone neuralgic symptoms are apt to linger, and too many carry with them throughout long years this final reminder of the battle field...”.2 The first scientific publication on CRPS was issued in 1900 from a German surgeon named Paul Sudeck.3 His name became tied to the syndrome for long (Sudecks’ dystrophy)

Applied information retrieval and multidisciplinary research: new mechanistic hypotheses in Complex Regional Pain Syndrome

Background: Collaborative efforts of physicians and basic scientists are often necessary in the investigation of complex disorders. Difficulties can arise, however, when large amounts of information need to reviewed. Advanced information retrieval can be beneficial in combining and reviewing data obtained from the various scientific fields. In this paper, a team of investigators with varying backgrounds has applied advanced information retrieval methods, in the form of text mining and entity relationship tools, to review the current literature, with the intention to generate new insights into the molecular mechanisms underlying a complex disorder. As an example of such a disorder the Complex Regional Pain Syndrome (CRPS) was chosen. CRPS is a painful and debilitating syndrome with a complex etiology that is still unraveled for a considerable part, resulting in suboptimal diagnosis and treatment. Results: A text mining based approach combined with a simple network analysis identified Nuclear Factor kappa B (NFκB) as a possible central mediator in both the initiation and progression of CRPS. Conclusion: The result shows the added value of a multidisciplinary approach combined with information retrieval in hypothesis discovery in biomedical research. The new hypothesis, which was derived in silico, provides a framework for further mechanistic studies into the underlying molecular mechanisms of CRPS and requires evaluation in clinical and epidemiological studies

Glomerular hyperfiltration predicts the development of microalbuminuria in stage 1 hypertension: The HARVEST

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The prevalence of autoantibodies in complex regional pain syndrome type i

Autoimmunity has been suggested as one of the pathophysiologic mechanisms that may underlie complex regional pain syndrome (CRPS). Screening for antinuclear antibodies (ANA) is one of the diagnostic tests, which is usually performed if a person is suspected to have a systemic autoimmune disease. Antineuronal antibodies are autoantibodies directed against antigens in the central and/or peripheral nervous system. The aim of this study was to compare the prevalence of these antibodies in CRPS patients with the normal values of those antibodies in the healthy population. Twenty seven (33%) of the 82 CRPS patients of whom serum was available showed a positive ANA test. This prevalence is significantly higher than in the general population. Six patients (7.3%) showed a positive result for typical antineuronal antibodies. This proportion, however, does not deviate from th

Acute-phase reactants after paediatric cardiac arrest. Procalcitonin as marker of immediate outcome

<p>Abstract</p> <p>Objective</p> <p>Procalcitonin (PCT) and C reactive protein (CRP) have been used as infection parameters. PCT increase correlates with the infection's severity, course, and mortality. Post-cardiocirculatory arrest syndrome may be related to an early systemic inflammatory response, and may possibly be associated with an endotoxin tolerance. Our objective was to report the time profile of PCT and CRP levels after paediatric cardiac arrest and to assess if they could be use as markers of immediate survival.</p> <p>Materials and methods</p> <p>A retrospective observational study set in an eight-bed PICU of a university hospital was performed during a period of two years. Eleven children younger than 14 years were admitted in the PICU after a cardiac arrest. PCT and CRP plasma concentrations were measured within the first 12 and 24 hours of admission.</p> <p>Results</p> <p>In survivors, PCT values increased 12 hours after cardiac arrest without further increase between 12 and 24 hours. In non survivors, PCT values increased 12 hours after cardiac arrest with further increase between 12 and 24 hours. Median PCT values (range) at 24 hours after cardiac arrest were 22.7 ng/mL (0.2 – 41.0) in survivors vs. 205.5 ng/mL (116.6 – 600.0) in non survivors (p < 0.05). CRP levels were elevated in all patients, survivors and non-survivors, at 12 and 24 hours without differences between both groups.</p> <p>Conclusion</p> <p>Measurement of PCT during the first 24 hours after paediatric cardiac arrest could serve as marker of mortality.</p

Dynamic modeling of Nrf2 pathway activation in liver cells after toxicant exposure

Cells are exposed to oxidative stress and reactive metabolites every day. The Nrf2 signaling pathway responds to oxidative stress by upregulation of antioxidants like glutathione (GSH) to compensate the stress insult and re-establish homeostasis. Although mechanisms describing the interaction between the key pathway constituents Nrf2, Keap1 and p62 are widely reviewed and discussed in literature, quantitative dynamic models bringing together these mechanisms with time-resolved data are limited. Here, we present an ordinary differential equation (ODE) based dynamic model to describe the dynamic response of Nrf2, Keap1, Srxn1 and GSH to oxidative stress caused by the soft-electrophile diethyl maleate (DEM). The time-resolved data obtained by single-cell confocal microscopy of green fluorescent protein (GFP) reporters and qPCR of the Nrf2 pathway components complemented with siRNA knock down experiments, is accurately described by the calibrated mathematical model. We show that the quantitative model can describe the activation of the Nrf2 pathway by compounds with a different mechanism of activation, including drugs which are known for their ability to cause drug induced liver-injury (DILI) i.e., diclofenac (DCF) and omeprazole (OMZ). Finally, we show that our model can reveal differences in the processes leading to altered activation dynamics amongst DILI inducing drugs.Toxicolog