Grading scale of radiographic findings in the pubic bone and symphysis in athletes.

Purpose: Radiographic abnormalities in the pubic bone and symphysis are often seen in athletes with groin pain. The aim was to create a grading scale of such radiologic changes. Material and Methods: Plain radiography of the pelvic ring including the pubic bone and the symphysis was performed in 20 male athletes, age 19-35, with long-standing uni- or bilateral groin pain. We used two control groups: Control group 1: 20 healthy age-matched men who had undergone radiologic examination of the pelvis due to trauma. Control group 2: 120 adults (66 men and 54 women) in 9 age groups between 15 and 90 years of age. These examinations were also evaluated for interobserver variance. Results and Conclusion: The grading scale was based on the type and the amount of the different changes, which were classified as follows: No bone changes (grade 0), slight bone changes (grade 1), intermediate changes (grade 2), and advanced changes (grade 3). The grading scale is easy to interpret and an otherwise troublesome communication between the radiologist and the physician was avoided. There was a high interobserver agreement with a high kappa value (0.8707). Male athletes with long-standing groin pain had abnormal bone changes in the symphysis significantly more frequently and more severely (p>0.001) than their age-matched references. In asymptomatic individuals such abnormalities increased in frequency with age both in men and women

Role of acid-sensing ion channel 3 in sub-acute-phase inflammation

<p>Abstract</p> <p>Background</p> <p>Inflammation-mediated hyperalgesia involves tissue acidosis and sensitization of nociceptors. Many studies have reported increased expression of acid-sensing ion channel 3 (ASIC3) in inflammation and enhanced ASIC3 channel activity with pro-inflammatory mediators. However, the role of ASIC3 in inflammation remains inconclusive because of conflicting results generated from studies of <it>ASIC3 </it>knockout (<it>ASIC3</it>^-/-) or dominant-negative mutant mice, which have shown normal, decreased or increased hyperalgesia during inflammation.</p> <p>Results</p> <p>Here, we tested whether ASIC3 plays an important role in inflammation of subcutaneous tissue of paw and muscle in <it>ASIC3</it>^-/-mice induced by complete Freund's adjuvant (CFA) or carrageenan by investigating behavioral and pathological responses, as well as the expression profile of ion channels. Compared with the <it>ASIC3</it>^+/+controls, <it>ASIC3</it>^-/-mice showed normal thermal and mechanical hyperalgesia with acute (4-h) intraplantar CFA- or carrageenan-induced inflammation, but the hyperalgesic effects in the sub-acute phase (1–2 days) were milder in all paradigms except for thermal hyperalgesia with CFA-induced inflammation. Interestingly, carrageenan-induced primary hyperalgesia was accompanied by an <it>ASIC3</it>-dependent <it>Nav1.9 </it>up-regulation and increase of tetrodotoxin (TTX)-resistant sodium currents. CFA-inflamed muscle did not evoke hyperalgesia in <it>ASIC3</it>^-/-or <it>ASIC3</it>^+/+mice, whereas carrageenan-induced inflammation in muscle abolished mechanical hyperalgesia in <it>ASIC3</it>^-/-mice, as previously described. However, <it>ASIC3</it>^-/-mice showed attenuated pathological features such as less CFA-induced granulomas and milder carrageenan-evoked vasculitis as compared with <it>ASIC3</it>^+/+mice.</p> <p>Conclusion</p> <p>We provide a novel finding that ASIC3 participates in the maintenance of sub-acute-phase primary hyperalgesia in subcutaneous inflammation and mediates the process of granuloma formation and vasculitis in intramuscular inflammation.</p

Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models.

Continuous de novo fatty acid synthesis is a common feature of cancer that is required to meet the biosynthetic demands of a growing tumor. This process is controlled by the rate-limiting enzyme acetyl-CoA carboxylase (ACC), an attractive but traditionally intractable drug target. Here we provide genetic and pharmacological evidence that in preclinical models ACC is required to maintain the de novo fatty acid synthesis needed for growth and viability of non-small-cell lung cancer (NSCLC) cells. We describe the ability of ND-646-an allosteric inhibitor of the ACC enzymes ACC1 and ACC2 that prevents ACC subunit dimerization-to suppress fatty acid synthesis in vitro and in vivo. Chronic ND-646 treatment of xenograft and genetically engineered mouse models of NSCLC inhibited tumor growth. When administered as a single agent or in combination with the standard-of-care drug carboplatin, ND-646 markedly suppressed lung tumor growth in the Kras;Trp53-/- (also known as KRAS p53) and Kras;Stk11-/- (also known as KRAS Lkb1) mouse models of NSCLC. These findings demonstrate that ACC mediates a metabolic liability of NSCLC and that ACC inhibition by ND-646 is detrimental to NSCLC growth, supporting further examination of the use of ACC inhibitors in oncology

Paramagnetic and fluorescent liposomes for target-specific imaging and therapy of tumor angiogenesis

Angiogenesis is essential for tumor growth and metastatic potential and for that reason considered an important target for tumor treatment. Noninvasive imaging technologies, capable of visualizing tumor angiogenesis and evaluating the efficacy of angiostatic therapies, are therefore becoming increasingly important. Among the various imaging modalities, magnetic resonance imaging (MRI) is characterized by a superb spatial resolution and anatomical soft-tissue contrast. Revolutionary advances in contrast agent chemistry have delivered versatile angiogenesis-specific molecular MRI contrast agents. In this paper, we review recent advances in the preclinical application of paramagnetic and fluorescent liposomes for noninvasive visualization of the molecular processes involved in tumor angiogenesis. This liposomal contrast agent platform can be prepared with a high payload of contrast generating material, thereby facilitating its detection, and is equipped with one or more types of targeting ligands for binding to specific molecules expressed at the angiogenic site. Multimodal liposomes endowed with contrast material for complementary imaging technologies, e.g., MRI and optical, can be exploited to gain important preclinical insights into the mechanisms of binding and accumulation at angiogenic vascular endothelium and to corroborate the in vivo findings. Interestingly, liposomes can be designed to contain angiostatic therapeutics, allowing for image-supervised drug delivery and subsequent monitoring of therapeutic efficacy

Sports-related groin pain: evaluation with MR imaging

Our purpose was to assess the role of MRI in evaluating the musculoskeletal system in athletes with chronic pain laterally in the groin of unknown etiology. Magnetic resonance imaging (MRI) of the pubic ring was performed in 11 young athletes (soccer players) with long-standing groin pain. MR findings were compared with plain films and isotope examination (bone scan Tc 99M). Abnormal MRI findings included a broadened and irregular symphysis with a characteristic pattern of low signal intensity on T1W and high signal intensity on T2W images localized in the superior pubic ramus at a distance from the symphysis. Positive findings were also observed on plain films and on nuclear medicine studies. However, the imaging findings in the superior public ramus of the symphysis was located considerably more laterally on MRI. MRI is a valuable method for evaluating discrete and ambiguous pelvic pain in athletes, particularly for identifying concomitant changes in the superior ramus, which may give rise to long-standing pain localized laterally in the groin