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Peroxisome proliferator-activated receptors (PPARs) alter the expression of genes involved in regulating lipid metabolism. Rosiglitazone, a PPARγ agonist, induces tissue-specific effects on lipid metabolism; however, its mode of action in skeletal muscle remains unclear. Since fatty acid translocase (FAT/CD36) was recently identified as a possible regulator of skeletal muscle fatty acid transport and mitochondrial fatty acid oxidation, we examined in this tissue the effects of rosiglitazone infusion (7 days, 1 mg day−1) on FAT/CD36 mRNA and protein, its plasmalemmal content and fatty acid transport. In addition, in isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria we examined rates of fatty acid oxidation, FAT/CD36 and carnitine palmitoyltransferase I (CPTI) protein, and CPTI and β-hydroxyacyl CoA dehydrogenase (β-HAD) activities. Rosiglitazone did not alter FAT/CD36 mRNA or protein expression, FAT/CD36 plasmalemmal content, or the rate of fatty acid transport into muscle ( P > 0.05). In contrast, rosiglitazone increased the rates of fatty acid oxidation in both SS (+21%) and IMF mitochondria (+36%). This was accompanied by concomitant increases in FAT/CD36 in subsarcolemmal (SS) (+43%) and intermyofibrillar (IMF) mitochondria (+46%), while SS and IMF CPTI protein content, and CPTI submaximal and maximal activities ( P > 0.05) were not altered. Similarly, citrate synthase (CS) and β-HAD activities were also not altered by rosiglitazone in SS and IMF mitochondria ( P > 0.05). These studies provide another example whereby changes in mitochondrial fatty oxidation are associated with concomitant changes in mitochondrial FAT/CD36 independent of any changes in CPTI. Moreover, these studies identify for the first time a mechanism by which rosiglitazone stimulates fatty acid oxidation in skeletal muscle, namely the chronic, subcellular relocation of FAT/CD36 to mitochondria. [ABSTRACT FROM AUTHOR]

This paper describes a preliminary evaluation of particle-mediated bombardment via the Helios gene gun for the delivery of therapeutic genes to synovial cells in culture. A reporter gene, enhanced green fluorescent protein, was delivered to rabbit synovial fibroblasts (HIG-82) using gold particle (1.0 µm) bombardment to evaluate transfection efficiency at helium pressures of 100 and 150 psi. Transfection of cells occurred at these pressures despite some cell death. The in vitro delivery of gold particles to samples of synovial membrane and articular cartilage from a freshly euthanased dog was also studied to examine depth of penetration of gold particles (1.0 µm) at helium pressures of 250 and 500 psi. Light microscopical examination of histological sections of the synovial membrane showed that particles of gold had penetrated the lining cells of the synovium. However, no gold particles had penetrated the articular cartilage even at 500 psi. [ABSTRACT FROM AUTHOR]

To determine the relationship between total body water (TBW) fraction and local water content measured in the skin (SW) this study assessed eight anesthetized piglets in an overhydration model. TBW was assessed by deuterium oxide dilution and body mass measurements taken throughout the experiments, and by whole body carcass analysis at the end of each experiment. Additionally, extracellular water and plasma volume were assessed using bromide dilution and Evan's blue dilution, respectively. SW was assessed by tissue biopsies taken at 60-mm intervals throughout the experiment. Lean body water (LBW) fraction and lean skin water (LSW) fraction were assessed by extracting the fat from the carcass and biopsy samples. A correlation does exist between TBW traction and SW fraction with r² = 0.58 (P < 0.05); however, the strongest correlation occurred between the LBW fraction and LSW traction with r² = 0.87 (P < 0.05) and an SE of prediction of 0.77%. These data demonstrate that LSW gives an accurate and precise estimate of LBW and could therefore be used to determine the hydration index in appropriate research settings. [ABSTRACT FROM AUTHOR]

Presents a study that examined whether the ovarian hormones alter insulin-responsiveness glucose transporter protein content in insulin-sensitive tissue. Influence of the ovarian hormones on basal and contraction-stimulated glucose uptake in skeletal muscle; Alterations in glucose transport attributable to transporter protein content; Enzymes representative of fatty acid flux into the mitochondria and β-oxidation.

Objective: To describe the MR appearance following autogenous osteochondral "plug" transfer for the treatment of focal chondral defects of the knee.Design and Patients: Twenty-nine 1.5-T MR knee studies including dynamic gadolinium enhancement were performed on 21 patients following autogenous osteochondral "plug" transfer. Three musculoskeletal radiologists retrospectively reviewed images to evaluate graft and donor site appearance and MR findings were correlated with clinical outcomes.Results: MR images demonstrated graft protuberance (n=12/21; range 1-2 mm), depression (n=2/21; range 1 mm), and surface incongruity: mild (n=17/21), moderate (n=2/21), marked (n=1/21). The T2 signal of graft cartilage was similar to that of adjacent cartilage in 25 of 29 examinations, and increased in four. Graft cartilage thickness relative to adjacent cartilage was <50% in six patients, 50-100% in 15. Graft enhancement in bone was absent at 2 weeks, but present at between 4 and 6 weeks following surgery. All patients had clinical follow-up examinations and knee outcome survey scores were obtained in 15 patients with follow-up greater than 3 months after surgery. All patients demonstrated the expected short-term progressive clinical improvement.Conclusion: MR images reveal a wide range of appearances following osteochondral "plug" transfer. Minor variations in graft orientation and surface congruity do not result in adverse clinical outcome in the short term. [ABSTRACT FROM AUTHOR]

Objective: To determine whether anteroposterior (AP) and lateral views of the knee are equivalent to four views in acute fracture detection.Design: Three musculoskeletal radiologists retrospectively interpreted the plain film knee examinations of each patient, establishing ground truth for the presence or absence of a fracture. Cases were presented to four masked senior radiology residents twice--once as a two-view study and again as a four-view study--with 4 weeks separating the two reading sessions to minimize recall bias. Sensitivity, specificity, and diagnostic performance were calculated.Patients: Ninety-two patients presenting to the emergency department with acute knee trauma were evaluated with at least a four-view plain film examination.Results and Conclusions: Mean sensitivity for fracture detection using four views (85%) was significantly higher than that using two views (79%). Mean specificity and receiver operating characteristic curve areas were not significantly different using two or four views. Four views are more sensitive than AP and lateral views alone in detection of acute knee fracture. [ABSTRACT FROM AUTHOR]

To evaluate gender-related differences in left ventricular (LV) structure and function in aortic stenosis, LV biplane cineangiography, micromanometry and endomyocardial biopsies were carried out in 56 patients with aortic stenosis and normal coronary arteries. Patients were divided into males (M: n= θ35), and females (F: n= θ21). Sixteen normal subjects 8 M, 8 F) served as haemodynamic controls. Control biopsy data were obtained from six pre-transplantation donor hearts (3 M and 3 F). LV systolic function was evaluated by ejection fraction and its relationship to mean systolic circumferential wall stress, diastolic function by the time constant of LV pressure decay, peak filling rates and passive myocardial stiffness constant. Biopsy samples were evaluated for interstitial fibrosis, muscle fibre diameter and volume fraction of myofibrils. In a subset of 27 consecutive patients, biopsy samples were evaluated with a morphometric-morphological method, for total collagen volume fraction, endocardial fibrosis and the extension and thickness of orthogonal collagen fibres (cross-hatching). In patients with aortic stenosis, aortic valve area, aortic valve resistance and mean aortic pressure gradient were comparable in males and females, whereas end-systolic and end-diastolic volumes were larger in males than females. Ejection fraction was lower (56%) in males than females (64%) (P<0.05); 20 of 35 males and four of 21 females had depressed systolic contractility when assessed with regard to the relationship ejection fraction-mean systolic stress (P<0.01). Myocardial stiffness constant was higher in males than in females (P<0.0I). Nine of 14 males and two of 13 females had endocardial fibrosis (P<0.009), whereas increased cross-hatching (> 1.5 grade) was present in 11 males and four females with aortic stenosis (P<0.0I). An abnormal collagen architecture was present in 13114 males and 5113 females (V<0.002). In aortic stenosis, males have a depressed systolic function and abnormal passive elastic properties when compared to females with valve lesions of similar severity. Changes in collagen architecture may account, at least in part, for these differences. [ABSTRACT FROM PUBLISHER]

Symptomatic heart failure is accompanied by diastolic ventricular dysfunction due largely to an extensive reactive and reparative fibrosis. Experimental evidence suggests a clear association between myocardial fibrosis and chronic inappropriate elevations in circulating angiotensin II (Ang II) and/or aldosterone. Although not entirely elucidated, injury follows Ang lI-associated release of adrenal medullary catecholamines and aldosterone-induced myocardial potassium depletion. Increasing evidence indicates locally produced cardiac Ang II plays an important role in tissue repair that may underlie myocardial remodelling, the fibrous tissue accumulation both at and remote to the site of myocardial infarction (MI). Angiotensin converting enzyme (ACE) binding density markedly increases at these fibrous tissue sites after experimental MI, indicating an involvement in wound healing regardless of the cause and location of fibrosis; cells expressing Ang II receptors are primarily myofibroblasts. Therapy with A CE inhibitors and aldosterone receptor antagonist have each been shown to attenuate development of fibrosis. [ABSTRACT FROM PUBLISHER]

Discusses research being done on the ACMEplus data collection tool. Reference to a study by J. E. Lynch and colleagues, presented at the autumn meeting of the British Geriatrics Societies in October 2004; Hospital sites where data collection was done; Results and conclusion.