No association between femoral or acetabular angles and patient-reported outcomes in patients with femoroacetabular impingement syndrome-results from the HAFAI cohort.

Patients with femoroacetabular impingement syndrome (FAIS) are diagnosed using imaging, but detailed description especially the acetabular shape is lacking and may help give more insight to the pathogenesis of FAIS. Furthermore, associations between patient-reported outcomes (PROs) and the radiological angles might highlight which radiological angles affect outcomes experienced by the patients. Hence, the aims of this study were (i) to describe computer tomography (CT) acquired angles in patients with FAIS and (ii) to investigate the association between radiological angles and the Copenhagen Hip and Groin Outcome Score (HAGOS) in patients with FAIS. Patients scheduled for primary hip arthroscopic surgery for FAIS were included. Based on CT, following angles were measured before and 1 year after surgery; femoral anteversion, alpha, lateral centre edge, acetabular index, anterior sector, posterior sector and acetabular anteversion. All patients completed the HAGOS. Sixty patients (63% females) aged 36 ± 9 were included. One year after surgery, significant alterations in the alpha angle and the acetabular index angle were found. Neither baseline PROs nor changes in PROs were associated with the radiological angles or changes in angles. Since neither changes in CT angles nor baseline scores were associated with HAGOS, the improvements felt by patients must origin from somewhere else. These findings further underlines that morphological changes seen at imaging should not be treated arthroscopically without a patient history of symptoms and clinical findings.

Similar patient positioning: A key factor in follow-up studies when using model-based radiostereometric analysis of the hip.

INTRODUCTION: Despite protocols, patients are not positioned exactly alike at radiostereometric (RSA) follow-up examinations, and it is unknown how much variation is tolerable. We report precision for optimal and extreme position differences from a phantom hip-study, and clinical precision of hip-RSA. METHODS: A femoral stem with 3 bead-towers was fixed in a saw bone with bone-markers (phantom), and series of RSA examinations within optimal (5 × 5 cm and 5°) and extreme (20 × 30 cm and 30°) phantom positions were obtained. Double-examination RSA of 12 patients with the same femoral stem type were analyzed. Both model-based (CAD) and marker-based (MM) analysis was used. Precision was reported as standard deviation of differences. RESULTS: Precision for translations in the optimal and extreme phantom position were below 0.06 mm and 0.02 mm for MM analysis, and below 0.05 mm and 0.18 mm for CAD analysis, respectively. Precision for rotations in the optimal and extreme phantom rotation were below 0.18° and 0.26° for MM analysis, and below 0.34° and 0.52° for CAD analysis, respectively. Clinical precision was 0.29 mm and 0.44° for MM analysis, and 0.40 mm and 1.59° for CAD analysis. CONCLUSION: Extreme differences in patient position during RSA examination negatively affects precision, and CAD model-analysis was more sensitive than MM analysis. Longitudinal translation and rotation about the long stem-axis are the effect parameters which are most affected by position and rotation changes, and also the best indicators of implant loosening. IMPLICATIONS FOR PRACTICE: Based on our research, we recommend that similar patient positioning between follow-up RSA examinations is debated and prioritized.

Is hip muscle strength normalised in patients with femoroacetabular impingement syndrome one year after surgery?: Results from the HAFAI cohort.

OBJECTIVES: Little is known about hip function after hip arthroscopic surgery in patients with femoroacetabular impingement syndrome. Hence, the aim of the study was (1) to investigate changes in hip muscle strength from before to one year after hip arthroscopic surgery, (2) to compare patients with a reference group. DESIGN: Cohort study with a cross-sectional comparison. METHODS: Before and after hip arthroscopic surgery, patients underwent hip muscle strength testing of their hip flexors and extensors during concentric, isometric and eccentric contraction in an isokinetic dynamometer. Reference persons with no hip problems underwent tests at a single time point. Participants completed completed the Copenhagen Hip and Groin Outcome Score (HAGOS) questionnaire and physical capacity (stair climbing loaded and unloaded, stepping loaded and unloaded and jumping) tests. RESULTS: After surgery, hip flexion strength improved during all tests (6-13%, p<0.01) and concentric hip extension strength improved (4%, p=0.002). Hip flexion and extension strength was lower for patients than for reference persons (9-13%, p<0.05) one year after surgery. Higher hip extension strength after surgery was associated with better patient reported outcomes. Patients, who were unable to complete at minimum one test of physical capacity, demonstrated significantly weaker hip muscle strength. Compared with their healthy counterparts, female patients were more impaired than male patients. CONCLUSIONS: One year after surgery, patients improved their maximal hip muscle strength. When compared to reference persons, maximal hip muscle strength was still impaired.

Exercise-induced dehydration alters pulmonary function but does not modify airway responsiveness to dry air in athletes with mild asthma.

Local airway water loss is the main physiological trigger for exercise-induced bronchoconstriction (EIB). Our aim was to investigate the effects of whole body water loss on airway responsiveness and pulmonary function in athletes with mild asthma and/or EIB. Ten recreational athletes with a medical diagnosis of mild asthma and/or EIB completed a randomized, crossover study. Pulmonary function tests, including spirometry, whole body plethysmography, and diffusing capacity of the lung for carbon monoxide (DlCO), were conducted before and after three conditions: 1) 2 h of exercise in the heat with no fluid intake (dehydration), 2) 2 h of exercise with ad libitum fluid intake (control), and 3) a time-matched rest period (rest). Airway responsiveness was assessed 2 h postexercise/rest via eucapnic voluntary hyperpnea (EVH) to dry air. Exercise in the heat with no fluid intake induced a state of mild dehydration, with a body mass loss of 2.3 ± 0.8% (SD). After EVH, airway narrowing was not different between conditions: median (interquartile range) maximum fall in forced expiratory volume in 1 s was 13 (7-15)%, 11 (9-24)%, and 12 (7-20)% in dehydration, control, and rest conditions, respectively. Dehydration caused a significant reduction in forced vital capacity (300 ± 190 ml, P = 0.001) and concomitant increases in residual volume (260 ± 180 ml, P = 0.001) and functional residual capacity (260 ± 250 ml, P = 0.011), with no change in DlCO Mild exercise-induced dehydration does not exaggerate airway responsiveness to dry air in athletes with mild asthma/EIB but may affect small airway function.NEW & NOTEWORTHY This study is the first to investigate the effect of whole body dehydration on airway responsiveness. Our data suggest that the airway response to dry air hyperpnea in athletes with mild asthma and/or exercise-induced bronchoconstriction is not exacerbated in a state of mild dehydration. On the basis of alterations in lung volumes, however, exercise-induced dehydration appears to compromise small airway function.

A standard, single dose of inhaled terbutaline attenuates hyperpnea-induced bronchoconstriction and mast cell activation in athletes.

Release of bronchoactive mediators from mast cells during exercise hyperpnea is a key factor in the pathophysiology of exercise-induced bronchoconstriction (EIB). Our aim was to investigate the effect of a standard, single dose of an inhaled ß2-adrenoceptor agonist on mast cell activation in response to dry air hyperpnea in athletes with EIB. Twenty-seven athletes with EIB completed a randomized, double-blind, placebo-controlled, crossover study. Terbutaline (0.5 mg) or placebo was inhaled 15 min prior to 8 min of eucapnic voluntary hyperpnea (EVH) with dry air. Pre- and postbronchial challenge, urine samples were analyzed by enzyme immunoassay for 11ß-prostaglandin F2α (11ß-PGF2α). The maximum fall in forced expiratory volume in 1 s of 14 (12-20)% (median and interquartile range) following placebo was attenuated to 7 (5-9)% with the administration of terbutaline (P < 0.001). EVH caused a significant increase in 11ß-PGF2α from 41 (27-57) ng/mmol creatinine at baseline to 58 (43-72) ng/mmol creatinine at its peak post-EVH following placebo (P = 0.002). The rise in 11ß-PGF2α was inhibited with administration of terbutaline: 39 (28-44) ng/mmol creatinine at baseline vs. 40 (33-58) ng/mmol creatinine at its peak post-EVH (P = 0.118). These data provide novel in vivo evidence of mast cell stabilization following inhalation of a standard dose of terbutaline prior to bronchial provocation with EVH in athletes with EIB.

AltitudeOmics: exercise-induced supraspinal fatigue is attenuated in healthy humans after acclimatization to high altitude.

AIMS: We asked whether acclimatization to chronic hypoxia (CH) attenuates the level of supraspinal fatigue that is observed after locomotor exercise in acute hypoxia (AH). METHODS: Seven recreationally active participants performed identical bouts of constant-load cycling (131 ± 39 W, 10.1 ± 1.4 min) on three occasions: (i) in normoxia (N, PI O2 , 147.1 mmHg); (ii) in AH (FI O2 , 0.105; PI O2 , 73.8 mmHg); and (iii) after 14 days in CH (5260 m; PI O2 , 75.7 mmHg). Throughout trials, prefrontal-cortex tissue oxygenation and middle cerebral artery blood velocity (MCAV) were assessed using near-infrared-spectroscopy and transcranial Doppler sonography. Pre- and post-exercise twitch responses to femoral nerve stimulation and transcranial magnetic stimulation were obtained to assess neuromuscular and corticospinal function. RESULTS: In AH, prefrontal oxygenation declined at rest (Δ7 ± 5%) and end-exercise (Δ26 ± 13%) (P < 0.01); the degree of deoxygenation in AH was greater than N and CH (P < 0.05). The cerebral O2 delivery index (MCAV × Ca O2 ) was 19 ± 14% lower during the final minute of exercise in AH compared to N (P = 0.013) and 20 ± 12% lower compared to CH (P = 0.040). Maximum voluntary and potentiated twitch force were decreased below baseline after exercise in AH and CH, but not N. Cortical voluntary activation decreased below baseline after exercise in AH (Δ11%, P = 0.014), but not CH (Δ6%, P = 0.174) or N (Δ4%, P = 0.298). A twofold greater increase in motor-evoked potential amplitude was evident after exercise in CH compared to AH and N. CONCLUSION: These data indicate that exacerbated supraspinal fatigue after exercise in AH is attenuated after 14 days of acclimatization to altitude. The reduced development of supraspinal fatigue in CH may have been attributable to increased corticospinal excitability, consequent to an increased cerebral O2 delivery.

Effects of inspiratory muscle training on exercise responses in Paralympic athletes with cervical spinal cord injury.

We asked whether specific inspiratory muscle training (IMT) improves respiratory structure and function and peak exercise responses in highly trained athletes with cervical spinal cord injury (SCI). Ten Paralympic wheelchair rugby players with motor-complete SCI (C5-C7) were paired by functional classification then randomly assigned to an IMT or placebo group. Diaphragm thickness (B-mode ultrasonography), respiratory function [spirometry and maximum static inspiratory (PI ,max ) and expiratory (PE ,max ) pressures], chronic activity-related dyspnea (Baseline and Transition Dyspnea Indices), and physiological responses to incremental arm-crank exercise were assessed before and after 6 weeks of pressure threshold IMT or sham bronchodilator treatment. Compared to placebo, the IMT group showed significant increases in diaphragm thickness (P = 0.001) and PI ,max (P = 0.016). There was a significant increase in tidal volume at peak exercise in IMT vs placebo (P = 0.048) and a strong trend toward an increase in peak work rate (P = 0.081, partial eta-squared = 0.33) and peak oxygen uptake (P = 0.077, partial eta-squared = 0.34). No other indices changed post-intervention. In conclusion, IMT resulted in significant diaphragmatic hypertrophy and increased inspiratory muscle strength in highly trained athletes with cervical SCI. The strong trend, with large observed effect, toward an increase in peak aerobic performance suggests IMT may provide a useful adjunct to training in this population.

Effect of terbutaline on hyperpnoea-induced bronchoconstriction and urinary club cell protein 16 in athletes.

Repeated injury of the airway epithelium caused by hyperpnoea of poorly conditioned air has been proposed as a key factor in the pathogenesis of exercise-induced bronchoconstriction (EIB) in athletes. In animals, the short-acting ß2-agonist terbutaline has been shown to reduce dry airflow-induced bronchoconstriction and the associated shedding of airway epithelial cells. Our aim was to test the efficacy of inhaled terbutaline in attenuating hyperpnoea-induced bronchoconstriction and airway epithelial injury in athletes. Twenty-seven athletes with EIB participated in a randomized, double-blind, placebo-controlled, crossover study. Athletes completed an 8-min eucapnic voluntary hyperpnoea (EVH) test with dry air on two separate days 15 min after inhaling 0.5 mg terbutaline or a matching placebo. Forced expiratory volume in 1 s (FEV1) and urinary concentration of the club cell (Clara cell) protein 16 (CC16, a marker of airway epithelial perturbation) were measured before and up to 60 min after EVH. The maximum fall in FEV1 of 17 ± 8% (SD) on placebo was reduced to 8 ± 5% following terbutaline (P < 0.001). Terbutaline gave bronchoprotection (i.e., post-EVH FEV1 fall <10%) to 22 (81%) athletes. EVH caused an increase in urinary excretion of CC16 in both conditions (P < 0.001), and terbutaline significantly reduced this rise (pre- to postchallenge CC16 increase 416 ± 495 pg/µmol creatinine after placebo vs. 315 ± 523 pg/µmol creatinine after terbutaline, P = 0.016). These results suggest that the inhalation of a single therapeutic dose of terbutaline offers significant protection against hyperpnoea-induced bronchoconstriction and attenuates acute airway epithelial perturbation in athletes.

Scaphoid kinematics before and after scaphotrapeziotrapezoidal ligament section. Assessment by radiostereometric analysis and computed tomography in a cadaver study.

The purpose of this study was to measure changes in scaphoid kinematics after division of scaphotrapeziotrapezoidal ligaments, with the intention of determining a clinical measure that could be detected by computed tomography. Twelve freshly frozen cadaver upper extremities were marked with tantalum beads and fixed in positions of neutral, 30° extension, and 40° ulnar deviation. Stereoradiographs for bone migration analysis by radiostereometric analysis and computed tomography scans for visible assessment were obtained before and after scaphotrapeziotrapezoidal ligament section. After ligament resection there was a scaphoid supination of 5° and a small (less than 1 mm) radial, distal, and dorsal translation of the distal pole in 30° of wrist extension. In computed tomography reconstructions, the ligament section appeared as a 1 to 2 mm gap in the scaphotrapeziotrapezoidal corner, with loss of articulation between the distal scaphoid pole and the trapezoid bone and increased scaphoid flexion.

Voluntary activation of human knee extensors measured using transcranial magnetic stimulation.

The aim of this study was to determine the applicability and reliability of a transcranial magnetic stimulation twitch interpolation technique for measuring voluntary activation of a lower limb muscle group. Cortical voluntary activation of the knee extensors was determined in nine healthy men on two separate visits by measuring superimposed twitch torques evoked by transcranial magnetic stimulation during isometric knee extensions of varying intensity. Superimposed twitch amplitude decreased linearly with increasing voluntary torque between 50 and 100% of mean maximal torque, allowing estimation of resting twitch amplitude and subsequent calculation of voluntary activation. There were no systematic differences for maximal voluntary activation within day (mean +/- s.d. 90.9 +/- 6.2 versus 90.7 +/- 5.9%; P = 0.98) or between days (90.8 +/- 6.0 versus 91.2 +/- 5.7%; P = 0.92). Systematic bias and random error components of the 95% limits of agreement were 0.23 and 9.3% within day versus 0.38 and 7.5% between days. Voluntary activation was also determined immediately after a 2 min maximal voluntary isometric contraction; in four of these subjects, voluntary activation was determined 30 min after the sustained contraction. Immediately after the sustained isometric contraction, maximal voluntary activation was reduced from 91.2 +/- 5.7 to 74.2 +/- 12.0% (P < 0.001), indicating supraspinal fatigue. After 30 min, voluntary activation had recovered to 85.4 +/- 8.8% (P = 0.39 versus baseline). These results demonstrate that transcranial magnetic stimulation enables reliable measurement of maximal voluntary activation and assessment of supraspinal fatigue of the knee extensors.

Luteolin protects rat PC12 and C6 cells against MPP+ induced toxicity via an ERK dependent Keap1-Nrf2-ARE pathway.

Oxidative stress is central to neuronal damage in neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. In consequence, activation of the cerebral oxidative stress defence is considered as a promising strategy of therapeutic intervention. Here we demonstrate that the flavone luteolin confers neuroprotection against oxidative stress via activation of the nuclear factor erythroid-2-related factor 2 (Nrf2), a transcription factor central to the maintenance of the cellular redox homeostasis. Luteolin protects rat neural PC12 and glial C6 cells from N-methyl-4-phenyl-pyridinium (MPP+) induced toxicity in vitro and effectively activates Nrf2 as shown by ARE-reporter gene assays. This protection critically depends on the activation of Nrf2 since downregulation of Nrf2 by shRNA completely abrogates the protection of luteolin in vitro. Furthermore, the neuroprotective effect of luteolin is abolished by the inhibition of the luteolin-induced ERK1/2-activation. Our results highlight the relevance of Nrf2 for neural cell survival conferred by flavones. In particular, we identified luteolin as a promising lead for the search of orally available, blood brain barrier permeable compounds to support the therapy of neurodegenerative disorders.

Ultrasound versus magnetic resonance arthrography in acetabular labral tear diagnostics: a prospective comparison in 20 dysplastic hips.

BACKGROUND: Acetabular labral tears are highly associated with hip dysplasia. Magnetic resonance arthrography (MR arthrography) is the expensive and time-consuming contemporary gold-standard method in the radiological assessment of acetabular labral tears. PURPOSE: To assess the diagnostic ability of noninvasive ultrasound (US) examination compared to MR arthrography in diagnosing acetabular labral tears in dysplastic hip joints. MATERIAL AND METHODS: The study compared US examination and MR arthrography diagnosis of labral tears in 20 consecutively referred dysplastic hip joints. RESULTS: The ability to diagnose acetabular labral tears upon US examination was calculated: sensitivity 44%, specificity 75%, positive predictive value 88%, and negative predictive value 25%. CONCLUSION: The ability of US examination in diagnosing acetabular labral tears is not yet good enough. The technique is still to be developed, and more experience, especially with the interpretation of US examinations, is needed.

Repeat exercise normalizes the gas-exchange impairment induced by a previous exercise bout in asthmatic subjects.

Twenty-one subjects with asthma underwent treadmill exercise to exhaustion at a workload that elicited approximately 90% of each subject's maximal O2 uptake (EX1). After EX1, 12 subjects experienced significant exercise-induced bronchospasm [(EIB+), %decrease in forced expiratory volume in 1.0 s = -24.0 +/- 11.5%; pulmonary resistance at rest vs. postexercise = 3.2 +/- 1.5 vs. 8.1 +/- 4.5 cmH2O.l(-1).s(-1)] and nine did not (EIB-). The alveolar-to-arterial Po2 difference (A-aDo2) was widened from rest (9.1 +/- 6.7 Torr) to 23.1 +/- 10.4 and 18.1 +/- 9.1 Torr at 35 min after EX1 in subjects with and without EIB, respectively (P < 0.05). Arterial Po2 (PaO2) was reduced in both groups during recovery (EIB+, -16.0 +/- -13.0 Torr vs. baseline; EIB-, -11.0 +/- 9.4 Torr vs. baseline, P < or = 0.05). Forty minutes after EX1, a second exercise bout was completed at maximal O2 uptake. During the second exercise bout, pulmonary resistance decreased to baseline levels in the EIB+ group and the A-aDo2 and PaO2 returned to match the values seen during EX1 in both groups. Sputum histamine (34.6 +/- 25.9 vs. 61.2 +/- 42.0 ng/ml, pre- vs. postexercise) and urinary 9alpha,11beta-prostaglandin F2 (74.5 +/- 38.6 vs. 164.6 +/- 84.2 ng/mmol creatinine, pre- vs. postexercise) were increased after exercise only in the EIB+ group (P < 0.05), and postexercise sputum histamine was significantly correlated with the exercise PaO2 and A-aDo2 in the EIB+ subjects. Thus exercise causes gas-exchange impairment during the postexercise period in asthmatic subjects independent of decreases in forced expiratory flow rates after the exercise; however, a subsequent exercise bout normalizes this impairment secondary in part to a fast acting, robust exercise-induced bronchodilatory response.

Gas exchange during exercise in habitually active asthmatic subjects.

We determined the relations among gas exchange, breathing mechanics, and airway inflammation during moderate- to maximum-intensity exercise in asthmatic subjects. Twenty-one habitually active (48.2 +/- 7.0 ml.kg(-1).min(-1) maximal O2 uptake) mildly to moderately asthmatic subjects (94 +/- 13% predicted forced expiratory volume in 1.0 s) performed treadmill exercise to exhaustion (11.2 +/- 0.15 min) at approximately 90% of maximal O2 uptake. Arterial O2 saturation decreased to < or =94% during the exercise in 8 of 21 subjects, in large part as a result of a decrease in arterial Po2 (PaO2): from 93.0 +/- 7.7 to 79.7 +/- 4.0 Torr. A widened alveolar-to-arterial Po2 difference and the magnitude of the ventilatory response contributed approximately equally to the decrease in PaO2 during exercise. Airflow limitation and airway inflammation at baseline did not correlate with exercise gas exchange, but an exercise-induced increase in sputum histamine levels correlated with exercise Pa(O2) (negatively) and alveolar-to-arterial Po2 difference (positively). Mean pulmonary resistance was high during exercise (3.4 +/- 1.2 cmH2O.l(-1).s) and did not increase throughout exercise. Expiratory flow limitation occurred in 19 of 21 subjects, averaging 43 +/- 35% of tidal volume near end exercise, and end-expiratory lung volume rose progressively to 0.25 +/- 0.47 liter greater than resting end-expiratory lung volume at exhaustion. These mechanical constraints to ventilation contributed to a heterogeneous and frequently insufficient ventilatory response; arterial Pco2 was 30-47 Torr at end exercise. Thus pulmonary gas exchange is impaired during high-intensity exercise in a significant number of habitually active asthmatic subjects because of high airway resistance and, possibly, a deleterious effect of exercise-induced airway inflammation on gas exchange efficiency.

Prospective bone density changes after periacetabular osteotomy: a methodological study.

We used computed tomography (CT) and 3D design-based sampling principles (stereology) to estimate changes in acetabular bone density after periacetabular osteotomy. We included six consecutive patients with hip dysplasia in the study. Baseline density was measured within the first 7 days following periacetabular osteotomy and compared with bone density 2 years later. Double measurements were performed on three patients, and the coefficient of error of the mean was estimated to 0.05. Bone density in zone 1 increased significantly in the anteromedial quadrant as well as in the posteromedial quadrant of the acetabulum. In the anterolateral and the posterolateral quadrant, bone density was unchanged. In zone 2 and 3, bone density was unchanged 2 years postoperatively. We suggest that the observed increase in bone density medially represents a remodelling response to an altered load distribution after osteotomy. The method used is a precise tool to estimate changes in acetabular bone density.

Respiratory muscle training in healthy humans: resolving the controversy.

Specific respiratory muscle training offers the promise of improved exercise tolerance and athletic performance for a wide range of users. However, the literature addressing respiratory muscle training in healthy people remains controversial. Studies into the effect of respiratory muscle training upon whole body exercise performance have used at least one of the following modes of training: voluntary isocapnic hyperpnea, flow resistive loading, and pressure threshold loading. Each of these training modes has the potential to improve specific aspects of respiratory muscle function. Some studies have demonstrated significant improvements in either time to exhaustion or time trial performance, whilst others have demonstrated no effect. We present an overview of the literature that rationalizes its contradictory findings. Retrospective analysis of the literature suggests that methodological factors have played a crucial role in the outcome of respiratory muscle training studies. We conclude that in most well controlled and rigorously designed studies, utilizing appropriate outcome measures, respiratory muscle training has a positive influence upon exercise performance. The mechanisms by which respiratory muscle training improves exercise performance are unclear. Putative mechanisms include a delay of respiratory muscle fatigue, a redistribution of blood flow from respiratory to locomotor muscles, and a decrease in the perceptions of respiratory and limb discomfort.

Arginine stimulates intestinal cell migration through a focal adhesion kinase dependent mechanism.

BACKGROUND: L-Arginine is a nutritional supplement that may be useful for promoting intestinal repair. Arginine is metabolised by the oxidative deiminase pathway to form nitric oxide (NO) and by the arginase pathway to yield ornithine and polyamines. AIMS: To determine if arginine stimulates restitution via activation of NO synthesis and/or polyamine synthesis. METHODS: We determined the effects of arginine on cultured intestinal cell migration, NO production, polyamine levels, and activation of focal adhesion kinase, a key mediator of cell migration. RESULTS: Arginine increased the rate of cell migration in a dose dependent biphasic manner, and was additive with bovine serum concentrate (BSC). Arginine and an NO donor activated focal adhesion kinase (a tyrosine kinase which localises to cell matrix contacts and mediates beta1 integrin signalling) after wounding. Arginine stimulated cell migration was dependent on focal adhesion kinase (FAK) signalling, as demonstrated using adenovirus mediated transfection with a kinase negative mutant of FAK. Arginine stimulated migration was dependent on NO production and was blocked by NO synthase inhibitors. Arginine dependent migration required synthesis of polyamines but elevating extracellular arginine concentration above 0.4 mM did not enhance cellular polyamine levels. CONCLUSIONS: These results showed that L-arginine stimulates cell migration through NO and FAK dependent pathways and that combination therapy with arginine and BSC may enhance intestinal restitution via separate and convergent pathways.

Identification and characterization of the imidazoline I2b-binding sites in the hamster brown adipose tissue as a study model for imidazoline receptors.

The imidazoline-type compound, MPV-1743, has been found to activate nonshivering thermogenesis (NST) in brown adipose tissue (BAT) of the genetically obese Zucker rats. The regulation of NST in BAT is linked to the catecholamine metabolism, and the imidazoline I2-binding sites have been found on the monoamine oxidase, a catecholamine metabolising enzyme. In this study, the I2-binding sites of hamster BAT have been characterised using a receptor binding assay with 3H-idazoxan as a radioligand, and the interaction of MPV-1743 with these I2-binding sites has been studied using the enantiomers of MPV 1743, that is, MPV 2088 and MPV 2089. Cirazoline was used to determine the specific binding of 3H-idazoxan to the imidazoline I2-binding sites. Rauwolscine was added in the 3H-idazoxan binding assay in order to inhibit any binding to potential alpha2-adrenergic sites. In the presence of rauwolscine mask 3H-Idazoxan labelled a population of non-adrenergic binding sites expressing the properties of the imidazoline I2b-receptor subtype similar to that found in the rat liver (cirazoline >> guanabenz = amiloride >> clonidine). The binding of 3H-idazoxan to the I2b-binding sites could be displaced by the imidazole compounds with the following affinities: detomidine (KiHigh 9.2 nM; KiLow 3200 nM), MPV-2088 (KiHigh 19 nM; IKiLow 760 nM) and MPV-2089 (KiHigh 190 nM; KiLow 1300 nM), atipamezole (3500 nM) and dexmedetomidine (Ki 8400 nM). These results have shown that the hamster BAT contains the imidazoline I2b-binding sites with heterogeneous binding properties for some test compounds. In addition, the enantiomers of MPV 1743, that is, MPV 2088 and MPV 2089, had high affinity to these BAT imidazoline I2b-binding sites. Therefore, it is suggested that the regulation of NST in the hamster BAT may be an attractive model to study the role of imidazoline I2b-binding sites.