Mitogenic signaling pathways in airway smooth muscle

Increased airway smooth muscle mass has been demonstrated in patients with asthma, bronchopulmonary dysplasia and most recently, cystic fibrosis. These observations emphasize the need for further knowledge of the events involved in airway smooth muscle mitogenesis and hypertrophy. Workers in the field have developed cell culture systems involving tracheal and bronchial myocytes from different species. An emergent body of literature indicates that mutual signal transduction pathways control airway smooth muscle cell cycle entry across species lines. This article reviews what is known about mitogen-activated signal transduction in airway myocytes. The extracellular signal regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI 3-kinase) pathways appear to be key positive regulators of airway smooth muscle mitogenesis; recent studies have also demonstrated specific roles for reactive oxygen and the JAK/STAT pathway. It is also possible that growth factor stimulation of airway smooth muscle concurrently elicits signaling through negative regulatory intermediates such as p38 mitogen-activated protein (MAP) kinase and protein kinase C (PKC) delta, conceivably as a defense against extreme growth.     

The impact of a nap opportunity during the night shift on the performance and alertness of 12-h shift workers

The purpose of this workplace evaluation was to assess the effects on performance, alertness and subsequent sleep of strategic napping on 12-h overnight shifts. In a counterbalanced crossover design, 24 male aircraft maintenance engineers working in a forward rotating 12-h shift pattern volunteered to take part in the study for two work weeks. During the experimental week, each subject was given the opportunity to take a 20-min nap at work between 01:00 and 03:00 h on each of their two overnight shifts. On the control week no naps were taken on the night shifts. A computerized neurobehavioural test battery was employed to assess performance and subjective levels of fatigue at the beginning and end of each night shift, and pre- and postnap. Subjects were also asked to rate how near they had come to falling asleep while driving to and from work. The results revealed that taking a single 20-min nap during the first night shift significantly improved speed of response on a vigilance task measured at the end of the shift compared with the control condition. On the second night shift there was no effect of the nap on performance. Taking a short nap during either night shift had no significant effect on subjective ratings of fatigue, the level of sleepiness reported while driving to and from work, or subsequent sleep duration and sleep quality. Overall the results suggest some promise for a short duration nap taken in the workplace to counteract performance deficits associated with the first night shift.     

Contribution of the serotonin 5-HT1A receptor agonism of 8-OH-DPAT and EMD 128130 to the regulation of haloperidol-induced muscle rigidity in rats

The aim of the present study was to find out whether (±)-8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), a prototypical 5-HT_1A agonist, and (R)-(−)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chromane HCl (EMD 128130), a compound with serotonin 5-HT_1A-agonist and dopamine D₂-like antagonist properties, are able to attenuate the haloperidol-induced (1 mg/kg) muscle rigidity in rats. Muscle tone was examined using a combined mechano- and electromyographic (EMG) method that simultaneously measured the mechanical muscle resistance (MMG) of the rat’s hind foot to passive movements in the ankle joint, and the EMG activity of two antagonist muscles. Both 8-OH-DPAT (0.125–0.5 mg/kg i.p.) and EMD 128130 (1–10 mg/kg i.p.) dose-dependently decreased the haloperidol-enhanced MMG to passive movements, as well as the tonic and the long-latency reflex EMG activities.

Provided these results can be extrapolated to humans, the efficacy of EMD 128130 in relieving the haloperidol-induced muscle rigidity supports the concept that novel antipsychotics with 5-HT_1A agonist and dopamine D₂ antagonist activities should have a favourable extrapyramidal side-effect profile.     

Validation of the French 'multidimensional fatigue inventory' (MFI 20)

Fatigue has become an important symptom in research and also for clinical diagnosis and follow up. Many physical illnesses, in particular chronic ones such as cancer, are highly associated with fatigue. Various questionnaires for measuring fatigue have been developed, but currently no validated questionnaire exists in French language. We selected the 'Multidimensional Fatigue Inventory' (MFI) which has been validated in its English version and then translated into French by the designers. This study describes the validation step of the French version of MFI and presents the psychometric properties of this instrument. A sample of 225 patients was divided into three groups 'Tired' (82 subjects), 'Moderately tired' (36) and 'Not tired' (107). The analysis of the structure validity found four dimensions: 'General Fatigue', 'Mental Fatigue', 'Reduced Activities' and 'Motivation'. The convergent validity showed highly significant correlation ( P  < 0.001) with a visual analogue scale. The French MFI has been able to distinguish patients with different fatigue levels. Cronbach's alpha measurement of the scale and the subscales are good, cronbach alpha > 0.70. The reproducibility and sensitivity to change in patients who were followed up one month later show satisfactory results. This validation study of the French version of MFI shows that this instrument is valid for clinical application and allows different dimensions of fatigue to be assessed which is of particular interest for physicians, especially for cancer carers, where fatigue assessment is an important aspect of the follow up.     

Cancer‐related fatigue – a difference of opinion? Results of a multicentre survey of healthcare professionals,patients and caregivers

The objective of this study was to investigate the perceptions of patients with cancer, their caregivers and healthcare professionals (HCPs) about fatigue and its impact on quality of life. It was a cross-sectional survey, the respondents were patients with cancer attending three UK regional cancer centres ( n  = 1370), their informal caregivers ( n  = 1370) and a random selection of HCPs (oncologists/nurses/radiographers/haematologists; n  = 1098). The response rates for patients, caregivers and HCPs were 42%, 33% and 34% respectively. Fatigue was reported to affect 56% of patients and to have a considerable impact on quality of life. Caregivers also recognized that fatigue was a common problem, with significant effects on patients' quality of life and impact on themselves. Healthcare professionals recognized that fatigue was a common problem for their patients but overestimated its impact on some aspects of patients' daily lives. Although most HCPs reported that they prescribed/recommended treatment for over half of their patients, only 14% of patients reported receiving any such treatment. The most common advice was to take more rest and relaxation. Conclusions: patients with cancer report that fatigue is a common and distressing symptom and the importance of this symptom is generally recognized by both HCPs and lay-carers. Healthcare professionals need more information about the effectiveness of existing interventions for cancer-related fatigue and further research is required to improve the current management of this debilitating symptom.     

Evaluation of the ability to make non-invasive estimation of muscle contractile properties on the basis of the muscle belly response

The histochemical and biomechanical relationships of limb muscles are examined in two groups of 15 men aged between 17 and 40 years. Seven muscles are chosen: biceps brachii, triceps brachii (TB), flexor digitorum superficialis, extensor digitorum, biceps femoris, tibialis anterior and gastrocnemius caput mediale (GCM). The aim of the preliminary study is to evaluate an alternative method based on a tensiomyographic (TMG) non-invasive measurement technique. The percentage of type I muscle fibres obtained with the histochemical method is 2.2 times higher for the slowest measured muscle (GCM) than for the fastest (TB). The contraction time of a muscle belly twitch response measured by TMG is 1.9 times higher for GCM than for TB. Statistical analysis of the data obtained by tensiomyographic and histochemical techniques shows a significant correlation between the contraction time of muscle response measured by TMG and the percentage of type I muscle fibres (correlation coefficient equals 0.93). Results of the study suggest using the TMG measuring technique as a basis for the estimation of the percentage of type I muscle fibres.     

No difference in net uptake or disposal of lactate by trained and untrained forearms during incremental sodium lactate infusion

A number of training adaptations in skeletal muscle might be expected to enhance lactate extraction during hyperlactataemia. The aim of the present study was to determine whether resting endurance-trained forearms exhibit an increased net lactate removal during hyperlactataemia. Six racquet-sport players attended the laboratory for two experiments, separated by 2 weeks. In the first experiment incremental handgrip exercise to fatigue was performed to identify trained (TRFA, n=6) and untrained (UTFA, n=5) forearms. In the second experiment net forearm lactate exchange was compared between TRFA and UTFA during an incremental infusion of sodium lactate. TRFA performed more work than UTFA during handgrip exercise [mean (SE) TRFA, 66.1 (9.5) J·100 ml^–1; UTFA, 35.1 (2.3) J·100 ml^–1; P=0.02] and UTFA exhibited a greater increase in net lactate output relative to work load (P=0.003). During lactate infusion net lactate uptake across the resting forearms increased linearly with the arterial lactate concentration in both groups (TRFA, r=–0.95 (0.03); UTFA, r=–0.92 (0.04); P<0.02], with no difference in the regression slopes [TRFA, –1.06 (0.13); UTFA, –1.07 (0.27); P=0.97] or y-intercepts [TRFA, 0.67 (0.20); UTFA, 1.36 (0.67); P=0.37] between groups. Almost all of the lactate taken up was disposed of by both groups of forearms [TRFA, 99.6 (0.2)%; UTFA, 98.5 (1.0)%; P=0.37]. It was concluded that the net uptake and removal of lactate by resting skeletal muscle is a function of the concentration of lactate in the blood perfusing the muscle rather than the muscle training status. Electronic Publication     

Differences between patients with chronic fatigue syndrome and with chronic fatigue at an infectious disease clinic in Stockholm,Sweden

Background data were collected from patients presenting with fatigue at the clinic of infectious diseases at Huddinge University Hospital, Stockholm. The main purpose was to look for differences as to demographic and functional status for patients fulfilling criteria for chronic fatigue syndrome (CFS) and chronic fatigue (CF). A cross-sectional questionnaire survey was performed using a variety of instruments. A thorough medical investigation was performed. No difference was found as to social situation, occupation and illness attributions for patients in the two categories. Patients with CFS reported in general a higher degree of 'sickness' with more self-reported somatic symptoms, more self-reported functional impairment and more absence from work. A higher degree of psychiatric comorbidity was observed in CF than in CFS patients. A majority of CFS patients (80%) had an acute infectious onset compared to 43% in the CF group. Presently used criteria might, according to findings presented here, define two different patient categories in a population characterized by severe, prolonged fatigue. Because CFS patients (compared to patients with CF) have more somatic symptoms, more often report an infectious, sudden onset and have less psychiatric comorbidity, and CF patients seem to have more of an emotional, burn-out-like component one could speculate about the existence of different pathogenetic backgrounds behind the two diagnoses.     

Effect of light finger touch on postural sway after lower-limb muscular fatigue

OBJECTIVE: To investigate whether a light finger touch can compensate for the increased postural sway induced by lower-limb muscular fatigue. DESIGN: Before-after trials. SETTING: General community. PARTICIPANTS: Nine healthy university students (mean age, 23.8+/-2.6y; mean body weight, 72.7+/-6.9 kg; mean height, 177.2+/-7.5 cm). INTERVENTIONS: Participants stood with their feet together and eyes closed. They were asked to sway as little as possible in 4 conditions: no fatigue/no touch, no fatigue/touch, fatigue/no touch, and fatigue/touch. Calf muscle fatigue was induced by having participants stand on their toes until exhaustion. Touch conditions involved a gentle light touch with the right index finger on a nearby surface at waist height. MAIN OUTCOME MEASURES: Center of pressure displacements were recorded by using a force platform. RESULTS: Light finger touch resulted in decreased postural sway in the no-fatigue and fatigue conditions. Interestingly, this stabilizing effect was more accentuated in the fatigue condition. CONCLUSIONS: Results suggest that the contribution of the haptic cues from the finger for regulating postural sway increases after muscular fatigue. These findings could have implications in clinical and rehabilitative areas.     

Enzymatic diagnostic test for Muscle-Eye-Brain type congenital muscular dystrophy using commercially available reagents

OBJECTIVES: Mutations disrupting the interaction of extra-cellular ligands and alpha-dystroglycan are responsible for an etiologically heterogeneous group of autosomal recessive congenital muscular dystrophies (CMD) that can have associated brain and eye abnormalities. The objective is to develop a diagnostic test for one of these CMDs, Muscle-Eye-Brain disease (MEB), due to mutations in the gene encoding Protein O-Mannosyl beta-1,2-N-acetylglucosaminyltransferase 1 (POMGnT1). DESIGN AND METHODS: POMGnT1 enzyme activity was determined in extracts of muscle biopsies from four MEB patients and various controls using commercially available reagents. RESULTS: All four MEB muscle samples showed a highly significant decrease in POMGnT1 activity relative to controls. CONCLUSIONS: The assay of POMGnT1 activity in MEB muscle provides a rapid and relatively simple diagnostic test for this disease. CMDs associated with brain malformations such as MEB, WWS and FCMD are heterogenous in clinical presentation and on radiologic examination, suggesting that POMGnT1 assays of muscle biopsies should be used as a screening procedure for MEB in all CMD patients associated with brain malformations.