Protein translation, proteolysis and autophagy in human skeletal muscle atrophy after spinal cord injury.

AIM: Spinal cord injury-induced loss of skeletal muscle mass does not progress linearly. In humans, peak muscle loss occurs during the first 6 weeks postinjury, and gradually continues thereafter. The aim of this study was to delineate the regulatory events underlying skeletal muscle atrophy during the first year following spinal cord injury. METHODS: Key translational, autophagic and proteolytic proteins were analysed by immunoblotting of human vastus lateralis muscle obtained 1, 3 and 12 months following spinal cord injury. Age-matched able-bodied control subjects were also studied. RESULTS: Several downstream targets of Akt signalling decreased after spinal cord injury in skeletal muscle, without changes in resting Akt Ser473 and Akt Thr308 phosphorylation or total Akt protein. Abundance of mTOR protein and mTOR Ser2448 phosphorylation, as well as FOXO1 Ser256 phosphorylation and FOXO3 protein, decreased in response to spinal cord injury, coincident with attenuated protein abundance of E3 ubiquitin ligases, MuRF1 and MAFbx. S6 protein and Ser235/236 phosphorylation, as well as 4E-BP1 Thr37/46 phosphorylation, increased transiently after spinal cord injury, indicating higher levels of protein translation early after injury. Protein abundance of LC3-I and LC3-II decreased 3 months postinjury as compared with 1 month postinjury, but not compared to able-bodied control subjects, indicating lower levels of autophagy. Proteins regulating proteasomal degradation were stably increased in response to spinal cord injury. CONCLUSION: Together, these data provide indirect evidence suggesting that protein translation and autophagy transiently increase, while whole proteolysis remains stably higher in skeletal muscle within the first year after spinal cord injury.

Use of medicines, adherence and attitudes to medicines among persons with chronic spinal cord injury.

STUDY DESIGN: A cross-sectional study. OBJECTIVES: To describe the use of medicines and adherence among persons with spinal cord injury (SCI). Further, to examine the influence of pain, spasms and beliefs about medicines on adherence. SETTING: Sunnaas Rehabilitation Hospital, Norway. METHODS: Persons (⩾18 years) with chronic SCI (more than 1-year post injury), using at least one drug regularly, and admitted for a follow-up stay at Sunnaas Rehabilitation Hospital were included. Participants were interviewed about their drug regimen and filled out validated self-report questionnaires: Morisky Medication Adherence Scale (MMAS-8), beliefs about medicines questionnaire (BMQ), visual analogue scale (VAS) for pain and modified Penn spasm frequency scale (mPSFS). RESULTS: The 105 participants used in average 4.2 drugs regularly (range, 1-15), and 70% reported high or moderate adherence to their treatment. Of the 39 participants using oral spasmolytics, 74% reported high or moderate adherence to these drugs. A total of 97% of the participants reported high perceptions of necessity to their treatment and 54% reported a high level of concern. CONCLUSION: The persons with SCI included in this study used in average the same number of regular drugs compared to persons with other chronic conditions. Regardless of high overall adherence, the participants were more concerned about their medicines compared to other patient groups. Further studies are required for understanding adherence and attitudes toward medicines in this population, especially to help the persons with chronic SCI feel safe about their drug regimen.

Psychological distress and user experiences with health care provision in persons living with spinal cord injury for more than 20 years.

STUDY DESIGN: Descriptive cross-sectional and retrospective study. OBJECTIVES: To gain more insight into the long-term health status in persons with traumatic spinal cord injury (SCI), especially perceived psychological distress as well as self-reports of utilization of healthcare services. SETTING: Sunnaas Rehabilitation Hospital, Norway. METHODS: In total, 147 persons with SCI were examined for more than 20 years and interviewed (in 2004/2005) using a self-administrated questionnaire and General Health Questionnaire (GHQ-20). Descriptive statistics and a logistic regression analysis were conducted to identify variables associated with psychological distress. RESULTS: Most participants had received SCI follow-up health services at least once after initial rehabilitation; 34% were satisfied, 51% neutral and 18% unsatisfied with the health services provided. Concerning psychological distress, 34 persons were cases according to the GHQ-20. The cases did not differ from non-cases concerning demography, time since injury, injury aetiology, injury severity, marital status or employment status. The regression analysis revealed that cases were associated (P<0.05) with more use of SCI-specific follow-ups. CONCLUSION: In a 20+ years' post-injury SCI population, psychological distress is common and associated with the use of follow-up services. The varying satisfaction of people with SCI about healthcare services is notable, as is the finding that 20% of people with paraplegia did not use specific SCI follow-up services. The experiences of people with SCI with healthcare services need further investigation, and there is also a need for studies that examine the effects of interventions aimed at improving services and patient satisfaction.

Circadian rhythms of hemostatic factors in tetraplegia: a double-blind, randomized, placebo-controlled cross-over study of melatonin.

STUDY DESIGN: This is a double-blind, randomized, placebo-controlled cross-over study of melatonin in complete tetraplegia. OBJECTIVES: Tetraplegic patients have an increased risk of venous thrombosis despite prophylaxis, blunted variations in melatonin and altered circadian variation of several hemostatic markers. To examine whether melatonin could modify the regulation of hemostasis, we measured plasma melatonin and several markers of hemostasis in tetraplegic subjects with or without melatonin supplement. SETTING: The study was conducted in the Section for Spinal Cord Injury, Sunnaas Hospital, Nesoddtangen, Norway. METHODS: Six subjects with long-standing complete tetraplegia were included in this cross-over study with 2 mg of melatonin or placebo given 4 days before sampling. We also included six able-bodied men without any intervention. Plasma samples were then collected frequently during a 24-h awake/sleep cycle. The plasma concentrations of melatonin and the various markers were analyzed using linear mixed models. RESULTS: The 24-h profiles of prothrombin fragment 1+2 and von Willebrand factor, but not D-dimer, activated FVII, tissue factor pathway inhibitor and plasminogen activator inhibitor type 1, differed (P<0.05) between tetraplegic patients and able-bodied subjects. The absolute plasma concentration of activated FVII was higher (P<0.05) among the able-bodied compared with the tetraplegic groups. Supplementation of melatonin had no impact on these findings. CONCLUSIONS: We found differences in circadian variation of several hemostatic markers between able-bodied and tetraplegics. These differences were apparently unrelated to fluctuations in the melatonin concentrations, suggesting little or no role of melatonin in the regulation of hemostasis in tetraplegia. SPONSORSHIP: Financial support was provided from the Throne Holst Foundation.

Differences in bone mineral density, markers of bone turnover and extracellular matrix and daily life muscular activity among patients with recent motor-incomplete versus motor-complete spinal cord injury.

Spinal cord injury (SCI) leads to severe bone loss, but the associated mechanisms are poorly described in incomplete SCI individuals. The purpose of the study is to compare alterations in bone mineral density (BMD) and serum biomarkers of bone turnover in recent motor-incomplete to -complete SCI men, as well as to describe their physical activity and spasticity. We studied 31 men with acute SCI. Whole-body DXA scans, serum biomarkers and self-reported activity and spasticity were examined 1 and/or 3 and 12 months after the injury. We observed a decrease in proximal femur BMD (p < 0.02) in both the groups. Serum phosphate and carboxy-terminal-collagen crosslinks were significantly lower in motor-incomplete versus complete SCI men, whereas albumin-corrected Ca(2+) (p = 0.02) were lower only 3 months after injury. When data from all 31 SCI participants were pooled, we observed increased serum matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of MMP-2 (TIMP-2) (p < 0.02) whereas TIMP-1 decreased (p = 0.03). BMD correlated positively with self-reported activity (r = 0.59, p = 0.04) and negatively with spasticity (r = 0.74, p = 0.02) 12 months after injury. As a summary, men with motor-incomplete SCI developed significant proximal femur bone loss 12 months after injury and exhibited increased bone resorption throughout the first year after the injury. Compared with complete SCI men, incomplete SCI men show attenuated bone resorption. Our pooled data show increased turnover of extracellular matrix after injury and that increased exercise before and after injury correlated with reduced bone loss.

Decreased levels of testosterone and gonadotrophins in men with long-standing tetraplegia.

STUDY DESIGN: Blood samples were frequently collected during a 24-h period from six tetraplegic men. The results were compared with those of eight able-bodied controls. OBJECTIVE: Previous studies have reported conflicting results regarding the plasma concentrations of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in tetraplegia. The objective of this study was to examine the pituitary-gonadal axis by determining the plasma concentrations and circadian variations of these hormones in men with long-standing tetraplegia. SETTING: Sunnaas Hospital, Norway. METHODS: The plasma concentrations of hormones were measured with standardized assays. RESULTS: All three hormones and free testosterone index were decreased in the tetraplegic subjects compared with the able-bodied controls (P<0.05). We also determined the morning levels of hormones with regulatory effects on testosterone, LH and FSH. Whereas plasma leptin was significantly higher in the tetraplegic group, no significant differences in the morning plasma values for insulin, SHBG, GH or IGF-1, or in the 24-h urine concentrations of cortisol were detected between the two groups. The plasma concentration of LH displayed a circadian variation (P<0.05) in the tetraplegic group, but not among the able-bodied. No circadian variation was noted for the plasma concentrations of testosterone and FSH in either group. CONCLUSION: Our data indicate that, over time, tetraplegic male subjects might be at risk of developing hypogonadism.