Atrogin-1, MuRF1, and FoXo, as well as phosphorylated GSK-3β and 4E-BP1 are reduced in skeletal muscle of chronic spinal cord-injured patients

Chronic complete spinal cord injury (SCI) is associated with severe skeletal muscle atrophy as well several atrophy and physical-inactivity-related comorbidity factors such as diabetes, obesity, lipid disorders, and cardiovascular diseases. Intracellular mechanisms associated with chronic complete SCI-related muscle atrophy are not well understood, and thus their characterization may assist with developing strategies to reduce the risk of comorbidity factors. Therefore, the aim of this study was to determine whether there was an increase in catabolic signaling targets, such as atrogin-1, muscle ring finger-1 (MuRF1), forkhead transcription factor (FoXO), and myostatin, and decreases in anabolic signaling targets, such as insulin-like growth factor (IGF), v-akt murine thymoma viral oncogene (Akt), glycogen synthase kinase-β (GSK-3β), mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and p70s6kinase in chronic complete SCI patients. In SCI patients, when compared with controls, there was a significant reduction in mRNA levels of atrogin-1 (59%; P < 0.05), MuRF1 (55%; P < 0.05), and myostatin (46%; P < 0.01), and in protein levels of FoXO1 (72%; P < 0.05), FoXO3a (60%; P < 0.05), and atrogin-1 (36%; P < 0.05). Decreases in the protein levels of IGF-1 (48%; P < 0.001) and phosphorylated GSK-3β (54%; P < 0.05), 4E-BP1 (48%; P < 0.05), and p70s6kinase (60%; P = 0.1) were also observed, the latter three in an Akt-and mTOR-independent manner. Reductions in atrogin-1, MuRF1, FoXO, and myostatin suggest the existence of an internal mechanism aimed at reducing further loss of muscle proteins during chronic SCI. The downregulation of signaling proteins that regulate anabolism, such as IGF, GSK-3β, and 4E-BP1, would reduce the ability to increase protein synthesis rates. © 2009 Wiley Periodicals, Inc

Health conditions in people with spinal cord injury: Contemporary evidence from a population-based community survey in Switzerland

BACKGROUND Health conditions in people with spinal cord injury are major determinants for disability, reduced well-being, and mortality. However, population-based evidence on the prevalence and treatment of health conditions in people with spinal cord injury is scarce. OBJECTIVE To investigate health conditions in Swiss residents with spinal cord injury, specifically to analyse their prevalence, severity, co-occurrence, and treatment. METHODS Cross-sectional data (n = 1,549) from the community survey of the Swiss Spinal Cord Injury (SwiSCI) cohort study, including Swiss residents with spinal cord injury aged over 16 years, were analysed. Nineteen health conditions and their self-reported treatment were assessed with the spinal cord injury Secondary Conditions Scale and the Self-Administered Comorbidity Questionnaire. Prevalence and severity were compared across demographics and spinal cord injury characteristics. Co-occurrence of health conditions was examined using a binary non-metric dissimilarity measure and multi-dimensional scaling. Treatment rates were also examined. RESULTS Number of concurrent health conditions was high (median 7; interquartile range 4-9; most frequent: spasticity, chronic pain, sexual dysfunction). Prevalence of health conditions increased with age and was higher in non-traumatic compared with traumatic spinal cord injury. Spinal cord injury specific conditions co-occurred. Relative frequencies of treatment were low (median 44%, interquartile range 25-64%), even for significant or chronic problems. DISCUSSION A high prevalence of multimorbidity was found in community-dwelling persons with spinal cord injury. Treatment for some highly prevalent health conditions was infrequent

Sciatica in the female patient: anatomical considerations, aetiology and review of the literature

The principal author was confronted few years ago with the case of a 38-year-old woman with a 5-month history of ill-defined L5 sciatic pain that was referred to an orthopaedic department for investigation and eventual surgical treatment for what was suspected to be herniated disc-related sciatica. Removal of her enlarged uterus found unexpectedly close to the sacroiliac joint upon lumbar MRI abolished her symptoms. Review of the literature showed that the lumbosacral trunk is vulnerable to pressure from any abdominal mass originating from the uterus and the ovaries. Physiological processes in the female patient and gynaecological diseases may be the source of sciatica, often not readily searched for, leading to fruitless investigations and surgical treatments. The aim of the paper is to highlight gynaecological and obstetrical causes of sciatica and sciatica-like symptoms. To prevent unproductive expenses and morbidity, a thorough gynaecological examination should be done even though neurological examination may be suggestive of a herniated intervertebral disc, and the cyclic pattern of pain related to menses should be routinely asked for