Rapid Communication: Dietary selenium improves skeletal muscle mitochondrial biogenesis in young equine athletes.

Exercise is known to promote mitochondrial biogenesis in skeletal muscle as well as enhance mitochondrial function and efficiency in human and rodent models. These adaptations help to decrease exercise-associated production of reactive oxygen species, which can negatively affect health and performance if antioxidant mechanisms are overwhelmed. Little is known about the adaptations of mitochondria in response to exercise training in the growing horse or if supplementation with a dietary antioxidant can improve mitochondrial function. To evaluate the separate and combined effects of selenium (Se) supplementation, training, and an acute strenuous exercise bout on mitochondrial adaptations in young horses, 30 American Quarter Horse yearlings were randomly assigned to an exercise training group or a no-training group and, within each group, received either 0.1 or 0.3 mg Se/kg DM for 14 wk. The study was split into 2 phases (wk 0 to 8 and wk 9 to 14), with half of the trained horses switched to the opposite dietary treatment in Phase 2. At the end of each phase, all horses underwent a 120-min submaximal exercise test (SET; SET 1 and SET 2). Biopsies of the middle gluteal muscle were collected before and after each phase of the study and in response to each SET and analyzed for markers of mitochondrial number and function. At rest, horses receiving 0.3 mg Se/kg DM had higher citrate synthase activity ( = 0.021) than horses receiving 0.1 mg Se/kg DM, indicating higher mitochondrial content. In contrast, cytochrome oxidase (CCO) activity was not affected by dietary Se overall, but horses that were dropped from 0.3 mg Se/kg DM to 0.1 mg Se/kg DM during Phase 2 showed a decrease ( = 0.034) in integrated CCO activity from wk 9 to 14, suggesting impaired mitochondrial function. Mitochondrial enzyme activities were unaffected by an acute, strenuous exercise bout (SET 1 and SET 2). Our relatively low-intensity exercise training protocol did not appear to induce functional mitochondrial adaptations. However, elevated dietary Se may impart beneficial effects on mitochondrial biogenesis during growth and training. A more strenuous exercise training protocol should be investigated to determine the potential benefits of elevated dietary Se for elite equine athletes.

Submaximal exercise training, more than dietary selenium supplementation, improves antioxidant status and ameliorates exercise-induced oxidative damage to skeletal muscle in young equine athletes.

Exercise is associated with increased production of reactive oxygen species (ROS) as metabolism is upregulated to fuel muscle activity. If antioxidant systems become overwhelmed, ROS can negatively affect health and performance. Adaptation to exercise through regular training has been shown to improve defense against oxidative insult. Given selenium's role as an antioxidant, we hypothesized that increased Se intake would further enhance skeletal muscle adaptations to training. Quarter Horse yearlings (18 ± 0.2 mo; 402 ± 10 kg) were randomly assigned to receive either 0.1 or 0.3 mg Se/kg DM and placed in either an untrained or a trained (30 min walk-trot-canter, 4 d/wk) group for 14 wk. Phase 1 (wk 1 to 8) consisted of 4 treatments: trained and fed 0.1 mg Se/kg DM through wk 14 (CON-TR; n = 10), trained and fed 0.3 mg Se/kg DM through wk 14 (HIGH-TR; n = 10), untrained and fed 0.1 mg Se/kg DM through wk 14 (CON-UN; n = 5), or untrained and fed 0.3 mg Se/kg DM through wk 14 (HIGH-UN; n = 5). During Phase 2 (wk 9 to 14), dietary Se level in half of the trained horses was reversed, resulting in 6 treatments: CON-TR (n = 5), trained and fed 0.1 mg/kg Se in Phase 1 and then switched to 0.3 mg/kg Se for Phase 2 (ADD-TR; n = 5), trained and fed 0.3 mg/kg Se in Phase 1 and then switched to 0.1 mg/kg Se for Phase 2 (DROP-TR; n = 5), HIGH-TR (n = 5), CON-UN (n = 5), or HIGH-UN (n = 5). All horses underwent a 120-min submaximal exercise test (SET) at the end of Phase 1 (SET 1) and 2 (SET 2). Blood samples and biopsies from the middle gluteal muscle were collected before and after each phase of the study and in response to each SET and analyzed for markers of oxidative damage and antioxidant enzyme activity. In both phases, serum Se was higher (P < 0.0001) when horses received a diet with 0.3 than 0.1 mg Se/kg DM. Throughout the 14-wk study, resting activities of muscle glutathione peroxidase (GPx; P = 0.004) and superoxide dismutase (SOD; P = 0.06) were greater in trained horses than in untrained horses. In response to SET 1, serum creatine kinase (CK) activity was lower in trained horses than in untrained horses (P < 0.0001), indicating less muscle damage, but plasma lipid hydroperoxides (LPO) and muscle GPx and SOD activities were unaffected by training or Se. In response to SET 2, trained horses had greater muscle SOD activity (P = 0.0002) and lower serum CK activity (P = 0.003) and showed a trend for lower plasma LPO (P = 0.09) and muscle malondialdehyde (P = 0.09) than untrained horses. Muscle GPx activity did not change in response to SET 2 and was unaffected by training or Se. Results indicate that exercise training lessens muscle damage and improves antioxidant defense following an acute bout of prolonged exercise and was not further enhanced by feeding Se above the NRC requirement.

Dietary selenium and prolonged exercise alter gene expression and activity of antioxidant enzymes in equine skeletal muscle.

Untrained Thoroughbred horses (6 mares and 6 geldings; 11 yr [SE 1] and 565 kg [SE 11]) were used to evaluate antioxidant gene expression and enzyme activity in blood and skeletal muscle in response to prolonged exercise after receiving 2 levels of dietary selenium for 36 d: 0.1 (CON; = 6) or 0.3 mg/kg DM (SEL; = 6). Horses were individually fed 1.6% BW coastal bermudagrass hay, 0.4% BW whole oats, and a mineral/vitamin premix containing no Se. Sodium selenite was added to achieve either 0.1 or 0.3 mg Se/kg DM in the total diet. On d 35, horses underwent 2 h of submaximal exercise in a free-stall exerciser. Blood samples were obtained before (d 0) and after 34 d of Se supplementation and on d 35 to 36 immediately after exercise and at 6 and 24 h after exercise. Biopsies of the middle gluteal muscle were obtained on d 0, before exercise on d 34, and at 6 and 24 h after exercise. Supplementation with Se above the NRC requirement (SEL) increased serum Se ( = 0.011) and muscle thioredoxin reductase (TrxR) activity ( = 0.051) but had no effect on glutathione peroxidase (GPx) activity in plasma, red blood cell (RBC) lysate, or muscle in horses at rest. Serum creatine kinase activity increased ( < 0.0001) in response to prolonged exercise but was not affected by dietary treatment. Serum lipid hydroperoxides were affected by treatment ( = 0.052) and were higher ( = 0.012) in horses receiving CON than SEL immediately following exercise. Muscle expression of was unchanged at 6 h but increased ( = 0.005) 2.8-fold 24 h after exercise, whereas muscle TrxR activity remained unchanged. Glutathione peroxidase activity increased in plasma (P < 0.0001) and decreased in RBC lysate ( = 0.010) after prolonged exercise. A Se treatment × time interaction was observed for RBC GPx activity (P = 0.048). Muscle and expression and GPx activity did not change during the 24-h period after exercise. Level of dietary Se had no overall effect on expression of , , , , , , or in muscle following exercise. The impact of prolonged exercise on the activities of antioxidant enzymes varied. Furthermore, changes in enzyme activity did not necessarily align with enzyme gene expression following exercise. A higher level of Se intake elevated Se status of untrained horses, increased GPx activity, and lessened lipid peroxidation following exercise, suggesting that Se may be beneficial for mitigating oxidative muscle damage and aiding in postexercise recovery.

Dietary supplements and military operations: caution is advised.

We describe the case of a 32-year-old soldier who presented with acute organic psychosis during an operational tour to Iraq. This was precipitated by excessive consumption of caffeine coupled with additional use of oral nutritional stimulants. Her biochemical profile was compounded by the additional use of exogenous creatine. We present a brief overview of the issue of exercise supplementation and highlight some of the potential problems and clinical issues surrounding their use. This has important implications for both serving soldiers and the wider medical community.

Back pain in a Bangladeshi worker in Iraq.

Pyogenic Spinal Infection (PSI) is an uncommon disorder encompassing a broad spectrum of diseases including septic spondylodiscitis, osteomyelitis, epidural and paravertebral abscess formation. Presentation can be vague and highly variable but usually includes back pain and fever. Whilst predisposing factors, such as trauma and diabetes can often be identified a pathogenic organism may not be identified in up to a half of all cases leading to significant delay in both accurate diagnosis and effective treatment. Precise spinal imaging is essential and includes plain X-ray, CT and preferably MRI. The treatment of PSI can be conservative (including antibiotics); however, spinal surgery may be required for the complications in up to 50% of cases, with varying degrees of success. We present a challenging case of PSI encountered in a locally-employed 42-year-old Bangladeshi civilian working in Iraq. Despite obvious resource limitations available within a Role 2 Field Hospital, clinical suspicion coupled with repeat spinal CT was pivotal in obtaining the diagnosis. The patient was repatriated to Bangladesh for MRI and definitive surgical treatment.

The Avon patellofemoral joint replacement: independent assessment of early functional outcomes.

We present a prospective review of the two-year functional outcome of 37 Avon patellofemoral joint replacements carried out in 29 patients with a mean age of 66 years (30 to 82) between October 2002 and March 2007. No patients were lost to follow-up. This is the first independent assessment of this prosthesis using both subjective and objective analysis of outcome. At two years the median Oxford knee score was 39 (interquartile range 32 to 44), the median American Knee Society objective score was 95 (interquartile range 90 to 100), the median American Knee Society functional score was 85 (interquartile range 60 to 100), and the median Melbourne Knee score was 28 (interquartile range 21 to 30). Two patients underwent further surgery. Only one patient reported an unsatisfactory outcome. We conclude that the promising early results observed by the designing centre are reproducible and provide further support for the role of patellofemoral joint replacement.

Revision of Oxford medial unicompartmental knee arthroplasty to total knee arthroplasty - results of a multicentre study.

The advantages of Unicompartmental Knee Replacement (UKR) over Total Knee Replacement (TKR) includes the preservation of soft tissue as well as bone stock, and better function with improved range of motion and more natural gait. It is therefore believed that the revision of failed UKR to TKR is technically easier than revision of failed TKR. In our study we tested this hypothesis by assessing the reconstruction requirements and early clinical and radiological outcome following the revision of UKR to TKR. During a 15-year period 1060 primary Oxford medial UKR procedures were performed at three centres, 36 of which underwent revision to TKR due to aseptic failure. The mean operating time for revision surgery was 113 min. Among the revision prostheses used, 28 were standard TKRs, six were constrained, and two were semi-constrained. Thirty had no intramedullary stems whereas six had intramedullary stems. In 30 cases reconstruction for bone loss was not required whereas metal augmentation was used in two knees, contained peg defects in the femur were filled with cement in two knees and contained keel defects in the tibia were grafted using the bone from revision cuts in two knees. After a mean follow-up of 2 years, the mean 'total knee score' was 86.3 and the mean functional score was 78.5. These findings suggest that the complexity of operation and complications encountered during Oxford medial UKR revision and the clinical outcome compare favorably with those of TKR revision.

Minimally invasive Oxford medial unicompartmental knee arthroplasty. A note of caution!

We present the peak outcome results of the Oxford medial unicompartmental arthroplasty through a minimally invasive surgical incision. This prospective study included 78 Oxford medial unicompartmental knee replacements in 68 patients. At the 2 year review the patients achieved a mean Oxford Knee Score of 38.3. This was not significantly different to the 2 year results of the phase 2 Oxford knee carried out using a standard parapatellar approach when patients achieved a mean OKS of 36.0. Four unicompartmental knee replacements required revision for unexplained pain, deep infection, aseptic loosening and bearing dislocation. Minimally invasive joint replacement is attractive to both patients and surgeons, but is technically demanding with complications inherent to limited access.

Mortality and toxin bioaccumulation in Bufo marinus following exposure to Cylindrospermopsis raciborskii cell extracts and live cultures.

Cylindrospermopsis raciborskii is a cyanobacterium responsible for the production of the toxin, cylindrospermopsin (CYN). Tadpoles of the cane toad Bufo marinus were exposed to freeze-thawed whole cell extracts or live cultures of C. raciborskii containing maximum CYN concentrations of 400 microg L-1 or 232 microg L-1, respectively. Exposure to live culture treatment solutions resulted in up to 66% mortality of B. marinus, whereas tadpoles exposed to whole cell extracts containing similar toxin concentrations survived. Decreases in relative growth rates and time spent for swimming were recorded from tadpoles during both types of exposure regimes. Bioconcentration of CYN was not evident following exposure to whole cell extracts containing extracellular toxin. In contrast exposure to live cultures, which contained cell-bound toxin, resulted in maximum average tissue concentrations of 895 microg free-CYN kg-1 fresh weight. This is the first investigation of C. raciborskii exposure effects and toxin bioaccumulation in the developmental stages of an amphibian.

Influence of intracellular toxin concentrations on cylindrospermopsin bioaccumulation in a freshwater gastropod (Melanoides tuberculata).

Scant information is available regarding the bioaccumulation of cylindrospermopsin (CYN) in aquatic organisms, particularly in invertebrates. This study examined toxin bioconcentration and bioaccumulation in the aquatic snail, Melanoides tuberculata, following exposure to freeze-thawed whole cell extracts and a live Cylindrospermopsis raciborskii culture containing CYN. Both bioconcentration and bioaccumulation were evident, but exposure to toxin in the freeze-thawed solutions resulted in minor tissue contamination compared with that resulting from live C. raciborskii exposure. Thus, whilst CYN uptake resulted from both extracellular and intracellular exposures, the availability of intracellular toxin was critical in affecting tissue CYN values. M. tuberculata did not bioconcentrate CYN into the shell. Bioaccumulation of the analog deoxy-CYN was also recorded. Knowledge of intracellular toxin concentrations may be critical in evaluating the bioaccumulation, ecological and human health risks associated with contaminated systems.

The effect of preoperative symptom severity on functional outcome of total knee replacement--patients with the lowest preoperative scores achieve the lowest marks.

To determine if the functional outcome of total knee replacement (TKR) was affected by the level of preoperative symptom severity, the association between preoperative Oxford Knee Scores (OKS), and 2 year OKS, American Knee Society clinical and function scores (AKSS) was assessed. Data were prospectively collected on 45 cases who had single joint osteoarthritis and no other comorbidities. We have specifically focused on patients with single knee involvement to remove the effect of multiple joint involvement and comorbidities on the OKS. The mean preoperative OKS was 21.4, postoperative OKS 40.0 and postoperative ROM 117 degrees. The postoperative mean AKSS was 86.7 and mean function score was 85.0. The 'usual pain' and 'limp' components of the OKS had the greatest rises and the 'kneel' component had the least improvement. Rather than all patients achieving uniform results post-TKR, patients with more severe symptoms achieved poorer absolute outcomes. The Spearman correlation coefficient between pre- and postoperative OKS was r = 0.4 (p = 0.006). Although the results suggest that waiting too long before intervention compromises the final outcome, a correlation of 0.4 is not strong enough to necessitate change in current practice.

Do protein-lipid interactions determine the recognition of transmembrane helices at the ER translocon?

Membrane-protein integration, folding and assembly processes in vivo depend on complex targeting, translocation, chaperoning, and sorting machineries that somehow read the 'molecular code' built into the nascent polypeptide, ultimately producing a properly folded protein integrated into the correct target membrane. Although the main molecular constituents and the basic mechanistic principles of many of these machines are known in outline, the codes remain poorly defined and there is little quantitative information on how protein sequence affects the final structure of membrane proteins. By carefully designing model protein constructs, we have derived the first true biological hydrophobicity scale and have been able to get a first impression of how the position of a given type of residue within a transmembrane segment affects its ability to promote membrane insertion.

Operating on patients wearing personal identity devices: a report of two cases.

We report on two patients who have recently required emergency surgery and who were wearing personal identity devices at the time of presentation. The devices bear a telephone number and a message stating that, if found, the management company should be informed of the whereabouts of their owner. We discuss the issues relating to the disclosure of information to a third party in this situation and whether there is any legal obligation to do so. The conclusion of a review of the relevant literature is that the only reason to divulge information to a third party would be if a patient posed a serious risk of death or serious harm to another party. In the majority of foreseeable circumstances, this would not be the case.

Analysis of the Leeds-Keio ligament for extensor mechanism repair: favourable mechanical and functional outcome.

Many techniques have been described for the challenging problem of extensor mechanism rupture, including the use of synthetic grafts. In 1994 Fujikawa et al. [J. Bone Surg. 1994:76B:200-203] reported excellent results using the Leeds-Keio polyester ligament. Patients were mobilised early, had few post operative complications and minimal extensor lag. This is the first independent assessment of this technique using both subjective and objective analysis of outcome. We reviewed 11 patients (12 knees) whose extensor mechanisms were repaired as described in the original paper. At a mean of 3 years after surgery there were no infections and no re-ruptures. Good functional recovery was observed with a mean Tegner activity score of 1.7, Lysholm score of 66 and Irrgang score of 58%. Indeed, 80% of working patients returned to their former employment. However, objective tests showed peak extensor torque recovered to only half normal strength. We conclude the results of this technique of repair compare favourably with other described techniques especially in complex cases.

Magnetic resonance imaging assessment for unicompartmental knee replacement: a limited role.

The purpose of this study was to see if MRI has a role in pre-operative assessment of patients for unicompartmental knee replacement. Until now, surgeons have been unable to predict whether a patient is suitable until the operation itself when the anterior cruciate ligament is inspected. We found that 33% of patients with anteromedial osteoarthritis had a degenerate anterior cruciate ligament according to magnetic resonance imaging, compared to only 13% on surgical inspection. We conclude that MRI is too sensitive to changes of the anterior cruciate ligament to be of much practical value.

Energetics, stability, and prediction of transmembrane helices.

We show that the peptide backbone of an alpha-helix places a severe thermodynamic constraint on transmembrane (TM) stability. Neglect of this constraint by commonly used hydrophobicity scales underlies the notorious uncertainty of TM helix prediction by sliding-window hydropathy plots of membrane protein (MP) amino acid sequences. We find that an experiment-based whole-residue hydropathy scale (WW scale), which includes the backbone constraint, identifies TM helices of membrane proteins with an accuracy greater than 99 %. Furthermore, it correctly predicts the minimum hydrophobicity required for stable single-helix TM insertion observed in Escherichia coli. In order to improve membrane protein topology prediction further, we introduce the augmented WW (aWW) scale, which accounts for the energetics of salt-bridge formation. An important issue for genomic analysis is the ability of the hydropathy plot method to distinguish membrane from soluble proteins. We find that the method falsely predicts 17 to 43 % of a set of soluble proteins to be MPs, depending upon the hydropathy scale used.