The heat shock protein response following eccentric exercise in human skeletal muscle is unaffected by local NSAID infusion.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely consumed in relation to pain and injuries in skeletal muscle, but may adversely affect muscle adaptation probably via inhibition of prostaglandin synthesis. Induction of heat shock proteins (HSP) represents an important adaptive response in muscle subjected to stress, and in several cell types including cardiac myocytes prostaglandins are important in induction of the HSP response. This study aimed to determine the influence of NSAIDs on the HSP response to eccentric exercise in human skeletal muscle. Healthy males performed 200 maximal eccentric contractions with each leg with intramuscular infusion of the NSAID indomethacin or placebo. Biopsies were obtained from m. vastus lateralis before and after (5, 28 hrs and 8 days) the exercise bout from both legs (NSAID vs unblocked leg) and analysed for expression of the HSPs HSP70, HSP27 and αB-crystallin (mRNA and protein). NSAID did not affect the mRNA expression of any of the HSPs. Compared to pre values, the mRNA expression of all HSPs was increased; αB-crystallin, 3.6- and 5.4-fold; HSP70, 26- and 3.4-fold; and HSP27: 4.8- and 6.5-fold at 5 and 28 hrs post-exercise, respectively (all p < 0.008). Immunohistochemical stainings for αB-crystallin and HSP70 revealed increased staining in some samples but with no differences between legs. Changes in force-generating capacity correlated with both αB-crystallin and HSP70 mRNA and immunohistochemisty data. Increased expression of HSPs was observed on mRNA and protein level following eccentric exercise; however, this response was unaffected by local intramuscular infusion of NSAIDs.

Stimulation of muscle protein synthesis by whey and caseinate ingestion after resistance exercise in elderly individuals.

Sarcopenia is a well-known phenomenon in elderly individuals and resistance exercise together with sufficient amino acid (AA) availability has proved to be a counteractive implement. However, the source of AA and supplement timing require further investigation. The objective was to compare muscle protein synthesis (MPS) to intakes of whey and caseinate after heavy resistance exercise in healthy elderly individuals, and, furthermore, to compare the timing effect of caseinate intake. Twenty-four elderly men and women (mean ± SEM; 68 ± 1 years) were randomized to one of four groups: caseinate intake before exercise (CasPre), caseinate intake immediately after exercise (CasPost), whey intake immediately after exercise (Whey), or intake of a non-caloric control drink (Control). Muscle myofibrillar and collagen fractional synthesis rates (FSR) were measured by a primed continuous infusion of L-[1-(13) C]leucine using labeled proteins during a 6-h recovery period. No differences were observed in muscle myofibrillar and collagen FSR with Whey (0.09 ± 0.01%/h) compared with CasPost (0.09 ± 0.003%/h), and it did not differ between CasPre (0.10 ± 0.01%/h) and CasPost. MPS does not differ with whey and caseinate feeding immediately after heavy resistance exercise in elderly individuals, and MPS is similar with caseinate ingestion before and after exercise.

Local NSAID infusion does not affect protein synthesis and gene expression in human muscle after eccentric exercise.

Unaccustomed exercise leads to satellite cell proliferation and increased skeletal muscle protein turnover. Several growth factors and cytokines may be involved in the adaptive responses. Non-steroidal anti-inflammatory drugs (NSAIDs) negatively affect muscle regeneration and adaptation in animal models, and inhibit the exercise-induced satellite cell proliferation and protein synthesis in humans. However, the cellular mechanisms eliciting these responses remain unknown. Eight healthy male volunteers performed 200 maximal eccentric contractions with each leg. To block prostaglandin synthesis locally in the skeletal muscle, indomethacin (NSAID) was infused for 7.5 h via microdialysis catheters into m. vastus lateralis of one leg. Protein synthesis was determined by the incorporation of 1,2-(13) C(2) leucine into muscle protein from 24 to 28 h post-exercise. Furthermore, mRNA expression of selected genes was measured in muscle biopsies (5 h and 8 days post-exercise) by real-time reverse transcriptase PCR. Myofibrillar and collagen protein synthesis were unaffected by the local NSAID infusion. Five hours post-exercise, the mRNA expression of cyclooxygenase-2 (COX2) was sixfold higher in the NSAID leg (P=0.016) compared with the unblocked leg. The expression of growth factors and matrix-related genes were unaffected by NSAID. Although NSAIDs inhibit the exercise-induced satellite cell proliferation, we observed only limited effects on gene expression, and on post-exercise protein synthesis.

Local NSAID infusion inhibits satellite cell proliferation in human skeletal muscle after eccentric exercise.

Despite the widespread consumption of nonsteroidal anti-inflammatory drugs (NSAIDs), the influence of these drugs on muscle satellite cells is not fully understood. The aim of the present study was to investigate the effect of a local NSAID infusion on satellite cells after unaccustomed eccentric exercise in vivo in human skeletal muscle. Eight young healthy males performed 200 maximal eccentric contractions with each leg. An NSAID was infused via a microdialysis catheter into the vastus lateralis muscle of one leg (NSAID leg) before, during, and for 4.5 h after exercise, with the other leg working as a control (unblocked leg). Muscle biopsies were collected before and 8 days after exercise. Changes in satellite cells and inflammatory cell numbers were investigated by immunohistochemistry. Satellite cells were identified using antibodies against neural cell adhesion molecule and Pax7. The number of Pax7(+) cells per myofiber was increased by 96% on day 8 after exercise in the unblocked leg (0.14 +/- 0.04, mean +/- SE) compared with the prevalue (0.07 +/- 0.02, P < 0.05), whereas the number of Pax7(+) cells was unchanged in the leg muscles exposed to the NSAID (0.07 +/- 0.01). The number of inflammatory cells (CD68(+) or CD16(+) cells) was not significantly increased in either of the legs 8 days after exercise and was unaffected by the NSAID. The main finding in the present study was that the NSAID infusion for 7.5 h during the exercise day suppressed the exercise-induced increase in the number of satellite cells 8 days after exercise. These results suggest that NSAIDs negatively affect satellite cell activity after unaccustomed eccentric exercise.

Traumatic knee extension deficit (the locked knee): can MRI reduce the need for arthroscopy?

In the present study we investigated the validity of magnetic resonance imaging (MRI) and arthroscopy in knees with acute, traumatic extension deficit (the "locked knee"), and evaluated whether arthroscopy of knees with no mechanical pathology could be avoided by MRI evaluation. The study consisted of 50 patients who had an acute, traumatic extension deficit of the knee. All patients were submitted to MRI prior to arthroscopy. Following MRI and surgery, standardized forms were filled out, attempting to objectify the findings. The orthopaedic surgeon was not aware of the MRI result prior to surgery. Evaluating MRI, all grade-3 meniscal lesions were considered able to cause a mechanical block as well as acute partial or total anterior cruciate ligament (ACL)-ruptures. ACL-ruptures with an old appearance were not considered able to cause locking. Assuming that arthroscopy was the gold standard, the following results were calculated for the overall appearance of a lesion able to cause locking: Positive predictive value = 0.85, negative predictive value = 0.77, sensitivity = 0.95, specificity = 0.53. Two knees were erroneously evaluated with no mechanical locking at MRI (one bucket-handle lesion and one pathological synovial plica). MRI of the knee with acute, traumatic extension deficit is in the acute or subacute phase a safe method to identify the patients that have a mechanical reason for locking and therefore can benefit from arthroscopic treatment.