Mette Hansen

Effect of estrogen on tendon collagen synthesis, tendon structural characteristics, and biomechanical properties in postmenopausal women

The knowledge about the effect of estradiol on tendon connective tissue is limited. Therefore, we studied the influence of estradiol on tendon synthesis, structure, and biomechanical properties in postmenopausal women. Nonusers (control, n = 10) or habitual users of oral estradiol replacement therapy (ERT, n = 10) were studied at rest and in response to one-legged resistance exercise. Synthesis of tendon collagen was determined by stable isotope incorporation [fractional synthesis rate (FSR)] and microdialysis technique (NH(2)-terminal propeptide of type I collagen synthesis). Tendon area and fibril characteristics were determined by MRI and transmission electron microscopy, whereas tendon biomechanical properties were measured during isometric maximal voluntary contraction by ultrasound recording. Tendon FSR was markedly higher in ERT users (P < 0.001), whereas no group difference was seen in tendon NH(2)-terminal propeptide of type I collagen synthesis (P = 0.32). In ERT users, positive correlations between serum estradiol (s-estradiol) and tendon synthesis were observed, whereas change in tendon synthesis from rest to exercise was negatively correlated to s-estradiol. Tendon area, fibril density, fibril volume fraction, and fibril mean area did not differ between groups. However, the percentage of medium-sized fibrils was higher in ERT users (P < 0.05), whereas the percentage of large fibrils tended to be greater in control (P = 0.10). A lower Youngs modulus (GPa/%) was found in ERT users (P < 0.05). In conclusion, estradiol administration was associated with higher tendon FSR and a higher relative number of smaller fibrils. Whereas this indicates stimulated collagen turnover in the resting state, collagen responses to exercise were negatively associated with s-estradiol. These results indicate a pivotal role for estradiol in maintaining homeostasis of female connective tissue.

Signatures of natural selection among lineages and habitats in Oncorhynchus mykiss.

Recent advances in molecular interrogation techniques now allow unprecedented genomic inference about the role of adaptive genetic divergence in wild populations. We used high-throughput genotyping to screen a genome-wide panel of 276 single nucleotide polymorphisms (SNPs) for the economically and culturally important salmonid Oncorhynchus mykiss. Samples included 805 individuals from 11 anadromous and resident populations from the northwestern United States and British Columbia, and represented two major lineages including paired populations of each life history within single drainages of each lineage. Overall patterns of variation affirmed clear distinctions between lineages and in most instances, isolation by distance within them. Evidence for divergent selection at eight candidate loci included significant landscape correlations, particularly with temperature. High diversity of two nonsynonymous mutations within the peptide-binding region of the major histocompatibility complex (MHC) class II (DAB) gene provided signatures of balancing selection. Weak signals for potential selection between sympatric resident and anadromous populations were revealed from genome scans and allele frequency comparisons. Our results suggest an important adaptive role for immune-related functions and present a large genomic resource for future studies

Sex hormones and skeletal muscle weakness

Human ageing is accompanied with deterioration in endocrine functions the most notable and well characterized of which being the decrease in the production of sex hormones. Current research literature suggests that low sex hormone concentration may be among the key mechanism for sarcopenia and muscle weakness. Within the European large scale MYOAGE project, the role of sex hormones, estrogens and testosterone, in causing the aging-related loss of muscle mass and function was further investigated. Hormone replacement therapy (HRT) in women is shown to diminish age-associated muscle loss, loss in fast muscle function (power), and accumulation of fat in skeletal muscle. Further HRT raises the protein synthesis rate in skeletal muscle after resistance training, and has an anabolic effect upon connective tissue in both skeletal muscle and tendon, which influences matrix structure and mechanical properties. HRT influences gene expression in e.g. cytoskeletal and cell–matrix proteins, has a stimulating effect upon IGF-I, and a role in IL-6 and adipokine regulation. Despite low circulating steroid-hormone level, postmenopausal women have a high local concentration of steroidogenic enzymes in skeletal muscle.

Influence of Sex and Estrogen on Musculotendinous Protein Turnover at Rest and After Exercise

Women differ from men with regard to muscle and tendon, most likely because of sex differences in estrogen. The present experimental findings suggest the hypothesis that estrogen has an anabolic effect on muscle primarily by lowering the protein turnover and enhancing sensitivity to resistance training. Furthermore, estrogen may reduce the stiffness of tendons, an effect that may be modified by physical training.

Exercise and Nsaids: Effect on Muscle Protein Synthesis in Patients with Knee Osteoarthritis

PURPOSE The purpose of this study was to determine muscle and tendon protein fractional synthesis rates (FSR) at rest and after a one-legged kicking exercise in patients with knee osteoarthritis (OA) receiving either placebo or nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS Twenty patients with knee OA (50-70 yr) were enrolled. For each of the 3 days before the exercise intervention, 9 patients were administered NSAIDs (1200 mg), and 11 patients were administered placebo in a double-blinded manner. Each patient performed 60 min of one-legged kicking at 55% of workload maximum while the contralateral leg remained rested. Twenty-four hours after exercise, we determined circulating concentrations of inflammatory parameters and measured FSR of myofibrillar and sarcoplasmic protein fractions of vastus lateralis muscle and patellar tendon collagen protein by the direct incorporation method using a flooding dose of 13C/12C-proline. RESULTS Circulating levels of prostaglandin F2α were lower in the NSAID group compared with the placebo group (P < 0.05). There was an overall significant effect of exercise on FSR in muscle myofibrillar (P = 0.003) and sarcoplasmic protein (P = 0.026) but not in tendon collagen protein (P = 0.52). No overall significant effect of the drug was seen on either of the tissue protein fractions (P > 0.05) or on the interaction between the drug and exercise on FSR in tendon collagen (P = 0.21), muscle myofibrillar (P = 0.68), or sarcoplasmic protein, FSR (P = 0.16). CONCLUSION In elderly patients with knee OA, an acute bout of moderate exercise significantly increases FSR of muscle myofibrillar and sarcoplasmic protein, but not tendon collagen, 24 h after exercise. NSAID administration in patients with knee OA reduced the level of circulating prostaglandin F2α but did not diminish the exercise-induced response of muscle contractile protein FSR. However, we cannot exclude that a minor inhibition of muscle sarcoplasmic proteins may have been present with NSAID treatment. This study suggests that muscle hypertrophy after long-term training is not influenced by NSAIDs.

The mystery of female connective tissue

females and males differ in many ways, including physiologically, and the fact that some types of connective tissue injuries (e.g., ligament ruptures and bone stress fractures) are more frequent in females than in males remains a puzzle. Estrogen receptors are known to be present in fibroblasts of

Serum levels of bioactive IGF1 and physiological markers of ageing in healthy adults.

OBJECTIVE Senescent changes in body composition and muscle strength are accompanied by reduced production of GH and IGF1, but the causal relationship remains elusive. We speculate that serum bioactive IGF1, measured by the IGF1 kinase receptor activation assay, is closer related to human physiological ageing than total IGF1 measured by immunoassay. DESIGN We conducted a cross-sectional study in 150 adult males and females, between 20 and 70 years. After an overnight fasting, serum levels of bioactive IGF1, total IGF1 and IGF-binding protein 1 (IGFBP1) and IGFBP3 were assessed. Furthermore, body composition and muscle strength was measured. RESULTS Total IGF1 levels were higher in females (P=0.048). Bioactive IGF1 were identical in males and females (P=0.31), decreasing with age. Total IGF1 tended to decrease more with age compared with bioactive IGF1 (-1.48 vs -0.89 percent/year, P=0.052). Total body fat (TBF) was lower and BMI was higher in males (P<0.001 and P=0.005), and both increased with age. Knee extension and elbow flexion force were higher in males (P=0.001 and P=0.001), but decreased with age in both genders.  Total but not bioactive IGF1 was positively correlated to TBF, knee extension and muscle function in males. In multiple linear regression, only age predicted total IGF1, whereas age and IGFBP1 predicted bioactive IGF1. CONCLUSIONS Bioactive IGF1 tends to decrease to a lesser extent than total IGF1 with age and was not correlated with measures of body composition or muscle strength. Therefore, levels of circulating bioactive IGF1 does not appear to be a better biomarker of physiological ageing than total IGF1.

Oral transmission as a route of infection for viral haemorrhagic septicaemia virus in rainbow trout, Oncorhynchus mykiss (Walbaum)

Surveys among wild marine fish have revealed occurrence of viral haemorrhagic septicaemia virus (VHSV) infections in a high number of diverse fish species. In marine aquaculture of rainbow trout, preying on invading wild fish might thus be a risk factor for introduction and adaptation of VHSV and subsequent disease outbreaks. Our objective was to determine whether an oral transmission route for VHSV in rainbow trout exists. Juvenile trout were infected through oral, waterborne and cohabitation transmission routes, using a recombinant virus strain harbouring Renilla luciferase as reporter gene. Viral replication in stomach and kidney tissue was detected through bioluminescence activity of luciferase and qRT-PCR. Replication was detected in both tissues, irrespective of transmission route. Replication patterns, however, differed among transmission routes. In trout infected through oral transmission, replication was detected in the stomach prior to kidney tissue. In trout infected through waterborne or cohabitation transmission, replication was detected in kidney prior to stomach or in both tissues simultaneously. We demonstrate the existence of an oral transmission route for VHSV in rainbow trout. This implies that preying on invading infected wild fish is a risk factor for introduction of VHSV into marine cultures of rainbow trout.

Effect of Whey Protein Hydrolysate on Performance and Recovery of Top-Class Orienteering Runners

This trial aimed to examine the effect of whey protein hydrolysate intake before and after exercise sessions on endurance performance and recovery in elite orienteers during a training camp. Eighteen elite orienteers participated in a randomized controlled intervention trial during a 1-week training camp (13 exercise sessions). Half of the runners (PRO-CHO) ingested a protein drink before (0.3 g kg(-1)) and a protein-carbohydrate drink after (0.3 g protein kg(-1) and 1 g carbohydrate kg(-1)) each exercise session. The others ingested energy and time-matched carbohydrate drinks (CHO). A 4-km run-test with 20 control points was performed before and on the last day of the intervention. Blood and saliva were obtained in the mornings, before and after run-tests, and after the last training session. During the intervention, questionnaires were fulfilled regarding psychological sense of performance capacity and motivation. PRO-CHO and not CHO improved performance in the 4-km run-test (interaction p < .05). An increase in serum creatine kinase was observed during the week, which was greater in CHO than PRO-CHO (interaction p < .01). Lactate dehydrogenase (p < .001) and cortisol (p = .057) increased during the week, but the change did not differ between groups. Reduction in sense of performance capacity during the intervention was greater in CHO (p < .05) than PRO-CHO. In conclusion, ingestion of whey protein hydrolysate before and after each exercise session improves performance and reduces markers of muscle damage during a strenuous 1-week training camp. The results indicate that protein supplementation in conjunction with each exercise session facilitates the recovery from strenuous training in elite orienteers.

General and family-specific gene expression responses to viral hemorrhagic septicaemia virus infection in rainbow trout (Oncorhynchus mykiss)

The ability of rainbow trout (Oncorhynchus mykiss) to respond successfully to infection by viral hemorrhagic septicaemia virus (VHSV) is expected to involve a large number of biochemical processes. We hypothesized that this would be reflected at the gene expression level in infected fish, and we tested it by examining gene expression levels in the head kidney of trout at a genome-wide scale with a 16K cDNA microarray for salmonids. Expression levels were recorded during 16 days following bath challenge. The challenge experiment included a relatively low susceptibility (32% survival following challenge) and a relatively high susceptibility (18% survival following challenge) trout family that were both split into a group exposed to virus and a non-exposed control group. In total, 939 genes were differentially expressed between infected and non-infected fish (FDR p=0.05). Five groups of Gene Ontology categories were involved in immune-related processes and over-represented in infected fish: (i) stress and defense response, (ii) NFkappaB signal transduction, (iii) response to non-self, (iv) antigen processing and presentation, and (v) proteasome complexes. The first four categories were also over-represented among the 642 differentially expressed genes in the low-susceptibility trout family but not among the 556 differentially expressed genes in the high-susceptibility trout family. Expression profiles for most immune genes discussed showed increased transcription from day 3 post-challenge. The results suggest that the innate immune system may play an important role in the successful response to VHSV in rainbow trout. In addition, the results indicate that a superior regulation of the transcription of several key innate immune-related genes contribute to the increased survival in resistant fish.