Time filter

Source Type

Zebrowska A.,Academy of Physical Education in Katowice | Waskiewicz Z.,Academy of Physical Education in Katowice | Zajac A.,Academy of Physical Education in Katowice | Gasior Z.,Medical University of Silesia, Katowice | And 2 more authors.
International Journal of Sports Medicine | Year: 2013

The study aimed at evaluating changes in plasma levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), testosterone, growth hormone (GH), cortisol, and insulin in resistance-trained male athletes with (n=9) and without (n=9) left ventricular hypertrophy (LVH) in response to eccentric (ECC) and concentric (CON) arm exercise. 10 age-matched healthy non-trained subjects served as controls. M-mode and 2D Doppler echocardiography were used to estimate LV mass. Resting IGF-1 concentration was higher in LVH athletes compared to controls (52±5nM vs. 46±7nM, p<0.05). ECC exercise resulted in higher (p<0.05) serum IGF-1 concentrations in athletes with LVH (70±11nM, n=9) compared to those without LVH (62±10nM, n=9), and to untrained controls (54±6nM). Both CON and ECC exercise resulted in higher serum IGFBP-3 levels in LVH athletes compared to controls (242±57 and 274±58, athletes, vs. 215±63 and 244±67, controls, nM, p<0.05). In ECC exercise, GH concentrations were lower in LVH than in non-LVH athletes (4.7±2.1 vs. 6.1±1.8ng·mL1, p<0.05). No differences in other hormones were found between groups. In conclusion, LVH is accompanied by elevated resting serum IGF-1 and enhanced response to eccentric arm exercise. These findings suggest a role of IGF-1, possibly released from contracting muscle, in stimulating LV hypertrophy in resistance training. © Georg Thieme Verlag KG Stuttgart · New York. Source

Pontoppidan P.L.,Exercise and Sports | Shen R.L.,Exercise and Sports | Petersen B.L.,Roskilde Hospital | Thymann T.,Exercise and Sports | And 4 more authors.
Experimental Biology and Medicine | Year: 2014

Chemotherapy-induced myeloablation prior to allogeneic hematopoietic stem cell transplantation (HSCT) may be associated with severe toxicity. The current understanding of the pathophysiology of oral and gastrointestinal (GI) toxicity is largely derived from studies in rodents and very little is known from humans, especially children. We hypothesized that milk-fed piglets can be used as a clinically relevant model of GI-toxicity related to a standard conditioning chemotherapy (intravenous busulfan, Bu plus cyclophosphamide, Cy) used prior to HSCT. In study 1, dose-response relationships were investigated in three-day-old pigs (Landrace × Yorkshire × Duroc, n = 6). Pigs were given one of three different dose combinations of Bu and Cy (A: 4 days Bu, 2 × 1.6 mg/kg plus 2 days Cy, 60 mg/kg; B: 4 days Bu, 2 × 0.8 mg/kg plus 2 days Cy, 30 mg/kg; C: 2 days Bu at 2 × 1.6 mg/kg plus 1 day Cy, 60 mg/kg) and bone marrow was collected on day 11. Histology of bone marrow samples showed total aplasia after treatment A. Using this treatment in study 2, Bu-Cy pigs showed lowered spleen and intestinal weights and variable clinical signs of dehydration, sepsis, and pneumonia at tissue collection. Oral mucositis was evident as ulcers in the soft palate in 4/9 Bu-Cy pigs and villus height and brush-border enzyme activities were reduced, especially in the proximal intestine. There were no consistent effects on tissue cytokine levels (IL-8, IL-6, IL-1β, TNF-α) or blood chemistry values (electrolytes, liver transaminases, bilirubin, alkaline phosphatase), except that blood iron levels were higher in Bu-Cy pigs. We conclude that a myeloablative Bu-Cy regimen to piglets results in clinical signs comparable to those seen in pediatric patients subjected to myeloablative treatment prior to HSCT. Piglets may be used as a model for investigating chemotherapy-induced toxicity and dietary and medical interventions. © 2013 by the Society for Experimental Biology and Medicine. Source

Jespersen J.G.,Copenhagen University | Nedergaard A.,Copenhagen University | Reitelseder S.,Copenhagen University | Mikkelsen U.R.,Copenhagen University | And 6 more authors.
PLoS ONE | Year: 2011

Background: Skeletal muscle mass is controlled by myostatin and Akt-dependent signaling on mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β) and forkhead box O (FoxO) pathways, but it is unknown how these pathways are regulated in critically ill human muscle. To describe factors involved in muscle mass regulation, we investigated the phosphorylation and expression of key factors in these protein synthesis and breakdown signaling pathways in thigh skeletal muscle of critically ill intensive care unit (ICU) patients compared with healthy controls. Methodology/Principal Findings: ICU patients were systemically inflamed, moderately hyperglycemic, received insulin therapy, and showed a tendency to lower plasma branched chain amino acids compared with controls. Using Western blotting we measured Akt, GSK3β, mTOR, ribosomal protein S6 kinase (S6k), eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), and muscle ring finger protein 1 (MuRF1); and by RT-PCR we determined mRNA expression of, among others, insulin-like growth factor 1 (IGF-1), FoxO 1, 3 and 4, atrogin1, MuRF1, interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and myostatin. Unexpectedly, in critically ill ICU patients Akt-mTOR-S6k signaling was substantially higher compared with controls. FoxO1 mRNA was higher in patients, whereas FoxO3, atrogin1 and myostatin mRNAs and MuRF1 protein were lower compared with controls. A moderate correlation (r2 = 0.36, p<0.05) between insulin infusion dose and phosphorylated Akt was demonstrated. Conclusions/Significance: We present for the first time muscle protein turnover signaling in critically ill ICU patients, and we show signaling pathway activity towards a stimulation of muscle protein synthesis and a somewhat inhibited proteolysis. © 2011 Jespersen et al. Source

Lauritzen H.P.M.M.,Harvard University | Brandauer J.,Gettysburg College | Schjerling P.,Copenhagen University | Koh H.-J.,Harvard University | And 4 more authors.
Diabetes | Year: 2013

Recent studies suggest that interleukin 6 (IL-6) is released from contracting skeletal muscles; however, the cellular origin, secretion kinetics, and signaling mechanisms regulating IL-6 secretion are unknown. To address these questions, we developed imaging methodology to study IL-6 in fixed mouse muscle fibers and in live animals in vivo. Using confocal imaging to visualize endogenous IL-6 protein in fixed muscle fibers, we found IL-6 in small vesicle structures distributed throughout the fibers under basal (resting) conditions. To determine the kinetics of IL-6 secretion, intact quadriceps muscles were transfected with enhanced green fluorescent protein (EGFP)-tagged IL-6 (IL-6-EGFP), and 5 days later anesthetized mice were imaged before and after muscle contractions in situ. Contractions decreased IL-6-EGFPcontaining vesicles and protein by 62% (P < 0.05), occurring rapidly and progressively over 25 min of contraction. However, contractionmediated IL-6-EGFP reduction was normal in muscle-specific AMP-activated protein kinase (AMPK) a2-inactive transgenic mice. In contrast, the AMPK activator AICAR decreased IL-6-EGFP vesicles, an effect that was inhibited in the transgenic mice. In conclusion, resting skeletal muscles contain IL-6positive vesicles that are expressed throughout myofibers. Contractions stimulate the rapid reduction of IL-6 in myofibers, occurring through an AMPKa2-independent mechanism. This novel imaging methodology clearly establishes IL-6 as a contraction-stimulated myokine and can be used to characterize the secretion kinetics of other putative myokines. © 2013 by the American Diabetes Association. Source

Langfort J.,Polish Academy of Sciences | Langfort J.,Academy of Physical Education in Katowice | Jagsz S.,Academy of Physical Education in Katowice | Dobrzyn P.,Nencki Institute of Experimental Biology | And 4 more authors.
Biochemical and Biophysical Research Communications | Year: 2010

Fatty acids, which are the major cardiac fuel, are derived from lipid droplets stored in cardiomyocytes, among other sources. The heart expresses hormone-sensitive lipase (HSL), which regulates triglycerides (TG) breakdown, and the enzyme is under hormonal control. Evidence obtained from adipose tissue suggests that testosterone regulates HSL activity. To test whether this is also true in the heart, we measured HSL activity in the left ventricle of sedentary male rats that had been treated with testosterone supplementation or orchidectomy with or without testosterone substitution. Left ventricle HSL activity against TG was significantly elevated in intact rats supplemented with testosterone. HSL activity against both TG and diacylglyceride was reduced by orchidectomy, whereas testosterone replacement fully reversed this effect. Moreover, testosterone increased left ventricle free fatty acid levels, caused an inhibitory effect on carbohydrate metabolism in the heart, and elevated left ventricular phosphocreatine and ATP levels as compared to control rats. These data indicate that testosterone is involved in cardiac HSL activity regulation which, in turn, may affect cardiac lipid and carbohydrate metabolism. © 2010 Elsevier Inc. Source

Discover hidden collaborations