ABSTRACT
Adequate nutrient intake in acute uremia is a key part of patient management especially as food utilization is usually impaired. Leucine is important as it comprises about one-fifth of essential amino acid needs and, apart from serving as a substrate, it directly activates the mTOR signaling pathway stimulating protein synthesis and inhibiting autophagy. Here we tested whether leucine activation of the mTOR signaling pathway in muscle is severely disrupted in acute uremia. Several abnormalities were identified in bilateral ureteral ligated (model of acute uremia) compared to sham-operated pair-fed control rats. Levels of several signaling proteins increased significantly while leucine-induced phosphorylation of mTOR and downstream proteins, 4e-BP1 and S6K1, was completely suppressed. Levels of LC3B-II, a specific autophagosomal membrane-associated protein used as a marker of autophagy, increased threefold in uremia. Furthermore, while leucine suppressed LC3B-II levels in controls, it failed to do so in uremic rats. Muscle IL-6 mRNA levels increased, while IGF-1 mRNA levels decreased in uremia. These findings establish that, in acute uremia, severe resistance to leucine-induced activation of the mTOR anabolic signaling pathway develops. Thus, leucine resistance, together with the reduction in IGF-1 and increase in IL-6 expression, may explain why the anabolic effect of nutritional therapy is diminished in acute uremic patients.
Subject(s)
Acute Kidney Injury/metabolism , Leucine/metabolism , Muscle, Skeletal/metabolism , Signal Transduction , Uremia/metabolism , Acute Disease , Acute Kidney Injury/etiology , Acute Kidney Injury/genetics , Acute Kidney Injury/physiopathology , Animals , Carrier Proteins/metabolism , Disease Models, Animal , Down-Regulation , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Intracellular Signaling Peptides and Proteins , Ligation , Male , Microtubule-Associated Proteins/metabolism , Nutritional Status , Phosphoproteins/metabolism , Phosphorylation , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Ribosomal Protein S6 Kinases/metabolism , TOR Serine-Threonine Kinases/metabolism , Uremia/etiology , Uremia/genetics , Uremia/physiopathology , Ureter/surgeryABSTRACT
Age related muscle loss, known as sarcopenia, is a major factor in disability, loss of mobility and quality of life in the elderly. There are many proposed mechanisms of age-related muscle loss that include the endocrine system. A variety of hormones regulate growth, development and metabolism throughout the lifespan. Hormone activity may change with age as a result of reduced hormone secretion or decreased tissue responsiveness. This review will focus on the complex interplay between the endocrine system, aging and skeletal muscle and will present possible benefits of therapeutic interventions for sarcopenia.
Subject(s)
Aging , Dietary Supplements , Endocrine System/drug effects , Hormone Replacement Therapy , Hormones/therapeutic use , Muscle, Skeletal/drug effects , Sarcopenia/drug therapy , Vitamin D/therapeutic use , Age Factors , Aged , Aged, 80 and over , Aging/metabolism , Animals , Endocrine System/metabolism , Endocrine System/pathology , Endocrine System/physiopathology , Exercise , Female , Hormones/metabolism , Humans , Male , Middle Aged , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Sarcopenia/metabolism , Sarcopenia/pathology , Sarcopenia/physiopathology , Treatment OutcomeABSTRACT
STUDY DESIGN: Prospective clinical trial. OBJECTIVES: To test the hypothesis that quantified trunk rotational strength training will equalize any strength asymmetry, increase strength overall, and stabilize adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Bracing, the only generally accepted form of adolescent idiopathic scoliosis nonoperative therapy, has many shortcomings. Paraspinal muscle abnormalities, which have been extensively documented in these patients, are generally considered to be secondary. A normal female's trunk strength in flexion and extension decreases from her juvenile to adolescent years, whereas a male's increases. METHODS: Patients received a 4-month supervised followed by a 4-month home trunk rotational strength training program. Trunk rotational strength was measured in both directions at 5 positions at baseline, 4 months, and 8 months. The patients were followed clinically. RESULTS: Fifteen patients (12 females and 3 males), with an average age of 13.9 years and an average main Cobb of 33 degrees were enrolled. At baseline there was no significant asymmetry. After 4 months of supervised strength training, involving an average of 32 training sessions, each lasting about 25 minutes, their strength had significantly increased by 28% to 50% (P<0.005 to P<0.001). After 4 months of unsupervised home strength training their strengths were unchanged. The 3 patients with baseline curves of 50 to 60 degrees all had main or compensatory curve progression and 2 had surgery. For patients with 20 to 40-degree curves, survivorship from main curve progression of >or=6 degrees was 100% at 8 months, but decreased to 64% at 24 months. CONCLUSIONS: Quantified trunk rotational strength training significantly increased strength. It was not effective for curves measuring 50 to 60 degrees. It appeared to help stabilize curves in the 20 to 40-degree ranges for 8 months, but not for 24 months. Periodic additional supervised strength training may help the technique to remain effective, although additional experimentation will be necessary to determine this.
Subject(s)
Exercise Therapy/methods , Muscle Strength/physiology , Physical Fitness/physiology , Scoliosis/therapy , Adolescent , Age Factors , Aging/physiology , Child , Exercise/physiology , Exercise Therapy/instrumentation , Female , Humans , Male , Movement/physiology , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/physiology , Pilot Projects , Prospective Studies , Range of Motion, Articular/physiology , Recovery of Function/physiology , Rotation , Sex Factors , Spine/physiology , Teaching/methods , Treatment Outcome , Weight-Bearing/physiologyABSTRACT
BACKGROUND: Recent reports have suggested a rotational strength weakness in rotations to the concave side in patients with idiopathic scoliosis. There have been no studies presenting normative values of female adolescent trunk rotational strength to which a comparison of female adolescents with idiopathic scoliosis could be made. The purpose of this study was to determine trunk rotational strength asymmetry in a group of female adolescents with AIS and a comparison group of healthy female adolescents without scoliosis. METHODS: Twenty-six healthy adolescent females served as the healthy group (HG) (average age 14 years) and fourteen otherwise healthy adolescent females with idiopathic scoliosis served as the idiopathic scoliosis group (ISG) (average age 13.5 years, average Cobb 28 degrees ). Participant's isometric trunk rotational strength was measured in five randomly ordered trunk positions: neutral, 18 degrees and 36 degrees of right and left pre-rotation. Rotational strength asymmetry was compared within each group and between the two groups using several different measures. RESULTS: The HG showed strength asymmetry in the 36 degrees pre-rotated trunk positions when rotating towards the midline (p < 0.05). The ISG showed strength asymmetry when rotating towards the concavity of their primary curve from the neutral position (p < 0.05) and when rotating towards the concavity from the 18 degrees (p < 0.05) and 36 degrees (p < 0.05) concave pre-rotated positions. The ISG is significantly weaker than the HG when rotating away from the midline toward the concave (ISG)-left (HG) side from the concave/left pre-rotated 18 degrees (p < 0.05) and 36 degrees (p < 0.05) positions. CONCLUSION: The AIS females were found to be significantly weaker when contracting toward their main curve concavity in the neutral and concave pre-rotated positions compared to contractions toward the convexity. These weaknesses were also demonstrated when compared to the group of healthy female adolescent controls. Possible mechanisms for the strength asymmetry in ISG are discussed.
