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Publications (156)
Background
Statin use is widely recognized for improving cardiovascular health, but questions remain on how statin use influences skeletal muscle, particularly mitochondrial function.
Study objective, design and participants
The influence of statin therapy and exercise (EX) on aerobic capacity was determined. In Study1, skeletal muscle aerobic cap...
Type 2 diabetes (T2D) presents with significant comorbidities and reported exercise intolerance affecting over 30 million people in the US alone. Aerobic metabolism is the predominant pathway for fueling exercise and utilizing glucose, therefore mitochondrial oxidative phosphorylation (MOP) is important in diabetes and the future of diabetic interv...
During aerobic exercise (>65% of VO2max) the primary source of acetyl-CoA to fuel oxidative ATP synthesis in muscle is the pyruvate dehydrogenase (PDH) reaction. This study investigated how regulation of PDH activity affects muscle energetics by determining whether activation of PDH with dichloroacetate (DCA) alters the dynamics of the phosphate po...
Microvascular function is reduced with age, disease, and inactivity. Exercise is well known to improve vascular health and has the potential to improve microvascular function in aging and disease.
Purpose:
The study aimed to assess changes in peripheral microvascular function in sedentary older adults following aerobic exercise training.
Methods...
Pyruvate dehydrogenase (PDH) is a mitochondrial matrix enzyme that regulates glucose oxidation in skeletal muscle. The activation status of PDH is regulated via reversible phosphorylation catalyzed by a set of pyruvate dehydrogenase phosphatases (PDP) and kinases (PDK) each with their own allosteric regulators. The PDKs are sensitive to energetical...
The increase in glucose oxidation during exercise is dependent upon the mitochondrial enzyme pyruvate dehydrogenase (PDH) which is allosterically regulated by reversible phosphorylation through a family of PDH kinases and phosphatases. However, the relationship between PDH activation and muscle fiber type during exercise has not been well described...
This study aimed to 1) quantitatively resolve in vivo muscle blood flow dynamics in response to contractile activity and 2) characterize the relationship between contraction‐induced hyperemia and metabolic demand in O 2 over the physiological range of muscle function in the rat hindlimb. Anesthetized Wistar rats (males, n=9) were placed supine in a...
Mitochondrial density is a key contributor to exercise capacity. Diseases such as diabetes and age related illnesses lower mitochondrial densities in skeletal muscle and result in a mismatch between energy supply and demand. The precise relationship between mitochondrial energetics and cell metabolism for these conditions is not well described. To...
Purpose The primary aim was to evaluate the influence of age on microvascular function in adults with similar physical activity levels (PA). Secondary aims were to assess the reliability of muscle functional MRI in older adults and the relationship between physical activity and microvascular function in older adults.
Methods Microvascular BOLD resp...
Introduction:
Forces applied to the skin cause a decrease in regional blood flow. This decrease in blood flow can cause tissue necrosis and lead to the formation of deep, penetrating wounds called pressure ulcers. These wounds are detrimental to individuals with compromised health, such as the elderly and spinal-cord injured. Although surface pres...
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and
Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early
dhildhood mortality and growth failure data and their association with maternal
Increased marrow adiposity is often associated with bone loss. Little is known about the regulation of marrow adiposity in humans. Marrow adiposity is increased in several mouse models including type I (T1)-diabetic mice, which also display bone loss. However, the impact of metabolic disease on marrow adiposity in humans has yet to be examined. Thi...
Past simulations of oxidative ATP metabolism in skeletal muscle have predicted that elimination of the creatine kinase (CK) reaction should result in dramatically faster oxygen consumption dynamics during transitions in ATP turnover rate. This hypothesis was investigated. Oxygen consumption of fast-twitch (FT) muscle isolated from wild-type (WT) an...
Previous studies show that transient increases in both blood flow and magnetic resonance image signal intensity (SI) occur in human muscle after brief, single contractions, and that the SI increases are threefold larger in physically active compared with sedentary subjects. This study examined the relationship between these transient changes by mea...
The sections in this article are:
The Central Role of Adenine Nucleotides
Components of the High‐Energy Phosphate System
Phosphate Metabolites are a Linked Network
Approaches to Understanding Metabolic Control
Classic Enzyme Kinetics
Nonequilibrium Thermodynamics
Regulated Enzymes and the Role of Calcium
Determinants of Muscle Cell ATPase R...
In many small animals there are distinct differences in fiber-type composition among limb muscles, and these differences typically correspond to marked disparities in the oxidative capacities. However, whether there are similar differences in the oxidative capacity among leg muscles in humans is less clear. The purpose of this study was to compare...
A previous study showed that ingestion of a liquid meal high in polyunsaturated lipids decreased the blood-oxygenation-level-dependent (BOLD) response measured by functional magnetic resonance imaging (fMRI) during a finger-tapping motor task, and suggested that this effect was due to a direct effect of blood lipids on the cerebral vasculature. Thi...
Previous studies have shown that high-intensity training improves biochemical markers of oxidative potential in skeletal muscle within a 2-week period. The purpose of this study was to examine the effect of short-term high-intensity interval training on the time constant () of phosphocreatine (PCr) recovery following moderate-intensity exercise, an...
Previous studies have suggested the recovery of phosphocreatine (PCr) after exercise is at least second-order in some conditions. Possible explanations for higher-order PCr recovery kinetics include heterogeneity of oxidative capacity among skeletal muscle fibers and ATP production via glycolysis contributing to PCr resynthesis. Ten human subjects...
Short-term creatine supplementation is reported to result in a decreased ratio of phosphocreatine (PCr) to total creatine (TCr) in human skeletal muscle at rest. Assuming equilibrium of the creatine kinase reaction, this decrease in PCr:TCr implies increased cytoplasmic ADP and decreased Gibbs free energy of ATP hydrolysis in muscle, which seems co...
Elevated skeletal muscle phosphodiesters (PDE) have previously been reported with muscle-related disorders. Myalgia is a side effect of using statin cholesterol-lowering medications and, therefore, statin use may be associated with increased skeletal muscle PDE. The effect of cholesterol-lowering drugs on skeletal muscle phosphorus metabolites was...
Muscle phosphocreatine (PCr) recovery time constant (an index of muscle aerobic capacity) and contractile ATP cost were estimated from a gated (31)P NMR protocol which does not require intense, repetitive exercise. Subjects performed 2-s duration, maximum voluntary isometric ankle dorsiflexion contractions at 30-s intervals for 8 min (total 15 cont...
in the last decade, there was a dramatic increase in our knowledge of the molecular events that accompany changes in skeletal muscle mass in response to resistance exercise training or to chronic unloading. For example, the role of myostatin in limiting skeletal muscle growth during development was
Decreased bone mass, osteoporosis, and increased fracture rates are common skeletal complications in patients with insulin-dependent diabetes mellitus (IDDM; type I diabetes). IDDM develops from little or no insulin production and is marked by elevated blood glucose levels and weight loss. In this study we use a streptozotocin-induced diabetic mous...
The signal intensity (SI) in gradient-echo, echo-planar magnetic resonance images (repetition time/echo time = 1,000/40) of anterior tibialis muscle in active [estimated energy expenditure 42.4 +/- 3.7 (SD), n = 8] vs. sedentary (32.3 +/- 0.6 kcal.kg(-1).day(-1), n = 8) young adult (18-34 yr old) human subjects was measured after single, 1-s-durati...
Metabolic control within skeletal muscle is designed to limit ADP accumulation even during conditions where ATP demand is out of balance with ATP synthesis. This is accomplished by the reactions of adenylate kinase (AK; ADP+ADP <--> AMP+ATP) and AMP deaminase (AMP+H(2)O --> NH(3)+IMP), which limit ADP accumulation under these conditions. The purpos...
To examine the effects of occupational keyboard typing on median nerve shape and T2 relaxation and on forearm muscle T2 in professional typists with and without symptoms of carpal tunnel syndrome.
Based on the Levine Carpal Tunnel Syndrome Symptom Severity scale (LCTSS), 12 female professional typist volunteers were divided into asymptomatic (LCTSS...
Spinal cord injury (SCI) results in a dramatic loss of bone mineral and a marked increase in fracture incidence in the femur; however, its effect on the femur's geometric structure and strength is poorly studied. The primary purpose of the present study was to assess the geometric structure, composition, and strength of the midfemur in men with lon...
the role of myoglobin as an oxygen storage protein in the muscles of diving birds and mammals is well-established ([8][1]). In contrast, the function of the lower myoglobin content in striated muscles of humans and other terrestrial vertebrates has long been a subject of debate. In a seminal review
Survey.
Determine intramuscular fat (IMF) in affected skeletal muscle after complete spinal cord injury using a novel analysis method and determine the correlation of IMF to plasma glucose or plasma insulin during an oral glucose tolerance test.
General community of Athens, GA, USA.
A total of 12 nonexercise-trained complete spinal cord injured (SC...
The aim of this study was to monitor the effects of topical heat and/or static stretch treatments on the recovery of muscle damage by eccentric exercise. For this purpose, 32 untrained male subjects performed intense eccentric knee extension exercise, followed by 2 weeks of treatment (heat, stretch, heat plus stretch) or no treatment (control, n=8/...
Transient increases in signal intensity (DeltaSI, peak 2.6 +/- 0.6 %, mean +/- SE, n = 14) were observed in axial, gradient-echo, echo-planar magnetic resonance images acquired at 1.5 T from human anterior tibialis muscle following single, 1 s duration, isometric ankle dorsiflexion contractions. The magnitude of the MRI-measured DeltaSI was not sig...
The purpose of this study was to determine whether the proportion of skeletal muscle in the fat-free soft tissue mass (FFST) is the same in men with spinal cord injury (SCI) and able-bodied controls. Skeletal muscle mass and FFST of the midthigh were determined by using magnetic resonance imaging and dual-energy X-ray absorptiometry, respectively,...
Muscle activation produces increases in magnetic resonance ( T(2)) signal intensity leading to recruitment images that demonstrate spatial patterns and intensity of muscle activation. These T(2) activation maps are useful for visualizing and quantifying various aspects of muscle function. Activity-dependent changes in T(2) result from an increase i...
Phosphocreatine (PCr) depletion during isometric twitch stimulation at 5 Hz was measured by (31)P-NMR spectroscopy in gastrocnemius muscles of pentobarbital-anesthetized MM creatine kinase knockout (MMKO) vs. wild-type C57B (WT) mice. PCr depletion after 2 s of stimulation, estimated from the difference between spectra gated to times 200 ms and 140...
The magnitude of transient increases in anterior tibialis muscle signal intensity after single, brief ankle dorsiflexion contractions was measured by GRE-EPI in human subjects at 1.5 vs. 3T. The peak magnitude was increased by 2.5-fold at 3T vs. 1.5T, corresponding to apparent ∆R2* of 0.85/s vs. 0.35/s, respectively. The results confirm that these...
This study tested the hypothesis that fatigue of a single member of musculus quadriceps femoris (QF) would alter use of the other three muscles during knee extension exercise (KEE). Six men performed KEE with the left QF at a load equal to 50% of the 4 x 10 repetitions maximum. Subsequently, electromyostimulation (EMS), intended to stimulate and fa...
Age-related increases in total body fat have been reported, but the impact of menopause on abdominal fat distribution is still unclear. The purpose of this study was to determine the impact of menopausal status on abdominal fat distribution using magnetic resonance imaging (MRI). In addition, we investigated the influence of abdominal fat distribut...
We hypothesized that activation of the quadriceps femoris muscle group during eccentric exercise is related to the increase in magnitude of several markers of muscle injury that developed during the next week. Fourteen male subjects performed six to eight sets of five to ten repetitions of single-leg eccentric-only seated knee extension exercise. M...
Previous studies suggest that the activity-induced increase in 1H-NMR transverse relaxation time (T2) observed in mammalian skeletal muscles is related to an osmotic effect of intracellular metabolite accumulation. This hypothesis was tested by comparing T2 (measured by 1H-NMR imaging at 4.7 T) and metabolite changes (measured by 31P-NMR spectrosco...
The increase in nuclear magnetic resonance transverse relaxation time (T(2)) of muscle water measured by magnetic resonance imaging after exercise has been correlated with work rate in human subjects. This study compared the T(2) increase in thigh muscles of trained (cycling VO(2 max) = 54.4 +/- 2.7 ml O(2). kg(-1). min(-1), mean +/- SE, n = 8, 4 f...
This study examined the relationships between muscle fiber type, metabolism, and blood flow vs. the increase in skeletal muscle (1)H-NMR transverse relaxation time (T2) after stimulation. Triceps surae muscles of anesthetized rats were stimulated in situ at 1-10 Hz for 6 min, and T2 was calculated from (1)H-NMR images acquired at 4.7 T immediately...
Introduction Previous studies show that transient increases in limb blood flow occur after single muscle contractions (1), and one preliminary report (2) suggests that this transient hyperemia is associated with a BOLD (Blood-Oxygenation-Level-Dependent) effect in muscle. While BOLD effects have been reported in skeletal muscle during ischemia and...
Muscle functional magnetic resonance imaging (MRI) is used to compare the relative involvement of different muscles recruited during exercise. The method relies on the activity-induced increase in the nuclear magnetic resonance transverse relaxation time (T2) of muscle water, which is caused by osmotically driven shifts of fluid into the myofibrill...
Creatine (Cr) supplementation has become a common practice among professional, elite, collegiate, amateur, and recreational athletes with the expectation of enhancing exercise performance. Research indicates that Cr supplementation can increase muscle phosphocreatine (PCr) content, but not in all individuals. A high dose of 20 g x d(-1) that is com...
Increases in skeletal muscle (1)H-NMR transverse relaxation time (T2) observed by magnetic resonance imaging have been used to map whole muscle activity during exercise. Some studies further suggest that intramuscular variations in T2 after exercise can be used to map activity on a pixel-by-pixel basis by defining an active T2 threshold and countin...
The purposes of this study were, first, to clarify the long-term pattern of T2 relaxation times and muscle volume changes in human skeletal muscle after intense eccentric exercise and, second, to determine whether the T2 response exhibits an adaptation to repeated bouts. Six young adult men performed two bouts of eccentric biceps curls (5 sets of 1...
The purposes of this study were, first, to clarify the long-term pattern of T2 relaxation times and muscle volume changes in human skeletal muscle after intense eccentric exercise and, second, to determine whether the T2 response exhibits an adaptation to repeated bouts. Six young adult men performed two bouts of eccentric biceps curls (5 sets of 1...
Magnetic resonance imaging (MRI) was used to characterize the volumes and rates of gastric emptying of both liquid and gas following the ingestion of beverages of varying carbonation and carbohydrate levels. Eight subjects drank 800 ml each of four test beverages in a counterbalanced order: water, a non-carbonated carbohydrate-electrolyte solution...
The hypothesis that increased muscle T2 after exercise is caused by increased extracellular fluid volume was tested by comparing the effects of exercise versus external leg negative pressure on muscle T2 relaxation in normal human subjects. T2 in lower leg muscles was measured by echo-planar imaging at 63 echo times from 24 to 272 ms, and the relax...
The hypothesis that increased muscle T2 after exercise is caused by increased extracellular fluid volume was tested by comparing the effects of exercise versus external leg negative pressure on muscle T2 relaxation in normal human subjects. T2 in lower leg muscles was measured by echo-planar imaging at 63 echo times from 24 to 272 ms, and the relax...
Studies of skinned fibers suggest that the rate of ATP turnover in skeletal muscle is depressed by acidosis. To examine whether this occurs in intact muscles, the ATP cost of isometric contractions was measured in ex vivo, arterially perfused cat biceps (predominantly fast-twitch) and soleus (slow-twitch) muscles under normocapnic (5% CO2) and hype...
The relationships between oxygen consumption (Q(O2)) and calculated cytoplasmic ADP concentration ([ADP]) and the free energy of ATP hydrolysis (deltaG(ATP)) were examined in ex vivo arterially perfused cat soleus muscles during repetitive twitch stimulation under normocapnic (5% CO2) and hypercapnic (70% CO2) conditions. Hypercapnia decreased extr...
The influence of muscle oxidative capacity on phosphocreatine (PCr) changes during and after stimulation was examined in the superficial (fast-twitch) section of rat gastrocnemius muscles. Muscle mitochondrial enzymes were increased in one group of rats by 8-10 wk of training on a running wheel (to a final regimen of 50 min/day at 38 m/min, 5 days/...