scholarly journals The effect of aging on adrenergic and nonadrenergic receptor expression and responsiveness in canine skeletal muscle

2012 ◽  
Vol 112 (5) ◽  
pp. 841-848 ◽  
Author(s):  
D. S. DeLorey ◽  
P. S. Clifford ◽  
S. Mittelstadt ◽  
M. M. Anton ◽  
H. A. Kluess ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Protein Expression ◽  
Receptor Expression ◽  
Treadmill Running ◽  
Receptor Protein ◽  
Y1 Receptor ◽  
Arterial Blood ◽  
Age Related ◽  
Feed Arteries

We tested the hypothesis that adrenergic and nonadrenergic receptor responsiveness and protein expression would be altered with advancing age. Young ( n = 6; 22 ± 1 mo; mean ± SE) and old ( n = 6; 118 ± 9 mo) beagles were instrumented with flow probes and an indwelling catheter for continuous measurement of external iliac blood flow and arterial blood pressure. Vascular conductance (VC) was calculated as hindlimb blood flow/mean arterial pressure. Selective agonists for α-1, α-2, neuropeptide-Y (NPY), and purinergic (P2X) receptors were infused at rest and during treadmill running at moderate (2.5 mph) and heavy (4 mph with 2.5% grade) exercise intensities. Feed arteries were dissected from gracilis muscles, and α-1D, α-1B, α-2A, P2X-4, P2X-1, and NPY-Y1 receptor protein expression was determined. Phenylephrine produced similar decreases ( P > 0.05) in VC in young and old beagles at rest (young: −62 ± 5%; old: −59 ± 5%) and during moderate (young: −67 ± 5%; old: −62 ± 4%) and heavy (young: −54 ± 4%; old: −49 ± 3%) exercise. Clonidine caused similar ( P > 0.05) decreases in VC in old compared with young dogs at rest (young: −59 ± 8%; old: −70 ± 6%) and during moderate (young: −52 ± 6%; old: −47 ± 5%)- and heavy (young: −42 ± 5%; old: −43 ± 5%)-intensity exercise. NPY infusion resulted in a similar decline in VC in young and old beagles at rest (young: −40 ± 7%; old: −39 ± 9%) and during moderate (young: −47 ± 6%; old: −40 ± 6%)- and heavy (young: −40 ± 3%; old: −38 ± 4%)-intensity exercise. α-β-Methylene-ATP also produced similar decreases in VC in young and old beagles at rest (young: −36 ± 6%; old: −40 ± 8%) and during exercise at moderate (young: −42 ± 5%; old: −40 ± 9%) and heavy (young: −47 ± 5%; old: −42 ± 8%) intensities. α-1B receptor protein expression was elevated ( P < 0.05) in old compared with young dogs, whereas there were no age-related differences in α-1D or α-2A receptor expression and nonadrenergic P2X-4, P2X-1, and NPY-Y1 receptor expression. The present findings indicate that postsynaptic adrenergic and nonadrenergic receptor responsiveness was not altered by advancing age. Moreover, the expression of adrenergic and nonadrenergic receptors in skeletal-muscle feed arteries was largely unaffected by aging.

Reduced exercise capacity in senescent beagles: an evaluation of the periphery

1991 ◽  
Vol 260 (1) ◽  
pp. H173-H182 ◽  
Author(s):  
G. C. Haidet ◽  
D. Parsons
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Exercise Capacity ◽  
Maximal Exercise ◽  
Flow Distribution ◽  
Capillary Density ◽  
Blood Flow Distribution ◽  
Arterial Blood ◽  
Age Related ◽  
Age Related Changes

This study investigated the effect of age on peripheral factors involved in the systemic response to maximal exercise. Skeletal muscle was analyzed and regional blood flow distribution was determined at rest and during maximal exercise in senescent (old) and in younger mature (young) beagles. Maximal exercise capacity was significantly reduced (P less than 0.05) in old and was associated with a reduction in cardiac output (CO), as well as a tendency for arteriovenous O2 difference to be reduced, with a concomitant reduction in maximal O2 consumption. In each regional circulation evaluated, resting blood flow was similar in young and old. During exercise, blood flow was similar in young and old to the diaphragm, heart, tongue, and six of seven locomotory muscles. Concomitant blood flow reductions in splanchnic regions tended to be more pronounced in old than in young. Skeletal muscle analyses of triceps, semitendinosus, and gastrocnemius muscles disclosed similar percent fiber type distribution in young and old but a reduction in type II fiber area in old. In addition, both muscle capillary density and capillary-to-fiber ratio were reduced in old. These results demonstrate that age-related changes in blood flow distribution during maximal exercise enable skeletal muscle blood flow to be maintained in old, despite reductions in maximal CO and in muscle capillary density. However, this pattern of blood flow distribution only partially compensates for the combined effects of age-related changes in metabolic potential of the periphery, O2 content of arterial blood, and cardiac function during maximal exercise in old.

scholarly journals Effects of aging and exercise training on skeletal muscle blood flow and resistance artery morphology

2012 ◽  
Vol 113 (11) ◽  
pp. 1699-1708 ◽  
Author(s):  
Bradley J. Behnke ◽  
Michael W. Ramsey ◽  
John N. Stabley ◽  
James M. Dominguez ◽  
Robert T. Davis ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Exercise Training ◽  
Old Age ◽  
Gastrocnemius Muscle ◽  
Muscle Blood Flow ◽  
Resistance Artery ◽  
Cross Sectional ◽  
Age Related ◽  
Feed Arteries

With old age, blood flow to the high-oxidative red skeletal muscle is reduced and blood flow to the low-oxidative white muscle is elevated during exercise. Changes in the number of feed arteries perforating the muscle are thought to contribute to this altered hyperemic response during exercise. We tested the hypothesis that exercise training would ameliorate age-related differences in blood flow during exercise and feed artery structure in skeletal muscle. Young (6–7 mo old, n = 36) and old (24 mo old, n = 25) male Fischer 344 rats were divided into young sedentary (Sed), old Sed, young exercise-trained (ET), and old ET groups, where training consisted of 10–12 wk of treadmill exercise. In Sed and ET rats, blood flow to the red and white portions of the gastrocnemius muscle (GastRed and GastWhite) and the number and luminal cross-sectional area (CSA) of all feed arteries perforating the muscle were measured at rest and during exercise. In the old ET group, blood flow was greater to GastRed (264 ± 13 and 195 ± 9 ml·min−1·100 g−1 in old ET and old Sed, respectively) and lower to GastWhite (78 ± 5 and 120 ± 6 ml·min−1·100 g−1 in old ET and old Sed, respectively) than in the old Sed group. There was no difference in the number of feed arteries between the old ET and old Sed group, although the CSA of feed arteries from old ET rats was larger. In young ET rats, there was an increase in the number of feed arteries perforating the muscle. Exercise training mitigated old age-associated differences in blood flow during exercise within gastrocnemius muscle. However, training-induced adaptations in resistance artery morphology differed between young (increase in feed artery number) and old (increase in artery CSA) animals. The altered blood flow pattern induced by exercise training with old age would improve the local matching of O2 delivery to consumption within the skeletal muscle.

ETB receptor-deficient rats exhibit reduced contraction to ET-1 despite an increase in ETA receptors

2001 ◽  
Vol 281 (6) ◽  
pp. H2680-H2686 ◽  
Author(s):  
Melvin G. Perry ◽  
Mariela M. Molero ◽  
Ararat D. Giulumian ◽  
Prasad V. G. Katakam ◽  
Jennifer S. Pollock ◽  
...  
Keyword(s):  
Protein Expression ◽  
Receptor Gene ◽  
Normal Diet ◽  
Receptor Expression ◽  
Receptor Protein ◽  
Elevated Plasma ◽  
Vascular Effects ◽  
Small Arteries ◽  
Arterial Blood ◽  
Vascular Segment

Several disease states, including hypertension, are associated with elevations in plasma endothelin-1 (ET-1) and variable changes in vascular contraction to ET-1. The spotting lethal ( sl) rat carries a deletion of the endothelin-B (ETB) receptor gene that prevents expression of functional ETB receptors, resulting in elevated plasma ET-1. On a normal diet, these rats are normotensive and thus provide an opportunity to study the vascular effects of chronically elevated ET-1 in the absence of hypertension. Studies were performed in rats homozygous for the ETBdeficiency ( sl/ sl; n = 8) and in transgenic rats heterozygous for the ETB deficiency ( sl/+; n = 8). Plasma ET-1 was elevated in sl/ sl rats (3.85 ± 0.55 pg/ml) compared with sl/+ rats (0.31 ± 0.11 pg/ml). Mean arterial blood pressure in conscious unrestrained sl/ sland sl/+ rats was 101 ± 5 and 107 ± 6 mmHg, respectively. Concentration-dependent contractions to ET-1 (10−11–10−8 M) were reduced in mesenteric small arteries (150–250 μm) from sl/ sl rats, as indicated by an ∼10-fold increase in EC50. A selective ETA antagonist, A-127722 (30 nM), abolished contraction to ET-1 in both groups, whereas a selective ETB antagonist had no effect. Also, ETB agonists (IRL-1620 and sarafatoxin 6c) produced neither contraction nor relaxation in either group, indicating that contraction to ET-1 in this vascular segment was exclusively ETAdependent. Despite increased plasma ET-1, protein expression of ETA receptors in membrane protein isolated from mesenteric small arteries was increased in sl/ sl compared with sl/+ rats, as shown by Western blotting. These results indicate that, in ETB-deficient rats, ETA-induced contraction is reduced in vessels normally lacking ETB-mediated effects. Reduced contraction may be related to elevated plasma ET-1 and occurs in the presence of increased ETA receptor protein expression, suggesting an uncoupling of ETA receptor expression from functional activity.

scholarly journals Effects of aging and exercise training on spinotrapezius muscle microvascular Po2 dynamics and vasomotor control

2011 ◽  
Vol 110 (3) ◽  
pp. 695-704 ◽  
Author(s):  
Danielle J. McCullough ◽  
Robert T. Davis ◽  
James M. Dominguez ◽  
John N. Stabley ◽  
Christian S. Bruells ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Exercise Training ◽  
Sodium Nitroprusside ◽  
Vascular Function ◽  
Treadmill Running ◽  
Aged Rats ◽  
Phosphorescence Quenching

With advancing age, there is a reduction in exercise tolerance, resulting, in part, from a perturbed ability to match O2 delivery to uptake within skeletal muscle. In the spinotrapezius muscle (which is not recruited during incline treadmill running) of aged rats, we tested the hypotheses that exercise training will 1) improve the matching of O2 delivery to O2 uptake, evidenced through improved microvascular Po2 (PmO2), at rest and throughout the contractions transient; and 2) enhance endothelium-dependent vasodilation in first-order arterioles. Young (Y, ∼6 mo) and aged (O, >24 mo) Fischer 344 rats were assigned to control sedentary (YSED; n = 16, and OSED; n = 15) or exercise-trained (YET; n = 14, and OET; n = 13) groups. Spinotrapezius blood flow (via radiolabeled microspheres) was measured at rest and during exercise. Phosphorescence quenching was used to quantify PmO2 in vivo at rest and across the rest-to-twitch contraction (1 Hz, 5 min) transition in the spinotrapezius muscle. In a follow-up study, vasomotor responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) stimuli were investigated in vitro. Blood flow to the spinotrapezius did not increase above resting values during exercise in either young or aged groups. Exercise training increased the precontraction baseline PmO2 (OET 37.5 ± 3.9 vs. OSED 24.7 ± 3.6 Torr, P < 0.05); the end-contracting PmO2 and the time-delay before PmO2 fell in the aged group but did not affect these values in the young. Exercise training improved maximal vasodilation in aged rats to acetylcholine (OET 62 ± 16 vs. OSED 27 ± 16%) and to sodium nitroprusside in both young and aged rats. Endurance training of aged rats enhances the PmO2 in a nonrecruited skeletal muscle and is associated with improved vascular smooth muscle function. These data support the notion that improvements in vascular function with exercise training are not isolated to the recruited muscle.

Muscle blood flow during exercise in sedentary and trained hypothyroid rats

1995 ◽  
Vol 269 (6) ◽  
pp. H1949-H1954 ◽  
Author(s):  
R. M. McAllister ◽  
M. D. Delp ◽  
K. A. Thayer ◽  
M. H. Laughlin
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Citrate Synthase ◽  
Vastus Lateralis ◽  
Muscle Blood Flow ◽  
Treadmill Running ◽  
Exercise Intolerance ◽  
Vastus Lateralis Muscle ◽  
Blood Flows ◽  
Vastus Intermedius

Hypothyroidism is characterized by exercise intolerance. We hypothesized that active muscle blood flow during in vivo exercise is inadequate in the hypothyroid state. Additionally, we hypothesized that endurance exercise training would restore normal blood flow during acute exercise. To test these hypotheses, rats were made hypothyroid (Hypo) over 3-4 mo with propylthiouracil. A subset of Hypo rats was trained (THypo) on a treadmill at 30 m/min (15% grade) for 60 min/day 5 days/wk over 10-15 wk. Hypothyroidism was evidenced by approximately 80% reductions in plasma triiodothyronine levels in Hypo and THypo and by 40-50% reductions in citrate synthase activities in high oxidative muscles in Hypo compared with euthyroid (Eut) rats. Training efficacy was indicated by increased (25-100%) citrate synthase activities in muscles of THypo vs. Hypo. Regional blood flows were determined by the radiolabeled microsphere method before exercise and at 1-2 min of treadmill running at 15 m/min (0% grade). Preexercise muscle blood flows were generally similar among groups. During exercise, however, flows were lower in Hypo than in Eut for high oxidative muscles such as the red section of vastus lateralis [277 +/- 24 and 153 +/- 13 (SE) ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01] and vastus intermedius (317 +/- 32 and 187 +/- 20 ml.min-1.100 g-1 for Eut and Hypo, respectively; P < 0.01) muscles. Training (THypo) did not normalize these flows (168 +/- 24 and 181 +/- 24 ml.min-1.100 g-1 for red section of vastus lateralis and vastus intermedius muscles, respectively). Blood flows to low oxidative muscle, such as the white section of vastus lateralis muscle, were similar among groups (21 +/- 5, 25 +/- 4, and 34 +/- 7 ml.min-1.100 g-1 for Eut, Hypo, and THypo, respectively; P = NS). These findings indicate that hypothyroidism is associated with reduced blood flow to skeletal muscle during exercise, suggesting that impaired delivery of nutrients to and/or removal of metabolites from skeletal muscle contributes to the poor exercise tolerance characteristic of hypothyroidism.

scholarly journals PL - 031 Skeletal muscle blood flow determination using gold standard invasive arterial input function and non-invasive image-based input function by positron emission tomography (PET)

2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Ilkka Heinonen ◽  
Kari Kalliokoski ◽  
Vesa Oikonen ◽  
Christopher Mawhinney ◽  
Warren Gregson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Data Analysis ◽  
Arterial Input Function ◽  
Muscle Blood Flow ◽  
Input Function ◽  
Invasive Approach ◽  
Skeletal Muscle Blood Flow ◽  
Non Invasive ◽  
Arterial Blood

Objective Skeletal muscle is unique among organs in that its blood flow, thus oxygen supply that is critical for muscular function, can change over a remarkably large range. Compared to the rest, muscle blood flow can increase over 20-fold during intense exercise. Positron emission tomography (PET) and [15O]-H2O tracer provide a unique tool for the direct measurement of muscle blood flow in specific muscle regions. Quantification of PET blood flow requires knowledge of the arterial input function, which is usually provided by arterial blood sampling. However, arterial sampling is an invasive approach requiring arterial cannulation. In the current study, we aimed to explore the analysis and error estimation based on non-invasive, PET image-based input function for skeletal muscle blood flow in PET [15O]-labeled radiowater study. Methods Thirty healthy untrained men volunteered to participate in this study. [15O]-labeled radio water PET perfusion scans were performed at rest and right after cycling exercise. GE Discovery PET-CT scanner was used for image acquisition. The 15O isotope was produced with a Cyclone 3 cyclotron (IBA Molecular, Belgium). After 455 MBq of 15O-H2O was injected intravenously and after 20 seconds, dynamic scanning images were performed in following frames: 6x5 seconds, 12x10 seconds, 7x30 seconds and 12x10 seconds. Arterial blood was sampled continuously from radial artery during imaging for radioactivity with a detector during PET scanning. All the data analysis was performed using all in-house developed programs. Arterial input function was preprocessed with delay correction. Image-based input function was defined based on sum image of dynamic images. Blood flow was calculated using the 1-tissue compartment model, k1 is considered as blood flow without any further correction. All data analysis was performed by Carimas software (http://www.turkupetcentre.fi/carimas). Data analysis was performed in five parts: 1) Modelling data using input function from artery. 2) By defining femoral artery Volume Of Interest (VOI) on PET images. 3) Modelling data using image-based input function. 4) Calculating the correlation for blood flow between artery (blood) input function and image-based input function. 5) Predicted true blood flow was calculated based on correlation based on the initial linear relationship between blood and image-based input functions. Results Skeletal muscle blood flow had a good linear relationship calculated by femoral artery VOI and by arterial (blood) input function (y = 2,9587x - 0,096, R² = 0,8852, p<0.0001). Further, by using the prediction equation obtained by the linear relationship between VOI-determined (femoral) artery blood flow and direct gold standard (radial) artery input function determined blood flow, image-based input function determined blood flow was well predicted using this non-invasive approach (y = 1,1812x + 0,1219, R² = 0,9259, p<0.0001). Conclusions It is concluded that there is a strong linear correlation between gold standard invasive approach and non-invasive image-based approach to measure skeletal muscle blood flow by PET, but if no further corrections are made, image-based approach overestimates correct blood flow. However, this can be corrected by linear prediction equation, suggesting that invasive arterial input function may not always be needed in the future when measuring skeletal muscle blood flow by PET. This will be of benefit particularly for exercise studies.

scholarly journals Acute bout of resistance exercise increases vitamin D receptor protein expression in rat skeletal muscle

2015 ◽  
Vol 100 (10) ◽  
pp. 1168-1176 ◽  
Author(s):  
Yuhei Makanae ◽  
Riki Ogasawara ◽  
Koji Sato ◽  
Yusuke Takamura ◽  
Kenji Matsutani ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Vitamin D ◽  
Protein Expression ◽  
Resistance Exercise ◽  
Vitamin D Receptor ◽  
Receptor Protein ◽  
Rat Skeletal Muscle ◽  
Acute Bout

Regulation of canine skeletal muscle and hindlimb blood flow in acute anemia

1988 ◽  
Vol 66 (1) ◽  
pp. 101-105 ◽  
Author(s):  
P. Kubes ◽  
C. K. Chapler ◽  
S. M. Cain
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Vascular Resistance ◽  
Nerve Stimulation ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Sympathetic Stimulation ◽  
Arterial Blood ◽  
Measured Resistance ◽  
Muscle Groups

Redistribution of blood flow away from resting skeletal muscle does not occur during anemic hypoxia even when whole body oxygen uptake is not maintained. In the present study, the effects of sympathetic nerve stimulation on both skeletal muscle and hindlimb blood flow were studied prior to and during anemia in anesthetized, paralyzed, and ventilated dogs. In one series (skeletal muscle group, n = 8) paw blood flow was excluded by placing a tourniquet around the ankle; in a second series (hindlimb group, n = 8) no tourniquet was placed at the ankle. The distal end of the transected left sciatic nerve was stimulated to produce a maximal vasoconstrictor response for 4-min intervals at normal hematocrit (Hct.) and at 30 min of anemia (Hct. = 14%). Arterial blood pressure and hindlimb or muscle blood flow were measured; resistance and vascular hindrance were calculated. Nerve stimulation decreased blood flow (p < 0.05) in the hindlimb and muscle groups at normal Hct. Blood flow rose (p < 0.05) during anemia and was decreased (p < 0.05) in both groups during nerve stimulation. However, the blood flow values in both groups during nerve stimulation in anemic animals were greater (p < 0.05) than those at normal Hct. Hindlimb and muscle vascular resistance fell significantly during anemia and nerve stimulation produced a greater increase in vascular resistance at normal Hct. Vascular hindrance in muscle, but not hindlimb, was less during nerve stimulation in anemia than at normal Hct. The data indicate that (i) maximal sympathetic stimulation produced a significant decrease in both skeletal muscle and hindlimb blood flow during anemia, (ii) the reduction in blood flow in these areas was less with sympathetic stimulation during anemia than at normal Hct., and (iii) the anemic stimulus (Hct. = 14%) does not activate maximal sympathetic vasoconstrictor tone in the skeletal muscle.

Muscle chemoreflex alters vascular conductance in nonischemic exercising skeletal muscle

1994 ◽  
Vol 77 (6) ◽  
pp. 2761-2766 ◽  
Author(s):  
S. W. Mittelstadt ◽  
L. B. Bell ◽  
K. P. O'Hagan ◽  
P. S. Clifford
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Arterial Blood Pressure ◽  
Blood Pressure Response ◽  
Pressor Response ◽  
Vascular Conductance ◽  
Arterial Blood ◽  
Response To Exercise ◽  
Muscle Chemoreflex

Previous studies have shown that the muscle chemoreflex causes an augmented blood pressure response to exercise and partially restores blood flow to ischemic muscle. The purpose of this study was to investigate the effects of the muscle chemoreflex on blood flow to nonischemic exercising skeletal muscle. During each experiment, dogs ran at 10 kph for 8–16 min and the muscle chemoreflex was evoked by reducing hindlimb blood flow at 4-min intervals (0–80%). Arterial blood pressure, hindlimb blood flow, forelimb blood flow, and forelimb vascular conductance were averaged over the last minute at each level of occlusion. Stimulation of the muscle chemoreflex caused increases in arterial blood pressure and forelimb blood flow and decreases in forelimb vascular conductance. The decrease in forelimb vascular conductance demonstrates that the muscle chemoreflex causes vasoconstriction in the nonischemic exercising forelimb. Despite the decrease in vascular conductance, the increased driving pressure caused by the pressor response was large enough to produce an increased forelimb blood flow.

Age-related changes in regional blood flow in the rat

1985 ◽  
Vol 249 (3) ◽  
pp. H485-H491 ◽  
Author(s):  
R. F. Tuma ◽  
G. L. Irion ◽  
U. S. Vasthare ◽  
L. A. Heinel
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Cardiac Index ◽  
Regional Blood Flow ◽  
Adult Rats ◽  
Blood Flows ◽  
Arterial Blood ◽  
Anesthetized Rats ◽  
Regional Blood Flows ◽  
Central Hemodynamic

The purpose of this investigation was to characterize the changes in regional blood flow and central hemodynamic measures that occur in the rat as a result of the aging process. The isotope-labeled microsphere technique was used to measure cardiac output and regional blood flows in conscious and anesthetized adult (12 mo) and senescent (24 mo) Fischer 344 virgin female rats. No significant changes were observed in central hemodynamic measurements or regional blood flows in conscious rats with the exception of a 25% reduction in splenic blood flow. Pentobarbital anesthesia significantly reduced cardiac index and heart rate but elevated total peripheral resistance and mean arterial blood pressure. There was a decrease in blood flow to skeletal muscle, spleen, duodenum, stomach, and brain tissue samples and increased hepatic arterial blood flow in both age groups. The use of anesthesia caused a greater reduction in the cardiac index and brain blood flow in the senescent anesthetized rats than in the adult rats. Heart and kidney blood flows were decreased by anesthesia in the senescent rats but not in the adult rats. Skeletal muscle blood flow, however, was significantly greater in the senescent anesthetized rats than in the younger anesthetized animals. Although body weight and organ weights of the liver, spleen, kidneys, stomach, heart, and brain were significantly greater for the senescent rats, no differences could be demonstrated in tibial length or lean body mass.

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