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Biomedical subjects

D P Thomas

Publications and source records attributed to D P Thomas.

At least 19 recordsLinked to original sources

The effect of pedaling frequency on glycogen depletion rates in type I and type II quadriceps muscle fibers during submaximal cycling exercise.

This study was conducted to determine whether the pedaling frequency of cycling at a constant metabolic cost contributes to the pattern of fiber-type glycogen depletion. On 2 separate days, eight men cycled for 30 min at approximately 85% of individual aerobic capacity at pedaling frequencies of either 50 or 100 rev.min-1. Muscle biopsy samples (vastus lateralis) were taken immediately prior to and after exercise. Individual fibers were classified as type I (slow twitch), or type II (fast twitch), using a myosin adenosine triphosphatase stain, and their glycogen content immediately prior to and after exercise quantified via microphotometry of periodic acid-Schiff stain. The 30-min exercise bout resulted in a 46% decrease in the mean optical density (D) of type I fibers during the 50 rev.min-1 condition [0.52 (0.07) to 0.28 (0.04) D units; mean (SEM)] which was not different (P > 0.05) from the 35% decrease during the 100 rev.min-1 condition [0.48 (0.04) to 0.31 (0.05) D units]. In contrast, the mean D in type II fibers decreased 49% during the 50 rev.min-1 condition [0.53 (0.06) to 0.27 (0.04) units]. This decrease was greater (P < 0.05) than the 33% decrease observed in the 100 rev.min-1 condition [0.48 (0.04) to 0.32 (0.06) units). In conclusion, cycling at the same metabolic cost at 50 rather than 100 rev.min-1 results in greater type II fiber glycogen depletion. This is attributed to the increased muscle force required to meet the higher resistance per cycle at the lower pedal frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of recovery mode following hind-limb suspension on soleus muscle composition in the rat.

The purpose of this study was to compare the effects of two different recovery modes from hind-limb suspension-induced hypodynamia on whole body and muscle (soleus) growth as well as soleus composition and size changes of different fiber types within this same muscle. Following 28 days of tail-suspension, rats were returned to their cages and sedentarily recovered (HS), or were exercised by running on a treadmill 5 days/wk, at progressively increasing workloads (HR) for one month. Sedentary and running control groups of animals (CS, CR) were also evaluated for comparative purposes. The exercise program, which was identical for CR and HR groups, had no effect on body wt., soleus wt., soleus muscle composition or fiber size in CR rats. Atrophied soleus muscle and reduced soleus wt./body wt. ratio (both 60% of control) had returned to control values by day 7 of recovery in both suspended groups despite the fact that whole body wt. gain was significantly reduced (p less than 0.05) in HR as compared to HS rats. Atrophied soleus Type I fiber mean cross-sectional area in both HR and HS groups demonstrated similar and significant (p less than 0.01) increases during recovery. Increases in Type IIa and IIc fiber area during this same period were significant only in the HR group. While the percentage area of muscle composed of Type I fibers increased in both hypodynamic groups during recovery, the reduction in area percentage of muscle made up of Type IIa fibers was again only significant in the HR group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Aging- and training-induced alterations in collagen characteristics of rat left ventricle and papillary muscle.

We evaluated the single and interactive effects of aging and exercise training on selected parameters of myocardial interstitium in both the left ventricle (LV) and LV papillary muscle of female Fischer 344 specific pathogen-free rats. Ten weeks of treadmill running resulted in significant LV hypertrophy as well as elevated plantaris muscle citrate synthase activity in both young adult (5-mo-old) and senescent (23-mo-old) trained animals (YT, young trained; OT, old trained) compared with age-matched sedentary controls (YC, young control; OC, old control). Proline and hydroxyproline pools were significantly higher (both P less than 0.05) in 23-mo-old vs. 5-mo-old papillary muscles. Degree of maturation (nonreducible cross-linking) of LV collagen was evaluated by measurement of hydroxylysylpyridinoline concentration ([HP]). In a comparison of YC with OC rats, ventricular [HP] increased approximately fivefold from 0.059 +/- 0.007 to 0.285 +/- 0.018 (SE) mol HP/mol collagen (P less than 0.001). Whereas training had no effect on ventricular [HP] in young adult rats, it significantly reduced LV collagen cross-linking in OT rats (0.131 +/- 0.027) so that HP values in this group were less than one-half of those observed in OC rats. Because both collagen concentration and degree of cross-linking are thought to affect muscle stiffness characteristics, we conclude that the observed changes should be considered in any explanation for aging- and training-induced alterations in LV and papillary muscle contractile indexes.

Aging

Exercise-induced satellite cell activation in senescent soleus muscle.

The purposes of this study were 1) to determine satellite cell mitotic activity and myofiber nuclear density in the soleus muscle of aged rats and 2) to examine the effect of exercise training on these same parameters. Twenty-four-month-old specific pathogen-free female Fischer 344 rats were assigned to either a training or a control group. The trained group performed 10 wk of progressive treadmill running that resulted in a significant increase (P less than or equal to 0.05) in vastus lateralis muscle malate dehydrogenase activity compared with control rats. Training produced a doubling of soleus muscle satellite cell mitotic activity (trained 1.28 +/- 0.33, control 0.52 +/- 0.13 thymidine-labeled satellite cells per 1,000 nuclei; P less than or equal to 0.05). Training also resulted in a doubling in the number of damaged fibers in the soleus muscle (P less than or equal to 0.05). Mean myofiber nuclear density was unaltered by exercise training but varied as a function of soleus muscle fiber size. Nuclear density of a subpopulation of small fibers (cross-sectional area less than one standard deviation below the mean cross-sectional area of all fibers examined) was significantly higher (P less than or equal to 0.05) than in other fibers in the soleus muscle. A high nuclear density and small size suggest that these fibers were immature. In addition, the soleus muscle from trained rats had significantly more (P less than or equal to 0.05) small fibers with high nuclear density than muscle from control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Training-induced alterations in young and senescent rat diaphragm muscle.

The current study sought to examine the effects of chronic endurance treadmill running on oxidative capacity and capillary density in specific diaphragm muscle fiber types in young (5 mo) and senescent (greater than or equal to 23 mo) female Fischer 344 rats. Both young and senescent animals trained at approximately 75% of maximal O2 consumption for 1 h/day 5 days/wk for 10 wk. Plantaris citrate synthase activity was significantly increased (P less than 0.01) in both young and old trained groups. Densitometric analysis of succinate dehydrogenase (SDH) activity in diaphragm type I, IIa, and IIb muscle fibers was done using a computerized image-processing system. There were no age-related differences in SDH activity between the young and old groups for any of the fiber types. In addition, SDH activity was found to be significantly increased (P less than 0.05) in all three fiber types in both the young and senescent trained animals compared with their sedentary counterparts. Fiber size and capillary density did not differ between young and senescent rats, nor did exercise affect this measure. Each fiber, irrespective of type, had an average of approximately four capillaries in contact with it. However, type IIb fibers had a significantly lower capillary density per unit area than type I or IIa muscle fibers. The results indicate that the senescent costal diaphragm maintains its ability to adapt to an increased metabolic demand brought about by locomotor exercise. Of further interest is the finding that training adaptations occurred in all three fiber types, suggesting that increased work of breathing from moderate exercise leads to recruitment of all three fiber types.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Myosin heavy chain composition in the rat diaphragm: effect of age and exercise training.

Increases in aerobic capacity in both young and senescent rats consequent to endurance exercise training are now known to occur not only in locomotor skeletal muscle but also in diaphragm. In the current study the effects of aging and exercise training on the myosin heavy chain (MHC) composition were determined in both the costal and crural diaphragm regions of female Fischer 344 rats. Exercise training [treadmill running at 75% maximal oxygen consumption (1 h/day, 5 day/wk, x 10 wk)] resulted in similar increases in plantaris muscle citrate synthase activity in both young (5 mo) and old (23 mo) trained animals (P < 0.05). Computerized densitometric image analysis of fast and slow MHC bands revealed the ratio of fast to slow MHC to be significantly higher (P < 0.005) in the crural compared with costal diaphragm region in both age groups. In addition, a significant age-related increase (P < 0.05) in percentage of slow MHC was observed in both diaphragm regions. However, exercise training failed to change the relative proportion of slow MHC in either the costal or crural region.

Aerobiosis

The effect of interleukin-1 on venous endothelium--an ultrastructural study.

The effect of systemic interleukin-1 (IL-1) on venous endothelium in the presence and absence of stasis has been studied by scanning electron microscopy (SEM). Recombinant human IL-1 beta at a concentration of 1 micrograms/kg or saline was injected intravenously into rabbits and allowed to circulate for 0.5 or 4.0 h after which complete stasis was induced for 1 h in an isolated segment of each jugular vein. One vein segment was then excised and the contents examined macroscopically for thrombi, while the other segment was fixed for SEM examination. When examined by SEM the endothelium from rabbits injected with IL-1 beta was perturbed with increased surface microvilli, blebs and gaps at cell junctions when compared with saline controls. Fibrin deposition was also observed after IL-1 beta, as was the adherence of essentially non-activated platelets to intact endothelium. However, macroscopic thrombi were not formed in isolated vein segments. We conclude that although fibrin strands and platelets were deposited on the endothelium, IL-1 is not a sufficiently powerful procoagulant stimulus to lead to an occlusive thrombus in acute experiments.

Animals

Effect of exercise training on antioxidant and metabolic functions in senescent rat skeletal muscle.

Aging is known to be associated with alterations of both oxidative capacity and antioxidant status in skeletal muscle. In the present investigation we compared the activity of enzymes involved in both metabolic functions and antioxidant defense capacity in young adult (5 months old) and senescent (27.5 months old) Fischer 344 rats. In addition, we studied the effects of chronic exercise training on these enzymes in the senescent skeletal muscle. Old sedentary rats had significantly lower glutathione peroxidase (GPX) activity (-22%, p less than 0.05) in the deep portion of vastus lateralis muscle (DVL) than young sedentary rats, but after a progressive 10-week treadmill training program GPX activity in DVL was significantly increased in old rats to a level higher than that seen in young sedentary rats. Superoxide dismutase and catalase activities in the DVL were not altered significantly with aging or by training. Glutathione S-transferase activity in the same muscle was elevated (p less than 0.05) with aging but unaffected by training. Citrate synthase and malate dehydrogenase activities in the DVL muscle were significantly decreased in senescence, whereas training increased these two enzyme activities by 71 and 48%, respectively (both p less than 0.05). Lactate dehydrogenase activity in the same muscle decreased with age but increased 23% (p less than 0.05) in old rats. These data indicate that while aging may significantly affect antioxidant and metabolic capacities in skeletal muscle, regular exercise can preserve functions of these enzyme systems at old age.

Aging

Effect of training on VO2max, thigh strength, and muscle morphology in septuagenarian women.

The purpose of this study was to determine the effects of a long-term (50 wk) combined aerobic-resistance training program on maximal oxygen consumption (VO2max, thigh strength, and vastus lateralis fiber morphology in healthy septuagenarian women (mean age = 72 +/- 6 yr). Subjects volunteered to be in either an exercise (Ex; N = 17) or control (Con; N = 10) group. Con subjects were 34% less active in winter than in summer, Ex subjects maintained their summer activity level on exercise days in winter. Initial, intermediate (20 wk), and final (50 wk) measurements were made for isokinetic knee extension/flexion strength; VO2max and morphological measurements from a muscle biopsy were made at the initial and final times only. Both groups gained in leg strength (Ex = +6.5%; Con = +7.8%; P less than or equal to 0.05) during the summer; in the winter the Ex group maintained leg strength and the Con group declined 12.2% (P less than or equal to 0.05). The fast-twitch muscle fiber area (Type IIb) increased 29% (P less than or equal to 0.001) in the Ex group and declined 26% (P = 0.014) in the Con group. VO2max increased only in the Ex group (16%; P less than 0.001). We conclude that healthy septuagenarian women can increase aerobic capacity, leg strength, and Type IIb muscle fiber area with a long-duration, combined aerobic-resistance exercise program.

Aged

Liposomes in arthritis: a new approach.

Intra-articular liposomal cortisol palmitate in a dose equivalent to 2 mg of cortisol produced a worthwhile therapeutic response in patients with rheumatoid arthritis. This may represent a valuable new approach to treatment.

Arthritis, Rheumatoid

Anticoagulant activities of high and low molecular weight heparin fractions.

The anticoagulant activities of high and low molecular weight heparin fractions were measured by three assay methods, both in vitro, and after intravenous injection in volunteers. The low molecular weight (LMW) fraction had similar anti-Xa activity in vitro to the high molecular weight (HMW) fraction, but in APTT assays the HMW fraction was about twice as potent. After intravenous injection, the two fractions gave equal heparin levels by anti-Xa assays, but in APTT assays using synthetic substrate S-2222 gave about 20% lower levels than anti-Xa clotting assays for both heparins. Complete protamine neutralization of the post-injection heparin activity was found in APTT and synthetic substrate assays, but about 20% of the clotting anti-Xa effect could not be neutralized. Complete neutralization of the fractions by protamine was shown by all three assays in vitro. This non-neutralizable activity probably accounts for the difference between the anti-Xa clotting and synthetic substrate assays. Studies by crossed immunoelectrophoresis and affinity chromatography indicated that the antithrombin III binding properties of the two fractions were similar.

Adult

Liposome-incorporated corticosteroids. II. Therapeutic activity in experimental arthritis.

The anti-inflammatory activity of liposomes containing cortisol palmitate was determined in experimental acute arthritis in the rabbit knee by measuring joint temperature and diameter. The therapeutic activity of the liposome preparation was dose-dependent for both these parameters of inflammation. Liposomal corticosteroid therapy was effective also in decreasing the joint temperature of an acute inflammatory 'flare' superimposed on an underlying chronic arthritis. Phosphatidic acid was necessary for expression of full anti-inflammatory activity of the liposome preparation.

Animals

Some problems in the bioassay of haematological drugs.

The principles of biological standardization are well understood and generally accepted. However, discrepancies in potency estimates due to inter-method and inter-laboratory variations in assay hinder general agreement on potency values for certain biological drugs used in treating disorders of haemostatis. While attempts are made to minimize these differences, the magnitude of existing inter-laboratory discrepancies should be acknowledged.

Antithrombin III

Liposome-incorporated corticosteroids: I. The interaction of liposomal cortisol palmitate with inflammatory synovial membrane.

Cortisol palmitate-containing liposomes were stable in rheumatoid synovial fluid at 37 degrees. Two hours after the intra-articular injection of such liposomes into experimentally arthritic rabbits relatively high proportions of the steroid and lecithin components were recovered from the synovialis. The level of cortisol in the tissue at this time was inversely related to the chronicity of the inflammation. It was found also that the degree and duration of the anti-inflammatory activity of the liposomes was greatest in the initial acute phases of the inflammation.

Animals