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X J Musacchia

Publications and source records attributed to X J Musacchia.

At least 37 records · Page 2Linked to original sources
PubMed1986

Thymic involution in the suspended rat: adrenal hypertrophy and glucocorticoid receptor content.

The thymus gland and skeletal muscle are sensitive to the catabolic effects of glucocorticoids (GC). Previous studies using suspended rats demonstrated that muscle disuse atrophy resulting from hindlimb unloading was associated with an increase in glucocorticoid receptor site concentration. The objectives of the current studies were: to assess the temporal relationship between adrenal hypertrophy and thymic involution in suspended rats, to evaluate the role of positioning--antiorthostatic, (AO) vs. orthostatic (O)--in the thymic and adrenal responses, and to determine whether or thymic involution, like muscle disuse atrophy, was associated with an increase in GC receptor site concentration. The wet weight of the thymus was reduced by 50% (p less than 0.001) during 7 d of AO suspension. Suspended (AO) rats exhibited a significant (p less than 0.001) hypertrophy of the adrenal glands (33%), primarily on the initial day of suspension. Recovery for 7 d was associated with a return of thymus weight to control levels, but adrenal hypertrophy was not completely reversed. Rats suspended in an O position exhibited thymic and adrenal responses comparable to those of AO rats. Thymic involution in both AO and O rats was associated with a 20% (p less than 0.001) decrease in glucocorticoid receptor site concentration (pmol X mg-1 protein). However, when expressed relative to tissue weight, receptor site concentrations were not significantly different from control values. These results suggest a temporal correlation between adrenal hypertrophy and thymic involution in the suspended rat, but neither of these responses were dependent upon AO positioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Diseases↗
PubMed1985

Glucocorticoids and hypothermic induction and survival in the rat.

Glucocorticoids (GC) are important for thermoregulatory responses to low environmental temperatures. Pretreatment of hamsters, which are capable of natural hibernation, with cortisone acetate has been demonstrated to improve carbohydrate homeostasis during hypothermia. The objectives of the current studies were to evaluate the effects of GC pretreatment of a nonhibernator, the rat, on (i) cooling time, (ii) carbohydrate homeostasis (in terms of liver and cardiac glycogen concentrations and plasma glucose concentration), and (iii) duration of survival in hypothermia. In addition, the effects of liver glycogen depletion on cooling times and survival were examined. Hypothermia was induced in rats by exposure to a helium:oxygen (80:20, Helox) atmosphere at 0 degree C. Pretreatment of rats with triamcinolone acetonide (1.5 mg/kg/day, sc, 48, 24, and 1 hr prior to induction) significantly (P less than 0.05) lengthened induction time, while fasting was associated with a significant decrement (25%). While liver and cardiac glycogen levels in control and GC-treated rats fell approximately 45% during cooling, this reduction occurred over a significantly greater period of time in treated rats and suggests a sparing of glycogen or increased capacity for its production in response to GC. Glycogen utilization was accompanied by a hyperglycemia in control, GC-treated, and fasted groups. Survival in hypothermia at a rectal temperature of 14-15 degrees C in GC-treated (9.5 +/- 1.2 hr) and fasted (10.9 +/- 0.9 hr) rats was not significantly different from control (10.5 +/- 1.1 hr) values. These findings suggest that treatment with GC can increase the thermogenic capacity of the rat (as evidenced by an increased induction time) and promote carbohydrate homeostasis, but does not contribute to an enhancement of survival in the hypothermic nonhibernator.

Animals↗
PubMed1985

Senile amyloidosis and neuron binding antibody in the aging Syrian hamster.

The effects of age, sex, and irradiation on the genesis of amyloidosis, neuron-binding antibody (NBA), and the concomitant appearance of these two phenomena were studied in a colony of Syrian hamsters. In nonirradiated controls amyloidosis increased in prevalence with age after 12 months, and prevalence was higher in females than in males. Irradiation had the effect of advancing the appearance of amyloidosis to the 7-12 months group but did not intensify the amyloidotic process. IgG binding to the nucleus or cytoplasm of neurons was rare, and, despite the fact that IgM and IgA binding to these structures was present in about one-third of the animals, there was neither an aging nor an irradiation effect. The only statistically significant findings with respect to the concomitant occurrence of amyloid and NBA were negative correlations between nuclear IgM and IgA binding and amyloidosis. Of the various species thus far studied, the hamster is the first in which there has been no aging effect in respect to NBA.

Aging↗
PubMed1985

Effect of hypokinesia-hypodynamia on rat muscle oxidative capacity and glucose uptake.

Whole-body hypokinetic-hypodynamic (H/H) suspension, unlike other models of muscle disuse, allows voluntary contractile activity. This study examined the oxidative capacity and insulin sensitivity of rat hindlimb muscles subjected to 7 days of suspension H/H conditions. Oxidative capacity was determined by measuring citrate synthase activity and cytochrome c concentration in soleus and gastrocnemius muscles. A perfused hindquarter preparation was used to measure glucose uptake rates at rest with physiological and supramaximal concentrations of insulin in the perfusate. Citrate synthase activity was 17% lower in soleus and 23% lower in gastrocnemius muscles from H/H rats. Similarly, a 29% decrease in H/H rat gastrocnemius cytochrome c concentration was observed. Rates of glucose uptake were lower in muscles from H/H rats compared with controls at physiological levels of insulin and did not increase in response to a further increase in insulin concentration. Muscles undergoing a significant loss in mass after 7 days suspension were found to have increased glycogen concentrations. In conclusion, data presented in this study suggest that hindlimb muscle disuse, brought about by whole-body suspension, results in a decreased aerobic capacity in load bearing muscles and a lowered insulin sensitivity in perfused rat hindlimb muscles.

Animals↗
PubMed1985

Fatigue and contraction of slow and fast muscles in hypokinetic/hypodynamic rats.

This investigation examined the effects of hypokinesia/hypodynamia (H/H) on fatigability and contractile properties of rat soleus (S) and gastrocnemius (G) muscles. Whole-body suspension for 1 wk was used to eliminate hindlimb load-bearing functions and simultaneously permit voluntary isotonic contractions. Train stimulations (45/min, 16 min) resulted in significantly (P less than 0.05) faster rates of fatigue to lower asymptotes in G from H/H rats. Fatigue in the S was minimal at this stimulation frequency and differences between H/H and control animals were not significant. Contractile properties (twitch and tetanic) were measured before and after train stimulations. H/H suspension resulted in an increased twitch tension in G. However, H/H did not change train or tetanic tensions per gram or other G contractile properties. Peak twitch, train, and tetanic tensions, time to peak tension, one-half relaxation time, and twitch and tetanic peak rates of tension development and decline were unchanged by H/H in S muscles. These results indicate that 1 wk of H/H-induced muscle atrophy significantly increases fatigability in G but does not effect contractile properties of fast-twitch (G) or slow-twitch (S) muscles.

Animals↗
PubMed1985

The use of suspension models and comparison with true weightlessness: "a resumé".

The topics for this workshop were selected to illustrate the manner in which particular physiological and biochemical phenomena can be assessed using specific animal model systems. Our speakers presented data which offer comparisons of experiments in earthside laboratories with experiments using subjects which have experienced weightlessness in response to orbital flight. In addition, there have been speculative assertions that the earthside experiments mimic or simulate responses which one may expect to see with exposure to micro or zero gravity conditions. The topics focused on at least three areas that appear to be amenable to earthside investigations; in addition, they serve as primary areas for flight experimentation. As the result of animal and human exposures to microgravity experienced during orbital space flight, there is ample evidence of pathophysiological functional and structural alterations in muscle, bone, cardiovascular and related body fluid shift responses. This Animal Model Workshop represents the first of a series of sessions planned for further meetings of the IUPS Commission on Gravitational Physiology.

Animals↗
PubMed1984

Analysis of 1- and 3-methylhistidines, aromatic and basic amino acids in rat and human urine.

A procedure based on automated amino acid analysis has been developed to simultaneously quantify 1-methylhistidine (1-MH), 3-methylhistidine (3-MH), tyrosine, phenylalanine, tryptophan, lysine, histidine and arginine levels in human and rat urines. Deproteinized urine samples containing amino acids in the range 1-10 nmol were analyzed using single-column methodology with ninhydrin detection. Standard curves produced correlation coefficients greater than or equal to 0.99 with duplicate analyses agreeing to within +/- 1.9%. Quantitative recovery was ensured by using L-alpha-amino-beta-guanidinopropionic acid as an internal standard. Elution was accomplished in less than 90 min at pH 5.7 with sodium citrate buffers at 45 degrees C and 65 degrees C. Since 3-MH in the rat is acetylated at the alpha-amino group, rat, but not human, urine ultrafiltrates required acid hydrolysis prior to analysis. The utility of the technique of analysis of 1-MH and 3-MH in human urine was demonstrated for an adult male on a meat-free diet for 21 days; urinary excretion rates for 3-MH and 1-MH were determined to be 3.06 +/- 0.10 and 0.72 +/- 0.07 mumol/kg body mass/day, respectively. The technique was also used to measure the effect of disuse atrophy of rat skeletal muscle which induced a 40-60% increase in 3-MH. The procedure is also highly suited for measurement of urinary aromatic and/or basic amino acids.

Amino Acids↗
PubMed1984

Comparative physiological and biochemical aspects of hypothermia as a model for hibernation.

It is obvious that research is far from the last chapter in developing a model for natural hibernation. The relationships and comparative mechanisms for thermogenesis and survival in hibernation and experimental hypothermia are still unclear. Yet, two primary areas appear to be most promising, namely, the control of thermogenesis via the glucocorticoids and the specific role of the central nervous system (CNS) in survival of hypothermic subjects and arousal of hibernating subjects. Although there have been several approaches to understanding the role of the CNS in terms of circulation, integrity of the blood-brain barrier (BBB) system, and CNS sites of activity, it may appear that more questions have been raised than have been answered. However, a more optimistic view can also be taken. The development of a laboratory model, using experimental hypothermia for natural hibernation, is progressing. This view is justified in terms of results from the use of glucocorticoids in metabolic regulation of available carbohydrates, i.e., available glucose in hypothermia, and the continued promising parallel studies of physiological and biochemical integrity of areas of the CNS in hypothermic and hibernating subjects.

Adaptation, Physiological↗
PubMed1984

Effect of hypokinesia and hypodynamia on protein, RNA, and DNA in rat hindlimb muscles.

Weightlessness is associated with a differential atrophic effect on skeletal muscle that has been attributed to both hypokinesia and hypodynamia. A suspension technique was developed to simulate this atrophic effect by inducing hypokinesia/hypodynamia (H/H) in the rat hindlimb. The purpose of the present studies was to assess the effects of H/H on protein, RNA, and DNA contents in hindlimb skeletal muscles. Suspended animals exhibited a differential reduction in absolute muscle protein content with some alterations in protein concentration. Absolute DNA levels did not change in atrophic muscles. There were pronounced effects of suspension on DNA concentration and on protein/DNA, which suggests that muscle atrophy was accompanied by a reduction in muscle cell size. Hindlimb H/H was associated with a decreased absolute content of RNA in atrophic muscles as well as reductions in RNA/DNA. RNA concentration was reduced 16-21% in atrophic muscles. These findings document a pronounced and differential effect of suspension on hindlimb muscle protein and suggest the potential for effects on the capacity for protein synthesis in muscles from suspended animals.

Animals↗
PubMed1984

Effect of antiorthostatic suspension on interferon-alpha/beta production by the mouse.

Mice were suspended in a model that simulates weightlessness that occurs during prolonged space flight. After 1 and 2 weeks of suspension in an antiorthostatic (head-down tilt) position, the mice were challenged with polyriboinosinic-polyribocytidylic acid to induce interferon-alpha/beta. Interferon production was severely reduced in mice that had been suspended. When mice were allowed to recover in cages for a week following removal from suspension, they recovered their full interferon-production capacity. Mice suspended in an orthostatic (horizontal) position did not have their interferon production capabilities affected, which indicates that stress per se was not a major component in the effects of antiorthostatic suspension on interferon induction.

Animals↗
PubMed1984

Thymic involution in the suspended rat model for weightlessness: decreased glucocorticoid receptor concentration.

Hindlimb muscle atrophy, thymic involution and adrenal hypertrophy in rats during spaceflight can be simulated using suspension models. Skeletal muscle and thymus are sensitive to glucocorticoids (GC) and previous studies have demonstrated that muscle atrophy in suspended rats is associated with increased GC receptor concentration. The objectives were to confirm thymic involution during suspension, and determine if involution correlated with increased GC receptor concentration. Seven days of antiorthostatic (AO) suspension of rats produced a significant (P<0.001) reduction in thymic wet weight not associated with an alteration of % water content. GC receptor concentration (pmol/mg protein) decreased 20% (P<0.025) in thymus glands from 7 day AO suspended rats. Suspension, therefore, is associated with involution of the thymus but this is not dependent upon AO positioning. Thymus GC receptor concentrations were depressed in 7 day suspended rats, in contrast with previous observations on skeletal muscle, suggesting that different mechanisms may underlie these responses.

Animals↗
PubMed1984

Cardiovascular and hormonal (aldosterone) responses in a rat model which mimics responses to weightlessness.

Cardiovascular responses and fluid/electrolyte shifts seen during spaceflight have been attributed to cephalad redistribution of vascular fluid. The antiorthostatic (AO) rat (suspended, head-down tilt of 15-20 degrees) is used to model these responses. This study documents that elevated blood pressures in AO rats are sustained for periods of up to seven days, compared with presuspension values. Increased blood pressures in AO rats suggests a specific response to AO positioning, potentially relatable to a cephalad fluid shift. To assess a role for hormonal regulation of sodium excretion, serum aldosterone levels were measured. Circulating aldosterone concentrations were seen to increase approximately 100% during seven days of AO suspension concurrently with a pronounced natriuresis. These results suggest that aldosterone many not be involved in the long term regulation of increased Na+ excretion in AO animals. These studies continue to show the usefulness of models for the development of animal protocols for space flight.

Adaptation, Physiological↗
PubMed1984

A suspension model for hypokinetic/hypodynamic and antiorthostatic responses in the mouse.

Hypokinetic/hypodynamic and antiorthostatic responses to weightlessness and bedrest were simulated in mice using a suspension technique. Animals were suspended for 1 or 2 weeks in an antiorthostatic posture and positioned to permit freedom of movement but eliminate load bearing by the hindlimbs. Suspended mice exhibited reduced food and water intakes and rapid 10% decrease in body weight to a level which was maintained for the remainder of the suspension period. Diuresis was evident in suspended mice, but the natriuresis and kaliuresis previously observed in the suspended rat were not evident. Differential hindlimb muscle atrophy (soleus greater than plantaris = gastrocnemius greater than EDL) and increased excretion of urea and ammonia were also noted in suspended mice. Postsuspension recovery studies indicated that the recovery process was highly effective. These results document specific responses to hypokinesia/hypodynamia and antiorthostasis in the mouse and demonstrate similarities in the responses of mice and rats to suspension. These studies expand the utility of the suspension model and suggest that the mouse may be useful in future studies simulating both weightlessness and bedrest.

Adrenal Glands↗
PubMed1983

Rat hindlimb muscle responses to suspension hypokinesia/hypodynamia.

Hypokinetic/hypodynamic (H/H) whole body suspension of rats eliminates hindlimb load bearing functions while permitting continued use of the forelimbs. Responses of hindlimb muscles were assessed in terms of absolute and relative weights during 1 and 2 weeks of H/H suspension. Muscle mass loss was in the order soleus greater than gastrocnemius = plantaris greater than extensor digitorum longus (EDL). The soleus, a postural antigravity muscle composed mainly of slow twitch fibers, was most sensitive, losing 35% and 45% of its weight during the first and second weeks, respectively. The gastrocnemius and plantaris showed losses during the first week but no significant loss during the second week. The EDL showed little or no weight loss. During post suspension recovery all muscles showed a weight gain. H/H suspended rats failed to grow; following removal from suspension they gained weight linearly, comparable to controls. Products of muscle metabolism including urea, ammonia, and 3-methylhistidine increased in the urine during H/H suspension and were significantly reduced approaching control levels during recovery. This suspension model offers considerable promise for comparison with H/H responses during weightlessness.

Ammonia↗
PubMed1980

A model for hypokinesia: effects on muscle atrophy in the rat.

Hypokinesia in the hindlimbs of rats were induced by suspension; a newly developed harness system was used. The animal was able to use its forelimbs to maneuver, within a 140 degrees arc, to obtain food and water and to permit limited grooming of the forequarters. The hindlimbs were nonload bearing for 7 days; following a 7-day period of hypodynamia, selected animals were placed in metabolic cages for 7 days to study recovery from hypokinesia. During the 7-day period of hypokinesia there was evidence of muscle atrophy. Gastrocnemius weight decreased, renal papillary urea content increased, and daily urinary losses of urea, NH3, and 3-methylhistidine increased. During the 7-day recovery period muscle mass and excretion rate of urea, NH3 and 3-methylhistidine returned to control levels. Calcium balance was positive throughout the 7-day period of hypokinesia. Hypertrophy of the adrenals suggested the occurrence of some level of stress despite the apparent behavioral adjustment to the suspension harness. It was concluded that significant muscle atrophy and parallel changes in nitrogen metabolism occur in suspended rats and these changes are readily reversible.

Ammonia↗