Clinical effects and treatment outcomes of long-term compulsory in-patient treatment of treatment-resistant patients with severe mental illness and substance-use disorder.

BACKGROUND: The treatment of homeless dual-diagnosis patients (i.e., those with severe mental illness and substance-use disorder) is difficult and often fails. For patients in the Netherlands who had not responded to earlier voluntary and compulsory treatment, a new treatment facility - Sustainable Residence (SuRe) - was developed to offer long-term compulsory in-patient treatment. AIM OF THE STUDY: To study patterns of changes in clinical and functional outcomes during treatment at SuRe and how these relate to eventual treatment outcome. METHODS: On the basis of the intensity of care needed after four years, three groups of patients were distinguished (total n = 165): those discharged to a less restrictive and less supportive setting (n = 70, 42%), those still hospitalized at SuRe at the end of the four-year study period (n = 69, 42%) and those referred to a more appropriate setting (n = 26, 16%). Random coefficient analysis was used to examine differences between groups regarding changes in clinical and functional outcomes during treatment. During treatment, outcomes were monitored using Routine Outcome Assessment. RESULTS: All three groups made small but significant improvements on global psychosocial functioning, distress and therapeutic alliance (effect sizes (ES) 0.11 to 0.16 per year). Patients who were discharged to a less restrictive setting showed small to moderate improvement in risk to self and others, psychiatric symptoms, and skills for daily living (ES 0.19-0.33 per year and 0.42-0.73 for their mean 2.2-year treatment period). Patients remaining at SuRe showed a small increase in risk to self (ES 0.20 per year; 0.80 for their treatment period of four years or more). Oppositional behaviour was consistently greater in referred patients than in the other groups (ES 0.74-0.75). CONCLUSION: Long-term compulsory treatment appeared to have helped improve clinical and functional outcomes in a substantial proportion (42%) of previously severely dysfunctional, treatment-resistant dual-diagnosis patients, who could then be discharged to a less restrictive and less supportive environment. However, risk-to-self increased in a similar proportion. A smaller number of patients (16%) showed marked oppositional behaviour and needed a higher level of care and protection in another facility.

Ubiquitin-proteasome-dependent proteolytic activity remains elevated after zymosan-induced sepsis in rats while muscle mass recovers.

We studied the role of the ubiquitin-proteasome system in rat skeletal muscle during sepsis and subsequent recovery. Sepsis was induced with intraperitoneal zymosan injections. This model allows one to study a sustained and reversible catabolic phase and mimics the events that prevail in septic and subsequently recovering patients. In addition, the role of the ubiquitin-proteasome system during muscle recovery is poorly documented. There was a trend for increased ubiquitin-conjugate formation in the muscle wasting phase, which was abolished during the recovery phase. The trypsin- and chymotrypsin-like peptidase activities of the 20S proteasome peaked at day 6 following zymosan injection (i.e. when both muscle mass and muscle fiber cross-sectional area were reduced the most), but remained elevated when muscle mass and muscle fiber cross-sectional area were recovering (11 days). This clearly suggests a role for the ubiquitin-proteasome pathway in the muscle remodeling and/or recovery process. Protein levels of 19S complex and 20S proteasome subunits did not increase throughout the study, pointing to alternative mechanisms regulating proteasome activities. Overall these data support a role for ubiquitin-proteasome dependent proteolysis in the zymosan septic model, in both the catabolic and muscle recovery phases.

Skeletal Muscle wasting and contractile performance in septic rats.

We investigated the temporal effects of sepsis on muscle wasting and function in order to study the contribution of wasting to the decline in muscle function; we also studied the fiber-type specificity of this muscle wasting. Sepsis was induced by injecting rats intraperitoneally with a zymosan suspension. At 2 h and at 2, 6, and 11 days after injection, muscle function was measured using in situ electrical stimulation, Zymosan injection induced severe muscle wasting compared to pair-fed and ad libitum fed controls. At 6 days, isometric force-generating capacity was drastically reduced in zymosan-treated rats. We conclude that this was fully accounted fo by the reduction of muscle mas. At day 6, we also observed increased activity of the 20S proteasome in gastrocnemius but not soleus muscle from septic rats. In tibialis anterior but not in soleus, muscle wasting occurred in a fiber-type specific fashion, i.e., the reduction in cross-sectional area was significantly smaller in type 1 than type 2A and 2B/X fibers. These findings suggest that both the inherent function of a muscle and the muscle fiber-type distribution affect the responsiveness to catabolic signals.

Increased muscle fatigability in GLUT-4-deficient mice.

GLUT-4 plays a predominant role in glucose uptake during muscle contraction. In the present study, we have investigated in mice whether disruption of the GLUT-4 gene affects isometric and shortening contractile performance of the dorsal flexor muscle complex in situ. Moreover, we have explored the hypothesis that lack of GLUT-4 enhances muscle fatigability. Isometric performance normalized to muscle mass during a single tetanic contraction did not differ between wild-type (WT) and GLUT-4-deficient [GLUT-4(-/-)] mice. Shortening contractions, however, revealed a significant 1.4-fold decrease in peak power per unit mass, most likely caused by the fiber-type transition from fast-glycolytic fibers (IIB) to fast-oxidative fibers (IIA) in GLUT-4(-/-) dorsal flexors. In addition, the resting glycogen content was significantly lower (34%) in the dorsal flexor complex of GLUT-4(-/-) mice than in WT mice. Moreover, the muscle complex of GLUT-4(-/-) mice showed enhanced susceptibility to fatigue, which may be related to the decline in the muscle carbohydrate store. The significant decrease in relative work output during the steady-state phase of the fatigue protocol suggests that energy supply via alternative routes is not capable to compensate fully for the lack of GLUT-4.

Impaired muscular contractile performance and adenine nucleotide handling in creatine kinase-deficient mice.

Creatine kinase (CK) forms a small family of isoenzymes playing an important role in maintaining the concentration of ATP and ADP in muscle cells. To delineate the impact of a lack of CK activity, we studied contractile performance during a single maximal tetanic contraction and during 12 repeated tetanic contractions of intact dorsal flexors of CK knockout (CK(-/-)) mice. To investigate the effect on ATP regeneration, muscular high-energy phosphate content was determined at rest, immediately after the contraction series, and after a 60-s recovery period. Maximal torque of the dorsal flexors was significantly lower in CK(-/-) mice than in wild-type animals, i.e., 23.7 +/- 5.1 and 33.3 +/- 6.8 mN. m. g(-1) wet wt, respectively. Lower muscle ATP (20.1 +/- 1.4 in CK(-/-) vs. 28.0 +/- 2.1 micromol/g dry wt in controls) and higher IMP (1.2 +/- 0.5 in CK(-/-) vs. 0.3 +/- 0.1 micromol/g dry wt in controls) levels at the onset of contraction may contribute to the declined contractility in CK(-/-) mice. In contrast to wild-type muscles, ATP levels could not be maintained during the series of 12 tetanic contractions of dorsal flexors of CK(-/-) mice and dropped to 15.5 +/- 2.4 micromol/g dry wt. The significant increase in tissue IMP (2.4 +/- 1.1 micromol/g dry wt) content after the contraction series indicates that ATP regeneration through adenylate kinase was not capable of fully compensating for the lack of CK. ATP regeneration via the adenylate kinase pathway is a likely cause of reduced basal adenine nucleotide levels in CK(-/-) mice.

Influence of exercise and menstrual cycle phase on plasma homocyst(e)ine levels in young women--a prospective study.

Plasma total homocysteine (tHcy) has been identified as an independent risk factor for cardiovascular diseases (CVD). The difference in tHcy between the sexes has most often been related to the sex hormones, but also to a higher muscle mass in men. The purpose of this study was to assess the effects of acute exercise, brief exhaustive training, and menstrual cycle phase on circulating plasma tHcy concentrations. Fifteen untrained eumenorrheic women (mean age [+/-SD]: 18.7+/-0.4 yr, body fat: 25.8+/-3.4%, VO2max: 43.8+/-2.3 ml x kg(-1) x min(-1)) volunteered for the present study, which covered two menstrual cycles. During the second cycle the subjects participated in two exhaustive 5-day training programs on a cycle ergometer: one in the follicular (FPh) and one in the luteal phase (LPh). Pre- and posttraining plasma tHcy and total estrogen (E) responses were determined in blood samples obtained immediately before, during and immediately after incremental exercise to exhaustion. tHcy levels showed a large between-subject variation, but differences between FPh and LPh levels were consistent (P=0.063). Mean tHcy levels at rest were 9.44+/-1.65 micromol/L and 8.93+/-1.71 micromol/L during the FPh and LPh, respectively. Brief exhaustive training did not elicit any changes in plasma tHcy concentrations, although posttraining LPh E levels were lower (P<0.01). Overall, the differences between FPh and LPh values for tHcy and E were attenuated by training. Acute exercise increased plasma tHcy concentrations (P<0.001). At exhaustion, tHcy levels increased by 17% and 16% during the FPh and LPh, respectively. This was also significantly above tHcy levels at submaximal exercise (P=0.044). After a short period of training tHcy levels did not increase as much during acute exercise as they did before training; however, the increments were still significant (P=0.048). In conclusion, acute exercise in women produces significant increases in plasma tHcy concentrations, whereas brief exhaustive training does not significantly alter plasma tHcy levels. Our findings also suggest that plasma tHcy concentrations are menstrual cycle phase-dependent and that there is a close association between estrogen status and tHcy levels.

Responsiveness of plasma 2- and 4-hydroxycatecholestrogens to training and to graduate submaximal and maximal exercise in an untrained woman. Interuniversity Project on Reproductive Endocrinology in Women and Exercise.

A single-subject experimental design was used to obtain some preliminary findings on the plasma responses of catecholestrogens (CE) to acute exercise and brief, but exhaustive training on a cycle ergometer. One previously untrained eumenorrheic female (body fat: 26% VO2max: 43.3 ml x kg(-1) x min[-1]) participated in this study. Resting CE levels were for "total" (unconjugated + conjugated) 2-hydroxyestrogens (2-OHE) 162pg/ ml and 350 pg/ml in the follicular (FPh) and luteal phase (LPh), respectively. Plasma total 4-hydroxyestrogen (4-OHE) levels were 41 pg/ml in the FPh and 66 pg/ml in the LPh. For "total" 2-methoxyestrogens (2-MeOE), we found 257 pgl/ml in the FPh and 374 pg/ml in the LPh. Resting levels of 2-hydroxy CE following a period of brief, intensive training were decreased during the LPh (2-OHE: -38%; 2-MeOE: -19%), whereas 4-hydroxy CE were unaffected. After training, the formation of CE as expressed by the 2-OHE:E and 4-OHE:E ratios, was increased by 75% and 200% at rest, respectively. CE activity or O-methylation, as estimated from the 2-MeOE:2-OHE ratio, was higher following training (FPh: +22%; LPh: +30%). During acute exercise before training, we observed a small rise proportional to the exercise intensity in the plasma "total" primary estrogen concentrations (FPh: +28%; LPh: +16%), and no changes in either 2-OHE or 2 MeOE levels. Plasma concentrations of 4-OHE, however, doubled during maximal exercise intensity. The 2-OHE:E and 2-MeOE:2-OHE ratios did not alter during incremental exercise. Training effects on acute exercise responses were only noticed for 4-OHE, which contrary to pre-training conditions, now progressively decreased. The major findings of this study are that in response to training: a) during rest, a greater proportion of CE are formed from a lower amount of precursor hormone, b) the rate of O-methylation of CE increases.

Responses of catecholestrogen metabolism to acute graded exercise in normal menstruating women before and after training.

It has been hypothesized that exercise-related hypo-estrogenemia occurs as a consequence of increased competition of catecholestrogens (CE) for catechol-O-methyltransferase (COMT). This may result in higher norepinephrine (NE) concentrations, which could interfere with normal gonadotropin pulsatility. The present study investigates the effects of training on CE responses to acute exercise stress. Nine untrained eumenorrheic women (mean percentage of body fat +/-SD: 24.8 +/- 3.1%) volunteered for an intensive 5-day training program. Resting, submaximal, and maximal (tmax) exercise plasma CE, estrogen, and catecholamine responses were determined pre- and post training in both the follicular (FPh) and luteal phase (LPh). Acute exercise stress increased total primary estrogens (E) but had little effect on total 2-hydroxyestrogens (2-OHE) and 2-hydroxyestrogen-monomethylethers (2-MeOE) (= O-methylated CE after competition for catechol-O-methyltransferase). This pattern was not significantly changed by training. However, posttraining LPh mean (+/-SE) plasma E, 2-OHE, and 2-MeOE concentrations were significantly lower (P < 0.05) at each exercise intensity (for 2-OHE: 332 +/- 47 vs. 422 +/- 57 pg/mL at tmax; for 2-MeOE: 317 +/- 26 vs. 354 +/- 34 pg/mL at tmax). Training produced opposite effects on 2-OHE:E ratios (an estimation of CE formation) during acute exercise in the FPh (reduction) and LPh (increase). The 2-MeOE:2-OHE ratio (an estimation of CE activity) showed significantly higher values at tmax in both menstrual phases after training (FPh: +11%; LPh: +23%; P < 0.05). After training, NE values were significantly higher (P < 0.05). The major findings of this study were that: training lowers absolute concentrations of plasma estrogens and CE; the acute exercise challenge altered plasma estrogens but had little effect on CE; estimation of the formation and activity of CE suggests that formation and O-methylation of CE proportionately increases. These findings may be of importance for NE-mediated effects on gonadotropin release.

4-Hydroxycatecholestrogen metabolism responses to exercise and training: possible implications for menstrual cycle irregularities and breast cancer.

OBJECTIVE: To investigate the behavior of C4-substituted estrogens, the so-called catecholestrogens, in response to acute exercise and training. The 4-hydroxyestrogens are known to have both a strong estrogenic potency and affinity for catechol-O-methyltransferase (COMT), the enzyme that deactivates catecholamines. DESIGN: A prospective trial covering three menstrual cycles: a control cycle, a moderate training cycle, and a heavy training cycle. PARTICIPANT(S): Six untrained, healthy, eumenorrheic women (mean pretraining maximum oxygen uptake: 40.9 +/- 4.9 mL/kg per minute, body fat: 27.9% +/- 3.6%) volunteered for this study. INTERVENTION(S): An incremental exercise test to exhaustion on a cycle ergometer, in the follicular and luteal phases, before and after a brief but exhaustive training program. MAIN OUTCOME MEASURE(S): Hormone measurements included follicular and luteal phase plasma E2, LH, catecholamines, PRL, total unconjugated and conjugated estrogens, total 4-hydroxyestrogens (4-OHE), and 4-hydroxyestrogen-monomethylethers (4-MeOE). RESULT(S): Pretraining baseline 4-OHE levels were significantly higher in the luteal phase (66 +/- 9 pg/mL; mean +/- SEM) than in the follicular phase (51 +/- 7 pg/mL). Pretraining and post-training baseline 4-MeOE values were below minimal detection limits (< 35 pg/mL). During incremental exercise, catecholamines, PRL, E2, unconjugated and conjugated estrogens, 4-OHE, and 4-MeOE always increased (the increases in 4-OHE during exercise were more pronounced before training, contrary to the 4-MeOE being most increased after training). The baseline 4-MeOE:4-OHE ratio (a measure of catecholestrogen activity) significantly increased with progressive training. CONCLUSION(S): Because 4-OHE have been shown to be able to control the hypothalamic gonadotropin oscillator and to stimulate the luteolytic prostaglandin PGF2 alpha, the acute exercise-induced increases of 4-OHE and their positive correlation with lactate levels may indicate a key process in the pathogenesis of exercise-associated menstrual irregularities. In addition, 4-OHE, when insufficiently O-methylated, are known to be capable of raising mutagenic superoxide free radicals and causing DNA damage that may lead to breast cancer. The results of the present study also may be of significance for the apparent protective effects of sports participation against cancer of the breast.

Plasma 2-hydroxycatecholestrogen responses to acute submaximal and maximal exercise in untrained women.

Exercise-induced menstrual problems are accompanied by an increase in catecholestrogen (CE) formation. It has been hypothesized that hypoestrogenemia may be secondary to an increased turnover from estrogens to CE, which then may disrupt luteinizing hormone release. In addition, the strong affinity of CE for the catecholamine-deactivating enzyme catechol-O-methyltransferase (COMT) has led to speculations about their possible role in safeguarding norepinephrine from premature decomposition during exercise. We investigated whether acute exercise on a cycle ergometer produces any changes in CE homeostasis. Nine untrained eumenorrheic women (body fat, 24.8 +/- 3.1%) volunteered for this study. Baseline plasma CE averages for total 2-hydroxyestrogens (2-OHE) were 218 +/- 29 (SE) pg/ml during the follicular phase (FPh) and 420 +/- 58 pg/ml during the luteal phase (LPh). 2-Methoxyestrogens (2-MeOE) measured 257 +/- 17 pg/ml in the FPh and 339 +/- 39 pg/ml in the LPh. During incremental exercise, total estrogens (E) increased, but 2-OHE and 2-MeOE levels did not significantly change in either phase. The 2-OHE/E ratio (measure of CE turnover) decreased during exercise in both menstrual phases, whereas the 2-MeOE/2-OHE ratio (correlates with COMT activity) did not significantly change. These findings suggest that there is insufficient evidence to conclude that brief incremental exercise in untrained eumenorrheic females acutely produces increased CE formation.

Effects of a training program on resting plasma 2-hydroxycatecholestrogen levels in eumenorrheic women.

Catecholestrogens (CE) represent a major metabolic pathway in estrogen metabolism. Previous information on CE and training is limited to two cross-sectional studies that did not involve standardized training. Our purpose, by means of a prospective design, was to evaluate the effects of a brief, exhaustive training program on resting plasma concentrations of 2-hydroxy CE. The experimental design spanned two menstrual cycles; a control cycle and a training cycle. The subjects were nine previously untrained, eumenorrheic women [body fat: 24.8 +/- 1.0 (SE) %]. Data were collected during the follicular (FPh) and the luteal phases (LPh). Posttraining FPh and LPh tests were held the day after the last day of a 5-day period of training on a cycle ergometer. Total 2-hydroxyestrogens (2-OHE) averaged 200 +/- 29 pg/ml during the FPh and 420 +/- 54 pg/ml during the LPh (P < 0.05). Levels of total 2-methoxyestrogens (2-MeOE) were 237 +/- 32 pg/ml during the FPh and 339 +/- 26 pg/ml during the LPh (P < 0.05). After training, although the plasma levels of 2-OHE significantly decreased (21%; P < 0.05) during the LPh, the actual CE formation (as estimated from the 2-OHE-to-total estrogens ratio) increased (+ 29%; P < 0.05). CE activity, as expressed by the 2-MeOE-to-2-OHE ratio, showed significantly higher values in both phases (FPh, + 14%; LPh, + 13%; P < 0.05). At the same time, resting levels of norepinephrine (NE) were increased by 42% (P < 0.05). CE strongly inhibit biological decomposition of NE by catechol-O-methyltransferase (COMT). Results of the present study suggest that, in response to training, CE are increasingly competing with the enzyme COMT, thus preventing premature NE deactivation.

Exercise-induced changes in enzymatic O-methylation of catecholestrogens by erythrocytes of eumenorrheic women.

The present study was designed to assess the effects of acute exercise and short-term intensive training on catechol-O-methyltransferase (COMT) activity. COMT inactivates catecholamines and converts primary catecholestrogens (CE) into their O-methylated form yielding the 2- (2-MeOE) and 4-methoxyestrogens (4-MeOE). Blood samples were obtained from 15 previously untrained eumenorrheic women (mean +/- SE, VO2max: 43.8 mL x kg-1 x min-1 +/- 0.6) before and after a 5-d intensive training period, at rest and during incremental exercise. COMT activity was determined in the erythrocytes (RBC-COMT) after incubation of blood lysate with primary CE. The formation of both 2- and 4-MeOE was significantly higher (P < 0.05) during the luteal (LPh) than during the follicular phase (FPh). The amount of 2-MeOE formed (FPh: 4.2 +/- 0.2%; LPh: 4.9 +/- 0.2%) was significantly greater than the produced amount of 4-MeOE (FPh: 1.4 +/- 0.1%; LPh: 1.5 +/- 0.1%) (P < 0.05). Both before and after training, incremental exercise did not significantly alter RBC-COMT activity although we observed a trend for RBC-COMT activity increasing proportionally with the exercise intensity. After a brief period of exhaustive training, during rest the formation of 2-MeOE (FPh: +16.7%, LPh: +15.7%) and 4-MeOE (FPh: +28.6%; LPh: +40%) was significantly (P < 0.05) increased. The results of the present study are consistent with earlier findings reporting increased plasma concentrations of O-methylated CE following training. It is concluded that RBC-COMT activity is increased by brief intensive training, but not by acute exercise. We speculate that an increase in COMT-catalyzed O-methylation of CE may indicate that less COMT is available to deactivate norepinephrine.

Modulation of glycogen metabolism of rat skeletal muscles by endurance training and testosterone treatment.

The effects of training and/or testosterone treatment on glycogen content and the activities of glycogen synthase, glycogen phosphorylase, and fructose-6-phosphate kinase were studied in extensor digitorum longus (EDL) and soleus muscles of intact adult female rats. One group of rats remained sedentary, whereas another group was trained for 7 weeks. Thereafter, both the sedentary and trained rats were subdivided into two control and four testosterone-treated subgroups. Testosterone was administered by a silastic implant. Training was continued for 2 weeks. On the final day of the experiment rats from one trained control and one trained testosterone-treated subgroup ran for 60 min submaximally. Upon testosterone treatment of sedentary rats the glycogen concentration was not changed. However, in the soleus, but not in the EDL, the glycogen content was increased by training (P < 0.05) which could, at least partly, be explained by a decrease in activity of active glycogen phosphorylase (P < 0.05). In the EDL of trained rats testosterone treatment increased glycogen content significantly by both an increase in activity of active glycogen synthase and a decrease in activity of active glycogen phosphorylase (P < 0.05). In the EDL and soleus of testosterone-treated animals from the exercised subgroup a significant sparing of glycogen was observed, which could be explained by an increase in activity of active glycogen synthase and, in the soleus, could also be explained by a concerted decrease in active glycogen phosphorylase (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise-induced changes in the percentage of free testosterone and estradiol in trained and untrained women.

We have studied the effect of exercise on the percentage of free plasma estradiol 17-beta (E2) and testosterone (T) in 13 untrained (UT) and 8 trained (marathon runners, MR) eumenorrheic women. All women performed a standardized bicycle ergometer (UT) or treadmill (MR) test in the follicular and luteal phases of their menstrual cycles (15-min consecutive work loads of 60%, 70%, and 80% VO2 max to exhaustion). Blood was drawn through an indwelling venous catheter at 15 and 2 min before and immediately after exercise. Free E2 and T was assayed by centrifugal ultrafiltration using undiluted plasma at 37 degrees C (basal samples) and 39 degrees C (exercise samples). Statistical analysis was performed by a two-tailed paired t test. In the UT, the basal percentage of free E2 was measured to be 1.55% +/- 0.24% (mean +/- SD) in the follicular phase and 1.62% +/- 0.32% in the luteal phase (differences NS). In the MR, these values were 1.22% +/- 0.25% and 1.25% +/- 0.12% for the follicular and luteal phases, respectively. The differences between the groups were not significant. Exercise did not provoke significant changes in free E2 in either of the groups. Constrastingly, exercise induced a significant (P less than 0.02) increase in the percentage of free T from 1.56% +/- 0.27% to 2.1% +/- 0.36% and from 1.6% +/- 0.27% to 2.12% +/- 0.33% in the UT in the follicular and luteal phases, respectively. In the MR, the free percentage of T increased from 1.04% +/- 0.39% to 1.6% +/-0.16% (follicular phase) and from 1.24% +/- 0.22% to 1.67% +/- 0.18% (P less than 0.02).

Effect of a 3-month endurance training program on metabolic and multiple hormonal responses to exercise.

We have investigated the effect of a 3-month endurance training program (running and cycling) on plasma hormone responses during standardized bicycle ergometer work (15-min consecutive work loads of 60%, 70%, 80%, and eventually 90% VO2 max) in eight previously untrained eumenorrheic women. The subjects were investigated before and after training both in the follicular and luteal phases of the menstrual cycle (between the 7th-10th and 20th-25th days of their menstrual cycle, respectively). Blood was obtained 15 and 2 min before the onset of exercise and at the end of each work load from an indwelling catheter. In each sample, the plasma concentrations of estradiol 17 beta (E2), progesterone (P), testosterone (T), androstenedione (delta 4-A), dehydroepiandrosterone sulfate (DHEA-S), prolactin (PRL), and adrenocorticotropic hormone (ACTH) were assayed in duplicate by RIA; lactate was assayed as well. The hormone concentrations were expressed in absolute as well as in relative values. After training basal DHEA-S and ACTH levels were significantly (P less than 0.05) lower in both phases of the menstrual cycle, whereas basal luteal phase E2 and T levels were significantly (0.05 greater than P greater than 0.01) lower after training. Exercise induced significant increments in the relative values of all hormones in both phases (0.05 greater than P greater than 0.001). After training, T and DHEA-S increased relatively more pronounced (0.05 greater than P greater than 0.02) in the follicular and luteal phase, respectively.

Influence of liquid and solid meals on muscle glycogen resynthesis, plasma fuel hormone response, and maximal physical working capacity.

The effect of forced liquid (L) or solid (S) carbohydrate (CHO)-rich feedings on plasma glucose, insulin, and glycogenesis after glycogen depletion was investigated. The relationship between glycogen restoration and maximal physical working capacity (MPWC) was studied as well. Eight males performed two experiments, with 2 weeks interval, on a bicycle ergometer. In each experiment, MPWC was determined in a graded test, which was immediately followed by interval work until exhaustion. After exercise cessation (EC), the subjects started to consume a standardized amount of concentrated L or CHO-rich food. Insulin and glucose concentration in blood were determined. Muscle glycogen was determined before, immediately after, 5 h after, and 22 h after EC. MPWC was determined again 22 h after EC. Four subjects performed a third experiment, in which solid food consumption was left ad libitum (AL). A rapid glycogen repletion was found 5 h after EC, i.e., from 72 +/- 40 to 198 +/- 38 mmol/kg in the S, and from 69 +/- 39 to 192 +/- 40 mmol/kg in the L experiment. The higher plasma glucose and insulin levels (P less than 0.05) during the 5 h after EC in the S experiments did not elicit a difference in glycogen repletion. Glycogen synthesis rate in the AL experiment was lower (P less than 0.05) than in the L and S experiments. Glycogen restoration in the L and S experiments was complete 22 h after depletion. However, despite repletion of glycogen, MPWC was decreased (P less than 0.05) in both experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Variability of aerobic performance in the laboratory and its physiologic correlates.

To study the physiologic basis of variability of physical performance in the laboratory, ten male subjects were studied once a week, during a 9-12 month period. Previously, the reference maximal work load attained (Wref) was determined in each subject. The test protocol of the actual study was based on the individual Wref and started at 70% Wref for 5 min whereupon the work load was increased by 5% Wref every 2.5 min to exhaustion. The maximal work load attained (Wmax) was considered as the test performance. Heart rate, respiratory variables, oxygen uptake (VO2), and blood lactate concentration were determined at each work load. The rate of perceived exertion during submaximal and maximal work was also scored. In all subjects, Wmax and VO2max varied randomly, while the coefficient of variation in VO2max (4.20% - 11.35%) exceeded that in Wmax (2.95%-6.83%). No seasonal influences on VO2 max and Wmax were observed. In all subjects the physiologic variables, when plotted as a function of external work load, were shifted to the right with higher Wmax values and to the left with lower Wmax values. With lower Wmax values, the rate of perceived exertion during submaximal work tended to increase. The results suggest that the magnitude of physiologic responses to exercise is related to relative work load and that variability of physical performance is related to changes in gross mechanical efficiency.

Muscle degeneration after exercise in rats.

To search for morphological changes in muscle, related to overuse syndromes of muscle due to exercise, groups of untrained rats ran on a treadmill for 1 h at submaximal intensity. Each group was sacrificed at a different interval after the end of the exercise. To evaluate the physiologic load, the colonic temperature and blood lactate level were determined. The right hindlimb was fixated with buffered glutaraldehyde, injected into the femoral artery, and different muscles were dissected and prepared for electron and light microscopy. The muscles of the left limb were frozen in liquid Freon and used for histochemistry. Signs of degeneration were noted in the soleus, rectus femoris, and vastus lateralis muscles, but were absent in the gastrocnemius, tibialis anterior, extensor digitorum, and biceps femoris muscles. Immediately after exercise, only minor signs of degeneration were observed at the ultrastructural level, while after 2-3 h degeneration became clearly visible at the light microscopic level. The most pronounced changes were observed 24-48 h after exercise, whereafter regeneration occurred. Only 2%-5% of all fibers in the soleus muscle showed signs of degeneration, while in the vastus lateralis and rectus femoralis muscle less than 0.5% of the fibers were affected. The affected fibers showed degeneration only in segments with a length between 150-1250 micrometers. The affected fibers in the soleus and vastus lateralis muscles belong to the type I population, while in the rectus femoris type I as well as type II fibers were affected.