Effect of exercise on natural cytotoxicity and pulmonary tumor metastases in mice

Exercise has been demonstrated to reduce experimental tumor formation in rodents when the exercise is present during the tumor initiation or promotion phases. This study evaluated whether exercise influenced the process of tumor metastasis and subsequent growth in a secondary implant site. Male C3H mice remained sedentary, were given free access to running wheels, ran on a treadmill (15 m.min-1, 30 min.d-1), or walked on a treadmill (5 m.min-1, 5 min.d-1)(N = 20/group). Following 9 wk of this protocol, exercise was discontinued. At this time all animals received a tumor cell dose (CIRAS 1, 3 x 10(5)) i.v., and remained sedentary until sacrificed 3 wk later. Splenic natural killer (NK) cell activity was elevated in the wheel running mice compared with sedentary controls 3 wk after cessation of exercise (F(3,74) = 6.266, P < 0.002). Exercised mice displayed lower tumor cell retention in the lungs relative to nonexercised mice (F(1,37) = 6.593, P < 0.02). Tumor incidence was not different across activity groups whereas tumor multiplicity was higher in mice that had been previously exposed to exercise. (However, it should be noted that the significant exercise-tumor effect was due to a small number of exercised mice with extreme multiplicity, > 200 foci/lung.) More extensive tumor colony formation was present in wheel-trained mice that displayed the greatest volumes of daily running. The results from this study suggest that exercise was able to augment natural immune cytotoxic function for up to 3 wk after cessation of activity. However, this augmentation of natural immune function was not associated with reduced tumor incidence in the exercised animals.     

Effect of hyperthermia on the radiosensitivity of normal and malignant cells in mice

The effect of systemic hyperthermia on the in vivo radiation response of normal and malignant mouse cells was evaluated. X-irradiation of L1210 cells and Ehrlich ascites cells at body temperatures above 41 degrees C resulted in strongly enhanced tumor cell death. The magnitude of this thermal effect increased with increasing temperatures. Hypoxic tumor cells were particularly sensitive to combined heat-radiation treatment. L1210 leukemia cells did not become resistant to the sensitizing effects of hyperthermia even after repeated heat exposures over several transplant generations. The sensitizing action of hyperthermia varied with different heating strategies. Heating before or during irradiation did not materially alter the radiation response of tumor cells. Maximal potentiation of radiation damage was achieved only when the tumorous mice were subjected to at least 20 minutes heat incubation after irradiation. LD studies on ICR mice revealed that moderate hyperthermia (41.5 degrees C) does not alter the radiation response of normal body tissues. These findings indicate that it is possible to devise hyperthermic treatment regimens that drastically enhance radiation-induced tumor cell death in vivo without reducing the radioresistance of normal tissues.     

Effects of voluntary exercise on nonspecific immunological mechanisms in mice

We studied the effects of voluntary exercise on nonspecific immunological mechanisms in mice. In this study, 7 week old male ICR mice were divided into two groups: a non-exercise group (control) and a group given voluntary exercise (Vex group). Each mouse of the Vex group was kept in an individual cage equipped with a voluntarily revolving wheel that the mouse had free access to. The duration of voluntary exercise was 3 days per week for 8 weeks. The following results were obtained: 1) After 8 weeks of voluntary exercise, food consumption, the weight of the anterior tibialis muscle and succinate dehydrogenase activity in the anterior tibialis muscle increased significantly in the Vex group compared to the control group. 2) By means of the carbon clearance method, phagocytosis of the reticuloendothelial system was increased in the Vex group. 3) Glucose consumption capacity and O-2 production capacity of peritoneal macrophages (M phi) were significantly increased in the Vex group compared to the control group. 4) The acid phosphatase (APH), beta-glucuronidase (GLU) and lactate dehydrogenase (LDH) activities of peritoneal M phi increased significantly in the Vex group. 5) Concanavalin A (Con A)-induced cell proliferation in the spleen was high in the Vex group. Based on the above findings, it may be surmised that voluntary exercise enhances nonspecific immunological mechanisms and thereby improves the host defense mechanisms in mice.     

Cardiovascular and respiratory adjustments in normal volunteers during modified exercise tests in comparison to standard exercise tests

We investigated the effect of ursodeoxycholic acid on major histocompatibility complex class I gene expression in cultured human hepatoma cells. Ursodeoxycholic acid, which is now being used for the treatment of various autoimmune liver diseases, paradoxically increased the mRNA level of major histocompatibility complex class I. However, endogenous bile acids, for example, chenodeoxycholic acid, increased major histocompatibility complex class I mRNA expression more strongly compared with ursodeoxycholic acid. Concerning the interplay between ursodeoxycholic and chenodeoxycholic acids, these bile acids additively induced major histocompatibility complex class I mRNA expression. In contrast, when the total concentration of ursodeoxycholic and chenodeoxycholic acids was kept constant, the expression of major histocompatibility complex class I mRNA appeared to decrease in a dose-dependent manner with an increasing ratio of ursodeoxycholic acid. These findings indicate that the beneficial action of ursodeoxycholic acid may be related to this relative decrease in major histocompatibility complex class I gene expression.     

Haemodynamics in children during rest and exercise: methods and normal values

Measuring haemodynamic performance in children is either invasive, and thus unacceptable, or noninvasive when the measured variable is often remote from the true variable. Measuring only maximum performance variables relies too heavily on motivation, especially in disease groups. We describe a method for the measurement of haemodynamic performance using respiratory mass spectrometry during rest, exercise and recovery therefrom. One hundred and six healthy children (55 male, 51 female) aged 8-16.9 yrs underwent an identical exercise protocol. Following studies at rest, they initially bicycled at 25 W x m(-2), increasing every 3 min by 15 W x m(-2) until exhaustion, after which measurements were made during recovery. Effective pulmonary blood flow, stroke volume, oxygen consumption, arteriovenous oxygen difference and functional residual capacity (FRC) together with estimates of pulmonary capillary blood volume and transit time were assessed at every exercise stage using inert gas rebreathing techniques. Haemodynamic performance is highly dependent on surface area, age, gender and pubertal stage. Many parameters, for example transfer factor, demonstrate pubertal stage-dependent differences at identical workloads even after correction for size. Females have a lower capillary blood volume at rest compared to age and size-matched males, but it is equalized during exercise. FRC unexpectedly rose with exercise, and peak exercise was associated with a falling stroke volume in 91% (95% CI 84-96%) of children, a possible demonstration of Starling's law of the heart. Oxygen pulse (oxygen consumption/cardiac frequency) is a very poor marker for pulmonary blood flow. Normal values are provided for all haemodynamic parameters for rest and every exercise stage for all subgroups of children. This should allow accurate comparison of normal and disease groups in future.     

Effect of exercise on acid-base status and ventilatory kinetics

OBJECTIVES: To study the clinical spectrum of an acute severe encephalopathy occurring in 2 patients after recovery from falciparum malaria infection and to compare it with the reported clinical features of the postmalaria neurological syndrome. DESIGN: Case report. SETTING: Tertiary care hospital. PATIENTS: Two patients presented with acute onset of fluctuating motor aphasia, severe generalized myoclonus, and postural tremor. Additional signs were cerebellar ataxia, and in 1 patient, generalized epileptic seizures. Magnetic resonance imaging of the brain revealed patchy white matter lesions in 1 patient. Clinically, the patients' conditions continued to worsen until corticosteroids were introduced, the use of which induced a rapid, albeit incomplete, recovery. CONCLUSIONS: We describe a new, severe variant of the still poorly defined postmalaria neurological syndrome. We propose a preliminary classification of this syndrome, according to its clinical characteristics, as follows: a mild or localized form, characterized by isolated cerebellar ataxia or postural tremor; a diffuse, but relatively mild encephalopathic form, characterized by acute confusion or epileptic seizures; and a severe, corticosteroid-responsive encephalopathy that is characterized by motor aphasia, generalized myoclonus, postural tremor, and cerebellar ataxia.     

Protective effect of clentiazem against epinephrine-induced cardiac injury in rats

We investigated the effects of clentiazem, a 1,5-benzothiazepine calcium antagonist, on epinephrine-induced cardiomyopathy in rats. With 2-week chronic epinephrine infusion, 16 of 30 rats died within 4 days, and severe ischemic lesions and fibrosis of the left ventricles were observed. In epinephrine-treated rats, left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced, but responses to calcium were normal or enhanced compared to controls. Left ventricular alpha and beta adrenoceptor densities were also reduced compared to controls. Treatment with clentiazem prevented epinephrine-induced death (P < .05), and attenuated the ventricular ischemic lesions and fibrosis, in a dose-dependent manner. Left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced compared to controls in groups treated with clentiazem alone, but combined with epinephrine, clentiazem restored left atrial responses and enhanced left ventricular papillary responses to isoproterenol. On the other hand clentiazem did not prevent epinephrine-induced down-regulation of alpha and beta adrenoceptors. Interestingly, clentiazem, infused alone, resulted in decreased adrenergic receptor densities in the left ventricle. Clentiazem also did not prevent the enhanced responses to calcium seen in the epinephrine-treated animals, although the high dose of clentiazem partially attenuated the maximal response to calcium compared to epinephrine-treated animals. In conclusion, clentiazem attenuated epinephrine-induced cardiac injury, possibly through its effect on the adrenergic pathway.     

Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs

A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.     

Effect of voluntary exercise and dietary protein levels on the activity of serum glutamic pyruvic transaminase and the morphological picture of liver in mice

In the present investigation, effects of voluntary exercise on serum glutamic pyruvic transaminase (SGPT) activity and histological alterations of liver tissue of mice fed 4%, 6% and 20% casein diet were examined. AGPT activity showed decreasing values accompanied by dietary protein level increases. In 4% casein diet groups, SGPT activity of the exercise group was markedly lower than that of the non-exercise group. Furthermore, there was a negative correlation between SGPT and LCAT activity. In histological evaluation, the non-exercise group on 4% casein diet revealed diffuse fatty degeneration of the liver, but the exercise group did not show such changes.     

Distribution of gallium-67 in normal and hypotransferrinemic tumor-bearing mice

The mechanism by which 67Ga accumulates in tumors is controversial. The most popular theory is that 67Ga binds to transferrin and gains access to cells by the transferrin receptor. However, substantial evidence suggests that uptake of 67Ga may not be universally mediated by transferrin in tumors. To determine whether transferrin is required for uptake of 67Ga in vivo, we compared the uptake of 67Ga by two types of implanted tumors and by normal tissues in normal and severely hypotransferrinemic strains of Balb/C mice. One type of tumor was strongly gallium-avid in normal mice; the other was not. Uptake of 67Ga by normal soft tissues was markedly less in hypotransferrinemic than in normal mice. Uptake of 67Ga by bone was equivalent in the two types of mice. For the more gallium-avid tumor, uptake of 67Ga was similar and the ratio of tumor-to-background activity was substantially higher in the hypotransferrinemic than in the normal mice. For the less gallium-avid tumor, uptake was significantly less in hypotransferrinemic than in normal mice. These data suggest that uptake of 67Ga by bone and by some tumors may be a transferrin-independent process.     

Effect of physical exercise in fibromyalgia

The aim of the present study was to review and discuss the literature on exercise-induced pain and physical fitness training in patients with fibromyalgia. Normal muscle metabolism during exercise and no muscle damage after physical activity are reported from recent studies. However, no rise in blood noradrenaline concentration during exercise was found in fibromyalgia patients as compared with a many-folded rise in healthy subjects. Exercise has been used in the treatment of fibromyalgia. Training has shown little benefit as regards pain, but has improved the physical fitness of the patients. Since pain may be exacerbated by physical activity, many patients become physically inactive, with possible development of reduced physical fitness. In the long run, fibromyalgia patients who exercise report less symptoms than sedentary patients do. Thus, exercise should be aimed at preventing physical inactivity and improving the patients' physical fitness.     

Plasma hormone levels in normal and lead-treated pregnant mice

Dietary lead (0.5%) was given to mice which, after mating, exhibited a vaginal plug. Estradiol, progesterone and prostaglandins E and F 2 alpha were determined in the plasma by radioimmuno assay at different times thereafter. The increase in estradiol and decrease in prostaglandins prior implantation are not greatly altered by lead treatment, whereas the subsequent increase in progesterone and later in estradiol is abolished. It is concluded that the lower number of pregnancies seen in lead-treated mothers is due to a maternal hormonal imbalance caused by lead.     

Predictability, controllability, and fear of symptoms of anxiety in epinephrine-induced panic

BACKGROUND: Psychological manipulations (supplied information, safety cues) may influence panic rates during pharmacologic challenge tests in subjects with panic disorder (PD). Psychological panic models assume that fear of stress-related bodily sensations is central to the etiology of PD. METHODS: Prior to infusion of epinephrine, 50 subjects with PD were randomly assigned to one out of four experimental conditions: with or without extensive information and with or without external control, according to a 2 x 2 design. The panic rate was hypothesized to be lower in subgroups possessing extensive information and/or control. Fear of bodily sensations was used as a predictor. RESULTS: Thirty-four out of 50 patients (68%) panicked during the infusion. Subjects who received extensive information were marginally less likely to panic, but manipulation of control did not influence panic rates. Panickers did not differ from nonpanickers in measures of fear of fear. Anxiety sensitivity best predicted baseline anxiety and cognitive symptom scores, but was not associated with other outcome measures in panickers. Only baseline partial pressure of CO2 discriminated between panickers and nonpanickers. CONCLUSIONS: Manipulating external safety cues appears to be of limited value in modulating responses to epinephrine challenge. Together with our finding that fear of anxiety symptoms does not predict panic rates, these data argue against "fear of fear" as a key mechanism in epinephrine-induced panic.     

Effect of estrogen supplementation on exercise thermoregulation in premenopausal women

This study examined the effects of 3 days of estrogen supplementation (ES) on thermoregulation during exercise in premenopausal (20-39 yr) adult women during the follicular phase of the menstrual cycle. Subjects (11 control, 10 experimental) performed upright cycle ergometer exercise at 60% of maximal O2 consumption in a neutral environment (25 degreesC, 30% relative humidity) for 20 min. Subjects were given placebo (P) or beta-estradiol (2 mg/tablet, 3 tablets/day for 3 days). All experiments were conducted between 6:30 and 9:00 AM after ingestion of the last tablet. Heart rate, forearm blood flow (FBF), mean skin temperature, esophageal temperature (Tes), and forearm sweat rate were measured. Blood analysis for estrogen and progesterone reflected the follicular phase of the menstrual cycle. Maximal O2 consumption (37.1 +/- 6.2 in P vs. 38.4 +/- 6.3 ml. kg-1. min-1 in ES) and body weight-to-surface area ratio (35.58 +/- 2.85 in P vs. 37.3 +/- 2.7 in ES) were similar between groups. Synthesis of 70-kDa heat shock protein was not induced by 3 days of ES. Neither the threshold for sweating (36.97 +/- 0.15 in P vs. 36.90 +/- 0.22 degreesC in ES), the threshold for an increase in FBF (37.09 +/- 0. 22 in P vs. 37.17 +/- 0.26 degreesC in ES), the slope of sweat rate-Tes relationship (0.42 +/- 0.16 in P vs. 0.41 +/- 0.17 in ES), nor the FBF-Tes relationship (10.04 +/- 4.4 in P vs. 9.61 +/- 3.46 in ES) was affected (P > 0.05) by 3 days of ES. We conclude that 3 days of ES by young adult women in the follicular phase of their menstrual cycle have no effect on heat transfer to the skin, heat dissipation by evaporative cooling, or leukocyte synthesis of 70-kDa heat shock protein.     

Effect of pubococcygeal exercise on coital orgasm in women.

16 20–41 yr old female volunteers participated in a study comparing the effects of Kegel exercises to an attention placebo and a waiting-list control condition. All Ss had a low (     

Effect of local exercise and vessel occlusion on fibrinolytic activity

Arterial occlusion of the upper limb did not affect the fibrinolytic activity in the venous blood of that limb; venous occlusion associated with venous distension resulted in a marked rise in activity. Local fibrinolytic activity was increased substantially by active exercise; passive exercise induced a smaller increase. Active exercise undertaken during arterial occlusion did not result in a rise in activator level. It is concluded from these results that blood flow into the venous system rather than accumulation of metabolites is responsible for the increased release of activator into the blood during local exercise and vessel occlusion.