Functional rearrangements in macrophages following intensive physical exercise

The effect of intensive physical exercise (swimming for 3 hours with a load of 4% body weight) on the function of hepatic, pulmonary and peritoneal macrophages has been studied in rats and mice. NBT values in alveolar and peritoneal macrophages of the experimental animals proved to be 1.5 and 1.6 times higher than in the controls. The activity of cathepsin D in the liver, lung and Kupffer cells was greater than the control values. The data obtained indicate that intensive physical exercise caused depression in phagocytic activity of Kupffer cells, the major compartment of the reticuloendothelial system, whereas a similar function in lung macrophages was even greater than in the controls and in peritoneal macrophages changed but insignificantly.     

Importance of the water regimen for animal growth in increased motor activity

Growth rate of male rats exposed to intensive physical exercise and the impact of exercise on the muscle system have been studied. To increase the locomotor activity the animals were kept in higher, as compared to the control, cages with the feeding rack attached to the ceiling. A tendency to an increase in body weight and specifically in gastrocnemius was noted. A reduction in water consumption was shown to slow the growth rate of rats in increased locomotor activity, while in low physical activity water shortage exerted but a negligible effect on the animal growth.     

Physical exercise improves glucose metabolism in lifestyle-related diseases

The beneficial effects of physical exercise on the decreased insulin sensitivity caused by detrimental lifestyle were reviewed based on experimental evidences. In epidemiological studies, disease prevention has been considered at three levels: primary (avoiding the occurrence of disease), secondary (early detection and reversal), and tertiary (prevention or delay of complications). The major purpose of physical exercise for primary prevention and treatment of lifestyle-related diseases is to improve insulin sensitivity. It is known that, during physical exercise, glucose uptake by the working muscles rises 7 to 20 times over the basal level, depending on the intensity of the work performed. However, intense exercise provokes the release of insulin-counter regulatory hormones such as glucagons and catecholamines, which ultimately cause a reduction in the insulin action. Continued physical training improves the reduced peripheral tissue sensitivity to insulin in impaired glucose tolerance and Type II diabetes, along with regularization of abnormal lipid metabolism. Furthermore, combination of salt intake restriction and physical training ameliorates hypertension. In practical terms, before diabetic patients undertake any program of physical exercise, various medical examinations are needed to determine whether they have good glycemic control and are without progressive complications. Because the effect of exercise that is manifested in improved insulin sensitivity decreases within 3 days after exercise and is no longer apparent after 1 week, a continued program is needed. For a safety practice, moderate- or low-intensity exercise is preferable. In conclusion, we have found sufficient evidences that support the theory that, combined with other forms of therapy, mild exercise training increases insulin action despite no influence on body mass index or maximal oxygen uptake. Along with evident benefits in health promotion, moderate-intensity exercise might play an important role in facilitating treatment of various diseases.     

Participation of the prostacyclin-thromboxane system in the mechanisms of prevention of arrhythmia caused by occlusion of the coronary artery in adapted rats]

It was found, that adaptation of rats to cold and physical exercise prevented ventricular fibrillation, caused by the occlusion of the left anterior coronary artery. An adaptation to cold only or to physical exercise do not prevent ventricular arrhythmias. An significant increase of prostacyclin/thromboxane index in plasma and heats was estimated in rats adapted to cold and physical exercise in relation to control non-adapted group in condition of functional rest or acute myocardial ischemia. It was assumed that an increase of prostacyclin/thromboxane ratio has a significant role in antiarrhythmic action of adaptation.     

The impact of exercise on thyroid hormone metabolism in children and adolescents.

Thyroid hormones are important regulators of energy metabolism and may influence energy processes during physical exercise. There are controversial results concerning thyroid hormone metabolism during strenuous exercise in adult athletes and only scant data concerning the impact of strenuous exercise on thyroid hormone metabolism in children and adolescents. Although some studies demonstrate a transient change in thyroid hormones during intense physical performance, most studies agree that these changes are of minor impact, practically reflecting the relative negative energy balance during strenuous exercise. This state of hypometabolism during intense physical performance has also been confirmed in highly trained female young athletes, who may be also characterized by reproductive axis dysfunction, manifested either as luteal-phase deficiency or amenorrhea, alongside the typical constellation of low T3, insulin and leptin levels. More importantly, strenuous exercise during childhood or adolescence is mostly accompanied by a delay of skeletal maturation, and height and may have a long-lasting negative effect on growth and acquisition of maximum bone mass. In conclusion, although thyroid hormones are only transiently or insignificantly changed during strenuous exercise, adequate caloric intake should be guaranteed in highly performing young athletes in order to counteract the relative negative energy balance and prevent alterations in endocrine-metabolic profile. Moreover, when growth and pubertal progression in very young athletes are significantly impaired, a reduction in the intensity of the physical exercise should be advocated in order to guarantee better final height and adequate acquisition of bone mass.     

Molecular targets of exercise mimetics and their natural activators

Physical exercise can be effective in preventing or ameliorating various diseases, including diabetes, cardiovascular diseases, neurodegenerative diseases, and cancer. However, not everyone may be able to participate in exercise due to illnesses, age-related frailty, or difficulty in long-term behavior change. An alternative option is to utilize pharmacological interventions that mimic the positive effects of exercise training. Recent studies have identified signaling pathways associated with the benefits of physical activity and discovered exercise mimetics that can partially simulate the systemic impact of exercise. This review describes the molecular targets for exercise mimetics and their effect on skeletal muscle and other tissues. We will also discuss the potential advantages of using natural products as a multi-targeting agent for mimicking the health-promoting effects of exercise.     

Recent advances in chromatographic and electrophoretic methods for the study of drug-protein interactions

Drug-protein binding is an important process in determining the activity and fate of a pharmaceutical agent once it has entered the body. This review examines various chromatographic and electrophoretic methods that have been developed to study such interactions. An overview of each technique is presented along with a discussion of its strengths, weaknesses and potential applications. Formats that are discussed include the use of both soluble and immobilized drugs or proteins, and approaches based on zonal elution, frontal analysis or vacancy peak measurements. Furthermore, examples are provided that illustrate the use of these methods in determining the overall extent of drug-protein binding, in examining the displacement of a drug by other agents and in measuring the equilibrium or rate constants for drug-protein interactions. Examples are also given demonstrating how the same methods, particularly when used in high-performance liquid chromatography or capillary electrophoresis systems, can be employed as rapid screening tools for investigating the binding of different forms of a chiral drug to a protein or the binding of different proteins and peptides to a given pharmaceutical agent.     

Dependence of the cytotoxic effect of guanethidine on the degree of sympathetic activity

Young rats aged 15-29 days received a subcutaneous injection of guanethidine sulphate (5 mg/kg body weight) every day. Owing to damage to the postganglionic sympathetic neurones, on about the 60th day of life we observed a significant decrease in the noradrenaline concentration in these animals' hearts compared with the controls. If every guanethidine injection was followed immediately by intensive physical exercise, there was no drop in the heart noradrenaline concentration. Physical exercise of the same intensity performed a few hours before injecting guanethidine did not prevent the drop in the noradrenaline concentration in the heart. The results show that an exercise-induced increase in sympathetic activity, at a time when guanethidine is circulating in the blood and accumulating in the adrenergic neurones, inhibits the cytotoxic effect of guanethidine. Isolated physical exercise performed between the 15th and 29th day of life leads to an increase in the noradrenaline content of the heart of rats aged 60 days.     

Effect of moderate physical activity on plasma leptin concentration in humans

In subjects who maintain a constant body mass, the increased energy expenditure induced by exercise must be compensated by a similar increase in energy intake. Since leptin has been shown to decrease food intake in animals, it can be expected that physical exercise would increase energy intake by lowering plasma leptin concentrations. This effect may be secondary either to exercise-induced negative energy balance or to other effects of exercise. To delineate the effects of moderate physical activity on plasma leptin concentrations, 11 healthy lean subjects (4 men, 7 women) were studied on three occasions over 3 days; in study 1 they consumed an isoenergetic diet (1.3 times resting energy expenditure) over 3 days with no physical activity; in study 2 the subjects received the same diet as in study 1, but they exercised twice daily during the 3 days (cycling at 60 W for 30 min); in study 3 the subjects exercised twice daily during the 3 days, and their energy intake was increased by 18% to cover the extra energy expenditure induced by the physical activity. Fasting plasma leptin concentration (measured on the morning of day 4) was unaltered by exercise [8.64 (SEM 2.22) 7.17 (SEM 1.66), 7.33 (SEM 1.72) 1 microg x l(-1) in studies 1, 2 and 3, respectively]. It was concluded that a moderate physical activity performed over a 3-day period does not alter plasma leptin concentrations, even when energy balance is slightly negative. This argues against a direct effect of physical exercise on plasma leptin concentrations, when body composition is unaltered.     

Abnormalities of Energy Expenditure and the Development of Obesity

The role of energy expenditure in the development of obesity remains unclear. This issue is examined using data from prospective studies of energy expenditure and obesity, the effects of overfeeding and diet composition on energy expenditure, and studies of the relationship between energy expenditure for physical activity and body composition. The combined results from these investigations strongly support the view that low energy expenditure can facilitate rapid weight gain in susceptible individuals. It is speculated that, in susceptible individuals, low energy expenditure for resting energy expenditure as well as physical activity are part of a range of mechanisms available for providing surplus energy for rapid weight gain. In addition, both cross-sectional and intervention studies indicate that there is an equilibration between the level of energy expenditure for physical activity and body fat content. While genetic and other factors clearly play an important role in this relationship, it appears that a modest reduction in body fat content can be achieved by increasing energy expenditure for physical activity in physical exercise programs.     

Sport,doping and male fertility

It is universally accepted that lifestyle interventions are the first step towards a good overall, reproductive and sexual health. Cessation of unhealthy habits, such as tobacco, alcohol and drug use, poor nutrition and sedentary behavior, is suggested in order to preserve/improve fertility in humans. However, the possible risks of physical exercise per se or sports on male fertility are less known. Being “fit” does not only improve the sense of well-being, but also has beneficial effects on general health: in fact physical exercise is by all means a low-cost, high-efficacy method for preventing or treating several conditions, ranging from purely physical (diabetes and obesity) to psychological (depression and anxiety), highly influencing male reproduction. If male sexual and reproductive health could be positively affected by a proper physical activity, inadequate bouts of strength – both excessive intensity and duration of exercise training – are more likely to have detrimental effects. In addition, the illicit use of prohibited drugs (i.e. doping) has reached pandemic proportions, and their actions, unfortunately very often underestimated by both amateur and professional athletes, are known to disrupt at different levels and throughout various mechanisms the male hypothalamic-pituitary-gonadal axis, resulting in hypogonadism and infertility.     

Effect of Various Centrally Acting Drugs on the Efflux of Dopamine Metabolites from the Rat Brain

The influence of chlorpromazine, haloperidol, morphine, chloral hydrate, gamma-butyrolactone, probenecid, kainic acid, oxotremorine, pargyline, yohimbine, (+)-amphetamine, and cocaine on the efflux rate of 3,4-dihydroxyphenylacetic acid (DOPAC) from four brain areas was studied. All drugs studied except pargyline and morphine had an effect on the transport of DOPAC and homovanillic acid (HVA) from the brain. Nine drugs inhibited the efflux of DOPAC and HVA, whereas (+)-amphetamine stimulated this transport. These data suggest that most centrally acting drugs can interfere with the elimination of 3,4-dihydroxyphenylethylamine (DA or dopamine) metabolites from the brain. These effects are heterogeneously distributed throughout the brain and are probably related to indirect nonspecific drug effects. This implies that drug-induced changes in DA metabolite concentrations, especially when these changes are slight to moderate, cannot directly be translated to changes in the production rate of these metabolites. By studying five control groups, we concluded that formation and transport of DOPAC are not synchronized in the various brain areas.     

Changing Diet and Exercise Behaviors in Individuals at Risk for Weight Gain

To date, there have been very few studies on the primary prevention of obesity and/or weight gain. This paper identifies three time periods that might be appropriate for such efforts at weight gain prevention-the 25 to 35 year age window, the perimeno pausal period, and the year following successful weight loss. Research is encouraged that compares these three time periods and various intervention strategies. Several different approaches to primary prevention are identified, including group treatment pro grams with weekly meetings vs. less intensive, community- based interventions; focusing on those who are currently at ideal body weight vs. including those who are over weight as well; and targeting weight gain prevention per se vs. attempting to produce modest weight losses and/or modify cardiovascular risk factors. This paper suggests that primary prevention efforts should include exercise, changes in quality and quantity of food consumed, behavior modification, and some degree of therapist contact, but the manner in which these changes should be implemented to produce long-term habit change remains unclear.     

mRNA sequence analysis and quantitative expression of the ADAMTS4 gene in the thoroughbred horse

Cartilage increases flexibility of motion and helps protect the body from physical shock. Strong physical shock or some biological factor could cause joint disease. ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4) has been related to degradation of aggrecans in cartilage. It has been associated with joint disease, which could influence the ability of horses to exercise. Here, we performed sequence analysis and expression profiling of the ADAMTS4 gene in thoroughbred horses. Quantitative real-time RT-PCR data indicated that higher expression of the ADAMTS4 gene appeared in the cartilage tissues compared to those of pancreas, stomach, lung and colon. The expression pattern was also higher in the muscle tissues after exercise than before exercise. These data could be of great use for further studies in relation to both horse racing and joint disease.     

Chromatographic methods for the determination of toxicants in faeces

Modern chromatographic techniques and their application in the determination of toxic compounds in faeces are reviewed. Faecal analysis may be of importance in toxicokinetic studies of xenobiotics in order to determine factors such as metabolism, body burden and major routes of elimination. Compounds of interest include various food constituents, drugs and occupational or environmental factors. Further, various mutagenic or carcinogenic compounds which are excreted by faeces have been indicated to represent risk factors for colorectal cancer. In this context, the chromatographic determination of the endogenously generated fecapentaenes and bile acids, both postulated etiological factors in colorectal carcinogenesis, is reviewed. For fecapentaene determination, several high-performance liquid chromatographic (HPLC) methods are available; however, the applicability of some of these methods is limited owing to insufficient separation of various isomeric forms or discrimination between fecapentaenes and their precursors. For the determination of bile acids in faeces, many chromatographic procedures have been reported, and the characteristics of the most relevant methods are compared and discussed. It is concluded that separation by gas chromatography (GC) in combination with mass spectrometry provides the highest selectivity and sensitivity. A relatively rapid alternative analysis for the determination of total and aqueous faecal bile acids is proposed. Further, methods for the determination of polycyclic aromatic hydrocarbons (PAHs) are reviewed. Although the use of radiolabelled PAHs in animal studies has many advantages, it cannot be applied for human biological monitoring and HPLC and GC provide sensitive alternatives. An HPLC method for the determination of non-metabolized PAHs in faeces is described.     

The relation between glutamine and the immunodepression observed in exercise

Summary. Glutamine is the most abundant amino acid in the body. It is an important fuel for some key cells of the immune system. Both the plasma concentration of glutamine and the functional ability of immune cells in the blood are decreased after prolonged, exhaustive exercise. Glutamine feeding has had beneficial effects in clinical situations, and the provision of glutamine after intensive exercise has decreased the incidence of infections, particularly of upper respiratory tract infections. However, the precise effect of glutamine on immunodepression in this situation is not yet established. Received January 2, 2000 / Accepted February 1, 2000     

Exertion-induced fatigue and thermoregulation in the cold

Cold exposure facilitates body heat loss which can reduce body temperature, unless mitigated by enhanced heat conservation or increased heat production. When behavioral strategies inadequately defend body temperature, vasomotor and thermogenic responses are elicited, both of which are modulated if not mediated by sympathetic nervous activation. Both exercise and shivering increase metabolic heat production which helps offset body heat losses in the cold. However, exercise also increases peripheral blood flow, in turn facilitating heat loss, an effect that can persist for some time after exercise ceases. Whether exercise alleviates or exacerbates heat debt during cold exposure depends on the heat transfer coefficient of the environment, mode of activity and exercise intensity. Prolonged exhaustive exercise leading to energy substrate depletion could compromise maintenance of thermal balance in the cold simply by precluding continuation of further exercise and the associated thermogenesis. Hypoglycemia impairs shivering, but this appears to be centrally mediated, rather than a limitation to peripheral energy metabolism. Research is equivocal regarding the importance of muscle glycogen depletion in explaining shivering impairments. Recent research suggests that when acute exercise leads to fatigue without depleting energy stores, vasoconstrictor responses to cold are impaired, thus body heat conservation becomes degraded. Fatigue that was induced by chronic overexertion sustained over many weeks, appeared to delay the onset of shivering until body temperature fell lower than when subjects were rested, as well as impair vasoconstrictor responses. When heavy physical activity is coupled with underfeeding for prolonged periods, the resulting negative energy balance leads to loss of body mass, and the corresponding reduction in tissue insulation, in turn, compromises thermal balance by facilitating conductive transfer of body heat from core to shell. The possibility that impairments in thermoregulatory responses to cold associated with exertional fatigue are mediated by blunted sympathetic nervous responsiveness to cold is suggested by some experimental observations and merits further study.     

Age-related changes in characteristics of evoked responses in the CA1 area of hippocampal slices after forelimb deafferentation

The effect of forelimb deafferentation (median nerve transection) on postnatal development of hippocampal synaptic transmission was studied. Paired-pulse paradigm was applied to determine the properties of short-term plasticity, such as paired-pulse facilitation (PPT) in hippocampal slices. Significant changes in the time course of the PPT development were observed after the forelimb deafferentation. It was shown that the earlier described decrease in a population spike amplitude can be related not only to modification of synaptic efficacy but to some destructive processes, i.e., elimination of synapses and neurons. It was followed by the period by intensive formation of new synapses. The data suggest that there is no acceleration or delay in hippocampal development after the forelimb deafferentation but new intrahippocampal networks are formed.     

Sports and Exercise at Different Ages and Leukocyte Telomere Length in Later Life – Data from the Berlin Aging Study II (BASE-II)

Physical activity and sports have repeatedly been reported to be associated with telomere length. We studied the association of different types of sports across different stages of life on relative leukocyte telomere length (rLTL) in advanced age.815 participants (397 men) from the Berlin Aging Study II aged over 61 years were included in the analysis. rLTL was measured by real time PCR and physical activity was determined retrospectively by questionnaire, assessing type and duration of sports in the past as well as currently. Five separate multiple linear regression models adjusted for various control variables were performed. 67.3% of participants exercised currently, whereas 19.4% performed sports only between the age of 20 and 30. rLTL was higher in subjects who stated to exercise currently (N = 456), and in subjects who engaged in endurance (N = 138) or intensive activity sports (N = 32). Current physical activity was positively associated with rLTL in the risk factor adjusted regression model (β = 0.26, p < 0.001) and practicing sports for a minimum of 10 years preceding the assessment had a significant effect on rLTL (β = 0.39, p = 0.011). The highest impact was seen for intensive activity sports (β = 0.79, p < 0.001) and physical activity since at least 42 years (β = 0.47, p = 0.001). However, physical activity only between 20 and 30 years of age did not affect rLTL in old age when compared to no sports at all (β = -0.16, p = 0.21). Physical activity is clearly associated with longer rLTL. The effect is seen with longer periods of physical activity (at least 10 years), with intensive sports activities having the greatest impact on rLTL. Our data suggest that regular physical activity for at least 10 years is necessary to achieve a sustained effect on rLTL.