Biological responses to overload training in endurance sports

Summary Five subjects undertook 10 days of twice daily interval training sessions on a treadmill followed by 5 days of active recovery. On days 1, 6, 11, and 16 the subjects were required to undertake a test of submaximal and maximal work capacity on a treadmill combined with a performance test consisting of a run to exhaustion with the treadmill set at 18 km · h^–1 and 1% gradient. Also on these days a pre-exercise blood sample was collected and analysed for a range of haematological, biochemical and immunological parameters. The subjects experienced a significant fall in performance on day 11 which had returned to pretraining levels on day 16. Serum ferritin concentrations were depressed significantly from pretraining concentrations at the conclusion of the recovery period while the expression of lymphocyte activation antigens (CD25⁺ and HLA-DR⁺) was increased both after the training phase and the recovery phase. The number of CD56⁺ cells in the peripheral circulation was depressed at the conclusion of the recovery period. Several parameters previously reported to change in association with overload training failing to reflect the decrease in performance experienced by subjects in this study, suggesting that overtraining may best be diagnosed through a multifactorial approach to the recognition of symptoms. The most important factor to consider may be a decrease in the level of performance following a regeneration period. The magnitude of this decreased performance necessary for the diagnosis of overtraining and the nature of an appropriate regeneration period are, however, difficult to define and may vary depending upon the training background of the subjects and the nature of the preceding training. It may or may not be associated with biochemical, haematological, physiological and immunological indicators. Individual cases may present a different range of symptoms and diagnosis of overtraining should not be excluded based on the failure of blood parameters to demonstrate variation. However, blood parameters may be useful to identify possible aetiology in each separate case report of overtraining. An outstanding factor to emerge from this study was the difficulty associated with an objective diagnosis of overtraining and this is a possible reason why there have been new accounts of overtraining research in the literature.     

Alteration by burn injury of the pharmacokinetics and pharmacodynamics of cimetidine in children

Summary We have studied the mechanisms of the increased dosage requirements of the H₂-receptor antagonist cimetidine in paediatric burned patients in a pharmacokinetic and pharmacodynamic study.Cimetidine (10–15 mg·kg^–1) was given to 21 burned children and multiple blood samples were obtained for determination of plasma cimetidine concentrations and pharmacokinetic analysis.The relation of gastric pH to plasma cimetidine concentrations was studied in five of these children who had nasogastric tubes. In an additional four patients the effects of cimetidine on gastric pH were studied during a continuous infusion of cimetidine, which maintained steady-state plasma cimetidine concentrations above 0.5 µg·ml^–1.The mean (SEM) clearance of cimetidine in burned children was 16.22 ml·kg^–1 and cimetidine half-life was 1.06 h. The cimetidine clearance and half-life values were significantly higher in burned children compared with our previously reported values for normal adult patients, 8.2 ml·min·kg^–1 and 2.21 h respectively.Endogenous creatinine clearance normalized to 70 kg in burned children was 190 ml·min^–1. In burned children 41% of the dose of intact cimetidine was excreted during 8 h of the study compared with 45% excretion during 24 h in healthy adult controls previously reported. The correlation coefficient between creatinine and cimetidine clearances was 0.93 (r ²=0.85).The plasma concentration of cimetidine needed to increase gastric pH to 4.0 was 1.0 µg·ml^–1, which contrasts with the value of >0.5 µg·ml^–1 required for adult burned patients.These findings support the hypothesis that the higher dosage requirements of cimetidine in burned children is due both to enhanced elimination kinetics and to alterations in target organ sensitivity, requiring higher than normal plasma concentrations for the desired effect. In burned children Cimetidine should be given in higher doses and/or more frequently.     

Hyperthermic modulation of macrophage-tumor cell interactions

Hyperthermia in the febrile (41° C) or tumor therapeutic (42° C) ranges is known to alter tumor-host interactions: there are reports of either inhibitory or enhancing effects on tumor metastasis and various host defense mechanisms. Historically, this has been an area of conflicting and often anecdotal reports, and there are still significant gaps in our knowledge of the effects of temperature on tumor-host interactions. However, we believe that the tools are now available to further our understanding of the complex relationships between febrile episodes or therapeutically applied heat and various tumor-host cytotoxic mechanisms, and that potentially important and exploitable relationships can be defined. In this review we give an overview of the current status of this field and the factors that have shaped it. We also describe our recent experimental work with macrophages and their monokines, primarily tumor necrosis factor (TNF), which we feel offers new scientific and clinical opportunities for future studies.     

Prediction of mean skin temperature in warm environments

Summary The data collected by the authors in four experimental series have been analysed together with data from the literature, to study the relationship between mean skin temperature and climatic parameters, subject metabolic rate and clothing insulation. The subjects involved in the various studies were young male subjects, unacclimatized to heat. The range of conditions examined involved mean skin temperatures between 33‡ C and 38‡ C, air temperatures (T_a) between 23‡ C and 50‡ C, ambient water vapour pressures (P_a) between 1 and 4.8 kPa, air velocities (V_a) between 0.2 and 0.9 m · s⁻¹, metabolic rates (M) between 50 and 270 W · m⁻², and Clo values between 0.1 and 0.6. In 95% of the data, mean radiant temperature was within ±3‡ C of air temperature. Based on 190 data averaged over individual values, the following equation was derived by a multiple linear regression technique: ˉT_sk=30.0+0.138T_a+0.254P_a−0.57V_a+1.28 · 10⁻³ M−0.553 Clo. This equation was used to predict mean skin temperature from 629 individual data. The difference between observed and predicted values was within ±0.6‡ C in 70% of the cases and within ±1‡ C in 90% of the cases. It is concluded that the proposed formula may be used to predict mean skin temperature with satisfactory accuracy in nude to lightly clad subjects exposed to warm ambient conditions with no significant radiant heat load.     

Psychological aspects of Crohn's disease

This is a critical review of 16 studies reporting a relationship between Crohn's disease and psychological variables. The studies reviewed indicate a relationship between the psychological variables of stressful life events, personality characteristics, and psychopathology and the onset and/or exacerbation of Crohn's symptoms. Personality characteristics such as depression, anxiety, and dependency are frequently reported as are the occurrence of stressful life events and the presence of psychopathology. The nature of the relationship is not explained by the research to date; however, the findings summarized in this report indicate that additional investigation into this association is warranted. A plan for such research is suggested.     

Contribution of redox-active iron and copper to oxidative damage in Alzheimer disease

Metal-catalyzed hydroxyl radicals are potent mediators of cellular injury, affecting every category of macromolecule, and are central to the oxidative injury hypothesis of Alzheimer disease (AD) pathogenesis. Studies on redox-competent copper and iron indicate that redox activity in AD resides exclusively within the neuronal cytosol and that chelation with deferoxamine, DTPA, or, more recently, iodochlorhydroxyquin, removes this activity. We have also found that while proteins that accumulate in AD possess metal-binding sites, metal-associated cellular redox activity is primarily dependent on metals associated with nucleic acid, specifically cytoplasmic RNA. These findings indicate aberrations in iron homeostasis that, we suspect, arise primarily from heme, since heme oxygenase-1, an enzyme that catalyzes the conversion of heme to iron and biliverdin, is increased in AD, and mitochondria, since mitochondria turnover, mitochondrial DNA, and cytochrome C oxidative activity are all increased in AD. These findings, as well as studies demonstrating a reduction in microtubule density in AD neurons, suggest that mitochondrial dysfunction, acting in concert with cytoskeletal pathology, serves to increase redox-active heavy metals and initiates a cascade of abnormal events culminating in AD pathology.     

Physiological unloading of cardiopulmonary mechanoreceptors by posture changes does not influence the pressor response to isometric exercise in healthy humans

Summary In recent studies in humans the role of cardiopulmonary baroreflexes in modulating the cardiovascular responses to isometric exercise (somatic pressor reflex) has been investigated by performing static hand-grip exercise during deactivation of cardiopulmonary receptors produced by low levels of lower body negative pressure; however, findings from these studies have not been consistent. The purpose of this study was to investigate whether a more physiological unloading stimulus of cardiopulmonary baroreceptors, obtained by sequentially changing posture, could influence the pressor response to somatic afferent stimulation induced by isometric, exercise. To accomplish this, ten healthy subjects performed a 2-min isometric handgrip (IHG) at 30% maximal voluntary contraction after 10 min of supine rest and, in rapid sequence, after 10 min of sitting and 10 min of standing, at the time when, owing to their transitory nature, the cardiovascular effects, due to arterial baroreceptor intervention should have been minimal. During IHG arterial pressure (BP_a) was continuously and noninvasively measured to quantify accurately the blood pressure response to IHG both in magnitude and time course. Results showed that the pressor response to IHG was not significantly influenced by change in posture, either in magnitude or in time course. The mean arterial pressure increased by 17.4 (SEM 2.5), 18.6 (SEM 1.2) and 17.0 (SEM 1.3) mmHg in supine, sitting and standing [2.3 (SEM 0.3), 2.5 (SEM 0.2) and 2.3 (SEM 0.2) kPa] positions, respectively. Also the heart rate response to IHG was unaffected by change in posture. Most important, the sum of the separate BP_a responses induced by supine IHG and by posture change from supine to sitting (summation of reflexes) was not significantly different from the pressor response observed during sitting IHG (interaction of reflexes). Likewise, the sum of the separate BP_a. responses induced by sitting IHG and by changing postures from sitting to standing was not significantly different from the pressor response to standing IHG. These data indicate that, under physiological conditions, cardiopulmonary baroreflexes do not exert a significant role in modulating the reflex pressor drive from muscles during isometric exercise in healthy humans.     

Family history of hypertension,gender, and cardiovascular reactivity and stereotypy during stress

Thirty subjects with a family history of hypertension and 28 subjects without such a history performed a Stroop Color-Word Interference task, a mental arithmetic task (serial subtraction of sevens), and a shock avoidance task (repeating digits backward while expecting to be shocked for mistakes). Systolic and diastolic blood pressure and pulse rate were recorded while subjects anticipated, undertook, and recovered from the shock avoidance task and undertook and recovered from the Stroop and mental arithmetic tasks. It was found that compared to nonfamily history subjects, family history subjects manifested reliably greater cardiovascular reactivity during each task and in anticipation of the shock avoidance task. These results are congruent with the notion that excessive sympathetic nervous system reactivity—possibly genetically determined—is involved in the development of some form(s) of essential hypertension. Further, the results indicated that family history subjects manifested greater consistency, or stereotypy, of cardiovascular response across the experimental tasks than nonfamily history subjects. The possible role of cardiovascular stereotypy in the development of essential hypertension is also discussed.This investigation was supported by University of Kansas General Research Allocation 3115-xO-0038 to B. Kent Houston.     

Psychopathy and Physiological Activity In a Mixed-Motive Game Situation

Heart rate (HR) and skin conductance (SC) were recorded while 17 psychopathic (P) and 17 nonpsychopathic (NP) inmates (referred to as A) were engaged in a mixed-motive game situation with another S (referred to as B). On each trial A had to choose the intensity of shock to be delivered to himself and to B. B then was given a chance to retaliate, although his choices were actually overridden by the experimenter. A 10 sec tone (CS) preceded delivery of shock to each S. There were no differences between Groups P and NP in the intensity of shock chosen for themselves and for the other (B) Ss. Compared with Group NP, Group P gave small unconditioned skin conductance (SC) responses to shock directly received and to shocks delivered to the other S. There were no differences between groups in the unconditioned HR response to either direct shock (acceleration) or to shocks delivered to the other S (slight deceleration). Group P gave small electrodermal orienting responses (ORs) and anticipatory responses (ARs) to the CS preceding shock to self and shock to other; Group NP gave relatively large ORs and ARs to the CS preceding shock to self, and small ones prior to shock to other. Both Groups gave a biphasic conditioned HR response–acceleration followed by deceleration; each component was larger in Group P than in Group NP, and the acceleratory component in Group P appeared on the first trial. The electrodermal data were consistent with the view that psychopaths experience little fear arousal prior to reception of aversive stimuli by themselves or by others. It was suggested that the anticipatory HR responses of the psychopathic Ss were part of an adaptive response that helped them to cope with stress.     

Development of a non-linear finite element modelling of the below-knee prosthetic socket interface

A non-linear finite element model has been established to predict the pressure and shear stress distribution at the limb-socket interface in below-knee amputees with consideration of the skin-liner interface friction and slip. In this model, the limb tissue and socket liner were respectively meshed into 954 and 450 three-dimensional eight-node isoparametric brick elements, based on measurements of an individual's amputated limb surface; the bone was meshed into three-dimensional six-node triangular prism elements, based on radiographic measurements of the individual's residual limb. The socket shell was assumed to be a rigid boundary. An important feature of this model is the use of 450 interface elements (ABAQUS INTER4) which mimic the interface friction condition. The results indicate that a maximum pressure of 226 kPa, shear stress of 53 kPa and less than 4 mm slip exist at the skin-liner interface when the full body weight of 800 N is applied to the limb. The results also show that the coefficient of friction is a very sensitive parameter in determining the interface pressures, shear stresses and slip. With the growth of coefficient of friction, the shear stresses will increase, while the pressure and slip will decrease.