Testosterone enhances dopamine depletion by methamphetamine in male, but not female, mice

We examined the effects of varying concentrations of testosterone propionate (T) treatment within intact and gonadectomized male and female mice with regard to its capacity to alter striatal dopamine (DA) depletion in response to a neurotoxic regimen of methamphetamine (MA). Administration of T at 24h prior to MA significantly increased striatal DA depletion in intact and gonadectomized male mice. Similar treatments administered to intact and gonadectomized female mice failed to alter striatal DA concentrations in response to MA. These results demonstrate that T can enhance MA-induced neurotoxicity in male, but not in female, mice. Such findings have important implications with regard to sex differences in nigrostriatal dopaminergic function, in general, and, in specific, to sex differences related to nigrostriatal dopaminergic neurotoxicity and neurodegeneration like that in response to MA and in Parkinson's disease, where a greater incidence is typically reported for males.     

Effects of pre-cooling procedures on intermittent-sprint exercise performance in warm conditions

The aim of this study was to determine whether pre-cooling procedures improve both maximal sprint and sub-maximal work during intermittent-sprint exercise. Nine male rugby players performed a familiarisation session and three testing sessions of a 2 × 30-min intermittent sprint protocol, which consisted of a 15-m sprint every min separated by free-paced hard-running, jogging and walking in 32°C and 30% humidity. The three sessions included a control condition, Ice-vest condition and Ice-bath/Ice-vest condition, with respective cooling interventions imposed for 15-min pre-exercise and 10-min at half-time. Performance measures of sprint time and % decline and distance covered during sub-maximal exercise were recorded, while physiological measures of core temperature (T _core), mean skin temperature (T _skin), heart rate, heat storage, nude mass, rate of perceived exertion, rate of thermal comfort and capillary blood measures of lactate [La⁻], pH, Sodium (Na⁺) and Potassium (K⁺) were recorded. Results for exercise performance indicated no significant differences between conditions for the time or % decline in 15-m sprint efforts or the distance covered during sub-maximal work bouts; however, large effect size data indicated a greater distance covered during hard running following Ice-bath cooling. Further, lowered T _core, T _skin, heart rate, sweat loss and thermal comfort following Ice-bath cooling than Ice-vest or Control conditions were present, with no differences present in capillary blood measures of [La⁻], pH, K⁺ or Na⁺. As such, the ergogenic benefits of effective pre-cooling procedures in warm conditions for team-sports may be predominantly evident during sub-maximal bouts of exercise.     

An acute dose of inorganic dietary nitrate does not improve high-intensity,intermittent exercise performance in temperate or hot and humid conditions

European Journal of Applied Physiology - Dietary nitrate (NO3−) has repeatedly been shown to improve endurance and intermittent, high-intensity events in temperate conditions. However, the...     

Acute exercise decreases airway inflammation, but not responsiveness, in an allergic asthma model

Previous studies have suggested that the asthmatic responses of airway inflammation, remodeling, and hyperresponsiveness (AHR) are interrelated; in this study, we used exercise to examine the nature of this interrelationship. Mice were sensitized and challenged with ovalbumin (OVA); mice were then exercised via running on a motorized treadmill at a moderate intensity. Data indicate that, within the lungs of OVA-treated mice, exercise attenuated the production of inflammatory mediators, including chemokines KC, RANTES, and MCP-1 and IL-12p40/p80. Coordinately, OVA-treated and exercised mice displayed decreases in leukocyte infiltration, including eosinophils, as compared with sedentary controls. Results also show that a single bout of exercise significantly decreased phosphorylation of the NFkappaB p65 subunit, which regulates the gene expression of a wide variety of inflammatory mediators. In addition, OVA-treated and exercised mice exhibited decreases in the levels of Th2-derived cytokines IL-5 and IL-13 and the prostaglandin PGE(2), as compared with sedentary controls. In contrast, results show that a single bout of exercise had no effect on AHR in OVA-treated mice challenged with increasing doses of aerosolized methacholine (0-50 mg/ml) as compared with sedentary mice. Exercise also had no effect on epithelial cell hypertrophy, mucus production, or airway wall thickening in OVA-treated mice as compared with sedentary controls. These findings suggest that a single bout of aerobic exercise at a moderate intensity attenuates airway inflammation but not AHR or airway remodeling in OVA-treated mice. The implication of these findings for the interrelationship between airway inflammation, airway remodeling, and AHR is discussed.     

Acute, but not chronic, exercise lowers the body weight set-point in male rats.

The influence of muscular training on overall energy balance and body weight is not clear. A group of male rats was trained to feed every day from 1000 to 1200. Then the intersect of regression line of food hoarded during meal time vs. body weight with the X-axis was measured. Finally, the rats were trained to run 1 h every day on a motor-driven treadmill. When the training took place in the morning, just before the hoarding session, the mean intersect was significantly lowered from control (497 +/- 18 g to 433 +/- 9 g). When the training took place in the afternoon, after the hoarding session, the mean intersect was not significantly different (504 +/- 21 g) from control. Food intake during the hoarding sessions was affected neither by body weight changes nor by muscular exercise. These results suggest that the set-point for body weight regulation is acutely lowered just after muscular exercise, but is not influenced by chronic training.     

Cerebral oxygenation decreases but does not impair performance during self-paced,strenuous exercise

Aim: The reduction in cerebral oxygenation (Cox) is associated with the cessation of exercise during constant work rate and incremental tests to exhaustion. Yet in exercises of this nature, ecological validity is limited due to work rate being either fully or partly dictated by the protocol, and it is unknown whether cerebral deoxygenation also occurs during self-paced exercise. Here, we investigated the cerebral haemodynamics during a 5-km running time trial in trained runners. Methods: Rating of perceived exertion (RPE) and surface electromyogram (EMG) of lower limb muscles were recorded every 0.5 km. Changes in Cox (prefrontal lobe) were monitored via near-infrared spectroscopy through concentration changes in oxy- and deoxyhaemoglobin (Δ[O₂Hb], Δ[HHb]). Changes in total Hb were calculated (Δ[THb] = Δ[O₂Hb] + Δ[HHb]) and used as an index of change in regional blood volume. Results: During the trial, RPE increased from 6.6 ± 0.6 to 19.1 ± 0.7 indicating maximal exertion. Cox rose from baseline to 2.5 km (↑Δ[O₂Hb], ↑Δ[HHb], ↑Δ[THb]), remained constant between 2.5 and 4.5 km, and fell from 4.5 to 5 km (↓Δ[O₂Hb], ↑Δ[HHb], ↔Δ[THb]). Interestingly, the drop in Cox at the end of the trial coincided with a final end spurt in treadmill speed and concomitant increase in skeletal muscle recruitment (as revealed by higher lower limb EMG). Conclusion: Results confirm the large tolerance for change in Cox during exercise at sea level, yet further indicate that, in conditions of self-selected work rate, cerebral deoxygenation remains within a range that does not hinder strenuous exercise performance.     

Acute and adaptive responses in humans to exercise in a warm, humid environment

 Acute and repeated exposure for 8–13 consecutive days to exercise in humid heat was studied. Twelve fit subjects exercised at 150 W [45% of maximum O₂ uptake (V.O₂,_max)] in ambient conditions of 35°C and 87% relative humidity which resulted in exhaustion after 45 min. Average core temperature reached 39.9 ± 0.1°C, mean skin temperature (T– _sk) was 37.9 ± 0.1°C and heart rate (HR) 152 ± 6 beats min^–1 at this stage. No effect of the increasing core temperature was seen on cardiac output and leg blood flow (LBF) during acute heat stress. LBF was 5.2 ± 0.3 l min^–1 at 10 min and 5.3 ± 0.4 l min^–1 at exhaustion (n = 6). After acclimation the subjects reached exhaustion after 52 min with a core temperature of 39.9 ± 0.1°C, T– _sk 37.7 ± 0.2°C, HR 146 ± 4 beats min^–1. Acclimation induced physiological adaptations, as shown by an increased resting plasma volume (3918 ± 168 to 4256 ± 270 ml), the lower exercise heart rate at exhaustion, a 26% increase in sweating rate, lower sweat sodium concentration and a 6% reduction in exercise V.O₂. Neither in acute exposure nor after acclimation did the rise of core temperature to near 40°C affect metabolism and substrate utilization. The physiological adaptations were similar to those induced by dry heat acclimation. However, in humid heat the effect of acclimation on performance was small due to physical limitations for evaporative heat loss. Received: 3 July 1996 / Received after revision: 26 September 1996 / Accepted: 7 January 1997     

The influence of menthol on thermoregulation and perception during exercise in warm, humid conditions

Menthol has recently been added to various cooling products that claim to enhance athletic performance. This study assessed the effect of two such solutions during exercise in warm, humid conditions. Twelve participants (22 ± 2.9 years; [(V)\dot]\textO_2\textpeak \dot{V}{\text{O}}_{{2{\text{peak}}}} 47.4 ± 6.2 mL kg⁻¹ min⁻¹) completed a peak power (PO_peak) test and three separate exercise bouts in 30°C and 70% relative humidity after being sprayed with 100 mL of water containing either 0.05 or 0.2% l-menthol, or a control spray. During each trial, participants underwent 15 min of rest, spraying, 15 min of rest and 45 min of exercise at 45% of PO_peak. The following variables were measured: rectal temperature (T _re), sweat rate (SR), skin blood flow (SBF), heart rate (HR), thermal comfort (TC) and sensation (TS) votes, irritation (IRR) and rating of perceived exertion (RPE). Mean skin (MST) and body temperatures ( [`(T)]<sub>\textbody</sub> \bar{T}_{\text{body}} ) were calculated. There was no significant difference in MST, [`(T)]_\textbody \bar{T}_{\text{body}} SR, SBF, HR, TC or RPE between conditions. Spraying with 0.2% menthol significantly (P < 0.05) elevated T _re by 0.2°C compared to the other conditions. Both menthol sprays caused participants to feel significantly cooler than control spraying (P = 0.001), but 0.2% spraying induced significantly cooler sensations (P = 0.01) than 0.05% spraying. Both menthol sprays induced greater irritation (P < 0.001) than control spraying. These findings suggest that 0.05% menthol spraying induced cooler upper body sensations without measurable thermoregulatory impairment. T _re was significantly elevated with 0.2% spraying. Irritation persisted with both menthol sprays while TC remained unchanged, suggesting a causal relationship. The use in sport of a spray similar to those tested here remains equivocal.     

Interleukin-6 enhances human Ig production,but not as a terminal differentiation factor for B lymphocytes

Most B-cell differentiation systems are complicated by the fact that they are both T-cell- and monocyte-dependent. Immobilized anti-CD3 antibodies induce monocyte-independent T-cell activation, allowing investigation of the role of interleukin-6 (IL6) in the process of B-cell differentiation. We observed that in this system, the addition of monocytes to purified lymphocytes does not influence T-cell proliferation but it does enhance the induction of Ig production. IL6 can specifically replace monocytes in this enhancing effect on both IgM and IgG production. Anti-CD3-induced Ig production appears to be dependent on both IL2 and IL6 since it was inhibited by anti-CD25 (anti-IL2-R) antibodies as well as by anti-IL6 antibodies. Kinetic studies of IL6 addition showed that IL6 is only necessary during the first two days of culture. Our data indicate that IL6 plays an essential role in anti-CD3-induced Ig production, but not as a terminal differentiation factor.     

Interleukin-6 enhances human Ig production, but not as a terminal differentiation factor for B lymphocytes

Most B-cell differentiation systems are complicated by the fact that they are both T-cell- and monocyte-dependent. Immobilized anti-CD3 antibodies induce monocyte-independent T-cell activation, allowing investigation of the role of interleukin-6 (IL6) in the process of B-cell differentiation. We observed that in this system, the addition of monocytes to purified lymphocytes does not influence T-cell proliferation but it does enhance the induction of Ig production. IL6 can specifically replace monocytes in this enhancing effect on both IgM and IgG production. Anti-CD3-induced Ig production appears to be dependent on both IL2 and IL6 since it was inhibited by anti-CD25 (anti-IL2-R) antibodies as well as by anti-IL6 antibodies. Kinetic studies of IL6 addition showed that IL6 is only necessary during the first two days of culture. Our data indicate that IL6 plays an essential role in anti-CD3-induced Ig production, but not as a terminal differentiation factor.     

Ovarian hormones and cognition in the aged female rat: I. Long-term, but not short-term, ovariectomy enhances spatial performance

Although research suggests that ovariectomy (ovx) is detrimental to spatial cognition in young rats, little work has evaluated the cognitive effects of ovx in aged rats. The authors investigated the effects of ovx in aged rats using the water radial-arm maze. In Study 1, young rats and aged rats receiving ovx 1.5 months before testing outperformed aged rats receiving sham surgery or ovx 21 days before testing. In Study 2, young rats and aged rats receiving ovx 2.0 or 6.0 months before testing outperformed aged sham rats. Aged rats exhibited estradiol and elevated progesterone levels comparable to those of young rats. The findings suggest that 1.5-6.0 months, but not 21 days, of ovx improves spatial memory in aged rats. The hypothesis that long-term ovarian hormone loss is detrimental to spatial memory in aged rats was not supported. The authors hypothesize that removal of elevated progesterone levels is related to the ovx-induced cognitive enhancement.     

TNFalpha inhibition in MRL/lpr mice ameliorates pulmonary but not renal disease

TNFalpha inhibition has a clearly beneficial effect in a number of arthritides and in Crohn's disease. The exact mechanism of action is uncertain with studies showing inhibition of chemokines, inhibition of adhesion molecule expression, and improved T-cell function. Unlike most therapeutic interventions for autoimmune disease, TNFalpha inhibition appears to act on specific pathologic processes. It is not known how wide-spread these TNFalpha-mediated pathologic processes are. Efforts to expand the use of TNFalpha inhibition have had notable successes but have been disappointing in other disorders. We hypothesized that TNFalpha-mediated pathologic processes might play a significant role in the end-organ effects seen in SLE. We modeled SLE by using MRL/lpr mice and treated with two types of TNFalpha inhibitor. Pulmonary disease was significantly improved in the treated groups compared to controls. In contrast, renal disease was unaffected suggesting that in lupus, where multiple organs are affected, different pathologic processes may be mediating the end-organ damage. This has important implications for designing therapeutics for SLE.     

IL-5 enhances the in vitro adhesion of human eosinophils, but not neutrophils, in a leucocyte integrin (CD11/18)-dependent manner.

In an attempt to explain the preferential accumulation of eosinophils at sites of allergic tissue reactions, we have studied the effects of interleukin-5 (IL-5) on the adherence of human eosinophils and neutrophils to plasma-coated glass (PCG) or human microvascular endothelial cells (HMVEC). IL-5 was compared with IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and platelet-activating factor (PAF), since all these agents have biological properties associated with eosinophil activation and/or survival in vitro. IL-5, IL-3 and GM-CSF induced a time-dependent increase in adherence of normal density eosinophils to PCG optimal at 60 min, whereas the effect of PAF was greater at 15 min. Similar results were obtained with neutrophils, with the exception that IL-5 had minimal and non-significant effects on this cell type. Unstimulated eosinophils and neutrophils also adhered to PCG or HMVEC, but in low numbers. Preincubation of eosinophils with IL-5, GM-CSF or PAF resulted in dose-dependent increases in the numbers of adherent cells to PCG. IL-3 had a smaller but significant effect on enhanced eosinophil adhesion to PCG, while IL-2 and lyso-PAF were ineffective. Neutrophils gave similar levels of baseline and stimulated adhesion to PCG as eosinophils, IL-5 again had no significant stimulatory effect. IL-5 also increased eosinophil, but not neutrophil, adherence to HMVEC in a concentration-dependent manner. Preincubation with the protein synthesis inhibitor cycloheximide had no effect on IL-5-, GM-CSF- or PAF-stimulated eosinophil adhesion. The contribution of the CD11/18 leucocyte integrins to IL-5- and PAF-induced eosinophil hyperadherence was investigated by inhibition experiments utilizing monoclonal antibodies (mAb). Enhanced adhesion to PCG (by PAF) or HMVEC (by IL-5) was inhibited by (ranked in order of potency) anti-CR3 alpha = common beta-chain greater than LFA-1 alpha. Anti-p150,95 alpha had no measurable effect. Baseline adhesion by unstimulated eosinophils was not significantly influenced by prior incubation with these mAb. Using flow cytometry, IL-5 and IL-3 were found to up-regulate cosinophil but not neutrophil CR3 expression. These findings demonstrate that IL-5 enhances cosinophil, but not neutrophil, adherence reactions, by a mechanism dependent, at least in part, on the CD11/18 family of adhesion glycoproteins.