Training mode does not affect orthostatic tolerance in chronically exercising subjects

This study tested the hypotheses that trained swimmers would have greater orthostatic tolerance than runners and, if present, it would be due to differences in their autonomic and hemodynamic responses to graded central hypovolemia. Twenty intercollegiate male athletes [11 runners and 9 swimmers; V˙O_2max =70.0 (1.6) vs 69.5 (2.6) ml·kg⁻¹·min⁻¹, respectively] underwent graded lower body negative pressure (LBNP) to presyncope. The swimmers were heavier [80.5 (1.9) vs 70.3 (1.9) kg, P<0.05], with larger resting cardiac [4.44 (0.29) vs 3.68 (0.18) l·min⁻¹·m⁻²] and total peripheral conductance [0.056 (0.04) vs 0.044 (0.02) units·m⁻²] indices. Neither spontaneous cardiac baroreflex sensitivity (sequence method) nor heart rate variability (spectral analysis) differed significantly between groups at rest. LBNP tolerance did not differ between groups, with an index value of 51 (2) kPa·min for the runners and 54 (4) kPa·min for the swimmers [383 (16) vs 402 (32) mmHg·min] , although the swimmers had larger declines in pulse pressure and tended (P=0.078) to have larger declines in total peripheral conductance index in the last completed stage of LBNP. These responses did not differ between groups in the last 2 min of LBNP. Neither the heart rate, mean arterial pressure nor forearm vascular conductance responses differed between groups throughout. Changes in heart rate variability indices did not differ significantly between groups, with similar declines in the high frequency component and increases in the low frequency/high frequency ratio. These data suggest that swim training does not lead to greater orthostatic tolerance than run training, and responses to maximal LBNP do not differ between swimmers and runners. Moreover, neither heart rate nor the autonomic modulation of the heart rate response to LBNP are affected by training modality. Electronic Publication     

Acute and chronic ethanol does not affect incisional pain in neonatal rats

We have previously found that in post-natal day 7 rats withdrawal from acute and chronic ethanol (EtOH) exposure lowers mechanical thresholds during withdrawal and exacerbates spontaneous pain responses to an inflammatory injury 4 days post-withdrawal. These findings suggested alterations in somatosensory pathways following EtOH exposure during the third trimester developmental equivalent. In this study we wanted to determine whether EtOH exposure during the third trimester equivalent exacerbates mechanical allodynia and thermal hyperalgesia produced by an incisional model of post-operative pain at post-natal day 21. The extent and duration of mechanical allodynia and thermal hyperalgesia following incision was measured and found to be unaffected by prior EtOH exposure.     

Cooling does not affect knee proprioception

The effect of cooling on proprioception of the knee has not been studied extensively. In this study, we investigated the movement reproduction (timing and accuracy) aspect of proprioception. Subjects were tested under two conditions: a 20-minute application of ice and control. Proprioceptive accuracy and timing were measured by passively moving the knee, then comparing the subject's active reproduction of the passive movement. Subjects were blindfolded, then tested in three sectors of the knee's range of motion: 90 degrees to 60 degrees , 60 degrees to 30 degrees , and 30 degrees to full extension. Ice application had no apparent effect on the subject's ability to perform accurate movement reproductions in the sectors tested. However, accuracy of the subject's final angle reproduction varied between the sectors as did the total time of the movement. One possible explanation for the difference between sectors is that different receptors are active at different points in the knee's range of motion. We conclude that cooling the knee joint for 20 minutes does not have an adverse effect on proprioception.     

Cdk4 deficiency inhibits skin tumor development but does not affect normal keratinocyte proliferation

Most human tumors have mutations that result in deregulation of the cdk4/cyclin-Ink4-Rb pathway. Overexpression of D-type cyclins or cdk4 and inactivation of Ink4 inhibitors are common in human tumors. Conversely, lack of cyclin D1 expression results in significant reduction in mouse skin and mammary tumor development. However, complete elimination of tumor development was not observed in these models, suggesting that other cyclin/cdk complexes play an important role in tumorigenesis. Here we described the effects of cdk4 deficiency on mouse skin proliferation and tumor development. Cdk4 deficiency resulted in a 98% reduction in the number of tumors generated through the two-stage carcinogenesis model. The absence of cdk4 did not affect normal keratinocyte proliferation and both wild-type and cdk4 knockout epidermis are equally affected after topical treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), resulting in epidermal hyperplasia. In similar fashion, cdk4 knockout keratinocytes proliferated well in an in vivo model of wound-induced proliferation. Biochemical studies in mouse epidermis showed that cdk6 activity increased twofold in cdk4-deficient mice compared to wild-type siblings. These results suggest that therapeutic approaches to inhibit cdk4 activity could provide a target to inhibit tumor development with minimal or no effect in normal tissue.     

Exogenous immunosuppression with methylprednisolone does not reactivate a type D retrovirus in rhesus monkeys

To determine whether immunosuppression would result in retrovirus expression in previously infected rhesus monkeys, chronic high dose methyl prednisolone therapy was administered to two groups of animals for 4 weeks. One group was antibody positive for a type D retrovirus, designated Type D/3/wisc. The second group of animals had no known exposure to Type D/3/wisc and was antibody negative to this virus. The monkeys were evaluated for immunosuppression and retrovirus re-expression following the corticosteroid therapy. Although this treatment induced a marked cellular immunosuppression in all animals, as measured by in vitro assays, in none of the animals was retrovirus viremia or retrovirus-associated disease detected.     

Hydrosalpinx fluid does not adversely affect the normal development of human embryos and implantation in vitro

Several retrospectively designed studies have shown an associationbetween the presence of hydrosalpinx and impaired implantationand pregnancy rates among in-vitro fertilization (IVF) patients.In the present study we have evaluated the influence of hydrosalpinxfluid on normal human embryo development and implantation. Surplus,donated frozen embryos (n = 183) from IVF patients were usedto study the effects on blastocyst development of hydrosalpinxfluid at concentrations of 50 and 100% compared with controlsin S2 medium. The fluids were analysed for concentrations ofelectrolytes, osmolarity, protein content, endotoxin levels,bacterial or fungal contamination, pH and haemoglobin content.There was no difference in blastocyst development in culturesunder mineral oil when control cultures (15/42 = 36%) were comparedwith cultures in 50% hydrosalpinx fluid (32/96 = 33%). The onlybiochemical parameter which correlated with capacity for blastocystdevelopment was pH in hydrosalpinx fluid/medium (50/50%) afterequilibration in 5% CO₂ in air. When embryos were cultured in100% hydrosalpinx fluid the blastocyst development was 14% (5/36)in comparison to control 33% (3/9). The original experimentwas repeated in an open culture system without the protectionof mineral oil but still in the presence of 50% hydrosalpinxfluid. The rate of blastocyst development was within the samerange in the open system. In three separate experiments, thecapability of expanded blastocyst to implant on multilayer artificialendometrium was tested. In these experiments, 1/3, 4/5 and 9/9blastocysts implanted. The present study demonstrates that hydrosalpinxfluid does not generally exert any major negative effects onin-vitro development of human embryos or on the implantationprocess in vitro.     

Endothelin does not affect aggregation of human platelets

Endothelin (ET-1) is a recently discovered endothelial-derived peptide with pronounced vasoconstrictor activity. The present study addressed whether ET-1, in analogy with several other vasoactive agents, can induce or modulate aggregation of human platelets in vitro. Venous blood from healthy donors was collected in citrate or heparin and platelet-rich plasma (PRP) was prepared. Portions of the PRP were added to drugs, and platelet aggregation was recorded according to Born & Cross (1963). ET-1 added to the PRP (final concentrations 1-100 nM) did not induce aggregation of platelets, either in citrate- or heparin-containing plasma. Adenosine-diphosphate (0.5-2 microM) or thrombin (0.1-0.4 NIH units ml-1) induced dose-dependent aggregation of platelets in citrate- or heparin-containing PRP; such aggregation was, however, not affected by ET-1 (1-100 microM) either. We conclude that ET-1, in contrast to other endothelial-derived vasoactive agents, lacks direct effect on platelet aggregation in vitro.     

Obstructive sleep apnea (OSA) does not affect ventilatory and perceptual responses to exercise in morbidly obese subjects

We have tested the hypothesis that high mass loading effects and obstructive sleep apnea (OSA) constrain the ventilatory response to exercise in morbidly obese subjects as compared to their counterparts without OSA. Fifteen obese patients with (8) and without OSA and 12 lean healthy subjects performed incremental cycle exercise. The functional evaluation included ventilation, oxygen uptake, carbon dioxide production, end-expiratory-lung-volumes (EELV), inspiratory capacity, heart rate, dyspnea and leg effort (by a modified Borg scale). Changes in ventilation and dyspnea per unit changes in work rate and metabolic variables were similar in the three groups. Breathing pattern and heart rate increased from rest to peak exercise similarly in the three groups. Leg effort was the prevailing symptom for stopping exercise in most subjects. In conclusion, OSA does not limit exercise capacity in morbidly obese subjects. Ventilation contributes to exertional dyspnea similarly as in lean subjects and in obese patients regardless of OSA.     

Erythropoietin does not affect nitric oxide system in rats with chronic renal failure

We investigated to see whether an altered role of nitric oxide (NO) system is involved in erythropoietin (EPO)-induced hypertension in chronic renal failure (CRF). Male Sprague-Dawley rats were five-sixths nephrectomized to induce CRF. Six weeks after the operation, EPO or vehicle was injected for another 6 weeks. Plasma and urine nitrite/nitrate (NOx) levels were determined. Expression of NO synthase (NOS) proteins in the aortae and kidneys were also determined. In addition, the isometric tension of isolated aorta in response to acetylcholine and nitroprusside was examined. Blood pressure progressively rose in CRF groups, the degree of which was augmented by EPO treatment. Plasma NOx levels did not differ among the groups, while urine NOx levels were lower in CRF groups. Endothelial NOS expression was lower in the kidney and aorta in CRF rats, which was not further affected by EPO-treatment. The inducible NOS expression in the kidney and aorta was not different among the groups. Acetylcholine and sodium nitroprusside caused dose-dependent relaxations of aortic rings, the degree of which was not altered by EPO-treatment. Taken together, EPO-treatment aggravates hypertension in CRF, but altered role of NO system may not be involved.     

Blockage of pituitary-adrenal activity does not affect conditioned suppression

Previous research has shown that exposure to stressful experimental procedures results in increased activity of the pituitary-adrenal system. In the present experiment, although normal animals showed elevated steroid levels during exposure to a conditioned suppression procedure, characteristic behavioral results were also obtained in animals for which pituitary-adrenal activity had been blocked by hypothalamic implants of cortisol.     

Acute over-the-counter pharmacological intervention does not adversely affect behavioral outcome following diffuse traumatic brain injury in the mouse

Following mild traumatic brain injury (TBI), patients may self-treat symptoms of concussion, including post-traumatic headache, taking over-the-counter (OTC) analgesics. Administering one dose of OTC analgesics immediately following experimental brain injury mimics the at-home treated population of concussed patients and may accelerate the understanding of the relationship between brain injury and OTC pharmacological intervention. In the current study, we investigate the effect of acute administration of OTC analgesics on neurological function and cortical cytokine levels after experimental diffuse TBI in the mouse. Adult, male C57BL/6 mice were injured using a midline fluid percussion (mFPI) injury model of concussion (6–10 min righting reflex time for brain-injured mice). Experimental groups included mFPI paired with either ibuprofen (60 mg/kg, i.p.; n = 16), acetaminophen (40 mg/kg, i.p.; n = 9), or vehicle (15 % ethanol (v/v) in 0.9 % saline; n = 13) and sham injury paired OTC medicine or vehicle (n = 7–10 per group). At 24 h after injury, functional outcome was assessed using the rotarod task and a modified neurological severity score. Following behavior assessment, cortical cytokine levels were measured by multiplex ELISA at 24 h post-injury. To evaluate efficacy on acute inflammation, cortical cytokine levels were measured also at 6 h post-injury. In the diffuse brain-injured mouse, immediate pharmacological intervention did not attenuate or exacerbate TBI-induced functional deficits. Cortical cytokine levels were affected by injury, time, or their interaction. However, levels were not affected by treatment at 6 or 24 h post-injury. These data indicate that acute administration of OTC analgesics did not exacerbate or attenuate brain-injury deficits which may inform clinical recommendations for the at-home treated mildly concussed patient.     

Simultaneous hand tracking does not affect human vergence pursuit

In order to find out whether human vergence eye movements are influenced by simultaneous hand tracking movements, vergence was studied when sinusoidal (expressed in vergence angles) target movements were tracked. The target motion was externally generated and the target actually moved in depth. Tracking was done by the eyes alone or by the eyes and hand together, in both light and dark viewing conditions. Our data show that the target motion was tracked by the eyes with a short delay (on average 48 ms), independent of the tracking condition. This suggests that vergence modeling should include some predictive mechanism similar to that proposed for the smooth pursuit subsystem. Furthermore, in contrast to effects on smooth pursuit, simultaneous hand tracking movements did not influence vergence eye movements. From this, we argue that the balance between smooth pursuit and saccadic eye movements is adjustable and can be adapted to the requirements of different tasks.     

Denervation does not affect the growth of rat vibrissae

This study examines the hypothesis that neural factors influence the growth of rat vibrissae. We divided the vibrissae in rows alpha-delta, 1 and 2 and examined their regrowth during the first complete growth period in normal and nerve-lesioned rats. The lesions used were denervation through neonatal capsaicin treatment, surgical sympathecomy in adult rats, neurectomy of the mandibular and buccal branches of the facial nerve in adult rats or division of the infraorbital nerve in adult rats. Normal vibrissae developed a length of 51.1 mm and a diameter of 178 microm (row alpha-delta), 44.1 mm and 181 microm (row 1) and 33.2 mm and 165 microm (row 2). In all experimental groups the examined vibrissae developed a normal final length and proximal diameter. This indicates that local nerves do not influence vibrissal growth to any major extent.     

Sustained mental workload does not affect subsequent sleep intensity

Mental activity is a neglected factor in sleep research. The few investigations on sleep that manipulate prior mental activity are inconclusive with respect to the possible effects of mental activity on recovery. In the present study, the effects of two levels of mental activity on subsequent sleep were studied. Thirteen male subjects (range 18-28 years) participated in one lightly and two heavily mentally strenuous conditions in a counterbalanced order. Light mental activity included 8 h of relaxed video watching. The second condition consisted of performing computer tasks involving sustained attention, memory, logical thinking and calculations for eight consecutive hours. In the third condition, the same heavy mental workload was interspersed with breaks. Subjectively, the subjects rated the condition with heavy mental activity (without breaks) as mentally more strenuous than the condition with light mental activity. Subjects were significantly less awake shortly after sleep onset in the heavy-workload condition than in the light-workload condition. There were no differences between the conditions in any of the other visually scored sleep variables. The total amount of slow wave activity (SWA) and its discharge during the night was not affected by the level of mental activity or by the presence of breaks. These findings fail to support the proposition that SWA reflects a need for sleep that accumulates at a rate depending on mental activity during prior wakefulness.     

Mental fatigue does not affect maximal anaerobic exercise performance

Purpose

Mental fatigue can negatively impact on submaximal endurance exercise and has been attributed to changes in perceived exertion rather than changes in physiological variables. The impact of mental fatigue on maximal anaerobic performance is, however, unclear. Therefore, the aim of the present study was to induce a state of mental fatigue to examine the effects on performance, physiological and perceptual variables from subsequent tests of power, strength and anaerobic capacity.

Methods

Twelve participants took part in the single-blind, randomised, crossover design study. Mental fatigue was induced by 90 min of the computer-based Continuous Performance Task AX version. Control treatment consisted of 90 min of watching emotionally neutral documentaries. Participants consequently completed countermovement jump, isometric leg extension and a 3-min all-out cycling tests.

Results

Results of repeated measures analysis of variance and paired t tests revealed no difference in any performance or physiological variable. Rating of perceived exertion tended to be greater when mentally fatigued (mental fatigue = 19 ± 1 vs control = 18 ± 1, p = 0.096, \(\eta^{2}_{\text{p}}\) = .232) and intrinsic motivation reduced (mental fatigue = 11 ± 4 vs control = 13 ± 6, p = 0.063, d = 0.597) in the mental fatigue condition.

Conclusions

Near identical responses in performance and physiological parameters between mental fatigue and control conditions suggest that peripheral mechanisms primarily regulate maximal anaerobic exercise. Whereas mental fatigue can negatively impact submaximal endurance exercise, it appears that explosive power, voluntary maximal strength and anaerobic work capacity are unaffected.