Effect of distance feedback on pacing strategy and perceived exertion during cycling

PURPOSE: The aim of this study was to investigate whether providing incorrect distance feedback would alter pacing strategies, perceived exertion, and heart rate during 20-km cycling time trials (TT). METHODS: Well-trained cyclists (N=15) performed a peak power output (PPO) test, familiarization trial, and four 20-km cycling TT during which they were provided with only distance feedback using 1-km distance splits. For the control trial, subjects received accurate feedback at each kilometer split. In the increase trial, they received inaccurate feedback at 0.775 km for the first kilometer split with the distance increasing by 25 m each subsequent split up to 1.25 km in the final kilometer split. For the decrease trial, inaccurate feedback was provided at 1.25 km for the first kilometer split with the distance decreasing by 25 m each subsequent split up to 0.775 km in the final split. For the random trial, distance splits were randomized. RESULTS: No significant differences were found in the finishing times between trials. Pacing strategies were unaltered as suggested by similar power output profiles during all trials. RPE scores were also similar for all trials. However, average heart rate varied significantly between trials (P<0.05). CONCLUSIONS: These results suggest that exercise performance, pacing strategy, and RPE during a 20-km cycling TT are not altered by incorrect distance feedback. The data supported the existence of a pacing strategy that is set before exercise and that is unaffected by external distance feedback.     

A novel means of identifying the neuraminidase type of currently circulating human A(H1) influenza viruses

With the recent emergence and spread of influenza A(H1N2) viruses which appear to have arisen by reassortment of circulating A(H1N1) and A(H3N2) strains, there is a need in epidemiological studies to determine the neuraminidase type in order to differentiate between influenza A(H1N2) and A(H1N1) strains. A fluorescence-based neuraminidase enzyme inhibition assay that has been developed to screen influenza viruses for potential resistance to the neuraminidase inhibitor drugs appears to be suitable for this purpose. When used with the neuraminidase inhibitor zanamivir the assay was able to provide a positive predictive value of 93.5% for the identification of neuraminidase type N1 or N2. This assay enables a large number of influenza A viruses to be screened at low cost to determine relative levels of A(H1N2) or A(H1N1) viruses circulating in the population.     

Contribution of sex differences in the acute stress response to sex differences in water maze performance in the rat

Male rats outperform females in spatial tasks, such as the water maze (WM). Female rats are known to have higher basal serum corticosterone (CORT) levels and to manifest a more rapid and stronger CORT response to novel stressors. Sex differences in stress responses to the handling and forced swimming in the WM task might contribute to the sex difference in WM performance. In Experiment 1, naive females were found to be impaired relative to naive males in swimming to a visible platform in a WM pool due to strongly thigmotaxic swimming by females. In Experiment 2, serum CORT, a physiological measure of stress, was highly elevated during and after WM training, with female > male values and strong inverse correlations between CORT and measures of WM performance in females. Familiarization with the WM pool and test procedures by strategies pretraining prior to spatial training reduced or eliminated the sex differences in the stress response and WM performance. In Experiment 3, adrenalectomy to eliminate the stress response eliminated sex differences in WM performance. Taken together, the results suggest that male and female rats may harbor brain circuitry that is equally capable of accurate spatial navigation and memory in the WM but which may be impaired to different degrees by the differential stress responses triggered by WM testing.     

In vitro generation and characterisation of an influenza B variant with reduced sensitivity to neuraminidase inhibitors

A contemporary influenza type B virus was passaged in vitro in the presence of increasing concentrations of the neuraminidase inhibitors, zanamivir and oseltamivir carboxylate (0.1-1000 microM over nine passages). After the fifth passage in the presence of zanamivir (10 microM), the virus acquired a Glu 119 Asp neuraminidase mutation (influenza A N2 subtype numbering) in the enzyme active site. After a further three passages, in which growth occurred in 100 microM of zanamivir, a Gln 218 Lys mutation (A (H3) numbering) in the HA1 domain of the haemagglutinin was found. In a fluorescence-based neuraminidase inhibition assay, viruses with the Glu 119 Asp NA mutation had a 32,000-fold reduction in sensitivity to the NA inhibitor zanamivir compared to the wild-type virus, while the mutation resulted in a 105-fold reduction in sensitivity to oseltamivir carboxylate. Viruses grown in the presence of 1000 microM oseltamivir carboxylate did not acquire any neuraminidase mutations but did have a His 103 Gln substitution (A (H3) numbering) in the HA1 region of the haemagglutinin which was demonstrated to significantly reduce receptor binding strength in vitro. Tissue culture assays demonstrated that the HA mutation caused a seven-fold reduction in sensitivity to oseltamivir carboxylate, and a 90-fold reduction in sensitivity to zanamivir.     

Interleukin-6 (IL-6), IL-1, receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin production by human osteoblastic cells: comparison of the effects of 17-beta oestradiol and raloxifene

Oestrogen inhibits bone resorption, at least in part, by regulating the production of several cytokines, including interleukin-6 (IL-6), IL-1, receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) by cells of the osteoblastic lineage. The selective oestrogen receptor modulator raloxifene (RAL) acts on bone in a similar manner to oestrogen, although the mechanisms of action of RAL on osteoblasts still remain unclear. We investigated and compared the effects of 17-beta oestradiol (E(2)) and RAL on the regulation of IL-6, IL-1, RANKL and OPG in vitro in primary human osteoblastic (HOB) cells and in an immortalised clonal human bone marrow stromal cell line (HCC1) with osteoblastic characteristics. We tested E(2) and RAL at concentrations ranging from 10(-12) to 10(-6) M. IL-6, IL-1alpha and IL-1beta, OPG and RANKL were measured by ELISA. RANKL and OPG mRNA steady state level was assessed by quantitative PCR analysis. Both E(2) and RAL led to a significant reduction in IL-6 production in the HOB cells, although the effect was more marked with E(2) (P<0.05). IL-1alpha and IL-1beta also decreased significantly following treatment with E(2) and RAL in the HCC1 cells (E(2) (10(-8), 10(-7) and 10(-6) M), % reduction (means+/-S.E.M.) compared with vehicle-treated cells - IL-1alpha: 84+/-7.4, 70.8+/-2.9*, 78.2+/-4.8*; IL-1beta: 79+/-10, 72.8+/-8.2*, 66.6+/-2.8*; RAL (10(-8), 10(-7) and 10(-6) M) - IL-1alpha: 72.4+/-5*, 79+/- 5.2*, 102+/-7.7; IL-1beta: 67.9+/-3.2*, 69+/-2.5*, 73.8+/- 6.2*; *P<0.05). OPG protein concentration decreased significantly in a dose-dependent manner following treatment with E(2) and RAL (% reduction E(2) (10(-8), 10(-7) and 10(-6) M) - HOB: 72.5+/-8.4*, 80+/-6.7*, 62.8+/-8.9*; HCC1: 109+/-4, 98.8+/-6, 54.5+/-3.4*; RAL (10(-8), 10(-7) and 10(-6) M) - HOB: 81.5+/-5.5*, 62.7+/-7.4*, 55.2+/-10.9*; HCC1: 92.7+/-7.4, 67+/-12.2*, 39+/-4.5*; *P<0.05). In the HCC1 cells, RANKL protein did not change significantly following E(2). In contrast, a significant reduction in RANKL was seen with RAL at 10(-7) and 10(-6) M (66+/-6.4% and 74+/-3% respectively). There was no change in OPG mRNA expression following E(2) or RAL in the HCC1 cells, although in the HOB cells we observed a significant reduction in OPG mRNA. RANKL mRNA decreased significantly in the HCC1 cells following RAL (10(-8), 10(-7)and 10(-6) M) treatment (% change from controls: 52+/-2*, 62+/-1*, 53+/-5.8*; *P<0.05). Similar results were seen in the HOB cells with RAL at 10(-6) M (RANKL mRNA: 72+/-5.5, P<0.05). In addition, there was a significant decrease in the RANKL/OPG ratio after RAL at 10(-6) M (HOB: 65.6+/-5*, HCC1: 56.9+/-20*; *P<0.05). RANKL/OPG ratio did not change significantly in the HCC1 cells following E(2). However, in contrast to RAL, we observed an increase in the RANKL/OPG ratio in the HOB cells following treatment with E(2). In conclusion, the study shows that RAL and E(2) have divergent cell-specific effects on the regulation of cytokines. The data also suggest that, in contrast to E(2), RAL may exert its anti-resorptive actions, at least in part, via the RANKL/OPG pathway. Further in vivo studies are required to confirm this.     

Treatment of radiation induced hemorrhagic cystitis with hyperbaric oxygen

PURPOSE: Hemorrhagic cystitis can occur 6 months to 10 years after pelvic radiation therapy with moderate to severe persistent rates of hematuria as 3% to 5% after radiotherapy for pelvic malignancies. Current treatment modalities for hemorrhagic cystitis include oral and intravenous agents, intravesical therapy and selective embolization of the hypogastric arteries. Hyperbaric oxygen therapy is now a widely accepted treatment option for radiation induced hemorrhagic cystitis. We assess the efficacy of hyperbaric oxygen for treatment of hemorrhagic cystitis. MATERIAL AND METHODS: From May 1988 through March 2001, 62 patients with radiation induced hemorrhagic cystitis were treated with hyperbaric oxygen at our institution. Followup ranged from 10 to 120 months. The primary pathological conditions were prostate cancer (81%) and bladder cancer (10%). Mean patient age was 70 years (range 15 to 88). Mean time between completion of radiation therapy and onset of hematuria was 48 months (range 0 to 355). Patients received an average of 33 hyperbaric oxygen treatments (range 9 to 68). RESULTS: Of the 62 patients treated information on 57 was available for analysis. Of the 57 patients (86%) 49 experienced complete resolution or marked improvement of hematuria following hyperbaric oxygen treatment. Of the 8 patients who did not improve 4 received fewer than 40 hyperbaric oxygen treatments and 7 prematurely terminated treatment (medical co-morbidities 4, claustrophobia 2, temporary resolution of symptoms 1). CONCLUSIONS: Hyperbaric oxygen therapy for radiation induced hemorrhagic cystitis is an efficacious treatment modality for patients in whom other forms of management have failed.     

Increasing viscosity of the intestinal contents alters small intestinal structure and intestinal growth, and stimulates proliferation of enterotoxigenic Escherichia coli in newly-weaned pigs

Sources of viscous soluble fibre, such as barley and oats, have often been included in the weaning diet of the pig to accelerate development of the large intestine. Inclusion of a non-fermentable, viscous compound, sodium carboxymethylcellulose (CMC), in a low-fibre weaning diet was tested to assess the influence of digesta viscosity on the gut in the absence of increased fermentation. Two CMC sources, of low and high viscosity, were added to cooked rice-based diet at 40 g/kg total diet. A third control rice diet did not contain any CMC. Diets were fed for 13 d following weaning at 3 weeks of age. Addition of CMC to the diet significantly increased the intestinal viscosity of digesta within the small (P<0.001) and large (P<0.05) intestine. No simple association was found between increases in intestinal viscosity and effects on intestinal morphology and whole-body growth. The average empty-body-weight gain and the small intestinal villus height increased with low-viscosity CMC, but decreased with the high-viscosity CMC group. The full large intestinal weight increased in all pigs fed CMC. Dietary CMC (both low- and high-viscosity) increased the percentage moisture of digesta and faeces, and was associated with increased faecal shedding of enterotoxigenic haemolytic Escherichia coli. Feed ingredients in weaning diets that excessively increase the viscosity of the intestinal digesta may be detrimental to pig health and production.