Intrapulmonary arteriovenous (IPAV) shunting has been shown to occur at rest in some subjects breathing a hypoxic gas mixture [fraction of inspired oxygen (FI(O(2))) = 0.12] for brief periods of time. In the present study we set out to determine if IPAV shunting could be induced at rest in all subjects exposed to hypoxia for 30 min. Twelve subjects (6 women) breathed four levels of hypoxia (FI(O(2)) = 0.16, 0.14, 0.12, and 0.10) for 30 min each in either an ascending or descending order with a 15-min normoxic break between bouts. Saline contrast echocardiography was used to detect IPAV shunt and a shunt score (0-5) was assigned based on contrast in the left ventricle with a shunt score ≥ 2 considered significant. Pulmonary artery systolic pressure (PASP) was determined using Doppler ultrasound. The total number of subjects demonstrating shunt scores ≥ 2 for FI(O(2)) = 0.16, 0.14, 0.12, and 0.10 was 1/12, 7/12, 9/12, and 12/12, respectively. Shunt scores were variable between subjects but significantly greater than normoxia for FI(O(2)) = 0.12 and 0.10. Shunt scores correlated with peripheral measurements of arterial oxygen saturation (SpO(2)) (r(w) = -0.67) and PASP (r(w) = 0.44), despite an increased shunt score but no increase in PASP while breathing an FI(O(2)) = 0.12. It is unknown how hypoxia induces the opening of IPAV shunts, but these vessels may be controlled via similar mechanisms as systemic vessels that vasodilate in response to hypoxia. Despite intersubject variability our results indicate significant IPAV shunting occurs at rest in all subjects breathing an FI(O(2)) = 0.10 for 30 min.
Concern has been raised that altering the fraction of inspired O₂ (Fi(O₂)) could accelerate or decelerate microbubble dissolution time within the pulmonary vasculature and thereby invalidate the ability of saline contrast echocardiography to detect intrapulmonary arteriovenous shunt in subjects breathing either a low or a high Fi(O₂). The present study determined whether the gaseous component used for saline contrast echocardiography affects the detection of exercise-induced intrapulmonary arteriovenous shunt under varying Fi(O₂). Twelve healthy human subjects (6 men, 6 women) performed three 11-min bouts of cycle ergometer exercise at 60% peak O₂ consumption (Vo(2peak)) in normoxia, hypoxia (Fi(O₂) = 0.14), and hyperoxia (Fi(O₂) = 1.0). Five different gases were used to create saline contrast microbubbles by two separate methods and were injected intravenously in the following order at 2-min intervals: room air, 100% N₂, 100% O₂, 100% CO₂, and 100% He. Breathing hyperoxia prevented exercise-induced intrapulmonary arteriovenous shunt, whereas breathing hypoxia and normoxia resulted in a significant level of exercise-induced intrapulmonary arteriovenous shunt. During exercise, for any Fi(O₂) there was no significant difference in bubble score when the different microbubble gas compositions made with either method were used. The present results support our previous work using saline contrast echocardiography and validate the use of room air as an acceptable gaseous component for use with saline contrast echocardiography to detect intrapulmonary arteriovenous shunt during exercise or at rest with subjects breathing any Fi(O₂). These results suggest that in vivo gas bubbles are less susceptible to changes in the ambient external environment than previously suspected.
Cardiopulmonary function is reduced in adults born very preterm, but it is unknown if this results in reduced pulmonary gas exchange efficiency during exercise and, consequently, leads to reduced aerobic capacity in subjects with and without bronchopulmonary dysplasia (BPD). We hypothesized that an excessively large alveolar to arterial oxygen difference (AaDO2) and resulting exercise-induced arterial hypoxemia (EIAH) would contribute to reduced aerobic fitness in adults born very preterm with and without BPD. Measurements of pulmonary function, lung volumes and diffusion capacity for carbon monoxide (DLco) were made at rest. Measurements of maximal oxygen consumption, peak workload, temperature- and tonometry-corrected arterial blood gases, and direct measure of hemoglobin saturation with oxygen (SaO2) were made preexercise and during cycle ergometer exercise in ex-preterm subjects ≤32-wk gestational age, with BPD (n = 12), without BPD (PRE; n = 12), and full term controls (CONT; n = 12) breathing room air. Both BPD and PRE had reduced pulmonary function and reduced DLco compared with CONT. The AaDO2 was not significantly different between groups, and there was no evidence of EIAH (SaO2 < 95% and/or AaDO2 ≥ 40 Torr) in any subject group preexercise or at any workload. Arterial O2 content was not significantly different between the groups preexercise or during exercise. However, peak power output was decreased in BPD and PRE subjects compared with CONT. We conclude that EIAH in adult subjects born very preterm with and without BPD does not likely contribute to the reduction in aerobic exercise capacity observed in these subjects.
Diosgenin, a yam-derived compound, was found to facilitate the repair of axonal atrophy and synaptic degeneration and improve memory dysfunction in a transgenic mouse model of Alzheimer’s disease (AD). It was also found to enhance neuronal excitation and memory function even in normal mice. We hypothesized that diosgenin, either isolated or in an extract, may represent a new category of cognitive enhancers with essential activities that morphologically and functionally reinforce neuronal networks. This study aimed to investigate the effects of a diosgenin-rich yam extract on cognitive enhancement in healthy volunteers. For this placebo-controlled, randomized, double-blind, crossover study, 28 healthy volunteers (age: 20–81 years) were recruited from Toyama Prefecture, Japan, and was randomly assigned to receive either a yam extract or placebo. Preliminary functional animal experiments indicated that an oil solvent mediated the most efficient distribution of diosgenin into the blood and brain after oral administration, and was a critical factor in the cognitive benefits. Therefore, test samples (placebo and yam extract) were prepared with olive oil and formulated as soft capsules. The intake period was 12 weeks, and a 6-week washout period separated the two crossover intake periods. The Japanese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test was used for neurocognitive assessment, and the adverse effects were monitored through blood testing. Diosgenin-rich yam extract consumption for 12 weeks yielded significant increases in total RBANS score. Among the 12 individual standard cognitive subtests, diosgenin-rich yam extract use significantly improved the semantic fluency. No adverse effects were reported. The diosgenin-rich yam extract treatment appeared to safely enhance cognitive function in healthy adults.
We have measured the differential production cross sections as a function of scaled momentum x p ϭ2 p/E c.m. of the identified hadron species ϩ , K ϩ , K 0 , K* 0 , , p, ⌳ 0 , and of the corresponding antihadron species in inclusive hadronic Z 0 decays, as well as separately for Z 0 decays into light (u, d, s), c and b flavors. Clear flavor dependences are observed, consistent with expectations based upon previously measured production and decay properties of heavy hadrons. These results were used to test the QCD predictions of Gribov and Lipatov, the predictions of QCD in the modified leading logarithm approximation with the ansatz of local parton-hadron duality, and the predictions of three fragmentation models. The ratios of production of different hadron species were also measured as a function of x p and were used to study the suppression of strange meson, strange and non-strange baryon, and vector meson production in the jet fragmentation process. The light-flavor results provide improved tests of the above predictions, as they remove the contribution of heavy hadron production and decay from that of the rest of the fragmentation process. In addition we have compared hadron and antihadron production as a function of x p in light quark ͑as opposed to antiquark͒ jets. Differences are observed at high x p , providing direct evidence that higher-momentum hadrons are more likely to contain a primary quark or antiquark. The differences for pseudoscalar and vector kaons provide new measurements of strangeness suppression for high-x p fragmentation products. ͓S0556-2821͑99͒06101-9͔
The pharmacological properties of Eleutherococcus senticosus leaf have not been clarified although it is taken as a food item. In this study, the effects of water extract of Eleutherococcus senticosus leaves on memory function were investigated in normal mice. Oral administration of the extract for 17 days significantly enhanced object recognition memory. Compounds absorbed in blood and the brain after oral administration of the leaf extract were detected by LC-MS/MS analyses. Primarily detected compounds in plasma and the cerebral cortex were ciwujianoside C3, eleutheroside M, ciwujianoside B, and ciwujianoside A1. Pure compounds except for ciwujianoside A1 were administered orally for 17 days to normal mice. Ciwujianoside C3, eleutheroside M, and ciwujianoside B significantly enhanced object recognition memory. These results demonstrated that oral administration of the leaf extract of E. senticosus enhances memory function, and that active ingredients in the extract, such as ciwujianoside C3, eleutheroside M, and ciwujianoside B, were able to penetrate and work in the brain. Those three compounds as well as the leaf extract had dendrite extension activity against primary cultured cortical neurons. The effect might relate to memory enhancement.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder resulting in structural brain changes and memory impairment. We hypothesized that reconstructing neural networks is essential for memory recovery in AD. Heat shock cognate 70 (HSC70), a member of the heat shock protein family of molecular chaperones, is upregulated in AD patient brains, and recent studies have demonstrated that HSC70 facilitates axonal degeneration and pathological progression in AD. However, the direct effects of HSC70 inhibition on axonal development and memory function have never been investigated. In this study, we examined the effects of a small-molecule HSC70 inhibitor, VER-155008, on axonal morphology and memory function in a mouse model of AD (5XFAD mice). We found that VER-155008 significantly promoted axonal regrowth in amyloid β-treated neurons in vitro and improved object recognition, location, and episodic-like memory in 5XFAD mice. Furthermore, VER-155008 penetrated into the brain after intraperitoneal administration, suggesting that VER-155008 acts in the brain in situ. Immunohistochemistry revealed that VER-155008 reduced bulb-like axonal swelling in the amyloid plaques in the perirhinal cortex and CA1 in 5XFAD mice, indicating that VER-155008 also reverses axonal degeneration in vivo. Moreover, the two main pathological features of AD, amyloid plaques and paired helical filament tau accumulation, were reduced by VER-155008 administration in 5XFAD mice. This is the first report to show that the inhibition of HSC70 function may be critical for axonal regeneration and AD-like symptom reversal. Our study provides evidence that HSC70 can be used as a new therapeutic target for AD treatment.
We present measurements of Rs using the SLD at the SLC. The analyses use 2D and 3D impact parameter tags and a displaced 3D vertex tag which all exploit the small size and stability of the e+e-interaction point and the precision 3D CCD pixel vertex detector to achieve high b&tagging efficiencies and purities. The combined measurement yields Rb = 0.229 f 0.011 and is consistent with standard model predictions.PACS number(s): 13.38.Dg, 13.65.+i
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