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91.
92.
Neuropeptide Y Attenuates Stress‐Induced Bone Loss Through Suppression of Noradrenaline Circuits
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PA Baldock S Lin L Zhang T Karl Y Shi F Driessler A Zengin B Hörmer NJ Lee IPL Wong EJD Lin RF Enriquez B Stehrer MJ During E Yulyaningsih S Zolotukhin ST Ruohonen E Savontaus A Sainsbury H Herzog 《Journal of bone and mineral research》2014,29(10):2238-2249
Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress‐induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress‐induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6‐week restraint, or cold‐stress protocol, Npy‐null mice exhibit three‐fold greater bone loss compared to wild‐type mice, owing to suppression of osteoblast activity. This stress‐protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin‐releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy‐null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy‐null mice blocks the increase in circulating noradrenaline and the stress‐induced bone loss. Thus, NPY protects against excessive stress‐induced bone loss, through Y2 receptor‐mediated modulation of central and peripheral noradrenergic neurons. © 2014 American Society for Bone and Mineral Research. 相似文献
93.
Zhenxing Yu Junjie Wang Na Zhang Jungwoo Shin Qiye Zheng Subing Qu Xiaoqing He Angus Rockett Hong Yang Paul V. Braun 《RSC advances》2018,8(68):38745
Here we show that dendritic architectures are attractive as the basis of hierarchically structured battery electrodes. Dendritically structured FeS2, synthesized via simple thermal sulfidation of electrodeposited dendritic α-Fe, was formed into an electrode and cycled vs. lithium. The reversible capacities of the dendritic FeS2 cathode were 560 mA h g−1 at 0.5C and 533 mA h g−1 at 1.0C after 50 cycles over 0.7–3.0 V. Over 0.7–2.4 V, where the electrode is more stable, the reversible capacities are 348 mA h g−1 at 0.2C and 179 mA h g−1 at 1.0C after 150 cycles. The good cycling performance and high specific capacities of the dendritic FeS2 cathodes are attributed to the ability of a dendritic structure to provide good ion and electron conducting pathways, and a large surface area. Importantly, the dendritic structure appears capable of accommodating volume changes imposed by the lithiation and delithiation process. The presence of a Li2−xFeS2 phase is indicated for the first time by high-resolution transmission electron microscopy (HRTEM) and scanning transmission electron microscopy (STEM) electron energy loss spectroscopy (EELS). We suspect this phase is what enables electrochemical cycling to possess high reversibility over 0.7–2.4 V.High performance dendritically structured FeS2 cathodes are systemically studied. The dendritic structure is resistant to volume changes during cycling, increasing cyclability. The presence of Li2–xFeS2, which also enhances cyclability, is confirmed. 相似文献
94.
Kidney-specific inactivation of the KIF3A subunit of kinesin-II inhibits renal ciliogenesis and produces polycystic kidney disease 总被引:21,自引:0,他引:21
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Lin F Hiesberger T Cordes K Sinclair AM Goldstein LS Somlo S Igarashi P 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(9):5286-5291
Polycystic kidney disease (PKD) is the most common genetic cause of renal failure in humans. Several proteins that are encoded by genes associated with PKD have recently been identified in primary cilia in renal tubular epithelia. These findings have suggested that abnormalities in cilia formation and function may play a role in the pathogenesis of PKD. To directly determine whether cilia are essential to maintain tubular integrity, we conditionally inactivated KIF3A, a subunit of kinesin-II that is essential for cilia formation, in renal epithelia. Constitutive inactivation of KIF3A produces abnormalities of left-right axis determination and embryonic lethality. Here we show that tissue-specific inactivation of KIF3A in renal tubular epithelial cells results in viable offspring with normal-appearing kidneys at birth. Cysts begin to develop in the kidney at postnatal day 5 and cause renal failure by postnatal day 21. The cyst epithelial cells lack primary cilia and exhibit increased proliferation and apoptosis, apical mislocalization of the epidermal growth factor receptor, increased expression of beta-catenin and c-Myc, and inhibition of p21(CIP1). These results demonstrate that the absence of renal cilia produces both the clinical and cell biological findings associated with PKD. Most generally, the phenotype of Kif3a mutant mice suggests a role for primary cilia in the maintenance of lumen-forming epithelial differentiation. 相似文献
95.
Vasodilator substances act either directly on vascular smooth muscle (e.g., adenosine) or indirectly (e.g., acetylcholine) on endothelial cells that respond by releasing an unknown powerful, short-lived relaxing factor. To determine whether chronic hypertension or hypercholesterolemia or both would alter the release of the endothelium-derived relaxing factor, experiments were performed in hypertensive rabbits (5-week cellophane wrap perinephritis; mean blood pressure, 134.7 mm Hg) and normotensive rabbits (mean blood pressure, 80 mm Hg) with a Doppler flow transducer and perivascular balloon implanted on the lower abdominal aorta. Rabbits were fed either 1% cholesterol or control diet for 4 weeks before the experiment. On the day of the experiment, resting hindlimb vascular resistance was greatest in hypertensive rabbits fed 1% cholesterol diet, followed (in descending order) by hypertensive rabbits, normotensive rabbits fed 1% cholesterol diet, and normotensive rabbits. Pharmacological autonomic reflex blockade was induced, and steady state intravenous infusion curves to acetylcholine, serotonin, and adenosine were constructed. Sensitivity (location of effective dose, 50%) to the three vasodilator agents was altered less than twofold from the values in normotensive rabbits for any treatment group. The maximum vasodilator response to acetylcholine, but not to adenosine or serotonin, infusion was reduced significantly in the treated rabbits compared with that in normal rabbits. Reactive hyperemic responses to 5 to 80 seconds of ischemia were not significantly different among the treatment groups. These results indicate that hypertension with or without hypercholesterolemia does not greatly alter the responsiveness of the hindlimb resistance vasculature to these three vasodilator agents or to ischemia. 相似文献
96.
Comparative effects of oxygen supplementation on theophylline and acetaminophen clearance in human cirrhosis 总被引:5,自引:0,他引:5
BACKGROUND & AIMS: Sinusoidal capillarization in cirrhosis may impair the transfer of oxygen into hepatocytes; this may contribute to impaired oxidative drug metabolism. The aim of this study was to test this hypothesis by comparing the effects of oxygen supplementation in cirrhotic patients on the clearance of theophylline, which is dependent on hepatic oxidative metabolism, with its effect on the clearance of acetaminophen, which is reliant on hepatic conjugation reactions. METHODS: Ten cirrhotic patients awaiting liver transplant and 5 control subjects were studied. Oral acetaminophen (1000 mg) and intravenous theophylline (3 mg/kg) were administered simultaneously on two separate occasions, 7 days apart. Subjects were randomized to breathe either room air or oxygen via face mask at 12 L/min for 9 hours of blood sampling. RESULTS: Theophylline and acetaminophen clearances were significantly reduced by a mean of 54% and 50%, respectively, in cirrhotic patients compared with controls. Oxygen supplementation improved plasma theophylline clearance in cirrhotic patients by a mean of 34% (P = 0. 001), whereas acetaminophen clearance remained unchanged. CONCLUSIONS: These findings indicate that, in cirrhosis, impaired hepatocyte oxygenation contributes to reduced oxidative drug metabolism and that oxidative drug metabolism can be improved by oxygen supplementation. 相似文献
97.
Posttraumatic Stress and Complicated Grief in Family Members of Patients in the Intensive Care Unit
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Background Family members of patients in intensive care units (ICUs) are at risk for mental health morbidity both during and after a
patient’s ICU stay.
Objectives To determine prevalences of and factors associated with anxiety, depression, posttraumatic stress and complicated grief in
family members of ICU patients.
Design Prospective, longitudinal cohort study.
Participants Fifty family members of patients in ICUs at a large university hospital participated.
Measurements We used the Control Preferences Scale to determine participants’ role preferences for surrogate decision-making. We used the
Hospital Anxiety and Depression Scale, Impact of Event Scale, and Inventory of Complicated Grief to measure anxiety and depression
(at enrollment, 1 month, 6 months), posttraumatic stress (6 months), and complicated grief (6 months).
Results We interviewed all 50 participants at enrollment, 39 (78%) at 1 month, and 34 (68%) at 6 months. At the three time points,
anxiety was present in 42% (95% CI, 29–56%), 21% (95% CI, 10–35%), and 15% (95% CI, 6–29%) of participants. Depression was
present in 16% (95% CI, 8–28%), 8% (95% CI, 2–19%), and 6% (95% CI, 1–18%). At 6 months, 35% (95% CI, 21–52%) of participants
had posttraumatic stress. Of the 38% who were bereaved, 46% (95% CI, 22–71%) had complicated grief. Posttraumatic stress was
not more common in bereaved than nonbereaved participants, and neither posttraumatic stress nor complicated grief was associated
with decision-making role preference or with anxiety or depression during the patient’s ICU stay.
Conclusions Symptoms of anxiety and depression diminished over time, but both bereaved and nonbereaved participants had high rates of
posttraumatic stress and complicated grief. Family members should be assessed for posttraumatic stress and complicated grief. 相似文献
98.
Parotid metastatic disease from cutaneous squamous cell carcinoma: Prognostic role of facial nerve sacrifice,lateral temporal bone resection,immune status and P‐stage
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99.
100.