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排序方式: 共有9547条查询结果,搜索用时 343 毫秒
951.
Joana Alma?a Patthara Kongsuphol Bernhard Hieke Jiraporn Ousingsawat Benoit Viollet Rainer Schreiber Margarida D. Amaral Karl Kunzelmann 《Pflügers Archiv : European journal of physiology》2009,458(4):713-721
The metabolic sensor adenosine-monophosphate-activated kinase (AMPK) detects the cellular energy status and adjusts metabolic
activity according to the cytosolic AMP to ATP ratio. Na+ absorption by epithelial Na+ channels (ENaC) is a highly energy-consuming process that is inhibited by AMPK. We show that the catalytic subunit α1 of
AMPK inhibits ENaC in epithelial tissues from airways, kidney, and colon and that AMPK regulation of ENaC is absent in AMPKα1−/−
mice. These mice demonstrate enhanced electrogenic Na+ absorption that leads to subtle changes in intestinal and renal function and may also affect Na+ absorption and mucociliary clearance in the airways. We demonstrate that AMPK uses the ubiquitin ligase Nedd4-2 to inhibit
ENaC by increasing ubiquitination and endocytosis of ENaC. Thus, enhanced expression of epithelial Na+ channels was detected in colon, airways, and kidney of AMPKα1−/− mice. Therefore, AMPKα1 is a physiologically important regulator
of electrogenic Na+ absorption and may provide a novel pharmacological target for controlling epithelial Na+ transport.
Categories: Membranes and Transport; bioenergetics, anabolic/catabolic processes studied at the molecular level. 相似文献
952.
Kongsuphol P Hieke B Ousingsawat J Almaca J Viollet B Schreiber R Kunzelmann K 《Pflügers Archiv : European journal of physiology》2009,457(5):1071-1078
Previous in vitro studies suggested that Cl(-) currents produced by the cystic fibrosis transmembrane conductance regulator (CFTR; ABCC7) are inhibited by the alpha1 isoform of the adenosine monophosphate (AMP)-stimulated kinase (AMPK). AMPK is a serine/threonine kinase that is activated during metabolic stress. It has been proposed as a potential mediator for transport-metabolism coupling in epithelial tissues. All previous studies have been performed in vitro and thus little is known about the regulation of Cl(-) secretion by AMPK in vivo. Using AMPKalpha1(-/-) mice and wild-type littermates, we demonstrate that phenformin, an activator of AMPK, strongly inhibits cAMP-activated Cl(-) secretion in mouse airways and colon, when examined in ex vivo in Ussing chamber recordings. However, phenformin was equally effective in AMPKalpha1(-/-) and wild-type animals, suggesting additional AMPK-independent action of phenformin. Phenformin inhibited CFTR Cl(-) conductance in basolaterally permeabilized colonic epithelium from AMPKalpha1(+/+) but not AMPKalpha1(-/-) mice. The inhibitor of AMPK compound C enhanced CFTR-mediated Cl(-) secretion in epithelial tissues of AMPKalpha1(-/-) mice, but not in wild-type littermates. There was no effect on Ca(2+)-mediated Cl(-) secretion, activated by adenosine triphosphate or carbachol. Moreover CFTR-dependent Cl(-) secretion was enhanced in the colon of AMPKalpha1(-/-) mice, as indicated in Ussing chamber ex vivo and rectal PD measurements in vivo. Taken together, these data suggest that epithelial Cl(-) secretion mediated by CFTR is controlled by AMPK in vivo. 相似文献
953.
Functional assembly and purinergic activation of bestrophins 总被引:1,自引:0,他引:1
Vladimir M. Milenkovic René Barro Soria Fadi Aldehni Rainer Schreiber Karl Kunzelmann 《Pflügers Archiv : European journal of physiology》2009,458(2):431-441
Proteins of the bestrophin family produce Ca2+-activated Cl− currents and regulate voltage-gated Ca2+ channels. Bestrophin 1 was first identified in the retinal pigment epithelium. Four human paralogs (hBest1–hBest4) exist,
and for some bestrophins, dimeric and heterotetrameric structures have been proposed. Here, we demonstrate that hBest1–hBest4
induce Cl− conductances of different amplitudes when expressed in HEK293 cells and when activated through purinergic stimulation. hBest1
mutants that are known to cause autosomal dominant macular dystrophy (Best disease) did not produce a Cl− current. Bestrophins were colocalized and showed molecular and functional interaction in HEK293 cells, overexpressing hBest1
and hBest2 or hBest4. Interaction was confirmed in airway epithelial cells coexpressing endogenous bestrophins. A fraction
of hBest2 and hBest4 was expressed in the membrane, while most of hBest1 was found in the endoplasmic reticulum. Nevertheless,
hBest1 has a clear role for the adenosine triphosphate (ATP; or uridine triphosphate)-induced Cl− current in both HEK293 and Calu-3 cells. Since native epithelial tissues typically express several bestrophin paralogs, these
proteins may exist as heterooligomeric structures.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
954.
von Wilmowsky C Bauer S Lutz R Meisel M Neukam FW Toyoshima T Schmuki P Nkenke E Schlegel KA 《Journal of biomedical materials research. Part B, Applied biomaterials》2009,89(1):165-171
Because of their ability to mimic the dimensions of constituent components of natural bone and the possibility to serve as a gene and drug-delivery carrier, nanotubes seem to be a promising coating for medical implants. Aim of this study was to investigate the effects of a TiO(2) nanotube structured surface on periimplant bone formation in vivo when compared with an untreated standard titanium surface. Twenty-five titanium implants covered with an ordered TiO(2) nanotube layer with an individual tube diameter of 30 nm and 25 commercially pure titanium (cp-Ti) implants were placed in the frontal skull of 25 domestic pigs. To evaluate the effects of the nanotube structured implants on the periimplant bone formation, bone-implant contact (BIC), and immunohistochemistry analysis were performed at day 3, 7, 14, 30, and 90. Evaluating immunohistochemistry, a significantly higher collagen type- I expression occurred at day 7 (p = 0.003), day 14 (p = 0.016), and day 30 (p = 0.044), for the nanostructured implants in comparison with the control group. It could be found that a nanotube structured implant surface with a diameter of 30 nm does influence bone formation and bone development by enhancing osteoblast function. SEM evaluation of the specimen surfaces revealed that the nanotube coatings do resist shearing forces that evoked by implant insertion. Because of their simple, low cost, flexible manufacturing and the possibility for the usage as drug or growth factor delivery system, nanotubes seem to be a promising method for future medical implant coatings. 相似文献
955.
Sack AT Cohen Kadosh R Schuhmann T Moerel M Walsh V Goebel R 《Journal of cognitive neuroscience》2009,21(2):207-221
Transcranial magnetic stimulation (TMS) is a tool for inducing transient disruptions of neural activity noninvasively in conscious human volunteers. In recent years, the investigative domain of TMS has expanded and now encompasses causal structure-function relationships across the whole gamut of cognitive functions and associated cortical brain regions. Consequently, the importance of how to determine the target stimulation site has increased and a number of alternative methods have emerged. Comparison across studies is precluded because different studies necessarily use different tasks, sites, TMS conditions, and have different goals. Here, therefore, we systematically compare four commonly used TMS coil positioning approaches by using them to induce behavioral change in a single cognitive study. Specifically, we investigated the behavioral impact of right parietal TMS during a number comparison task, while basing TMS localization either on (i) individual fMRI-guided TMS neuronavigation, (ii) individual MRI-guided TMS neuronavigation, (iii) group functional Talairach coordinates, or (iv) 10-20 EEG position P4. We quantified the exact behavioral effects induced by TMS using each approach, calculated the standardized experimental effect sizes, and conducted a statistical power analysis in order to calculate the optimal sample size required to reveal statistical significance. Our findings revealed a systematic difference between the four approaches, with the individual fMRI-guided TMS neuronavigation yielding the strongest and the P4 stimulation approach yielding the smallest behavioral effect size. Accordingly, power analyses revealed that although in the fMRI-guided neuronavigation approach five participants were sufficient to reveal a significant behavioral effect, the number of necessary participants increased to n = 9 when employing MRI-guided neuronavigation, to n = 13 in case of TMS based on group Talairach coordinates, and to n = 47 when applying TMS over P4. We discuss these graded effect size differences in light of the revealed interindividual variances in the actual target stimulation site within and between approaches. 相似文献
956.
Rudi Beschorner Jens Schittenhelm Eva Bueltmann Rainer Ritz Richard Meyermann Michel Mittelbronn 《Neuropathology》2009,29(2):176-180
Extragonadal teratomas in adulthood are exceptionally rare and usually not located within the cerebellum. We here report on a 66‐year‐old male patient clinically presenting with chronic occipital headache and episodes of severe vertigo. Neuroradiological investigations revealed a hemorrhagic tumor mass in the cerebellar vermis which was surgically removed and histologically diagnosed as mature teratoma. Hence, the presented case is extraordinary with regard to age, late clinical onset of symptoms and cerebellar location. Late clinical manifestation of the tumor in this case is probably due to an acute late‐onset hemorrhage within the tumor. 相似文献
957.
When Percutaneous Dilation Tracheotomy Maybe Hazardous: Abnormal Course of the Brachiocephalic Trunk
Jens Minnerup Oliver Summ Christian Oelschlaeger Thomas Niederstadt Ralf Dittrich Johannes Kleinheinz Rainer Dziewas 《Neurocritical care》2009,10(3):336-338
Introduction Percutaneous dilatational tracheotomy (PDT) is becoming increasingly popular in present day critical care medicine. In contrast
to the surgical approach, PDT involves a blind puncture and dilation of the pretracheal space, which may predispose to dangerous
complications in the case of anatomical, in particular vascular, anomalies.
Methods and Results We report on two patients, in whom an abnormal pulsation was detected when the infracricoid region was palpated in preparation
for PDT. An immediately performed ultrasound scan revealed an arterial blood vessel in front of the upper part of the trachea.
A subsequent CT-angiography showed an anomalous course of the brachiocephalic trunk. While too dangerous for PDT, the local
department of cranio-maxillofacial surgery was consulted for surgical tracheotomy.
Conclusion To avoid hazardous bleeding complications in PDT we recommend at least an ultrasound scan in case of an abnormal pulsation
and an enlarged thyroid gland.
J. Minnerup and O. Summ contributed equally to this study. 相似文献
958.
Background Moderate hypothermia (MH) is a therapeutic approach for ischemic stroke as well as cardiac arrest. Two different technical
strategies of ventilation during MH called alpha- and pH-stat dramatically influence cerebral blood flow (CBF). In turn this
might influence neuronal damage and intracranial pressure (ICP). Therefore, effects of ventilation on CBF and ICP were measured
in patients undergoing MH because of large ischemic stroke to address optimal ventilation management.
Methods Eight patients (n = 8) with large ischemic stroke in the territory of the middle cerebral artery (MCA) were treated by MH of 33°C within 24 h
after symptom onset. MH was applied at least for 72 h. Each day, patients were ventilated repetitively with either alpha-stat
or pH-stat for 60 min periods. Alpha-stat was applied between the measurements. ICP, CBF, and mean arterial blood pressure
(MABP) were measured. The xenon clearance method was used to assess CBF at the bedside.
Results There were no significant differences between ICP values for alpha-stat or pH-stat during days 1 and 2 after induction of
hypothermia. However, ICP was higher in the pH- as compared to the alpha-stat group (P < 0.05) and exceeded a mean of 20 mmHg on day 3. pH-stat led to a significant increase of CBF in all measures (P < 0.05), while MABP was unaffected.
Conclusions pH-stat implies a better CBF to the injured brain, while it might be dangerous by elevating ICP in more subacute stages. 相似文献
959.