共查询到20条相似文献,搜索用时 15 毫秒
1.
Desheng Lu Jerry X. Liu Tomoyuki Endo Haowen Zhou Shiyin Yao Karl Willert Ingo G. H. Schmidt-Wolf Thomas J. Kipps Dennis A. Carson 《PloS one》2009,4(12)
Background
Aberrant activation of Wnt/β-catenin signaling promotes the development of several cancers. It has been demonstrated that the Wnt signaling pathway is activated in chronic lymphocytic leukemia (CLL) cells, and that uncontrolled Wnt/β-catenin signaling may contribute to the defect in apoptosis that characterizes this malignancy. Thus, the Wnt signaling pathway is an attractive candidate for developing targeted therapies for CLL.Methodology/Principal Findings
The diuretic agent ethacrynic acid (EA) was identified as a Wnt inhibitor using a cell-based Wnt reporter assay. In vitro assays further confirmed the inhibitory effect of EA on Wnt/β-catenin signaling. Cell viability assays showed that EA selectively induced cell death in primary CLL cells. Exposure of CLL cells to EA decreased the expression of Wnt/β-catenin target genes, including LEF-1, cyclin D1 and fibronectin. Immune co-precipitation experiments demonstrated that EA could directly bind to LEF-1 protein and destabilize the LEF-1/β-catenin complex. N-acetyl-L-cysteine (NAC), which can react with the α, β-unsaturated ketone in EA, but not other anti-oxidants, prevented the drug''s inhibition of Wnt/β-catenin activation and its ability to induce apoptosis in CLL cells.Conclusions/Significance
Our studies indicate that EA selectively suppresses CLL survival due to inhibition of Wnt/β-catenin signaling. Antagonizing Wnt signaling in CLL with EA or related drugs may represent an effective treatment of this disease. 相似文献2.
Ricardo Saute Kevin Dabbs Jana E. Jones Daren C. Jackson Michael Seidenberg Bruce P. Hermann 《PloS one》2014,9(4)
Background
Attention deficit hyperactivity disorder (ADHD) is a common comorbidity of childhood epilepsy, but the neuroanatomical correlates of ADHD in epilepsy have yet to be comprehensively characterized.Methods
Children with new and recent-onset epilepsy with (n = 18) and without (n = 36) ADHD, and healthy controls (n = 46) underwent high resolution MRI. Measures of cortical morphology (thickness, area, volume, curvature) and subcortical and cerebellar volumes were compared between the groups using the program FreeSurfer 5.1.Results
Compared to the control group, children with epilepsy and ADHD exhibited diffuse bilateral thinning in the frontal, parietal and temporal lobes, with volume reductions in the brainstem and subcortical structures (bilateral caudate, left thalamus, right hippocampus). There were very few group differences across measures of cortical volume, area or curvature.Conclusions
Children with epilepsy and comorbid ADHD exhibited a pattern of bilateral and widespread decreased cortical thickness as well as decreased volume of subcortical structures and brainstem. These anatomic abnormalities were evident early in the course of epilepsy suggesting the presence of antecedent neurodevelopmental changes, the course of which remains to be determined. 相似文献3.
Background
An opioid peptide neuron/humoral feedback regulation might be involved in changes of intraocular pressure (IOP). The aims of this study are to investigate the effects of arcuate nucleus (ARC) and opioid peptides on intraocular pressure (IOP).Methods
Fifty-four healthy purebred New Zealand white rabbits (108eyes) were randomly divided into 4 groups, including control group, electrical stimulation group, [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) group, and [D-Pen 2, D-Pen5]- enkephalin (DPDPE) group. Bilateral IOP was measured after unilateral electrical stimulation of the ARC or unilateral microinjection into the ARC of the selective μ-opioid receptor agonist DAMGO or the selective δ opioid receptor agonist DPDPE, both alone and after pre-administration of either the non-selective opioid receptor antagonist naloxone or saline.Results
Both electrical stimulation in ARC and micro-injection either <mu> or <delta> opioid receptor agonists, DAMGO or DPDPE, respectively, caused a significant bilateral reduction in IOP (P<0.05) which was more pronounced in the ipsilateral than in the contralateral eye. Pretreatment with naloxone prevented some, but not all IOP reductions.Conclusion
The ARC takes part in the negative regulation of IOP, an action that may involve opioid neurons. 相似文献4.
Jangsup Moon Soon-Tae Lee Jiye Choi Keun-Hwa Jung Hyunwoo Yang Arshi Khalid Jeong-Min Kim Kyung-Il Park Jung-Won Shin Jae-Jun Ban Gwan-Su Yi Sang Kun Lee Daejong Jeon Kon Chu 《PloS one》2014,9(1)
Background
Pharmacoresistance is a major issue in the treatment of epilepsy. However, the mechanism underlying pharmacoresistance to antiepileptic drugs (AEDs) is still unclear, and few animal models have been established for studying drug resistant epilepsy (DRE). In our study, spontaneous recurrent seizures (SRSs) were investigated by video-EEG monitoring during the entire procedure.Methods/Principal Findings
In the mouse pilocarpine-induced epilepsy model, we administered levetiracetam (LEV) and valproate (VPA) in sequence. AED-responsive and AED-resistant mice were naturally selected after 7-day treatment of LEV and VPA. Behavioral tests (open field, object exploration, elevated plus maze, and light-dark transition test) and a microRNA microarray test were performed. Among the 37 epileptic mice with SRS, 23 showed significantly fewer SRSs during administration of LEV (n = 16, LEV sensitive (LS) group) or VPA (n = 7, LEV resistant/VPA sensitive (LRVS) group), while 7 epileptic mice did not show any amelioration with either of the AEDs (n = 7, multidrug resistant (MDR) group). On the behavioral assessment, MDR mice displayed distinctive behaviors in the object exploration and elevated plus maze tests, which were not observed in the LS group. Expression of miRNA was altered in LS and MDR groups, and we identified 4 miRNAs (miR-206, miR-374, miR-468, and miR-142-5p), which were differently modulated in the MDR group versus both control and LS groups.Conclusion
This is the first study to identify a pharmacoresistant subgroup, resistant to 2 AEDs, in the pilocarpine-induced epilepsy model. We hypothesize that modulation of the identified miRNAs may play a key role in developing pharmacoresistance and behavioral alterations in the MDR group. 相似文献5.
Purpose
To evaluate the effects of electroacupuncture (EA) on the International Prostate Symptom Score (IPSS), postvoid residual urine (PVR), and maximum urinary flow rate (Qmax), and explore the difference between EA at acupoints and non-acupoints in patients with moderate to severe benign prostate hyperplasia (BPH).Subjects and Methods
Men with BPH and IPSS ≥8 were enrolled. Participants were randomly allocated to receive EA at acupoint (treatment group, n = 50) and EA at non-acupoint (control group, n = 50). The primary outcome measure includes the change of IPSS at the 6th week and the secondary outcome measures include changes of PVR and Qmax at the 6th week and change of IPSS at the 18th week.Results
100/192 patients were included. At the 6th week, treatment group patients had a 4.51 (p<0.001) and 4.12 (p<0.001) points greater decline in IPSS than the control group in the intention to treat (ITT) and per-protocol (PP) populations. At the 18th week, a 3.2 points (p = 0.001) greater decline was found in IPSS for the treatment. No significant differences were found between the two groups in Qmax at the 6th week (p = 0.819). No significant difference was observed in PVR (P = 0.35).Conclusion
Acupoint EA at BL 33 had better effects on IPSS, but no difference on PVR and Qmax as compared with non-acupoint EA. The results indicate that EA is effective in improving patient''s quality of life and acupoint may have better therapeutic effects than non-acupoints in acupuncture treatments of BPH.Trial Registration
ClinicalTrials.gov . NCT01218243相似文献6.
Study objectives
To search for early abnormalities in electroencephalogram (EEG) during sleep which may precede motor symptoms in a transgenic mouse model of hereditary neurodegenerative Huntington’s disease (HD).Design
In the R6/1 transgenic mouse model of HD, rhythmic brain activity in EEG recordings was monitored longitudinally and across vigilance states through the onset and progression of disease.Measurements and results
Mice with chronic electrode implants were recorded monthly over wake-sleep cycles (4 hours), beginning at 9–11 weeks (presymptomatic period) through 6–7 months (symptomatic period). Recording data revealed a unique β rhythm (20–35 Hz), present only in R6/1 transgenic mice, which evolves in close parallel with the disease. In addition, there was an unusual relationship between this β oscillation and vigilance states: while nearly absent during the active waking state, the β oscillation appeared with drowsiness and during slow wave sleep (SWS) and, interestingly, strengthened rather than dissipating when the brain returned to an activated state during rapid eye movement (REM) sleep.Conclusions
In addition to providing a new in vivo biomarker and insight into Huntington''s disease pathophysiology, this serendipitous observation opens a window onto the rarely explored neurophysiology of the cortico-basal ganglia circuit during SWS and REM sleep. 相似文献7.
Dae Ryoung Park Jeong Seok Kim Chang Keun Kim 《Journal of Exercise Nutrition & Biochemistry》2014,18(1):1-7
[Purpose]
The purpose of this study was to investigate the effect of Sirtuin 1 (SIRT1) and General control nonderepressible 5 (GCN5) knock down on peroxisome proliferator- activated receptor gamma coactivator 1-alpha (PGC-1α) deacetylation during electrical stimulated skeletal muscle contraction.[Methods]
Skeletal muscle primary cell were isolated from C57BL/6 mice gastrocnemius and transfected lentiviral SIRT1 and GCN5 shRNA. Knock downed muscle cell were stimulated by electrical stimulation (1Hz, 3min) and collected for PGC-1α deceatylation assays. Immunoprecipitation performed for PGC-1α deacetylation, acetyl-lysine level was measured.[Results]
Our resulted showed SIRT1 knock down not influenced to PGC-1α deacetylation during electrical stimulation induced muscle contraction while GCN5 knock down decreased PGC-1α deacetylation significantly (p<0.05).[Conclusion]
This study can be concluded that GCN5 is a critical factor for muscle contraction induced PGC-1α deacetylation. 相似文献8.
May A. Beydoun Alyssa A. Gamaldo Jose A. Canas Hind A. Beydoun Mauli T. Shah Jessica M. McNeely Alan B. Zonderman 《PloS one》2014,9(8)
Background
The associations between nutritional biomarkers and measures of sleep quantity and quality remain unclear.Methods
Cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES) 2005–2006 were used. We selected 2,459 adults aged 20–85, with complete data on key variables. Five sleep measures were constructed as primary outcomes: (A) Sleep duration; (B) Sleep disorder; (C) Three factors obtained from factor analysis of 15 items and labeled as “Poor sleep-related daytime dysfunction” (Factor 1), “Sleepiness” (Factor 2) and “Sleep disturbance” (Factor 3). Main exposures were serum concentrations of key nutrients, namely retinol, retinyl esters, carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein+zeaxanthin, lycopene), folate, vitamin B-12, total homocysteine (tHcy), vitamin C, 25-hydroxyvitamin D (25(OH)D) and vitamin E. Main analyses consisted of multiple linear, logistic and multinomial logit models.Results
Among key findings, independent inverse associations were found between serum vitamin B-12 and sleep duration, 25(OH)D and sleepiness (as well as insomnia), and between folate and sleep disturbance. Serum total carotenoids concentration was linked to higher odds of short sleep duration (i.e. 5–6 h per night) compared to normal sleep duration (7–8 h per night).Conclusions
A few of the selected serum nutritional biomarkers were associated with sleep quantity and quality. Longitudinal studies are needed to ascertain temporality and assess putative causal relationships. 相似文献9.
Factors Influencing Sleep Disturbances among Spouse Caregivers of Cancer Patients in Northeast China
Background
In China, spouse caregivers of cancer patients (SCCPs) are involved in all aspects of patient care and experience psychological distress which could result in sleep disturbance and fatigue. However, few studies have explored the differences between SCCPs and the general population, or what factors affect SCCPs'' sleep. This study aims to (1) Compare the differences in sleep disturbances and fatigue severity between SCCPs and the age- and gender-matched general population, and (2) Identify selected personal characteristics, including coping style that affect sleep disturbances in SCCPs.Methodology/Principal Findings
The Stress and Coping Model was used to guide this study. Participants were recruited from the northeast part of China and included 600 people from the general population and 300 SCCPs. Participants completed a socio-demographic form, Fatigue Scale-14, trait Coping Style Questionnaire, and Symptom Checklist-90.Results
The majority of the participants were middle age, most of whom (78.7%) spent more than 8 hours each day taking care of their spouses. Compared to the general population, the SCCPs experienced significant sleep disturbances with a mean of 7.30 (SD = 1.27), and fatigue severity with a mean of 8.11 (SD = 3.25). Among the selected SCCPs'' personal characteristics, current poor health status (β = 0.14, P<0.001), having a spouse under mixed treatment (β = 0.13, p<0.001), and financial burden (β = 0.14, P<0.001) are the significant predictors for sleep disturbances. Positive coping is the predictor for fewer sleep disturbances (β = 0.27, P<0.001). Those who reported sleep disturbances also experienced higher physical and mental fatigue severity (P<0.001).Conclusion
Intervention to improve coping style in SCCPs is needed. Further research is also needed to explore the other mediators and moderators that regulate sleep disturbance and health outcomes in the SCCPs. 相似文献10.
Masayuki Ikeda Moritoshi Hirono Takashi Sugiyama Takahiro Moriya Masami Ikeda-Sagara Naomi Eguchi Yoshihiro Urade Tohru Yoshioka 《PloS one》2009,4(11)
Background
The sleep sequence: i) non-REM sleep, ii) REM sleep, and iii) wakefulness, is stable and widely preserved in mammals, but the underlying mechanisms are unknown. It has been shown that this sequence is disrupted by sudden REM sleep onset during active wakefulness (i.e., narcolepsy) in orexin-deficient mutant animals. Phospholipase C (PLC) mediates the signaling of numerous metabotropic receptors, including orexin receptors. Among the several PLC subtypes, the β4 subtype is uniquely localized in the geniculate nucleus of thalamus which is hypothesized to have a critical role in the transition and maintenance of sleep stages. In fact, we have reported irregular theta wave frequency during REM sleep in PLC-β4-deficient mutant (PLC-β4−/−) mice. Daily behavioral phenotypes and metabotropic receptors involved have not been analyzed in detail in PLC-β4−/− mice, however.Methodology/Principal Findings
Therefore, we analyzed 24-h sleep electroencephalogram in PLC-β4−/− mice. PLC-β4−/− mice exhibited normal non-REM sleep both during the day and nighttime. PLC-β4−/− mice, however, exhibited increased REM sleep during the night, their active period. Also, their sleep was fragmented with unusual wake-to-REM sleep transitions, both during the day and nighttime. In addition, PLC-β4−/− mice reduced ultradian body temperature rhythms and elevated body temperatures during the daytime, but had normal homeothermal response to acute shifts in ambient temperatures (22°C–4°C). Within the most likely brain areas to produce these behavioral phenotypes, we found that, not orexin, but group-1 metabotropic glutamate receptor (mGluR)-mediated Ca2+ mobilization was significantly reduced in the dorsal lateral geniculate nucleus (LGNd) of PLC-β4−/− mice. Voltage clamp recordings revealed that group-1 mGluR-mediated currents in LGNd relay neurons (inward in wild-type mice) were outward in PLC-β4−/− mice.Conclusions/Significance
These lines of evidence indicate that impaired LGNd relay, possibly mediated via group-1 mGluR, may underlie irregular sleep sequences and ultradian body temperature rhythms in PLC-β4−/− mice. 相似文献11.
Background
The use of both upper extremities (UE) is necessary for the completion of many everyday tasks. Few clinical assessments measure the abilities of the UEs to work together; rather, they assess unilateral function and compare it between affected and unaffected UEs. Furthermore, clinical assessments are unable to measure function that occurs in the real-world, outside the clinic. This study examines the validity of an innovative approach to assess real-world bilateral UE activity using accelerometry.Methods
Seventy-four neurologically intact adults completed ten tasks (donning/doffing shoes, grooming, stacking boxes, cutting playdough, folding towels, writing, unilateral sorting, bilateral sorting, unilateral typing, and bilateral typing) while wearing accelerometers on both wrists. Two variables, the Bilateral Magnitude and Magnitude Ratio, were derived from accelerometry data to distinguish between high- and low-intensity tasks, and between bilateral and unilateral tasks. Estimated energy expenditure and time spent in simultaneous UE activity for each task were also calculated.Results
The Bilateral Magnitude distinguished between high- and low-intensity tasks, and the Magnitude Ratio distinguished between unilateral and bilateral UE tasks. The Bilateral Magnitude was strongly correlated with estimated energy expenditure (ρ = 0.74, p<0.02), and the Magnitude Ratio was strongly correlated with time spent in simultaneous UE activity (ρ = 0.93, p<0.01) across tasks.Conclusions
These results demonstrate face validity and construct validity of this methodology to quantify bilateral UE activity during the performance of everyday tasks performed in a laboratory setting, and can now be used to assess bilateral UE activity in real-world environments. 相似文献12.
Introduction
Alcohol-induced neuroinflammation is mediated by pro-inflammatory cytokines and chemokines including tumor necrosis factor-α (TNFα), monocyte chemotactic protein-1 (MCP1) and interleukin-1-beta (IL-1β). Toll-like receptor-4 (TLR4) pathway induced nuclear factor-κB (NF-κB) activation is involved in the pathogenesis of alcohol-induced neuroinflammation. Inflammation is a highly regulated process. Recent studies suggest that microRNAs (miRNAs) play crucial role in fine tuning gene expression and miR-155 is a major regulator of inflammation in immune cells after TLR stimulation.Aim
To evaluate the role of miR-155 in the pathogenesis of alcohol-induced neuroinflammation.Methods
Wild type (WT), miR-155- and TLR4-knockout (KO) mice received 5% ethanol-containing or isocaloric control diet for 5 weeks. Microglia markers were measured by q-RTPCR; inflammasome activation was measured by enzyme activity; TNFα, MCP1, IL-1β mRNA and protein were measured by q-RTPCR and ELISA; phospho-p65 protein and NF-κB were measured by Western-blotting and EMSA; miRNAs were measured by q-PCR in the cerebellum. MiR-155 was measured in immortalized and primary mouse microglia after lipopolysaccharide and ethanol stimulation.Results
Chronic ethanol feeding up-regulated miR-155 and miR-132 expression in mouse cerebellum. Deficiency in miR-155 protected mice from alcohol-induced increase in inflammatory cytokines; TNFα, MCP1 protein and TNFα, MCP1, pro-IL-1β and pro-caspase-1 mRNA levels were reduced in miR-155 KO alcohol-fed mice. NF-κB was activated in WT but not in miR-155 KO alcohol-fed mice. However increases in cerebellar caspase-1 activity and IL-1β levels were similar in alcohol-fed miR-155-KO and WT mice. Alcohol-fed TLR4-KO mice were protected from the induction of miR-155. NF-κB activation measured by phosphorylation of p65 and neuroinflammation were reduced in alcohol-fed TLR4-KO compared to control mice. TLR4 stimulation with lipopolysaccharide in primary or immortalized mouse microglia resulted in increased miR-155.Conclusion
Chronic alcohol induces miR-155 in the cerebellum in a TLR4-dependent manner. Alcohol-induced miR-155 regulates TNFα and MCP1 expression but not caspase-dependent IL-1β increase in neuroinflammation. 相似文献13.
Purpose
The current study was undertaken to investigate whether glaucoma affects the sleep quality and whether there is any difference between patients with primary glaucoma (primary open angle glaucoma, POAG and primary angle-closure glaucoma, PACG) and healthy subjects, using a validated self-rated questionnaire, the Pittsburgh Sleep Quality Index (PSQI).Methods
The sleep quality of patients with POAG and PACG was tested against normal controls. Subjects were divided into three sub-groups according to age. Differences in the frequency of sleep disturbances (PSQI score >7) were assessed. The differences of sleep quality within the three groups and within the POAG group depending on the patients’ intraocular pressure (IOP) and impairment of visual field (VF) were also studied.Results
92 POAG patients, 48 PACG patients and 199 controls were included. Sleep quality declined with age in control and POAG group (tendency chi-square, P<0.05). The prevalence of sleep disturbances was higher in POAG and PACG group than in the control group, the differences were statistically significant. The prevalence of sleep disturbances was higher in patients with PACG, compared to POAG patients in the age interval of 61–80. In POAG group, the ratio of patients with sleep disorders increased with augmented impairment of VF, but the differences were not statistically significant (χ2-test, P>0.05). No significant differences were found in POAG group between patients with a highest IOP in daytime and at nighttime (χ2-test, P>0.05).Conclusions
The prevalence of sleep disorders was higher in patients with POAG and PACG than in controls. PACG patients seemed to have a more serious problem of sleep disorders than POAG patients between 61 to 80 years old. No correlation was found between the prevalence of sleep disorders and impairment of VF or the time when POAG patients showed a highest IOP. 相似文献14.
Fangjun Bao Hao Chen Ye Yu Jiguo Yu Shi Zhou Jing Wang QinMei Wang Ahmed Elsheikh 《PloS one》2013,8(8)
Purpose
To investigate the bilateral symmetry of the global corneal topography in normal corneas with a wide range of curvature, astigmatism and thickness valuesDesign
Cross-Sectional StudyMethods
Topography images were recorded for the anterior and posterior surfaces of 342 participants using a Pentacam. Elevation data were fitted to a general quadratic model that considered both translational and rotational displacements. Comparisons between fellow corneas of estimates of corneal shape parameters (elevation, radius in two main directions, Rx and Ry, and corresponding shape factors, Qx and Qy) and corneal position parameters (translational displacements: x0, y0 and z0, and rotational displacements: α, β and γ) were statistically analyzed.Results
The general quadratic model provided average RMS of fit errors with the topography data of 1.7±0.6 µm and 5.7±1.3 µm in anterior and posterior corneal surfaces. The comparisons showed highly significant bilateral correlations with the differences between fellow corneas in Rx, Ry, Qx and Qy of anterior and posterior surfaces remaining insignificantly different from zero. Bilateral differences in elevation measurements at randomly-selected points in both corneal central and peripheral areas indicated strong mirror symmetry between fellow corneas. The mean geometric center (x0, y0, z0) of both right and left corneas was located on the temporal side and inferior-temporal side of the apex in anterior and posterior topography map, respectively. Rotational displacement angle α along X axis had similar distributions in bilateral corneas, while rotation angle β along Y axis showed both eyes tilting towards the nasal side. Further, rotation angle γ along Z axis, which is related to corneal astigmatism, showed clear mirror symmetry.Conclusions
Analysis of corneal topography demonstrated strong and statistically-significant mirror symmetry between bilateral corneas. This characteristic could help in detection of pathological abnormalities, disease diagnosis, measurement validation and surgery planning. 相似文献15.
Background
The blood based interferon-gamma release assays (IGRA) for the diagnosis of tuberculosis do not discriminate between active TB disease and latent TB infection (LTBI). The search for distinguishing biomarkers therefore continues, as the accurate diagnosis of tuberculosis is particularly challenging in children. IFN-γ-inducible protein 10 (IP-10/CXCL10) has recently been evaluated as a marker for active TB in adults with promising results.Aim
To investigate this new biomarker for active TB and LTBI in paediatrics.Method
We measured IP-10 levels using ELISA in supernatants of whole blood samples stimulated with TB-specific-antigens and negative control antigen.Results
IP-10 is produced in high levels following mycobacterial antigen stimulation in active TB (n = 17) and LTBI (n = 16) compared to controls (n = 16) and to IFN-γ. The baseline levels of IP-10 are increased in active TB and in LTBI, but there is no significant difference of stimulated levels of IP-10 between active TB and LTBI.Conclusions
IP-10 is a biomarker for tuberculosis in children. However like IFNγ, IP-10 also does not distinguish between active TB and LTBI. 相似文献16.
Neil E. O’Connell John Cossar Louise Marston Benedict M. Wand David Bunce G. Lorimer Moseley Lorraine H. De Souza 《PloS one》2012,7(10)
Background
Many double-blind clinical trials of transcranial direct current stimulation (tDCS) use stimulus intensities of 2 mA despite the fact that blinding has not been formally validated under these conditions. The aim of this study was to test the assumption that sham 2 mA tDCS achieves effective blinding.Methods
A randomised double blind crossover trial. 100 tDCS-naïve healthy volunteers were incorrectly advised that they there were taking part in a trial of tDCS on word memory. Participants attended for two separate sessions. In each session, they completed a word memory task, then received active or sham tDCS (order randomised) at 2 mA stimulation intensity for 20 minutes and then repeated the word memory task. They then judged whether they believed they had received active stimulation and rated their confidence in that judgement. The blinded assessor noted when red marks were observed at the electrode sites post-stimulation.Results
tDCS at 2 mA was not effectively blinded. That is, participants correctly judged the stimulation condition greater than would be expected to by chance at both the first session (kappa level of agreement (κ) 0.28, 95% confidence interval (CI) 0.09 to 0.47 p = 0.005) and the second session (κ = 0.77, 95%CI 0.64 to 0.90), p = <0.001) indicating inadequate participant blinding. Redness at the reference electrode site was noticeable following active stimulation more than sham stimulation (session one, κ = 0.512, 95%CI 0.363 to 0.66, p<0.001; session two, κ = 0.677, 95%CI 0.534 to 0.82) indicating inadequate assessor blinding.Conclusions
Our results suggest that blinding in studies using tDCS at intensities of 2 mA is inadequate. Positive results from such studies should be interpreted with caution. 相似文献17.
18.
Background
The pathological hallmarks of chronic obstructive pulmonary disease (COPD) are inflammation of the small airways (bronchiolitis) and destruction of lung parenchyma (emphysema). These forms of disease arise from chronic prolonged infections, which are usually never present in the normal lung. Despite the fact that primary hygiene and defense of the airways presumably requires a well controlled fluid environment on the surface of the bronchiolar airway, very little is known of the fluid and electrolyte transport properties of airways of less than a few mm diameter.Methods
We introduce a novel approach to examine some of these properties in a preparation of minimally traumatized porcine bronchioles of about 1 mm diameter by microperfusing the intact bronchiole.Results
In bilateral isotonic NaCl Ringer solutions, the spontaneous transepithelial potential (TEP; lumen to bath) of the bronchiole was small (mean ± sem: -3 ± 1 mV; n = 25), but when gluconate replaced luminal Cl-, the bionic Cl- diffusion potentials (-58 ± 3 mV; n = 25) were as large as -90 mV. TEP diffusion potentials from 2:1 NaCl dilution showed that epithelial Cl- permeability was at least 5 times greater than Na+ permeability. The anion selectivity sequence was similar to that of CFTR. The bionic TEP became more electronegative with stimulation by luminal forskolin (5 μM)+IBMX (100 μM), ATP (100 μM), or adenosine (100 μM), but not by ionomycin. The TEP was partially inhibited by NPPB (100 μM), GlyH-101* (5–50 μM), and CFTRInh-172* (5 μM). RT-PCR gave identifying products for CFTR, α-, β-, and γ-ENaC and NKCC1. Antibodies to CFTR localized specifically to the epithelial cells lining the lumen of the small airways.Conclusion
These results indicate that the small airway of the pig is characterized by a constitutively active Cl- conductance that is most likely due to CFTR. 相似文献19.
20.
Yannick Degboé Séverine Fruchon Michel Baron Delphine Nigon Cédric Olivier Turrin Anne-Marie Caminade Rémy Poupot Alain Cantagrel Jean-Luc Davignon 《Arthritis research & therapy》2014,16(2):R98