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101.
Ashley E. Lepack Manabu Fuchikami Jason M. Dwyer Mounira Banasr Ronald S. Duman 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2015,18(1)
Background:
Recent studies demonstrate that the rapid antidepressant ketamine increases spine number and function in the medial prefrontal cortex (mPFC), and that these effects are dependent on activation of glutamate α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and brain-derived neurotrophic factor (BDNF). In vitro studies also show that activation of AMPA receptors stimulates BNDF release via activation of L-type voltage-dependent calcium channels (VDCC).Methods:
Based on this evidence, we examined the role of BDNF release and the impact of L-type VDCCs on the behavioral actions of ketamine.Results:
The results demonstrate that infusion of a neutralizing BDNF antibody into the mPFC blocks the behavioral effects of ketamine in the forced swim test (FST). In addition, we show that pretreatment with nifedipine or verapamil, two structurally-different L-type calcium channel antagonists, blocks the behavioral effects of ketamine in the FST. Finally, we show that ketamine treatment stimulates BDNF release in primary cortical neurons and that this effect is blocked by inhibition of AMPA receptors or L-type VDCCs.Conclusions:
Taken together, these results indicate that the antidepressant effects of ketamine are mediated by activation of L-type VDCCs and the release of BDNF. They further elucidate the cellular mechanisms underlying this novel rapid-acting antidepressant. 相似文献102.
Helen Sawaya Kevin Johnson Matthew Schmidt Ashley Arana George Chahine Mia Atoui David Pincus Mark S. George Jaak Panksepp Ziad Nahas 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2015,18(6)
Background:
Major depressive disorder has been associated with abnormal resting-state functional connectivity (FC), especially in cognitive processing and emotional regulation networks. Although studies have found abnormal FC in regions of the default mode network (DMN), no study has investigated the FC of specific regions within the anterior DMN based on cytoarchitectonic subdivisions of the antero-medial pre-frontal cortex (PFC). Studies from different areas in the field have shown regions within the anterior DMN to be involved in emotional intelligence. Although abnormalities in this region have been observed in depression, the relationship between the ventromedial PFC (vmPFC) function and emotional intelligence has yet to be investigated in depressed individuals.Methods:
Twenty-one medication-free, non–treatment resistant, depressed patients and 21 healthy controls underwent a resting state functional magnetic resonance imaging session. The participants also completed an ability-based measure of emotional intelligence: the Mayer-Salovey-Caruso Emotional Intelligence Test. FC maps of Brodmann areas (BA) 25, 10m, 10r, and 10p were created and compared between the two groups.Results:
Mixed-effects analyses showed that the more anterior seeds encompassed larger areas of the DMN. Compared to healthy controls, depressed patients had significantly lower connectivity between BA10p and the right insula and between BA25 and the perigenual anterior cingulate cortex. Exploratory analyses showed an association between vmPFC connectivity and emotional intelligence.Conclusions:
These results suggest that individuals with depression have reduced FC between antero-medial PFC regions and regions involved in emotional regulation compared to control subjects. Moreover, vmPFC functional connectivity appears linked to emotional intelligence. 相似文献103.
Kui Zeng Ilan Geerlof-Vidavisky Ashley Gucinski Xiaohui Jiang Michael T. Boyne II 《The AAPS journal》2015,17(3):643-651
A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed using three peptide drugs: salmon calcitonin, bivalirudin, and exenatide as model systems to assess the suitability of this approach for monitoring peptide drug product quality. Calcitonin and its related impurities displayed linear responses over the range from 0.1 to 10 μM (R2 values for calcitonin salmon, Glu14-calcitonin, and acetyl-calcitonin were 0.995, 0.996, and 0.993, respectively). Intra-assay precision in terms of relative standard deviation (%RSD) was less than 10% at all tested concentrations. The accuracy of the method was greater than 85% as measured by spiking 0.1, 0.3, and 1% of Glu14-calcitonin and acetyl-calcitonin into a stock calcitonin solution. Limits of detection for calcitonin, Glu14-calcitonin, and acetyl-calcitonin were 0.02, 0.03, and 0.04 μM, respectively, indicating that an impurity present at less than 0.1% (0.1 μM) of the drug product API concentration (107 μM) could be detected. Method validation studies analyzing bivalirudin and exenatide drug products exhibited similar results to calcitonin salmon in regard to high selectivity, sensitivity, precision, and linearity. Added benefits of using LC-HRMS-based methods are the ability to also determine amino acid composition, confirm peptide sequence, and quantify impurities, even when they are co-eluting, within a single experiment. LC-HRMS represents a promising approach for the quality control of peptides including the measurement of any peptide-related impurities. While the development work performed here is focus on peptide drug products, the principles could be adapted to peptide drug substance.KEY WORDS: High resolution mass spectrometry, impurity profiling, LC-HRMS, peptide drug 相似文献
104.
Ashley Edwards Nicholas Blickenstaff Howard Maibach 《Cutaneous and ocular toxicology》2015,34(2):167-170
Today’s fragrances are present in more than just perfumes, having become ubiquitous in skin care products such as creams, shampoos, sun tan lotion and deodorants. While aromatics can arouse the senses, aromatic compounds applied to skin can also cause allergic contact dermatitis. This article describes diagnosis, limitations of patch testing for fragrance mix 1 and fragrance mix 2, the relevance of fragrance concentration in products, use testing of common consumer products and our current recommendations in regards to the management of fragrance contact allergy. 相似文献
105.
106.
Robert T. Faillace Gregory W. Yost Yashasvi Chugh Jeffrey Adams Beni R. Verma Zaid Said Ibrahim Ismail Sayed Ashley Honushefsky Sanjay Doddamani Peter B. Berger 《The American journal of medicine》2018,131(2):201.e9-201.e15
Background
The Centers for Medicare and Medicaid Services (CMS) model for publicly reporting national 30-day-risk-adjusted mortality rates for patients admitted with heart failure fails to include clinical variables known to impact total mortality or take into consideration the culture of end-of-life care. We sought to determine if those variables were related to the 30-day mortality of heart failure patients at Geisinger Medical Center.Methods
Electronic records were searched for patients with a diagnosis of heart failure who died from any cause during hospitalization or within 30 days of admission.Results
There were 646 heart-failure-related admissions among 530 patients (1.2 admissions/patient). Sixty-seven of the 530 (13%) patients died: 35 (52%) died during their hospitalization and 32 (48%) died after discharge but within 30 days of admission; of these, 27 (40%) had been transferred in for higher-acuity care. Fifty-one (76%) died from heart failure, and 16 (24%) from other causes. Fifty-five (82%) patients were classified as American Heart Association Stage D, 58 (87%) as New York Heart Association Class IV, and 30 (45%) had right-ventricular systolic dysfunction. None of the 32 patients who died after discharge met recommendations for beta-blockers. Criteria for prescribing angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor blockers were not met by 33 of the 34 patients (97%) with heart failure with reduced ejection fraction not on one of those drugs. Fifty-seven patients (85%) had a do-not-resuscitate (DNR) status.Conclusion
A majority of heart failure-related mortality was among patients who opted for a DNR status with end-stage heart failure, limiting the appropriateness of administering evidence-based therapies. No care gaps were identified that contributed to mortality at our institution. The CMS 30-day model fails to take important variables into consideration. 相似文献107.
108.
109.
Histamine is a biogenic amine naturally present in many body cells. It is also a contaminant that is mostly found in spoiled food. The consumption of foods containing high levels of histamine may lead to an allergy-like food poisoning. Analytical methods that can routinely screen histamine are thus urgently needed. In this paper, we developed a facile and cost-effective molecularly imprinted polymer (MIP)-based fluorometric assay to directly quantify histamine. Histamine-specific MIP nanoparticles (nanoMIPs) were synthesized using a modified solid-phase synthesis method. They were then immobilized in the wells of a microplate to bind the histamine in aqueous samples. After binding, o-phthaldialdehyde (OPA) was used to label the bound histamine, which converted the binding events into fluorescent signals. The obtained calibration curve of histamine showed a linear correlation ranging from 1.80 to 44.98 μM with the limit of detection of 1.80 μM. This method was successfully used to detect histamine in spiked diary milk with a recovery rate of more than 85%.A new molecularly imprinted polymer (MIP)-based fluorometric assay was developed to directly quantify histamine in real samples. 相似文献
110.
Re‐endothelialization of rat lung scaffolds through passive,gravity‐driven seeding of segment‐specific pulmonary endothelial cells 下载免费PDF全文
Michelle E. Scarritt Nicholas C. Pashos Jessica M. Motherwell Zachary R. Eagle Brian J. Burkett Ashley N. Gregory Ricardo Mostany Daniel J. Weiss Diego F. Alvarez Bruce A. Bunnell 《Journal of tissue engineering and regenerative medicine》2018,12(2):e786-e806
Effective re‐endothelialization is critical for the use of decellularized scaffolds for ex vivo lung engineering. Current approaches yield insufficiently re‐endothelialized scaffolds that haemorrhage and become thrombogenic upon implantation. Herein, gravity‐driven seeding coupled with bioreactor culture facilitated widespread distribution and engraftment of endothelial cells throughout rat lung scaffolds. Initially, human umbilical vein endothelial cells were seeded into the pulmonary artery by either gravity‐driven, variable flow perfusion seeding or pump‐driven, pulsatile flow perfusion seeding. Gravity seeding evenly distributed cells and supported cell survival and re‐lining of the vascular walls while perfusion pump‐driven seeding led to increased cell fragmentation and death. Using gravity seeding, rat pulmonary artery endothelial cells and rat pulmonary vein endothelial cells attached in intermediate and large vessels, while rat pulmonary microvascular endothelial cells deposited mostly in microvessels. Combination seeding of these cells led to positive vascular endothelial cadherin staining. In addition, combination seeding improved barrier function as assessed by serum albumin extravasation; however, leakage was observed in the distal portions of the re‐endothelialized tissue suggesting that recellularization of the alveoli is necessary to complete barrier function of the capillary–alveolar network. Overall, these data indicate that vascular recellularization of rat lung scaffolds is achieved through gravity seeding. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献