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11.
The endogenous substrate(s) and physiological function(s) of semicarbazide-sensitive amine oxidase (SSAO), a group of enzymes exhibiting highest activity in vascular smooth muscle cells of the mammalian aortic wall, remain undetermined. This study examines the pathophysiological effects in the thoracic aortic wall resulting from specific in vivo SSAO inhibition. Weanling Sprague-Dawley rats were treated acutely or chronically with either semicarbazide hydrochloride or the allylamine derivatives MDL-72274 or MDL-72145 (Marion Merrell Dow Research Institute, Cincinnati, OH). Treatment with these compounds produced acute (6 and 24 h) and chronic (21 day) lowering of SSAO activity in aorta and lung with little effect on the activity of the vital matrix-forming enzyme, lysyl oxidase, in aortas of chronically treated animals. Chronic SSAO inhibition produced lesions consisting of striking disorganization of elastin architecture within the aortic media accompanied by degenerative medial changes and metaplastic changes in vascular smooth muscle cells. No significant difference in the total weight of dry, lipid-extracted aortic elastin and collagen components were observed between chronically SSAO inhibited and control animals. However, the amount of mature elastin was lowered and mature collagen was raised in the aortas of animals treated chronically with semicarbazide. Descending thoracic aortic rings isolated from chronically SSAO-inhibited animals had larger cross-sectional diameters (i.e., exhibited dilation) when compared to corresponding rings from control animals. This study demonstrates that developmental toxicity, characterized by striking vascular lesions and dilated thoracic aortas, can result from specific in vivo SSAO inhibition, suggesting a role for SSAO in connective tissue matrix development and maintenance, and specifically in the development of normal elastin. 相似文献
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Absorption of inhaled NO2 across the pulmonary gas/tissue interface is principally governed by chemical reaction(s) rather than by physical solubility. While the kinetics of NO2 transfer into reactant-containing aqueous solutions appear to be bulk phase independent, it is unclear whether unreacted NO2 diffuses appreciably through the epithelial lining fluid (ELF) to cellular compartments. We avoided the difficulties associated with directly quantifying NO2 dissolved in biological fluids by indirectly determining the potential for NO2 penetration to underlying tissues. An in vitro system was developed which horizontally suspended a wettable, gas permeable, fibrous material between two gas chambers. Aqueous substrates were applied to the sieve material and NO2 (10.9 ppm) was introduced into one chamber and sampled for in the other. O2 served as a tracer gas. We determined the influence of ELF, a model biochemical (reduced glutathione; GSH), and PO4 buffer (control) on NO2 transfer as evaluated by "breakthrough time." (A) Both O2 and NO2 rapidly diffused through the sieve material when dry. Under PO4 wetted conditions, O2 continued to penetrate rapidly but NO2 transfer was slightly inhibited relative to O2. (B) Addition of GSH (1 mM) significantly prolonged NO2 breakthrough time. Increasing initial [GSH] resulted in concomitant prolongation of NO2 breakthrough time. (C) We observed a direct correlation between oxidation of sieve GSH and NO2 breakthrough. (D) Freshly harvested rat ELF inhibited NO2 transfer in a concentration-dependent manner similar to GSH. These data suggest that in the presence of reactant solutes, unreacted NO2 does not penetrate through the ELF layer. Reactive absorption must, therefore, occur primarily within the ELF compartment so that reaction products which induce subsequent toxicity are generated as a result of the initial uptake interactions. 相似文献
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Hyperpolarized 13C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model
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Aisha True‐Yasaki Jeremy W. Gordon Cornelius von Morze Justin Delos Santos David M. Wilson Robert Raffai Patrick M. Cowley Anthony J. Baker John Kurhanewicz David H. Lovett Zhen Jane Wang 《NMR in biomedicine》2017,30(10)
Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease (CKD). Persistent oxidative stress and mitochondrial dysfunction are implicated across diverse forms of AKI and in the transition to CKD. In this study, we applied hyperpolarized (HP) 13C dehydroascorbate (DHA) and 13C pyruvate magnetic resonance spectroscopy (MRS) to investigate the renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity, respectively, in a murine model of AKI at baseline and 7 days after unilateral ischemia reperfusion injury (IRI). Compared with the contralateral sham‐operated kidneys, the kidneys subjected to IRI showed a significant decrease in the HP 13C vitamin C/(vitamin C + DHA) ratio, consistent with a decrease in redox capacity. The kidneys subjected to IRI also showed a significant decrease in the HP 13C bicarbonate/pyruvate ratio, consistent with impaired PDH activity. The IRI kidneys showed a significantly higher HP 13C lactate/pyruvate ratio at day 7 compared with baseline, although the 13C lactate/pyruvate ratio was not significantly different between the IRI and contralateral sham‐operated kidneys at day 7. Arterial spin labeling magnetic resonance imaging (MRI) demonstrated significantly reduced perfusion in the IRI kidneys. Renal tissue analysis showed corresponding increased reactive oxygen species (ROS) and reduced PDH activity in the IRI kidneys. Our results show the feasibility of HP 13C MRS for the non‐invasive assessment of oxidative stress and mitochondrial PDH activity following renal IRI. 相似文献
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Stacy Loeb Shomik Sengupta Mohit Butaney Joseph N. Macaluso Stefan W. Czarniecki Rebecca Robbins R. Scott Braithwaite Lingshan Gao Nataliya Byrne Dawn Walter Aisha Langford 《European urology》2019,75(4):564-567
YouTube is a social media platform with more than 1 billion users and >600 000 videos about prostate cancer. Two small studies examined the quality of prostate cancer videos on YouTube, but did not use validated instruments, examine user interactions, or characterize the spread of misinformation. We performed the largest, most comprehensive examination of prostate cancer information on YouTube to date, including the first 150 videos on screening and treatment. We used the validated DISCERN quality criteria for consumer health information and the Patient Education Materials Assessment Tool, and compared results for user engagement. The videos in our sample had up to 1.3 million views (average 45 223) and the overall quality of information was moderate. More videos described benefits (75%) than harms (53%), and only 50% promoted shared decision-making as recommended in current guidelines. Only 54% of the videos defined medical terms and few provided summaries or references. There was a significant negative correlation between scientific quality and viewer engagement (views/month p = 0.004; thumbs up/views p = 0.015). The comments section underneath some videos contained advertising and peer-to-peer medical advice. A total of 115 videos (77%) contained potentially misinformative and/or biased content within the video or comments section, with a total reach of >6 million viewers.
Patient summary
Many popular YouTube videos about prostate cancer contained biased or poor-quality information. A greater number of views and thumbs up on YouTube does not mean that the information is trustworthy. 相似文献18.
19.
AbstractMycotoxins pose severe health hazards in animals, humans, and poultry birds. More than 400 chemically different mycotoxins have been identified to date. Twenty-five percent of world’s crops are potentially contaminated with mycotoxins. Luckily, nature has provided the ruminants a unique property of inactivating and detoxifying most of the mycotoxins with the help of microflora and microfauna present within their ruminal fluid; however, unfortunately avian species lack such ability putting them at high risk to the deleterious effects of mycotoxins. This review elaborates different strategies for diagnosis, prevention and control of mycotoxins. 相似文献
20.
I. Stanganelli G. Argenziano F. Sera A. Blum F. Ozdemir I.K. Karaarslan D. Piccolo K. Peris H. Kirchesch R. Bono M.A. Pizzichetta S. Gasparini R.P. Braun O. Correia L. Thomas P. Zaballos S. Puig J. Malvehy M. Scalvenzi H. Rabinovitz A. Bergamo G. Pellacani C. Longo M. Pavlovic C. Rosendahl R. Hofmann‐Wellenhof H. Cabo A.A. Marghoob D. Langford S. Astorino A.M. Manganoni J.‐Y. Gourhant J. Keir J.M. Grichnik G. Fumo H. Dong A.M. Sortino Rachou G. Ferrara I. Zalaudek 《Journal of the European Academy of Dermatology and Venereology》2012,26(8):953-963
Background Little is known about the dermoscopic features of scalp tumours. Objective To determine the dermoscopic features of scalp tumours. Methods Retrospective analysis of dermoscopic images of histopathologically diagnosed scalp tumours from International Dermoscopy Society members. Results A total of 323 tumours of the scalp from 315 patients (mean age: 52 years; range 3–88 years) were analysed. Scalp nevi were significantly associated with young age (<30 years) and exhibited a globular or network pattern with central or perifollicular hypopigmentation. Melanoma and non‐melanoma skin cancer were associated with male gender, androgenetic alopecia, age >65 years and sun damage. Atypical network and regression were predictive for thin (≤1 mm) melanomas, whereas advanced melanomas (tumour thickness > 1 mm) revealed blue white veil, unspecific patterns and irregular black blotches or dots. Conclusions The data collected provide a new knowledge regarding the clinical and dermoscopy features of pigmented scalp tumours. 相似文献