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Further studies are needed, however, to better document the long-term cardiovascular safety and its ability to reduce the exacerbation rate.Cigarette smoke is highly toxic and is a major risk factor for airway inflammation, oxidative stress, and decline in lung function-the starting points for chronic obstructive pulmonary disease. Quercetin is a potent dietary antioxidant that displays anti-inflammatory activities. The goal of this study was to evaluate the effects of quercetin on reducing the redox imbalance and inflammation induced by short-term cigarette smoke exposure. In vitro, 25 and 50 μM quercetin attenuated the effects of cigarette smoke extract (increased generation of reactive oxygen species and nitric oxide) on J774A.1 cells (macrophages). We further examined the effects of quercetin in vivo. Male C57Bl/6 mice that received 10 mg/kg/day of quercetin via orogastric gavage before exposure to five days of cigarette smoke demonstrated reduced levels of leukocyte, oxidative stress, histological pattern changes of pulmonary parenchyma, and lung function alterations compared to the group that did not receive quercetin. These results suggest that quercetin may be an effective adjuvant for treating the effects of cigarette smoke exposure.Botanical insecticides as a means of controlling insects present an alternative approach that is safer than the use of synthetic insecticides. The present study identified the insecticidal activity of extracts of the rhizomes of Alpinia galanga (L.) Willd. and seven isolated phenylpropanoids against the second instar of Spodoptera litura Fab. by topical application. The ethyl acetate extract had the highest toxicity on this insect with LD50 values of 1.68 and 1.25 μg/larva after 24 and 48 h posttreatment, respectively. Among the seven phenylpropanoids separated from the ethyl acetate extract, 1'S-1'-acetoxychavicol acetate was identified as the most active compound with LD50 values of 1.63 and 1.40 μg/larva after 24 and 48 h posttreatment, respectively, followed by p-coumaryl diacetate. In addition, the two active compounds decreased glutathione S-transferase activity and increased acetylcholinesterase activity. p-Coumaryl diacetate also decreased carboxylesterase activity.Patients who have chronic obstructive pulmonary disease (COPD) and bronchial asthma (BA) share symptoms such as, dyspnoea, cough and wheeze. Differentiating these diseases in the ambulatory setting can be challenging especially in older adult smokers who are being treated with a variety of medications. The objective of this study was to test the value of adding a maximal inspiratory manoeuvre to basic spirometry to differentiate COPD and BA. One hundred forty-three COPD patients and 142 BA patients had measurements of maximal inspiratory and expiratory flow during routine spirometry. Parameters from these tests were used to assess diagnostic accuracy using receiver-operating characteristic (ROC) analyses followed by logistic regression. The association of two independent parameters were analyzed using linear regression analyses. Results show that forced expiratory volume in one second/forced vital capacity (FEV1/FVC%) 3.29 were both independent predictors of COPD. The post-test probability for COPD was 94.4% when patients had both parameters. The association between FEV1/FVC% and PIF/MEF50 was significantly different between COPD and BA. In conclusion, the addition of the maximal inspiratory effort to routine pulmonary function measurements provides a simple test to help differentiate COPD and BA.We investigated the expression of A disintegrin and metalloprotease with thrombospondin type I repeats-13 (ADAMTS-13) in the central nervous system (CNS), because it is related to blood-brain barrier (BBB) permeability. We also investigated 8-OHdG, caspase-3 and neuronal nitric oxide synthase (nNOS) expression for the cytotoxic effects of oxidative stress (OS) and nNOS, and their relation to apoptosis. We also investigated the neuroimmunopathology caused by L. monocytogenes. Brain tissues were obtained from 10 lambs and 10 kids with listeric meningoencephalitis, and healthy brain tissue from six lambs and six kids. Serial sections of brain were stained by hematoxylin and eosin (H & E), and using immunohistochemistry (IHC) for L. monocytogenes antigen, ADAMTS-13, 8-hydroxy-2'-deoxyguanosine (8-OHdG), nNOS and caspase-3. We found that ADAMTS-13, 8-OHdG, nNOS and caspase-3 expression in the brain was increased in L. https://www.selleckchem.com/products/MK-1775.html Monocytogenes infected animals compared to uninfected controls. Intense staining for 8-OHdG was observed only in neurons and glia that were exposed to OS. ADAMTS-13 was increased significantly, which may play a role in regulating and protecting BBB integrity and cells of the CNS in cases of listeric encephalitis. Increased expression of ADAMTS-13 may be critical for supporting the survival of neurons and glia. We found that L. monocytogenes-related increases in OS and nNOS, and that the associated apoptosis, may participate in neurodegeneration and neuropathology in listeric encephalitis.Inhaled medications play a pivotal role in the management of COPD and asthma. Provider knowledge and ability to teach various devices is paramount as poor inhaler technique directly correlates with worse disease control. The goal of our survey was to assess the knowledge and comfort level with various inhaled devices among providers involved in patient inhaler education. We constructed a 20-question survey consisting of a five-question Likert scale-based comfort assessment and a 15-question multiple-choice inhaler knowledge test that was distributed both internally and nationwide. Groups surveyed included internal medicine residents, family medicine residents, pulmonary fellows, respiratory therapists, nursing staff, and pharmacists. A total of 557 providers responded to the survey. The overall correct response rate among all respondents was only 47%. There was no significant difference between correct response rates among prescribers (internal medicine residents, family medicine residents, and pulmonary fellows) and non-prescribers (respiratory therapists, nursing staff, and pharmacists), 47% and 47%, respectively (p = 0.6919). However, respiratory therapists had the overall highest correct response rate of 85%. Over 72% of respondents indicated that they educate patients on inhaler technique as part of their clinical duties. Furthermore, the correct response rates for various inhaler devices varied with 55% among metered dose inhalers, 52% among dry powder inhalers, and 34% among soft-mist inhalers. Our study reveals that there is a continued need for education on the subject of inhaler devices among providers given their overall poor knowledge, particularly in an era of fast-changing inhaler devices. We continue without knowing what we teach.OBJECTIVE It remains to be elucidated whether and how endothelial functions are impaired in peripheral circulation of patients with coronary functional disorders, such as vasospastic angina (VSA) and microvascular angina (MVA). We simultaneously examined endothelial functions of peripheral conduit and resistance arteries in patients with coronary functional disorders, with a special reference to NO and endothelium-dependent hyperpolarization factors. Approach and Results Based on the results of invasive coronary acetylcholine testing and coronary physiological measurements, we divided 43 patients into 3 groups; VSA, MVA, and VSA+MVA. Endothelium-dependent vasodilatations of the brachial artery and fingertip arterioles to intra-arterial infusion of bradykinin were simultaneously evaluated by ultrasonography and peripheral arterial tonometry, respectively. To assess NO and endothelium-dependent hyperpolarization factors, measurements were repeated after oral aspirin and intra-arterial infusion of NG-monomethyl-L-arginine. Additionally, endothelium-independent vasodilatations to sublingual nitroglycerin and plasma levels of biomarkers for endothelial functions were measured. Surprisingly, digital vasodilatations to bradykinin were almost absent in patients with MVA alone and those with VSA+MVA compared with those with VSA alone. Mechanistically, both NO- and endothelium-dependent hyperpolarization-mediated digital vasodilatations were markedly impaired in patients with MVA alone. In contrast, endothelium-independent vasodilatations to nitroglycerin were comparable among the 3 groups. Plasma levels of soluble VCAM (vascular cell adhesion molecule)-1 were significantly higher in patients with MVA alone compared with those with VSA alone. CONCLUSIONS These results provide the first evidence that both NO- and endothelium-dependent hyperpolarization-mediated digital vasodilatations are markedly impaired in MVA patients, suggesting that MVA is a cardiac manifestation of the systemic small artery disease.OBJECTIVE Integrin β3 is implicated in numerous biological processes such as its relevance to blood triglyceride, yet whether β3 deficiency affects this metabolic process remains unknown. Approach and Results We showed that the Chinese patients with β3-deficient Glanzmann thrombasthenia had a 2-fold higher serum triglyceride level together with a lower serum LPL (lipoprotein lipase) level than those with an αIIb deficiency or healthy subjects. The β3 knockout mice recapitulated these phenotypic features. The elevated plasma triglyceride level was due to impaired LPL-mediated triglyceride clearance caused by a disrupted LPL secretion. Further analysis revealed that β3 directly bound LPL via a juxtamembrane TIH720-722 motif in its cytoplasmic domain and functioned as an adaptor protein by interacting with LPL and PKD (protein kinase D) to form the PKD/β3/LPL complex that is required for β3-mediated LPL secretion. Furthermore, the impaired triglyceride clearance in β3 knockout mice could be corrected by adeno-associated virus serotype 9 (AAV9)-mediated delivery of wild-type but not TIH720-722-mutated β3 genes. CONCLUSIONS This study reveals a hypertriglyceridemia in both β3-deficient Chinese patients and mice and provides novel insights into the molecular mechanisms of the significant roles of β3 in LPL secretion and triglyceride metabolism, drawing attention to the metabolic consequences in patients with β3-deficient Glanzmann thrombasthenia.Cardiovascular disease due to atherosclerosis is still the main cause of morbidity and mortality worldwide. This disease is a complex systemic disorder arising from a network of pathological processes within the arterial vessel wall, and, outside of the vasculature, in the hematopoietic system and organs involved in metabolism. Recent years have seen tremendous efforts in the development and validation of quantitative imaging technologies for the noninvasive evaluation of patients with atherosclerotic cardiovascular disease. Specifically, the advent of combined positron emission tomography and magnetic resonance imaging scanners has opened new exciting opportunities in cardiovascular imaging. In this review, we will describe how combined positron emission tomography/magnetic resonance imaging scanners can be leveraged to evaluate atherosclerotic cardiovascular disease at the whole-body level, with specific focus on preclinical animal models of disease, from mouse to nonhuman primates. We will broadly describe 3 major areas of application (1) vascular imaging, for advanced atherosclerotic plaque phenotyping and evaluation of novel imaging tracers or therapeutic interventions; (2) assessment of the ischemic heart and brain; and (3) whole-body imaging of the hematopoietic system.
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