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31.
Genome‐wide association study of a nicotine metabolism biomarker in African American smokers: impact of chromosome 19 genetic influences
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![点击此处可从《Addiction (Abingdon, England)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Meghan J. Chenoweth Jennifer J. Ware Andy Z. X. Zhu Christopher B. Cole Lisa Sanderson Cox Nikki Nollen Jasjit S. Ahluwalia Neal L. Benowitz Robert A. Schnoll Larry W. Hawk Jr Paul M. Cinciripini Tony P. George Caryn Lerman Joanne Knight Rachel F. Tyndale 《Addiction (Abingdon, England)》2018,113(3):509-523
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Rodriguez-Porcel M Lerman A Herrmann J Schwartz RS Sawamura T Condorelli M Napoli C Lerman LO 《Cardiovascular research》2003,58(1):213-221
OBJECTIVE: Hypercholesterolemia (HC) and hypertension (HT) are both major risk factors for the development and progression of atherosclerotic heart disease, and their co-existence has been associated with an increased incidence of cardiac events in clinical studies. HC and HT are individually associated with abnormal myocardial vascular function, but whether HT exacerbates the HC-induced myocardial vascular dysfunction remains unclear. METHODS: We studied in pigs the effect of renovascular HT superimposed on diet-induced HC (HC+HT) on myocardial perfusion and microvascular permeability in vivo (using electron-beam computed tomography) in response to cardiac challenge (i.v. adenosine and dobutamine). The involvement of systemic and myocardial tissue oxidative stress in vitro was assessed by oxidizability of LDL, levels of endogenous antioxidants, and tissue activities of radical-scavenger systems. RESULTS: While in normal animals myocardial perfusion increased in response to i.v. adenosine (+36+/-13%, P<0.05), in HC and HT alone the increase was blunted. In HC+HT myocardial perfusion response was further attenuated and significantly lower than normal, and myocardial vascular resistance failed to decrease (+7.6+/-8.8 vs. -21.0+/-5.8%, P=0.02 versus normal). HC+HT also showed blunted response to dobutamine, and augmented increases in microvascular permeability in vivo. These functional abnormalities were associated with increased systemic and myocardial tissue oxidative stress compared to HC or HT alone, and a synergistic decrease in endogenous antioxidant defenses in myocardial tissue. Furthermore, chronic antioxidant vitamin supplementation in combined HC and HT improved myocardial vascular responses. CONCLUSION: HT amplifies the HC-induced myocardial microvascular dysfunction in vivo and increased oxidative stress in vitro. These alterations may potentially play a role in the increased incidence of cardiac events observed when HC and HT co-exist. 相似文献
36.
Biomaterial characterization of off‐the‐shelf decellularized porcine pericardial tissue for use in prosthetic valvular applications
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Joshua A. Choe Soumen Jana Brandon J. Tefft Ryan S. Hennessy Jason Go David Morse Amir Lerman Melissa D. Young 《Journal of tissue engineering and regenerative medicine》2018,12(7):1608-1620
Fixed pericardial tissue is commonly used for commercially available xenograft valve implants, and has proven durability, but lacks the capability to remodel and grow. Decellularized porcine pericardial tissue has the promise to outperform fixed tissue and remodel, but the decellularization process has been shown to damage the collagen structure and reduce mechanical integrity of the tissue. Therefore, a comparison of uniaxial tensile properties was performed on decellularized, decellularized‐sterilized, fixed, and native porcine pericardial tissue versus native valve leaflet cusps. The results of non‐parametric analysis showed statistically significant differences (p < .05) between the stiffness of decellularized versus native pericardium and native cusps as well as fixed tissue, respectively; however, decellularized tissue showed large increases in elastic properties. Porosity testing of the tissues showed no statistical difference between decellularized and decell‐sterilized tissue compared with native cusps (p > .05). Scanning electron microscopy confirmed that valvular endothelial and interstitial cells colonized the decellularized pericardial surface when seeded and grown for 30 days in static culture. Collagen assays and transmission electron microscopy analysis showed limited reductions in collagen with processing; yet glycosaminoglycan assays showed great reductions in the processed pericardium relative to native cusps. Decellularized pericardium had comparatively low mechanical properties among the groups studied; yet the stiffness was comparatively similar to the native cusps and demonstrated a lack of cytotoxicity. Suture retention, accelerated wear, and hydrodynamic testing of prototype decellularized and decell‐sterilized valves showed positive functionality. Sterilized tissue could mimic valvular mechanical environment in vitro, therefore making it a viable potential candidate for off‐the‐shelf tissue‐engineered valvular applications. 相似文献
37.
Sheera F. Lerman Claudia M. Campbell Luis F. Buenaver Mary Medak Jane Phillips Michelle Polley Michael T. Smith Jennifer A. Haythornthwaite 《The journal of pain》2018,19(11):1342-1351
Negative cognitions are central to the perpetuation of chronic pain and sleep disturbances. Patients with temporomandibular joint disorder (TMJD), a chronic pain condition characterized by pain and limitation in the jaw area, have a high comorbidity of sleep disturbances that possibly exacerbate their condition. Ethnic group differences are documented in pain, sleep, and coping, yet the mechanisms driving these differences are still unclear, especially in clinical pain populations. We recruited 156 women (79% white, 21% African American) diagnosed with TMJD as part of a randomized, controlled trial evaluating the effectiveness of interventions targeting sleep and pain catastrophizing on pain in TMJD. Analysis of baseline data demonstrated that, relative to white participants, African Americans exhibited higher levels of clinical pain, insomnia severity, and pain catastrophizing, yet there was no ethnic group difference in negative sleep-related cognitions. Mediation models revealed pain catastrophizing, but not sleep-related cognitions or insomnia severity, to be a significant single mediator of the relationship between ethnicity and clinical pain. Only the helplessness component of catastrophizing together with insomnia severity sequentially mediated the ethnicity–pain relationship. These findings identify pain catastrophizing as a potentially important link between ethnicity and clinical pain and suggest that interventions targeting pain-related helplessness could improve both sleep and pain, especially for African American patients.Perspective:Pain-related helplessness and insomnia severity contribute to ethnic differences found in clinical pain among woman with TMJD. Findings can potentially inform interventions that target insomnia and catastrophizing to assist in reducing ethnic disparities in clinical pain. 相似文献
38.
Hypercholesterolemia impairs myocardial perfusion and permeability: role of oxidative stress and endogenous scavenging activity 总被引:5,自引:0,他引:5
Rodriguez-Porcel M Lerman A Best PJ Krier JD Napoli C Lerman LO 《Journal of the American College of Cardiology》2001,37(2):608-615
OBJECTIVES: We intended to study the effect of hypercholesterolemia (HC) on myocardial perfusion and permeability response to increased cardiac demand. BACKGROUND: Hypercholesterolemia is associated with increased incidence of cardiac events and characterized by impaired coronary vascular function, possibly mediated partly through increased pro-oxidative conditions in plasma and tissue. However, it is yet unclear whether HC is also associated with impaired myocardial perfusion and vascular permeability responses in vivo. METHODS: For 12 weeks pigs were fed a normal, HC or HC diet supplemented daily with antioxidants (HC + AO, 100 IU/kg vitamin E and 1 g vitamin C). Myocardial perfusion and vascular permeability were measured in vivo using electron beam computed tomography before and after cardiac challenge with intravenous adenosine. Plasma and tissue oxidative status was determined ex vivo. RESULTS: Plasma cholesterol increased in all cholesterol-fed pigs but was associated with increased markers of oxidative stress only in HC pigs. Myocardial perfusion increased in response to adenosine in normal and HC + AO (+37 +/- 13% and +58 +/- 22%, respectively, p < 0.05 vs. baseline) but not in HC, whereas vascular permeability index increased only in HC pigs (+ 92 +/- 25%, p = 0.002). In HC animals, tissue endogenous oxygen radical scavengers and antioxidant vitamins were depleted and LDL oxidizability enhanced, but both were normalized in HC + AO pigs. Myocardial perfusion response was directly, and permeability inversely, associated with plasma and tissue vitamin concentrations. CONCLUSIONS: This study demonstrates that experimental HC is associated with blunted myocardial perfusion and increased vascular permeability responses in vivo to increased cardiac demand, which may be partly mediated by a shift in oxidative status. 相似文献
39.
Chade AR Rodriguez-Porcel M Rippentrop SJ Lerman A Lerman LO 《American journal of hypertension》2003,16(2):111-115
BACKGROUND: Hypercholesterolemia (HC) is a risk factor for renal disease that may activate the angiotensin II type 1 (AT1) receptor and accelerate renal damage. Early diet-induced HC impairs renal perfusion responses, but it is yet unknown whether the AT1 receptor is involved. This study tested the hypothesis that AT1 receptor blockade improved renal perfusion and functional responses in hypercholesterolemic pigs. METHODS: Regional renal hemodynamics and function in vivo were quantified bilaterally in pigs, at baseline and during vasoactive challenge (acetylcholine or sodium nitroprusside), using electron beam computed tomography after 12 weeks of normal (n = 6) or HC diet (n = 6), or HC diet supplemented (100 mg/d) with the AT1-receptor antagonist irbesartan (HC + AT1, n = 6). RESULTS: Basal cortical and medullary perfusion was similar among the groups. Basal tubular function was similar on normal and HC diets, whereas HC + AT1 showed decreased proximal and distal fluid reabsorption. Hypercholesterolemic pigs had blunted cortical perfusion (P = .22) and augmented tubular responses to acetylcholine, whereas on HC + AT1 diet, cortical perfusion (P = .002) and tubular function were similar to normal animals. This was associated with decreased systemic levels of the oxidative stress markers thiobarbituric acid reactive substances. CONCLUSIONS: The AT1 receptor blockade in HC improves renal perfusion and tubular functional responses to endothelium-dependent vasodilators, in association with a decrease in oxidative stress. These results imply involvement of the renin-angiotensin system in the blunted renal cortical perfusion responses observed in HC, and suggest a potential role for these agents in preservation of intrarenal hemodynamics and function in HC. 相似文献
40.
Mittal S Stein KM Markowitz SM Iwai S Guttigoli A Lerman BB 《Cardiac Electrophysiology Review》2003,7(3):285-289
Atrial fibrillation is the most frequently encountered sustained arrhythmia in clinical practice. Electrical cardioversion of atrial fibrillation using damped sine wave shocks has been a mainstay of therapy for nearly 4 decades; its limitation remains a failure rate that approaches 20%. Although several alternatives have been proposed, including delivering 720 J shocks using dual monophasic defibrillators, ibutilide pretreatment and internal cardioversion, each of these approaches has significant limitations, which preclude its routine use. Recent data demonstrate that routine use of biphasic shocks for cardioversion of atrial fibrillation is associated with a marked improvement in cardioversion efficacy and suggest that biphasic shocks may be the preferred method for the transthoracic electrical cardioversion of atrial fibrillation. 相似文献