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  • Ovid Technologies (Wolters Kluwer Health)  (16)
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  • Ovid Technologies (Wolters Kluwer Health)  (16)
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  • 1
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 131, No. 5 ( 2022-08-19), p. 442-455
    Abstract: Timely and complete restoration of blood flow is the most effective intervention for patients with acute myocardial infarction. However, the efficacy is limited by myocardial ischemia-reperfusion (MI/R) injury. PDE4 (phosphodiesterase-4) hydrolyzes intracellular cyclic adenosine monophosphate and it has 4 subtypes A-D. This study aimed to delineate the role of PDE4B (phosphodiesterase-4 subtype B) in MI/R injury. Methods: Mice were subjected to 30-minute coronary artery ligation, followed by 24-hour reperfusion. Cardiac perfusion was assessed by laser Doppler flow. Vasomotor reactivities were determined in mouse and human coronary (micro-)arteries. Results: Cardiac expression of PDE4B, but not other PDE4 subtypes, was increased in mice following reperfusion. PDE4B was detected primarily in endothelial and myeloid cells of mouse and human hearts. PDE4B deletion strikingly reduced infarct size and improved cardiac function 24-hour or 28-day after MI/R. PDE4B in bone marrow–derived cells promoted MI/R injury and vascular PDE4B further exaggerated this injury. Mechanistically, PDE4B mediated neutrophil-endothelial cell interaction and PKA (protein kinase A)-dependent expression of cell adhesion molecules, neutrophil cardiac infiltration, and release of proinflammatory cytokines. Meanwhile, PDE4B promoted coronary microcirculatory obstruction and vascular permeability in MI/R, without affecting flow restriction-induced thrombosis. PDE4B blockade increased flow-mediated vasodilatation and promoted endothelium-dependent dilatation of coronary arteries in a PKA- and nitric oxide–dependent manner. Furthermore, postischemia administration with piclamilast, a PDE4 pan-inhibitor, improved cardiac microcirculation, suppressed inflammation, and attenuated MI/R injury in mice. Incubation with sera from patients with acute myocardial infarction impaired acetylcholine-induced relaxations in human coronary microarteries, which was abolished by PDE4 inhibition. Similar protection against MI/R-related coronary injury was recapitulated in mice with PDE4B deletion or inhibition, but not with the pure vasodilator, sodium nitroprusside. Conclusions: PDE4B is critically involved in neutrophil inflammation and microvascular obstruction, leading to MI/R injury. Selective inhibition of PDE4B might protect cardiac function in patients with acute myocardial infarction designated for reperfusion therapy.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467838-X
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 5 ( 2022-05), p. 1580-1588
    Abstract: In patients undergoing mechanical thrombectomy (MT), adjunctive antithrombotic might improve angiographic reperfusion, reduce the risk of distal emboli and reocclusion but possibly expose patients to a higher intracranial hemorrhage risk. This study evaluated the safety and efficacy of combined MT plus eptifibatide for acute ischemic stroke. Methods: This was a propensity-matched analysis of data from 2 prospective trials in Chinese populations: the ANGEL-ACT trial (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke) in 111 hospitals between November 2017 and March 2019, and the EPOCH trial (Eptifibatide in Endovascular Treatment of Acute Ischemic Stroke) in 15 hospitals between April 2019 and March 2020. The primary efficacy outcome was good outcome (modified Rankin Scale score 0–2) at 3 months. Secondary efficacy outcomes included the distribution of 3-month modified Rankin Scale scores and poor outcome (modified Rankin Scale score 5–6) and successful recanalization. The safety outcomes included any intracranial hemorrhage, symptomatic intracranial hemorrhage, and 3-month mortality. Mixed-effects logistic regression models were used to account for within-hospital clustering in adjusted analyses. Results: Eighty-one combination arm EPOCH subjects were matched with 81 ANGEL-ACT noneptifibatide patients. Compared with the no eptifibatide group, the eptifibatide group had significantly higher rates of successful recanalization (91.3% versus 81.5%; P =0.043) and 3-month good outcomes (53.1% versus 33.3%; P =0.016). No significant difference was found in the remaining outcome measures between the 2 groups. All outcome measures of propensity score matching were consistent with mixed-effects logistic regression models in the total population. Conclusions: This matched-control study demonstrated that MT combined with eptifibatide did not raise major safety concerns and showed a trend of better efficacy outcomes compared with MT alone. Overall, eptifibatide shows potential as a periprocedural adjunctive antithrombotic therapy when combined with MT. Further randomized controlled trials of MT plus eptifibatide should be prioritized. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03844594 (EPOCH), NCT03370939 (ANGEL-ACT).
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 5 ( 2021-05), p. 1589-1600
    Abstract: A recent randomized controlled trial DIRECT-MT (Direct Intra-Arterial Thrombectomy to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals) compared the safety and efficacy of mechanical thrombectomy (MT) versus combined intravenous thrombolysis (IVT) and MT for acute large vessel occlusion. The current study utilized a prospective, nationwide registry to validate the results of the DIRECT-MT trial in a real-world practice setting. Methods: Subjects were selected from a prospective cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals from 26 provinces in China (ANGEL-ACT registry [Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke]) between November 2017 and March 2019. All patients eligible for IVT and receiving MT were reviewed and then grouped according to whether prior IVT or not (MT and combined IVT+MT). After a 1:1 propensity score matching, the outcome measures including the 90-day modified Rankin Scale, successful recanalization, door-to-puncture time, symptomatic intracranial hemorrhage, and intraprocedural embolization were compared. Results: A total of 1026 patients, 600 in the MT group and 426 in the combined group, were included. Among 788 patients identified after matching, there were no significant differences in the 90-day modified Rankin Scale (median, 3 versus 3 points; P =0.82) and successful recanalization (86.6% versus 89.3%; P =0.23) between the two groups; however, patients of the MT group had a shorter door-to-puncture time (median, 112 versus 136 minutes; β=−45.02 [95% CI, −68.31 to −21.74]), lower rates of symptomatic intracranial hemorrhage (5.5% versus 10.1%; odds ratio, 0.52 [95% CI, 0.30–0.91] ), and embolization (4.6% versus 8.1%; odds ratio, 0.54 [95% CI, 0.30–0.98]) than those of the combined group. Conclusions: This matched-control study largely confirmed the findings of the DIRECT-MT trial in a real-world practice setting, suggesting that MT may carry similar effectiveness to combined IVT+MT for acute large vessel occlusion patients, despite MT alone seems to be associated with a shorter in-hospital delay until procedure, lower risks of symptomatic intracranial hemorrhage, and embolization. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03370939.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 6 ( 2022-06), p. 1984-1992
    Abstract: The role of stroke etiology subtype in patients with acute large vessel occlusion on the occurrence of hemorrhagic transformation (HT) after endovascular treatment is poorly studied, and which factors mediate their relationship remains largely unknown. We utilized nationwide registry data to explore the association of stroke subtype (cardioembolism versus large artery atherosclerosis) with HT and to identify the possible mediators. Methods: A total of 1015 subjects were selected from the ANGEL-ACT registry (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke)—a prospective consecutive cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals in China between November 2017 and March 2019—and divided into large artery atherosclerosis (n=538) and cardioembolism (n=477) according to the Trial of ORG 10172 in Acute Stroke Treatment criteria. The types of HT included any intracerebral hemorrhage (ICH), parenchymal hematoma, and symptomatic ICH within 24 hours after endovascular treatment. The association between stroke subtype and HT was analyzed using a logistic regression model. Mediation analysis was done to assess how much of the effect of stroke subtype on HT was mediated through the identified mediators. Results: Stroke subtype (cardioembolism versus large artery atherosclerosis) was associated with increased risk of any ICH (29.8% versus 16.5%; odds ratio, 2.03 [95% CI, 1.22–3.36]), parenchymal hematoma (14.3% versus 5.4%; odds ratio, 2.90 [95% CI, 1.38–6.13] ), and symptomatic ICH (9.9% versus 4.7%; odds ratio, 2.59 [95% CI, 1.09–6.16]) after adjustment for potential confounders. The more thrombectomy passes in cardioembolism patients had a significant mediation effect on the association of stroke subtype with increased risk of HT (any ICH, 15.9%; parenchymal hematoma, 13.4%; symptomatic ICH, 14.2%, respectively). Conclusions: Stroke subtype is an independent risk factor for HT within 24 hours following endovascular treatment among acute large vessel occlusion patients. Mediation analyses propose that stroke subtype contributes to HT partly through thrombectomy pass, suggesting a possible pathomechanistic link. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03370939.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 5
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 4 ( 2021-04), p. 1203-1212
    Abstract: The benefit of endovascular treatment (EVT) for large vessel occlusion in clinical practice in developing countries like China needs to be confirmed. The aim of the study was to determine whether the benefit of EVT for acute ischemic stroke in randomized trials could be generalized to clinical practice in Chinese population. Methods: We conducted a prospective registry of EVT at 111 centers in China. Patients with acute ischemic stroke caused by imaging-confirmed intracranial large vessel occlusion and receiving EVT were included. The primary outcome was functional independence at 90 days defined as a modified Rankin Scale score of 0 to 2. Outcomes of specific subgroups in the anterior circulation were reported and logistic regression was performed to predict the primary outcome. Results: Among the 1793 enrolled patients, 1396 (77.9%) had anterior circulation large vessel occlusion (median age, 66 [56–73] years) and 397 (22.1%) had posterior circulation large vessel occlusion (median age, 64 [55–72] years). Functional independence at 90 days was reached in 45% and 44% in anterior and posterior circulation groups, respectively. For anterior circulation population, underlying intracranial atherosclerotic disease was identified in 29% of patients, with higher functional independence at 90 days (52% versus 44%; P =0.0122) than patients without intracranial atherosclerotic disease. In the anterior circulation population, after adjusting for baseline characteristics, procedure details, and early outcomes, the independent predictors for functional independence at 90 days were age 〈 66 years (odds ratio [OR], 1.733 [95% CI, 1.213–2.476] ), time from onset to puncture 〉 6 hours (OR, 1.536 [95% CI, 1.065–2.216]), local anesthesia (OR, 2.194 [95% CI, 1.325–3.633] ), final modified Thrombolysis in Cerebral Infarction 2b/3 (OR, 2.052 [95% CI, 1.085–3.878]), puncture-to-reperfusion time ≤1.5 hours (OR, 1.628 [95% CI, 1.098–2.413] ), and National Institutes of Health Stroke Scale score 24 hours after the procedure 〈 11 (OR, 9.126 [95% CI, 6.222–13.385]). Conclusions: Despite distinct characteristics in the Chinese population, favorable outcome of EVT can be achieved in clinical practice in China. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03370939.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 6
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 2 ( 2017-02-02)
    Abstract: Most cardiovascular diseases occur in low‐ and middle‐income regions of the world, but the socioeconomic distribution within China remains unclear. Our study aims to investigate whether the prevalence of cardiovascular diseases differs among high‐, middle‐, and low‐income regions of China and to explore the reasons for the disparities. Methods and Results We enrolled 46 285 individuals from 115 urban and rural communities in 12 provinces across China between 2005 and 2009. We recorded their medical histories of cardiovascular diseases and calculated the INTERHEART Risk Score for the assessment of cardiovascular risk‐factor burden, with higher scores indicating greater burden. The mean INTERHEART Risk Score was higher in high‐ and middle‐income regions than in low‐income regions (9.47, 9.48, and 8.58, respectively, P 〈 0.0001). By contrast, the prevalence of total cardiovascular disease (stroke, ischemic heart disease, and other heart diseases that led to hospitalization) was lower in high‐ and middle‐income regions than in low‐income regions (7.46%, 7.42%, and 8.36%, respectively, P trend =0.0064). In high‐ and middle‐income regions, urban communities have higher INTERHEART Risk Score and higher prevalent rate than rural communities. In low‐income regions, however, the prevalence of total cardiovascular disease was similar between urban and rural areas despite the significantly higher INTERHEART Risk Score for urban settings. Conclusions We detected an inverse trend between risk‐factor burden and cardiovascular disease prevalence in urban and rural communities in high‐, middle‐, and low‐income regions of China. Such asymmetry may be attributed to the interregional differences in residents’ awareness, quality of healthcare, and availability and affordability of medical services.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2653953-6
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  • 7
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 8, No. 16 ( 2019-08-20)
    Abstract: The predictive value of adiposity indices and the newly developed index for cardiometabolic risk factors and cardiovascular diseases ( CVD s) remains unclear in the Chinese population. This study aimed to compare the predictive value of A Body Shape Index with other 5 conventional obesity‐related anthropometric indices (body mass index, waist circumference, hip circumference, waist‐to‐hip ratio, waist‐to‐height ratio) in Chinese population. Methods and Results A total of 44 048 participants in the study were derived from the baseline data of the PURE ‐China (Prospective Urban and Rural Epidemiology) study in China. All participants’ anthropometric parameters, CVD s, and risk factors (dyslipidemia, abnormal blood pressure, and hyperglycemia) were collected by standard procedures. Multivariable logistic regression models and receiver operator characteristic curve analysis were used to evaluate the predictive values of obesity‐related anthropometric indices to the cardiometabolic risk factors and CVD s. A positive association was observed between each anthropometric index and cardiometabolic risk factors and CVD s in all models ( P 〈 0.001). Compared with other anthropometric indices (body mass index, waist circumference, hip circumference, waist‐to‐hip ratio, and A Body Shape Index), waist‐to‐height ratio had significantly higher areas under the curve ( AUC s) for predicting dyslipidemia ( AUC s: 0.646, sensitivity: 65%, specificity: 44%), hyperglycemia ( AUC s: 0.595, sensitivity: 60%, specificity: 45%), and CVD s ( AUC s: 0.619, sensitivity: 59%, specificity: 41%). Waist circumference showed the best prediction for abnormal blood pressure ( AUC s: 0.671, sensitivity: 66%, specificity: 40%) compared with other anthropometric indices. However, the new body shape index did not show a better prediction to either cardiometabolic risk factors or CVD s than that of any other traditional obesity‐related indices. Conclusions Waist‐to‐height ratio appeared to be the best indicator for dyslipidemia, hyperglycemia, and CVD s, while waist circumference had a better prediction for abnormal blood pressure.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2005
    In:  Circulation Research Vol. 97, No. 8 ( 2005-10-14), p. 821-828
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 97, No. 8 ( 2005-10-14), p. 821-828
    Abstract: Transforming growth factor-βs (TGF-βs) are pleiotropic cytokines involved in many physiological and pathological processes, including heart development and heart disease. Smad4 is the central intracellular mediator of TGF-β signaling. To investigate the function of Smad4 in heart development further, we generated a strain of cardiomyocyte-specific Smad4 knockout mice using the Cre– lox P system. Unexpectedly, the deletion of Smad4 in cardiomyocytes resulted in cardiac hypertrophy characterized by an increase in the size of cardiac myocytes, age-associated fibrosis, and reexpression of certain fetal genes. Approximately 70% of the Smad4 mutant mice died spontaneously between 5 and 12 months of age. Echocardiography and an invasive hemodynamic study of the left ventricle revealed markedly decreased cardiac contractility in Smad4 mutant mice compared with littermate controls. Moreover, phosphorylated extracellular signal–regulated kinase (ERK) 1/2 and mitogen-activated protein kinase–ERK (MEK) 1 were increased in the Smad4 mutants, suggesting that an upregulation of MEK1–ERK1/2 signaling as a consequence of deletion of Smad4 underlies the impaired cardiac function. These results reveal an important function of Smad4 in cardiac remodeling and suggest that an altered cellular response to TGF-β could be a mechanism by which cardiac myocytes undergo hypertrophy.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2005
    detail.hit.zdb_id: 1467838-X
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  • 9
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 94, No. 50 ( 2015-12), p. e2258-
    Type of Medium: Online Resource
    ISSN: 0025-7974
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 2049818-4
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  • 10
    In: Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 96, No. 30 ( 2017-07), p. e7501-
    Type of Medium: Online Resource
    ISSN: 0025-7974
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2049818-4
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