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141.
142.
Rausch MK Bothe W Kvitting JP Göktepe S Miller DC Kuhl E 《Journal of biomechanics》2011,44(6):1149-1157
Understanding the mechanics of the mitral valve is crucial in terms of designing and evaluating medical devices and techniques for mitral valve repair. In the current study we characterize the in vivo strains of the anterior mitral valve leaflet. On cardiopulmonary bypass, we sew miniature markers onto the leaflets of 57 sheep. During the cardiac cycle, the coordinates of these markers are recorded via biplane fluoroscopy. From the resulting four-dimensional data sets, we calculate areal, maximum principal, circumferential, and radial leaflet strains and display their profiles on the averaged leaflet geometry. Average peak areal strains are 13.8±6.3%, maximum principal strains are 13.0±4.7%, circumferential strains are 5.0±2.7%, and radial strains are 7.8±4.3%. Maximum principal strains are largest in the belly region, where they are aligned with the circumferential direction during diastole switching into the radial direction during systole. Circumferential strains are concentrated at the distal portion of the belly region close to the free edge of the leaflet, while radial strains are highest in the center of the leaflet, stretching from the posterior to the anterior commissure. In summary, leaflet strains display significant temporal, regional, and directional variations with largest values inside the belly region and toward the free edge. Characterizing strain distribution profiles might be of particular clinical significance when optimizing mitral valve repair techniques in terms of forces on suture lines and on medical devices. 相似文献
143.
Koukoulitsa C Durdagi S Siapi E Villalonga-Barber C Alexi X Steele BR Micha-Screttas M Alexis MN Tsantili-Kakoulidou A Mavromoustakos T 《European biophysics journal : EBJ》2011,40(7):865-875
In previous studies it was shown that cannabinoids (CBs) bearing a phenolic hydroxyl group modify the thermal properties of
lipid bilayers more significantly than methylated congeners. These distinct differential properties were attributed to the
fact that phenolic hydroxyl groups constitute an anchoring group in the vicinity of the head-group, while the methylated analogs
are embedded deeper towards the hydrophobic region of the lipid bilayers. In this work the thermal effects of synthetic polyphenolic
stilbenoid analogs and their methylated congeners have been studied using differential scanning calorimetry (DSC). Molecular
dynamics (MD) simulations have been performed to explain the DSC results. Thus, two of their phenolic hydroxyl groups orient
in the lipid bilayers in such a way that they anchor in the region of the head-group. In contrast, their methoxy congeners
cannot anchor effectively and are embedded deeper in the hydrophobic segment of the lipid bilayers. The MD results explain
the fact that hydroxystilbenoid analogs exert more significant effects on the pretransition than their methoxy congeners,
especially at low concentrations. To maximize the polar interactions, the two phenolic hydroxyl groups are localized in the
vicinity of the head-group region, directing the remaining hydroxy group in the hydrophobic region. This topographical position
of stilbenoid analogs forms a mismatch that explains the significant broadening of the width of the phase transition and lowering
of the main phase-transition temperature in the lipid bilayers. At high concentrations, hydroxy and nonhydroxy analogs appear
to form different domains. The correlation of thermal effects with antioxidant activity is discussed. 相似文献
144.
145.
Svitlana Demyanets Walter S. Speidl Ioannis Tentzeris Rudolf Jarai Katharina M. Katsaros Serdar Farhan Konstantin A. Krychtiuk Anna Wonnerth Thomas W. Weiss Kurt Huber Johann Wojta 《PloS one》2014,9(4)
Objectives
ST2 is a receptor for interleukin (IL)-33. We investigated an association of soluble ST2 (sST2) and IL-33 serum levels with different clinical stages of coronary artery disease. We assessed the predictive value of sST2 and IL-33 in patients with stable angina, non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI).Methods
We included 373 patients of whom 178 had stable angina, 97 had NSTEMI, and 98 had STEMI. Patients were followed for a mean of 43 months. The control group consisted of 65 individuals without significant stenosis on coronary angiography. Serum levels of sST2 and IL-33 were measured by ELISAs.Results
sST2 levels were significantly increased in patients with STEMI as compared to patients with NSTEMI and stable angina as well as with controls. IL-33 levels did not differ between the four groups. During follow-up, 37 (10%) patients died and the combined endpoint (all cause death, MI and rehospitalisation for cardiac causes) occurred in 66 (17.6%) patients. sST2 serum levels significantly predicted mortality in the total cohort. When patients were stratified according to their clinical presentation, the highest quintile of sST2 significantly predicted mortality in patients with STEMI, but not with NSTEMI or stable coronary artery disease. sST2 was a significant predictor for the combined endpoint in STEMI patients and in patients with stable angina. Serum levels of IL-33 were not associated with clinical outcome in the total cohort, but the highest quintile of IL-33 predicted mortality in patients with STEMI.Conclusions
Serum levels of sST2 are increased in patients with acute coronary syndromes as compared to levels in patients with stable coronary artery disease and in individuals without coronary artery disease. sST2 and IL-33 were associated with mortality in patients with STEMI but not in patients with NSTEMI or stable angina. 相似文献146.
Jiqing Guo Serdar Durdagi Mohamed Changalov Laura L. Perissinotti Jason M. Hargreaves Thomas G. Back Sergei Y. Noskov Henry J. Duff 《PloS one》2014,9(9)
One of the main culprits in modern drug discovery is apparent cardiotoxicity of many lead-candidates via inadvertent pharmacologic blockade of K+, Ca2+ and Na+ currents. Many drugs inadvertently block hERG1 leading to an acquired form of the Long QT syndrome and potentially lethal polymorphic ventricular tachycardia. An emerging strategy is to rely on interventions with a drug that may proactively activate hERG1 channels reducing cardiovascular risks. Small molecules-activators have a great potential for co-therapies where the risk of hERG-related QT prolongation is significant and rehabilitation of the drug is impractical. Although a number of hERG1 activators have been identified in the last decade, their binding sites, functional moieties responsible for channel activation and thus mechanism of action, have yet to be established. Here, we present a proof-of-principle study that combines de-novo drug design, molecular modeling, chemical synthesis with whole cell electrophysiology and Action Potential (AP) recordings in fetal mouse ventricular myocytes to establish basic chemical principles required for efficient activator of hERG1 channel. In order to minimize the likelihood that these molecules would also block the hERG1 channel they were computationally engineered to minimize interactions with known intra-cavitary drug binding sites. The combination of experimental and theoretical studies led to identification of functional elements (functional groups, flexibility) underlying efficiency of hERG1 activators targeting binding pocket located in the S4–S5 linker, as well as identified potential side-effects in this promising line of drugs, which was associated with multi-channel targeting of the developed drugs. 相似文献
147.
Satar B Hidir Y Serdar MA Kucuktag Z Ural AU Avcu F Safali M Oguztuzun S 《Cytotherapy》2012,14(5):522-528
Background aimsThe types of proteins released from mesenchymal stromal cells (MSC) are still unclear. Our aim was to compare apoptosis scores and the expression of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), neural cell adhesion molecule (NCAM)-1,matrix metalloproteinase (MMP)-1A, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-1/MMP-1A ratio, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), neurotrophin (NT)-3, NT-4, glial cell-derived neurotropic factor (GDNF), leukemia inhibitory factor (LIF), basic fibroblast growth factor (FGF)-2, insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)-α and transforming growth factor (TGF)-β1 in anastomosed facial nerves that had been treated with or without MSC.MethodsIn seven rats, the buccal branch of the right facial nerve was transected, anastomosed and treated with MSC (anastomosed + MSC group). The left buccal branch was anastomosed only (anastomosed-only group). The left mandibular branch served as an intact nerve group. On days 18–20, the distal segments of the branches were examined in terms of expression of the mentioned proteins and apoptosis scores using polymerase chain reaction (PCR) and terminal deoxynucleotidyl transferase-mediated digoxigenin-UTP nick end labeling (TUNEL) assays.ResultsMSC application significantly increased CNTF, PDGF-α, LIF, TGF-β1, BDNF and NT-3 expression (P < 0.05). MAG expression slightly decreased whereas NCAM-1, MMP-1A and FGF-2 slightly increased(P > 0.05). Changes in other proteins and apoptosis scores were not significant.ConclusionsThese results suggest that MSC increases expression of CNTF, PDGF-α, LIF,TGF-β1, BDNF and NT-3. MAG, NCAM-1, MMP-1A and FGF-2 expressions were slightly changed in this stage of nerve regeneration. The comparison of apoptotic activity was not conclusive. Overall, it appears that MSC might have differential effects on the mentioned tissue-related proteins and trophic/growth factors. 相似文献
148.
149.
Aydemir M Ozturk N Dogan S Aslan M Olgar Y Ozdemir S 《Biological trace element research》2012,148(2):216-223
Recently, sodium tungstate was suggested to improve cardiac performance of diabetic rats in perfused hearts based on its insulinomimetic activity. In this study, we aimed to investigate the cellular and molecular mechanisms underlying this beneficial effect of sodium tungstate. Tungstate was administered (100 mg/kg/day) to diabetic and control rats intragastrically for 6 weeks. Blood glucose levels increased, whereas body weight, heart weight and plasma insulin levels decreased significantly in diabetic animals. Interestingly, none of these parameters was changed by tungstate treatment. On the other hand, fractional shortening and accompanying intracellular Ca(2+) [Ca(2+)](i) transients of isolated ventricular myocytes were measured, and sodium tungstate was found to improve the peak shortening and the amplitude of [Ca(2+)](i) transients in diabetic cardiomyocytes. Potassium and L-type Ca(2+) currents were also recorded in isolated ventricular cells. Significant restoration of suppressed I (to) and I (ss) was achieved by tungstate administration. Nevertheless, L-type calcium currents did not change either in untreated or treated diabetic rats. Tissue biochemical parameters including TBARS, protein carbonyl content, xanthine oxidase (XO) and xanthine dehydogenase (XDH) were also determined, and diabetes revealed a marked increase in TBARS and carbonyl content which were decreased significantly by tungstate treatment. Conversely, although XO and XDH activities didn't change in untreated diabetic rats, a remarkable but insignificant decrease was detected in treated animals. In conclusion, tungstate treatment improved diabetes-induced contractile abnormalities via restoration of dysregulated [Ca(2+)](i) and altered ionic currents. This beneficial effect is due to antioxidant property of sodium tungstate rather than normalization of hyperglycemia. 相似文献
150.
Balaydin HT Durdaği S Ekinci D Sentürk M Göksu S Menzek A 《Journal of enzyme inhibition and medicinal chemistry》2012,27(4):467-475
Carbonic anhydrase inhibitors (CAI) are valuable molecules as they have several therapeutic applications, including anti-glaucoma activity. In this study, inhibition of three human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I, II and VI with a series of bisphenol and bromophenol derivatives was investigated. Molecular docking studies of a set of such inhibitors within CA I and II were also performed. K(I) values of the molecules 2-9 were in the range of 10.025-892.109 μM for hCA I, 1.437-59.107 μM for hCA II and 11.143-919.182 μM for hCA VI, respectively. Reported inhibitory activities of molecules 2-9 will assist in better understanding of structure-activity relationship studies of CAI. 相似文献