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- Gore Helex septal occluder for percutaneous closure of patent foramen ovale associated with atrial septal aneurysm: short- and mid-term clinical and echocardiographic outcomes. [Comparative Study, Evaluation Studies, Journal Article]
- J Invasive Cardiol 2012 Oct; 24(10):510-4.
To evaluate the short- and mid-term clinical and echocardiographic outcome of HELEX Septal Occluder (HSO) implantation in patients with patent foramen ovale (PFO) and atrial septal aneurysm (ASA).Percutaneous closure of PFO and ASA with HSO device has not been systematically studied.We studied 90 patients with PFO and ASA with documented paradoxical embolic events. The procedural and clinical results of 30 consecutive patients treated with HSO were compared with those obtained in 30 consecutive patients treated with the Amplatzer PFO (APO) and with those of a further 30 consecutive patients treated with the Amplatzer Cribriform (AMF). Primary endpoint was the persistence of moderate to severe residual right-to-left shunting (rRLS) at 6-month follow-up. The incidence of death or recurrent embolic events (REE) at 1-year follow-up were also investigated.The procedure was successfully completed in all patients. There was one HSO device embolization. Immediate moderate RLS was significantly higher in the HSO group compared to APO and AMF groups (20% vs 3% vs 0%, respectively; P=.008). The incidence of moderate rRLS decreased but was still significant at 6-month follow-up (17% in the HSO group vs 3% in the APO group; P=.02). At 1-year follow-up, moderate rRLS persisted only in the HSO group (7%). No deaths or REE were observed during hospitalization or at 1-year follow-up.HSO device seems to be a second-line device as compared to Amplatzer occluders for the treatment of PFO and ASA.
- BM-573 inhibits the development of early atherosclerotic lesions in Apo E deficient mice by blocking TP receptors and thromboxane synthase. [Journal Article, Research Support, Non-U.S. Gov't]
- Prostaglandins Other Lipid Mediat 2011 Apr; 94(3-4):124-32.
Atherosclerosis is the principal cause of mortality in industrialized countries. Its development is influenced by several mediators of which thromboxane A(2) (TXA(2)) and 8-iso-PGF(2α) have recently received a lot of attention. This study aimed to investigate the effect of a dual thromboxane synthase inhibitor and thromboxane receptor antagonist (BM-573) and ASA on lesion formation in apolipoprotein E-deficient mice. The combination of ASA and BM-573 was also studied. Plasma measurements demonstrated that the treatments did not affect body weight or plasma cholesterol levels. BM-573, but not ASA, significantly decreased atherogenic lesions as demonstrated by macroscopic analysis. Both treatments alone inhibited TXB(2) synthesis but only BM-573 and the combination therapy were able to decrease firstly, plasma levels of soluble intracellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) and secondly, the expression of these proteins in the aortic root of Apo E. These results were confirmed in endothelial cell cultures derived from human saphenous vein endothelial cells (HSVECs). In these cells, BM-573 also prevented the increased mRNA expression of ICAM-1 and VCAM-1 induced by U-46619 and 8-iso-PGF(2α). Our results show that a molecule combining receptor antagonism and thromboxane synthase inhibition is more efficient in delaying atherosclerosis in Apo E(-/-) mice than sole inhibition of TXA(2) formation.
- An enhancing effect of visible light and UV radiation on phenolic compounds and various antioxidants in broad bean seedlings. [Journal Article]
- Plant Signal Behav 2010 Oct; 5(10):1197-203.
Exposure of dark- or ambient visible light-grown broad bean seedlings to low (LL) and high (HL) visible light intensities, UV-A or UV-C, either alone or in combination, induced significant increases in total phenolic compounds as well as in anthocyanins content, throughout the germination period, as compared with the respective levels in control seedlings. In general, as compared with control levels, exposure of both dark- or light-grown broad bean seedlings to LL, HL, UV-A or UV-C, induced significant increases in the contents of non-enzymatic antioxidants (total ascorbate; ASA-DASA and total glutathione; GSSG-GSH) and enzymatic antioxidant activities (superoxide dismutase; SOD, catalase; CAT, ascorbate peroxidase; APO and glutathione reductase; GR). The obtained results are discussed in relation to induced mechanisms of protection and repair from the inevitable exposure to damaging visible light and UV-radiation.
- The calcium-modulated structures of calmodulin and S100b proteins are useful to monitor hydrogen/deuterium exchange efficiency using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. [Journal Article, Research Support, Non-U.S. Gov't]
- Eur J Mass Spectrom (Chichester, Eng) 2009; 15(6):739-46.
Hydrogen/deuterium exchange (HDX) using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) is a sensitive, salt-tolerant and high-throughput method useful to probe protein conformation and molecular interactions. However, a drawback of the MALDI HDX technique is that sample preparation methods can typically result in higher levels of artificial deuterium in-exchange and/or hydrogen back- exchange just prior to or during mass analysis; this may impair data reproducibility and impede structural and kinetic data interpretation. While methods to minimize effects of back-exchange during protein analyte deposition on MALDI plates have been reported, this study presents a readily available, highly sensitive protein control set to facilitate rapid MALDI HDX protocol workup. The Ca(2+)-induced solvent accessible surface area (ASA) changes of calmodulin (CaM) and S100 proteins were employed to monitor and optimize HDX protocol efficiency. Under non- stringent room temperature conditions, the Ca(2+)-induced deuterium exchange of CaM, DeltaD(ca2+ -apo), MH(+) shifts -17 to -24 Da, while S100 DeltaD(ca2+ -apo) MH(+) shifts +8 to +12 Da. By comparing the divergent CaM and S100 Ca(2+)-induced deuterium mass shift differences, HDX sample workup and MALDI plate spotting conditions can easily be monitored.
- Transcatheter closure of patent foramen ovale associated with atrial septal aneurysm with Amplatzer Cribriform septal occluder. [Journal Article]
- J Invasive Cardiol 2009 Jun; 21(6):290-3.
We sought to evaluate the short- and longterm outcomes of Amplatzer Multi-Fenestrated Septal Occluder Cribriform (AMF) device use in the percutaneous closure of patent foramen ovale (PFO) associated with atrial septal aneurysm (ASA).Since patients with PFO, associated with ASA, are at higher risk of embolic events (EE), the AMF device might offer advantages in this subgroup of patients.Overall, 38 consecutive patients, with both PFO and ASA, underwent percutaneous closure of the defect with the AMF device, and the results were compared to those in 38 patients with PFO and ASA treated with the Amplatzer PFO device (APO). Death due to embolism, stroke or transient ischemic attack (TIA) were considered recurrent EE. Pre- and post-intervention shunting and 6-month residual shunting were evaluated echocardiographically with intravenous contrast injection.The procedure was successfully completed in all patients in both groups. No procedure-related complications were observed during hospitalization. Immediate closure was achieved in all patients in the AMF group, whereas 3 patients in the APO group showed a small residual shunt. Residual shunting was observed at 6 months in 2 patients in the APO group. No recurrence of EE was recorded in the AMF group. Recurrent TIA was observed in 3 patients in the APO group; 2/3 patients had a small residual shunt following the procedure and at 6-month follow up.The AMF device might offer advantages in terms of rate of EE recurrence or residual shunt compared to the APO device in PFO patients associated with ASA.
- Identification of evolutionary conserved mouse sperm surface antigens by human antisperm antibodies (ASA) from infertile patients. [In Vitro, Journal Article, Research Support, Non-U.S. Gov't]
- Am J Reprod Immunol 2006 May; 55(5):321-30.
The presence of antisperm antibodies (ASA) in semen may impair sperm function leading to immunological infertility. The aim of the study was to identify the evolutionary conserved antigens on mouse sperm surface that react with human ASA in order to study the mechanism of autoimmune infertility.The binding of human ASA to mouse sperm was investigated by means of indirect immunofluorescence. 2D-electrophoresis was applied to separate the biotin-labelled mouse membrane proteins using isoelectric focusing followed by polyacrylamide gel electrophoresis. Cognate antigens of ASA from seminal plasma of infertile patients were analysed by Western blotting. Performing avidin-blots it was detected which of the proteins recognized were sperm surface proteins. The spots of interest were analysed by means of mass spectrometry.ASA bound most frequently (36%) to the post-acrosomal region and to the midpiece of mouse spermatozoa. About 30% of ASA recognized apo lactate dehydrogenase (LDHC4) as a cognate antigen, 30% voltage-dependent anion channel (VDAC2). ASA of 20% bound to outer dense fibre protein and 20% of samples recognized glutathione S-transferase mu5.Human ASA bound to specific cognate antigens of mouse spermatozoa, offering the possibility to study their functional relevance in the mouse model.
- Effect of L-ascorbic acid on the oxidative modification of apolipoprotein E in human very-low-density lipoprotein. [Journal Article]
- J Nutr Sci Vitaminol (Tokyo) 2004 Feb; 50(1):66-8.
Antioxidant activity of L-ascorbic acid (AsA) against oxidative modification of apolipoprotein (apo) E in human very-low-density lipoprotein (VLDL) was investigated. The VLDL oxidation induced by peroxyl radicals and peroxynitrite led to lipid peroxidation and oxidative modification of apoE. The binding activity of apoE to heparin was decreased by the oxidative modification. AsA (200, 500, and 1,000 microm) inhibited both the lipid peroxidation and the oxidative modification of apoE. These results suggest that AsA prevents the biological function of apoE in VLDL from the oxidation by free radicals.
- Extracellular matrix components in atherosclerotic arteries of Apo E/LDL receptor deficient mice: an immunohistochemical study. [Journal Article, Research Support, Non-U.S. Gov't]
- Histol Histopathol 2004 Apr; 19(2):337-47.
During accelerated vascular remodeling such as in atherosclerosis, the composition of the extracellular matrix becomes altered. The matrix components of the diseased artery influence cellular processes such as adhesion, migration and proliferation. Furthermore, in atherosclerosis, the inability of the cells within the lesion to produce a mechanically stable matrix may lead to plaque rupture. In this immunohistochemical study of atherosclerotic mice aorta, we have reviewed the presence of ECM components with roles in maintaining tissue structure and function. These components include osteopontin and COMP as well as the leucine rich repeats proteins decorin, PRELP, and fibromodulin. Immunohistochemistry demonstrated presence of osteopontin, COMP, decorin, PRELP and fibromodulin in lesion areas of ApoE/LDLr deficient mice. Some advanced lesions exhibited areas of cartilage-like morphology and were shown to represent cartilage by their content of the cartilage specific proteins collagen II and aggrecan. The results suggest that cartilage-associated cell/collagen binding ECM proteins may be involved in the pathogenesis of atherosclerosis.
- Cyclooxygenase inhibition is associated with downregulation of apolipoprotein AI promoter activity in cultured hepatoma cell line HepG2. [Journal Article, Research Support, Non-U.S. Gov't]
- Metabolism 2004 Feb; 53(2):174-81.
Prostanoids have been implicated in the transcriptional control of several genes. Since prostanoid synthesis inhibitors are commonly used in subjects with coronary heart disease we studied the effect of cyclooxygenase (COX) inhibition on apolipoprotein AI (apoAI) expression in a human hepatoma cell line (HepG2) transfected with full-length apoAI promoter attached to the chloramphenicol acetyl transferase (CAT) reporter gene. To control for transfection efficiency, the cells were cotransfected with the plasmid pCMV.SPORT-beta-gal containing the beta-galactosidase gene driven by the cytomegalovirus promoter. Treatment of these cells with varying concentrations of indomethacin (INDO, 0, 50, 100, and 300 micromol/L) resulted in a dose-dependent decrease in apoAI promoter activity (% acetylation corrected for beta-galactosidase activity: were 46.1 +/- 2.6, 29.9 +/- 1.2, 25.2 +/- 2.9, and 17.2 +/- 2.8, respectively, P <.001). INDO treatment did not cause significant changes in beta-galactosidase activity. A similar reduction in apoAI promoter activity was found after treating the cells with 50 micromol/L acetylsalicylic acid (ASA) (31.8 +/- 1.8%, P <.001), suggesting that the effect of INDO is related to COX inhibition rather than a peculiar effect of INDO. Nuclear run-off assays indicated that treatment of cells with 50 micromol/L INDO resulted in 31.4% reduction in apo A1 transcription rate (P <.0002). Northern blot analysis of RNA from HepG2 cells treated with 50 micromol/L of INDO for 72 hours showed that the apoAI mRNA concentration relative to G3PDH mRNA was 4,043.0 +/- 84.6 and 3,064.0 +/- 49.8 in control and INDO-treated cells, respectively (P <.0006). Kinetic studies of apoAI mRNA in HepG2 cells indicated that the half-life of apoAI mRNA was not significantly altered with 50 micromol/L INDO treatment. Apo AI mRNA half-life was 25.3 hours in control cells and 26.9 hours in INDO-treated cells. Western blot analysis of culture media of HepG2 cells treated with 50 micromol/L of INDO for 72 hours showed a significant reduction in apoAI protein (6,760.0 +/- 318.1 v 4,773.0 +/- 112.0 arbitrary units, P <.004). Treatment of cells with either arachidonic acid (COX substrate) or various prostanoids including prostaglandin I(2), thromboxane B(2), (+/-)5-HETE, or (+/-)12-HETE did not significantly alter apoAI promoter activity. However, prostaglandin E(1) and E(2) at the highest concentration tested (50 nmol/L) significantly repressed apoAI promoter activity. COX activity measurements in HepG2 cells verified the efficacy of COX inhibition by INDO. It is concluded that COX inhibition with INDO or ASA downregulates apoAI expression at the transcriptional level. This effect could not be attributed to either arachidonic acid excess or to a deficiency in various prostanoids tested.
- Plasma protein adsorption pattern on characterized ceramic biomaterials. [In Vitro, Journal Article, Research Support, Non-U.S. Gov't]
- Biomaterials 2002 Feb; 23(4):1237-47.
The protein/biomaterial interactions of three biomaterials used in hard tissue surgery were studied in vitro. A dynamic flow system and two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) were used to investigate the adsorption of proteins from diluted human plasma on hydroxyapatite, alumina and zirconia, with regard to total protein binding capacity, relative binding capacity for specific proteins and flow-through and desorption patterns. The ceramics were characterized regarding physicochemical properties; namely, chemical composition by elementary analyses and specific surface, pore volume and pore size distribution using the BET-method and Hg-porosimetry. The materials were found to adsorb a surprisingly low amount of plasma proteins, leaving more than 70% of the surface free. The cellular response will therefore be highly affected by the physico-chemical properties of the material, in contrast to a surface fully covered with proteins. Regarding the adsorption of proteins, most proteins exhibited similar flow-through patterns on the three adsorbents. The exceptions with different flow-through patterns were apolipoprotein D (Apo D), apolipoprotein J (Apo J), complement factor C1s (C1s), complement factor C3 (C3), ceruloplasmin, fibrinogen, alpha1 B glycoprotein and alpha2 HS glycoprotein and serum retinal-binding protein (SRBP). The role of these proteins on acceptance or rejection of implants has to be investigated.