95 research outputs found

    Phosphorylation and translocation of heat shock protein 27 and αB-crystallin in human myocardium after cardioplegia and cardiopulmonary bypass

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    ObjectivesCardiac surgery using cardioplegia and cardiopulmonary bypass subjects myocardium to hypothermic reversible ischemic injury that can impair cardiac function. Research in animal and cell models demonstrates that acute myocardial ischemia/reperfusion injury causes phosphorylation of heat shock protein 27 and αB-crystallin. Phosphorylation of heat shock protein 27 and αB-crystallin is implicated in the regulation of both beneficial and detrimental responses to ischemic injury. The phosphorylation status of these proteins in human myocardium after ischemic insults associated with cardioplegia and cardiopulmonary bypass is unknown.MethodsRight atrial appendage and chest wall skeletal muscle samples were collected from patients before and after cardioplegia and cardiopulmonary bypass. Cardioplegia and cardiopulmonary bypass-induced changes in phosphorylation and localization of heat shock protein 27 and αB-crystallin were determined using immunoblot and confocal microscopy with total and phospho-specific antibodies.ResultsCardioplegia and cardiopulmonary bypass increased the phosphorylation of heat shock protein 27 on serine 15, 78, and 82, and αB-crystallin on serine 59 and 45, but not serine 19. The majority of heat shock protein 27 and αB-crystallin localized to I-bands of cardiac myofilaments and shifted to a detergent insoluble fraction after cardioplegia and cardiopulmonary bypass. Cardioplegia and cardiopulmonary bypass–induced phosphorylation of specific heat shock protein 27 and αB-crystallin residues were associated with additional subcellular locations. Increases in phosphorylation of heat shock protein 27 and αB-crystallin were negatively correlated with cardiac function after surgery.ConclusionCardiac surgery using cardioplegia and cardiopulmonary bypass is associated with phosphorylation and myofilament translocation of heat shock protein 27 and αB-crystallin in human myocardium. Phosphorylation of specific heat shock protein 27 and αB-crystallin serine residues is associated with distinct localization. Understanding the human myocardial small heat shock protein response may have significant implications for surgical myocardial protection

    String Sanitization Under Edit Distance: Improved and Generalized

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    Let W be a string of length n over an alphabet Σ, k be a positive integer, and S be a set of length-k substrings of W. The ETFS problem asks us to construct a string XED such that: (i) no string of S occurs in XED; (ii) the order of all other length-k substrings over Σ is the same in W and in XED; and (iii) XED has minimal edit distance to W. When W represents an individual's data and S represents a set of confidential patterns, the ETFS problem asks for transforming W to preserve its privacy and its utility [Bernardini et al., ECML PKDD 2019]. ETFS can be solved in O(n2k) time [Bernardini et al., CPM 2020]. The same paper shows that ETFS cannot be solved in O(n2−δ) time, for any δ>0, unless the Strong Exponential Time Hypothesis (SETH) is false. Our main results can be summarized as follows: (i) an O(n2log2k)-time algorithm to solve ETFS; and (ii) an O(n2log2n)-time algorithm to solve AETFS, a generalization of ETFS in which the elements of S can have arbitrary lengths. Our algorithms are thus optimal up to polylogarithmic factors, unless SETH fails. Let us also stress that our algorithms work under edit distance with arbitrary weights at no extra cost. As a bonus, we show how to modify some known techniques, which speed up the standard edit distance computation, to be applied to our problems. Beyond string sanitization, our techniques may inspire solutions to other problems related to regular expressions or context-free grammars

    Acid-suppressive effects of generic omeprazole: Comparison of three brands of generic omeprazole with original omeprazole

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    Background: Generic omeprazole contains the same active ingredient as original omeprazole and require verification of the bioequivalence with original omeprazole. However, very few clinical studies have been reported. Aims: A prospective, randomised, open-label, crossover study to compare acid-suppressive effect of generic omeprazole with that of original omeprazole. Subjects: Seven healthy Helicobacter pylori-negative subjects of CYP2C19 extensive metaboliser. Methods: Intragastric pH was measured for 24 h without medications (placebo) and on day 7 of repeated administration of 10 mg once daily after breakfast of original omeprazole, Omeprazon, or three brands of generic omeprazole, Omeprazole-Towa, Ovulanze or Omerap. Results: Median values of intragastric pH and percentages of time with pH > 4 for 24 h were significantly higher with administration of any omeprazole formulation compared with placebo (P 4 with Omeprazole-Towa and Omerap were not significantly higher than placebo. Compared with Omeprazon, these two parameters for 24 h showed significantly greater inter-subject variations with Omeprazole-Towa (P < 0.05 and P < 0.01, F-test) and Ovulanze (P < 0.05). Conclusions: Acid-suppressive effects of some brands of generic omeprazole are not the same as original omeprazole. These differences might be reflected in clinical outcomes

    String Sanitization Under Edit Distance: Improved and Generalized

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    Let W be a string of length n over an alphabet Σ, k be a positive integer, and S be a set of length-k substrings of W. The ETFS problem asks us to construct a string XED such that: (i) no string of S occurs in XED; (ii) the order of all other length-k substrings over Σ is the same in W and in XED; and (iii) XED has minimal edit distance to W. When W represents an individual's data and S represents a set of confidential patterns, the ETFS problem asks for transforming W to preserve its privacy and its utility [Bernardini et al., ECML PKDD 2019]. ETFS can be solved in O(n2k) time [Bernardini et al., CPM 2020]. The same paper shows that ETFS cannot be solved in O(n2−δ) time, for any δ>0, unless the Strong Exponential Time Hypothesis (SETH) is false. Our main results can be summarized as follows: (i) an O(n2log2k)-time algorithm to solve ETFS; and (ii) an O(n2log2n)-time algorithm to solve AETFS, a generalization of ETFS in which the elements of S can have arbitrary lengths. Our algorithms are thus optimal up to polylogarithmic factors, unless SETH fails. Let us also stress that our algorithms work under edit distance with arbitrary weights at no extra cost. As a bonus, we show how to modify some known techniques, which speed up the standard edit distance computation, to be applied to our problems. Beyond string sanitization, our techniques may inspire solutions to other problems related to regular expressions or context-free grammars

    Comparison between Culture Conditions Improving Growth and Differentiation of Blood and Bone Marrow Cells Committed to the Endothelial Cell Lineage

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    The aim of this study was to compare different cell sources and culture conditions to obtain endothelial progenitor cells (EPCs) with predictable antigen pattern, proliferation potential and in vitro vasculogenesis. Pig mononuclear cells were isolated from blood (PBMCs) and bone marrow (BMMCs). Mesenchymal stem cells (MSCs) were also derived from pig bone marrow. Cells were cultured on fibronectin in the presence of a high concentration of VEGF and low IGF-1 and FGF-2 levels, or on gelatin with a lower amount of VEGF and higher IGF-1 and FGF-2 concentrations. Endothelial commitment was relieved in almost all PBMCs and BMMCs irrespective of the protocol used, whilst MSCs did not express a reliable pattern of EPC markers under these conditions. BMMCs were more prone to expand on gelatin and showed a better viability than PBMCs. Moreover, about 90% of the BMMCs pre-cultured on gelatin could adhere to a hyaluronan-based scaffold and proliferate on it up to 3 days. Pre-treatment of BMMCs on fibronectin generated well-shaped tubular structures on Matrigel, whilst BMMCs exposed to the gelatin culture condition were less prone to form vessel-like structures. MSCs formed rough tubule-like structures, irrespective of the differentiating condition used. In a relative short time, pig BMMCs could be expanded on gelatin better than PBMCs, in the presence of a low amount of VEGF. BMMCs could better specialize for capillary formation in the presence of fibronectin and an elevated concentration of VEGF, whilst pig MSCs anyway showed a limited capability to differentiate into the endothelial cell lineage

    Release of soluble vascular endothelial growth factor receptor-1 (sFlt-1) during coronary artery bypass surgery

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    <p>Abstract</p> <p>Background</p> <p>This study was conducted to follow plasma concentrations of sFlt-1 and sKDR, two soluble forms of the vascular endothelial growth factor (VEGF) receptor in patients undergoing coronary artery bypass graft (CABG) surgery with extracorporeal circulation (ECC).</p> <p>Methods</p> <p>Plasma samples were obtained before, during and after surgery in 15 patients scheduled to undergo CABG. Levels of sFlt-1 and KDR levels were investigated using specific ELISA.</p> <p>Results</p> <p>A 75-fold increase of sFlt-1 was found during cardiac surgery, sFlt-1 levels returning to pre-operative values at the 6<sup>th </sup>post-operative hour. In contrast sKDR levels did not change during surgery. The ECC-derived sFlt-1 was functional as judge by its inhibitory effect on the VEGF mitogenic response in human umbilical vein endothelial cells (HUVECs). Kinetic experiments revealed sFlt-1 release immediately after the beginning of ECC suggesting a proteolysis of its membrane form (mFlt-1) rather than an elevated transcription/translation process. Flow cytometry analysis highlighted no effect of ECC on the shedding of mFlt-1 on platelets and leukocytes suggesting vascular endothelial cell as a putative cell source for the ECC-derived sFlt-1.</p> <p>Conclusion</p> <p>sFlt-1 is released during CABG with ECC. It might be suggested that sFlt-1 production, by neutralizing VEGF and/or by inactivating membrane-bound Flt-1 and KDR receptors, might play a role in the occurrence of post-CABG complication.</p

    Low Lipoprotein(a) Concentration Is Associated with Cancer and All-Cause Deaths: A Population-Based Cohort Study (The JMS Cohort Study)

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    Background: Experimental studies support the anti-neoplastic effect of apo(a), but several clinical studies have reported contradictory results. The purpose of this study was to determine whether a low lipoprotein(a) [Lp(a)] concentration is related to mortality from major causes of death, especially cancer. Methods The subjects were 10,413 participants (4,005 men and 6,408 women) from a multi-center population-based cohort study in Japan (The Jichi Medical School cohort study). The average age at registration was 55.0 years, and the median observation period was 4,559 days. As the estimated hazard ratio was high for both the low and very high Lp(a) levels, we defined two Lp(a) groups: a low Lp(a) group [Lp(a)<80 mg/L] and an intermediate-to-high Lp(a) group [Lp(a)≥80]. Participants who died from malignant neoplasms (n = 316), cardiovascular disease (202), or other causes (312) during the observation period were examined. Results: Cumulative incidence plots showed higher cumulative death rates for the low Lp(a) group than for the intermediate-to-high Lp(a) group for all-cause, cancer, and miscellaneous-cause deaths (p<0.001, p = 0.03, and p = 0.03, respectively). Cox proportional hazards analyses with the sex and age of the participants, body mass index, and smoking and drinking histories as covariates showed that a low Lp(a) level was a significant risk for all-cause, cancer, and miscellaneous-cause deaths (p<0.001, p = 0.003, and p = 0.01, respectively). The hazard ratio (95% CI) [1.48, 1.15–1.92] of a low Lp(a) level for cancer deaths was almost the same as that for a male sex (1.46, 1.00–2.13). Conclusions: This is the first report to describe the association between a low Lp(a) level and all-cause or cancer death, supporting the anti-neoplastic effect of Lp(a). Further epidemiological studies are needed to confirm the present results
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