119 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

    Insulin treatment enhances the myocardial angiogenic response in diabetes

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    ObjectiveGrowth factor and cell-based angiogenesis are attractive therapeutic options for diabetic patients with end-stage coronary disease. Reduced collateral vessel formation observed in diabetes is associated with increased expression of anti-angiogenic proteins, angiostatin and endostatin. The aim of this study was to determine the effects of insulin treatment on the diabetic angiogenic response to chronic myocardial ischemia.MethodsYucatan miniswine were treated with alloxan (pancreatic β-cell specific toxin, 150 mg/kg) and divided into two groups. In the diabetic group (DM, n = 8), blood glucose levels were kept greater than 250 mg/dL, and in the insulin-treated group (IDM, n = 6), intramuscular insulin was administered daily to keep blood glucose less than 150 mg/dL. A third group of age-matched swine served as nondiabetic controls (ND; n = 8). Eight weeks later, all animals underwent circumflex artery ameroid constrictor placement to induce chronic ischemia. Myocardial perfusion was assessed at 3 and 7 weeks after ameroid placement using microspheres. Microvascular function, capillary density, and myocardial expression of anti-angiogenic mediators were evaluated.ResultsDiabetic animals exhibited significant impairments in endothelium-dependent microvessel relaxation to adenosine diphosphate and substance P, which were reversed in insulin-treated animals. Collateral-dependent perfusion in the ischemic circumflex territory, which was profoundly reduced in diabetic animals (−0.18 ± 0.02 vs +0.23 ± 0.07 mL · min−1 · g−1; P < .001), improved significantly with insulin treatment (0.12 ± 0.05 mL · min−1 · g−1; P < .01). Myocardial expression of anti-angiogenic proteins, angiostatin and endostatin, showing a 4.3- and 3.6-fold increase in diabetic animals respectively (both P < .01 vs ND), was markedly reduced in insulin-treated animals (2.3- and 1.8-fold vs ND; both P < .01).ConclusionsInsulin treatment successfully reversed diabetic coronary endothelial dysfunction and significantly improved the endogenous angiogenic response. These pro-angiogenic effects may be mediated through downregulation of anti-angiogenic mediators. Insulin therapy appears to be a promising modality to enhance the angiogenic response in diabetic patients

    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
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