Stability of Boundary Conditions for the Sadowsky Functional

It has been proved by the authors that the (extended) Sadowsky functional can be deduced as the Γ -limit of the Kirchhoff energy on a rectangular strip, as the width of the strip tends to 0. In this paper, we show that this Γ -convergence result is stable when affine boundary conditions are prescribed on the short sides of the strip. These boundary conditions include those corresponding to a Möbius band. This provides a rigorous justification of the original formal argument by Sadowsky about determining the equilibrium shape of a free-standing Möbius strip. We further write the equilibrium equations for the limit problem and show that, under some regularity assumptions, the centerline of a developable Möbius band at equilibrium cannot be a planar curve

NO DOCUMENTABLE ROLE FOR XANTHINE-OXIDASE IN THE PATHOGENESIS OF HEPATIC IN-VIVO ISCHAEMIA/REPERFUSION INJURY

An investigation was made into the possible involvement of the enzyme xanthine oxidase (XO) (EC 1.1.3.22), both reversible (XOrev) and irreversible (XOirr), in damage observed after short-term in vivo hepatic ischaemia/reperfusion (60 or 120 min I and 15 min R) in fasted rats with: (i) a physiological content of XO (25%); and (ii) higher XO percentage (45%). In the latter the hepatic XO physiological percentage was increased by diethylmaleate treatment (300 mg kg(-1)) that depleted the cytosolic glutathione (GSH) to 14% of the controls. It was shown that, in animals with physiological content of XO, 60 and 120 min of hepatic ischaemia followed by 15 min reperfusion results in decreased GSH levels, and significantly increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels, without any modification of either the percentages of XO (XOirr and XOrev) or the hepatic thiobarbituric acid reactive substances (TBARS). Sixty minutes of ischaemia/reperfusion in rats with the higher XO level and lower hepatic GSH content led to further conversion of XDH to XOrev, with no increase in XOirr. In addition, the ALT and AST serum levels in these animals rose to the same extent as in normal rats after 120 min ischaemia and 15 min reperfusion, this extent being observed to be associated with a moderate increase in thiobarbituric acid reactive substances (TBARS). However, the administration of allopurinol, at a dose of 50 mg kg(-1), which almost completely inhibits XO activity, did not lead to any decrease in liver damage or TBARS. These findings exclude any role of XO in liver damage in the short term following ischaemia/reperfusion events, also when marked GSH depletion could increase the enzymatic physiological XO level

Oxidative Stress Markers to Investigate the Effects of Hyperoxia in Anesthesia

Oxygen (O-2) is commonly used in clinical practice to prevent or treat hypoxia, but if used in excess (hyperoxia), it may act as toxic. O-2 toxicity arises from the enhanced formation of Reactive Oxygen Species (ROS) that exceed the antioxidant defenses and generate oxidative stress. In this study, we aimed at assessing whether an elevated fraction of inspired oxygen (FiO(2)) during and after general anesthesia may contribute to the unbalancing of the pro-oxidant/antioxidant equilibrium. We measured five oxidative stress biomarkers in blood samples from patients undergoing elective abdominal surgery, randomly assigned to FiO(2) = 0.40 vs. 0.80: hydroperoxides, antioxidants, nitrates and nitrites (NOx), malondialdehyde (MDA), and glutathionyl hemoglobin (HbSSG). The MDA concentration was significantly higher 24 h after surgery, and the body antioxidant defense lower, in the FiO(2) = 0.80 group with respect to both the FiO(2) = 0.40 group and the baseline values (p <= 0.05, Student's t-test). HbSSG in red blood cells was also higher in the FiO(2) = 0.80 group at the end of the surgery. NOx was higher in the FiO(2) = 0.80 group than the FiO(2) = 0.40 group at t = 2 h after surgery. MDA, the main end product of the peroxidation of polyunsaturated fatty acids directly influenced by FiO(2), may represent the best marker to assess the pro-oxidant/antioxidant equilibrium after surgery

Probiotic Lactobacillus and Bifidobacterium Strains Counteract Adherent-Invasive Escherichia coli (AIEC) Virulence and Hamper IL-23/Th17 Axis in Ulcerative Colitis, but Not in Crohn's Disease

Hypersecretion of proinflammatory cytokines and dysregulated activation of the IL-23/Th17 axis in response to intestinal microbiota dysbiosis are key factors in the pathogenesis of inflammatory bowel diseases (IBD). In this work, we studied how Lactobacillus and Bifidobacterium strains affect AIEC-LF82 virulence mechanisms and the consequent inflammatory response linked to the CCR6-CCL20 and IL-23/Th17 axes in Crohn's disease (CD) and ulcerative colitis (UC) patients. All Lactobacillus and Bifidobacterium strains significantly reduced the LF82 adhesion and persistence within HT29 intestinal epithelial cells, inhibiting IL-8 secretion while not affecting the CCR6-CCL20 axis. Moreover, they significantly reduced LF82 survival within macrophages and dendritic cells, reducing the secretion of polarizing cytokines related to the IL-23/Th17 axis, both in healthy donors (HD) and UC patients. In CD patients, however, only B. breve Bbr8 strain was able to slightly reduce the LF82 persistence within dendritic cells, thus hampering the IL-23/Th17 axis. In addition, probiotic strains were able to modulate the AIEC-induced inflammation in HD, reducing TNF-\u3b1 and increasing IL-10 secretion by macrophages, but failed to do so in IBD patients. Interestingly, the probiotic strains studied in this work were all able to interfere with the IL-23/Th17 axis in UC patients, but not in CD patients. The different interaction mechanisms of probiotic strains with innate immune cells from UC and CD patients compared to HD suggest that testing on CD-derived immune cells may be pivotal for the identification of novel probiotic strains that could be effective also for CD patients

Overexpression of lpxT Gene in Escherichia coli Inhibits Cell Division and Causes Envelope Defects without Changing the Overall Phosphorylation Level of Lipid A

LpxT is an inner membrane protein that transfers a phosphate group from the essential lipid undecaprenyl pyrophosphate (C-55PP) to the lipid A moiety of lipopolysaccharide, generating a lipid A tris-phosphorylated species. The protein is encoded by the non-essential lpxT gene, which is conserved in distantly related Gram-negative bacteria. In this work, we investigated the phenotypic effect of lpxT ectopic expression from a plasmid in Escherichia coli. We found that lpxT induction inhibited cell division and led to the formation of elongated cells, mostly with absent or altered septa. Moreover, the cells became sensitive to detergents and to hypo-osmotic shock, indicating that they had cell envelope defects. These effects were not due to lipid A hyperphosphorylation or C-55PP sequestering, but most likely to defective lipopolysaccharide transport. Indeed, lpxT overexpression in mutants lacking the L,D-transpeptidase LdtD and LdtE, which protect cells with outer membrane defects from osmotic lysis, caused cell envelope defects. Moreover, we found that pyrophosphorylated lipid A was also produced in a lpxT deletion mutant, indicating that LpxT is not the only protein able to perform such lipid A modification in E. coli

Osteoporosis prevention in postmenopausal female workers : Beneficial effects of silicon dietary supplementation on oxidative status. A pilot study

In the last years, the employment of ageing women is increased, and the well-being of these workers, together with the prevention of chronic disabling diseases, is an issue of great importance. Moreover, as postmenopausal ageing is associated with the loss of bone density and consequent increased fracture risk, promoting bone health in these women could be the best strategy for avoiding osteoporotic fractures. We aimed to evaluate the effects of 3-month supplementation with a commercial antioxidant product containing Silica on oxidative status and bone markers in a sample of Italian female workers. Subjects were menopausal and osteopenic women (N=29, age 59.34\ub16.37, mean BMI 26.19\ub14.01 kg/m2). At baseline (T0) and after three-month treatment (T1) bone mineral density (BMD) was evaluated by phalangeal osteosonogrammetry. Haematological, serum biochemical parameters, reactive oxygen species (ROS), total antioxidant capacity (TAC), oxydated low-density lipoproteins (oxLDL) and urinary cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) were assessed. Parametric or non-parametric tests were performed at T0 and T1. To analyse the possible association between two variables a linear correlation test was performed. At T0, slightly high levels of ROS (86% of subjects), oxLDL (59%), Total Cholesterol (T-Chol) (90%) and LDL-Chol (59%) were observed, together with suboptimal or deficient 25-OH vitamin D (98%) concentrations. At T1, oxLDL levels and the ratio oxLDL/LDL-Chol significantly decreased (p<0.01). At T0 significant negative correlations between BMD T-score and cross-links were observed (DPD/Crea: r=-0.57, p=0.001; PYD/ Crea: r=-0.45, p=0.01). At T1, a significant reduction (p=0.03) was observed only for DPD (\u3bcg/L) but not for cross-links normalized by creatinine amounts. In conclusion 3-months Silica supplementation improves significantly oxidative status and bone resorption markers in most postmenopausal female workers, representing a complementary treatment for early phases of BMD reduction

Inflammatory extracellular vesicles prompt heart dysfunction via TRL4-dependent NF-κB activation.

Background: After myocardial infarction, necrotic cardiomyocytes release damage-associated proteins that stimulate innate immune pathways and macrophage tissue infiltration, which drives inflammation and myocardial remodeling. Circulating inflammatory extracellular vesicles play a crucial role in the acute and chronic phases of ischemia, in terms of inflammatory progression. In this study, we hypothesize that the paracrine effect mediated by these vesicles induces direct cytotoxicity in cardiomyocytes. Thus, we examined whether reducing the generation of inflammatory vesicles within the first few hours after the ischemic event ameliorates cardiac outcome at short and long time points. Methods: Myocardial infarction was induced in rats that were previously injected intraperitoneally with a chemical inhibitor of extracellular-vesicle biogenesis. Heart global function was assessed by echocardiography performed at 7, 14 and 28 days after MI. Cardiac outcome was also evaluated by hemodynamic analysis at sacrifice. Cytotoxic effects of circulating EV were evaluated ex-vivo in a Langendorff, system by measuring the level of cardiac troponin I (cTnI) in the perfusate. Mechanisms undergoing cytotoxic effects of EV derived from pro-inflammatory macrophages (M1) were studied in-vitro in primary rat neonatal cardiomyocytes. Results: Inflammatory response following myocardial infarction dramatically increased the number of circulating extracellular vesicles carrying alarmins such as IL-1α, IL-1β and Rantes. Reducing the boost in inflammatory vesicles during the acute phase of ischemia resulted in preserved left ventricular ejection fraction in vivo. Hemodynamic analysis confirmed functional recovery by displaying higher velocity of left ventricular relaxation and improved contractility. When added to the perfusate of isolated hearts, post-infarction circulating vesicles induced significantly more cell death in adult cardiomyocytes, as assessed by cTnI release, comparing to circulating vesicles isolated from healthy (non-infarcted) rats. In vitro inflammatory extracellular vesicles induce cell death by driving nuclear translocation of NF-κB into nuclei of cardiomyocytes. Conclusion: Our data suggest that targeting circulating extracellular vesicles during the acute phase of myocardial infarction may offer an effective therapeutic approach to preserve function of ischemic heart