Effetti di un programma combinato di esercizio con e senza sovraccarico (acqua termale) sulla massa e qualit\ue0\ua0 ossea in un gruppo di donne in et\ue0\ua0 post-menopausale con deficit minerale osseo.

Scopi. Valutare gli effetti che un programma combinato di esercizio, con e senza sovraccarico (in palestra e in acqua termale, rispettivamente), pu\uf2 avere sulla massa e qualit\ue0 ossea, in un gruppo di donne in et\ue0 post-menopausale con deficit minerale osseo.Materiali e Metodi. 125 donne in et\ue0 post-menopausale con osteopenia/osteoporosi sono state sottoposte ad una valutazione della massa ossea (Dual-Energy X-ray Absorbimetry, DEXA) e della qualit\ue0 (osteosonografia alle falangi) del tessuto osseo. 58 di loro hanno partecipato, per 11 mesi, ad programma specifico di esercizio (E). Le altre hanno costituito un gruppo di controllo (C). Al termine del programma tutti i soggetti sono stati rivalutati. Risultati. Tra prima e dopo l\u2019attivit\ue0 motoria e tra i due gruppi, in merito alla massa ossea (DEXA) si \ue8 riscontrato un significativo incremento del t-score al collo del femore nel gruppo E (p < 0,05). Non si sono riscontrate differenze significative, invece, negli altri parametri considerati. Riguardo all\u2019osteosonografi a, nel gruppo C si \ue8 riscontrato un signifi cativo peggioramento della qualit\ue0 ossea (p < 0,05).Conclusioni. Un programma specifico di esercizio per l\u2019osteoporosi si \ue8 dimostrato efficace nel rallentare la fisiologica perdita di massa ossea e mantenere una buona qualit\ue0 dell\u2019osso, in un gruppo di donne in et\ue0 post-menopausale con deficit minerale osseo

Electrical characterization of in situ polymerized polyaniline thin films

The alternating conductivity, sigma*(f) = sigma'(f) + i sigma ''(f), of in situ polymerized polyaniline thin films doped with hydrochloric acid, deposited on top of an interdigitated gold line array previously deposited on glass substrates, were measured in the frequency (f) range between 0.1 Hz to 10 MHz and in the temperature range from 100 to 430 K. The results for sigma'(f) are typical of a disordered solid material: for frequencies lower than a certain hopping frequency gamma(hop), log[sigma'(f)] is frequency-independent rising almost linearly for in logf > gamma(hop). A master curve was thus obtained by plotting the real component of the conductivity using normalized scales sigma'(f)/sigma(dc) and f/gamma(hop) which is indicative of a single process operating in the whole frequency range. An expression encompassing the conduction through a disordered structure taken from previous random free energy barrier model for hopping carriers, as well a dielectric function to represent the capacitive behavior of the PAni was employed to fit the experimental results. The dielectric constant and activation energy for hopping carriers were obtained as function of the polymer doping level. (c) 2007 Elsevier B.V. All rights reserved

A white paper on Phospholipid Hydroperoxide Glutathione Peroxidase (GPx4) forty years later

The purification of a protein inhibiting lipid peroxidation led to the discovery of the selenoperoxidase GPx4 forty years ago. Thus, the evidence of the enzymatic activity was reached after identifying the biological effect and unambiguously defined the relationship between the biological function and the enzymatic activity. In the syllogism where GPx4 inhibits lipid peroxidation and its inhibition is lethal, cell death is operated by lipid peroxidation. Based on this rationale, this form of cell death emerged as regulated iron-enforced oxygen toxicity and was named ferroptosis in 2012. In the last decades, we learned that reduction of lipid hydroperoxides is indispensable and, in cooperation with prooxidant systems, controls the critical steady state of lipid peroxidation. This concept defined the GPx4 reaction as both the target for possible anti-cancer therapy and if insufficient, as cause of degenerative diseases. We know the reaction mechanism, but the details of the interaction at the membrane cytosol interface are still poorly defined. We know the gene structure, but the knowledge about expression control is still limited. The same holds true for post-transcriptional modifications. Reverse genetics indicate that GPx4 has a role in inflammation, immunity, and differentiation, but the observations emerging from these studies need a more specifically addressed biochemical evidence. Finally, the role of GPx4 in spermatogenesis disclosed an area unconnected to lipid peroxidation. In its mitochondrial and nuclear form, the peroxidase catalyzes the oxidation of protein thiols in two specific aspects of sperm maturation: stabilization of the mid-piece and chromatin compaction. Thus, although available evidence converges to the notion that GPx4 activity is vital due to the inhibition of lipid peroxidation, it is reasonable to foresee other unknown aspects of the GPx4 reaction to be disclosed

Protein disulfide isomerase and glutathione are alternative substrates in the one Cys catalytic cycle of glutathione peroxidase 7.

BACKGROUND: Mammalian GPx7 is a monomeric glutathione peroxidase of the endoplasmic reticulum (ER), containing a Cys redox center (CysGPx). Although containing a peroxidatic Cys (CP) it lacks the resolving Cys (CR), that confers fast reactivity with thioredoxin (Trx) or related proteins to most other CysGPxs. METHODS: Reducing substrate specificity and mechanism were addressed by steady-state kinetic analysis of wild type or mutated mouse GPx7. The enzymes were heterologously expressed as a synuclein fusion to overcome limited expression. Phospholipid hydroperoxide was the oxidizing substrate. Enzyme-substrate and protein-protein interaction were analyzed by molecular docking and surface plasmon resonance analysis. RESULTS: Oxidation of the CP is fast (k+1&gt;10(3)M(-1)s(-1)), however the rate of reduction by GSH is slow (k&#39;+2=12.6M(-1)s(-1)) even though molecular docking indicates a strong GSH-GPx7 interaction. Instead, the oxidized CP can be reduced at a fast rate by human protein disulfide isomerase (HsPDI) (k+1&gt;10(3)M(-1)s(-1)), but not by Trx. By surface plasmon resonance analysis, a KD=5.2&mu;M was calculated for PDI-GPx7 complex. Participation of an alternative non-canonical CR in the peroxidatic reaction was ruled out. Specific activity measurements in the presence of physiological reducing substrate concentration, suggest substrate competition in vivo. CONCLUSIONS: GPx7 is an unusual CysGPx catalyzing the peroxidatic cycle by a one Cys mechanism in which GSH and PDI are alternative substrates. GENERAL SIGNIFICANCE: In the ER, the emerging physiological role of GPx7 is oxidation of PDI, modulated by the amount of GSH

Modulation of immune response by the acute and chronic exposure to high altitude

PURPOSE:The chronic exposure at high altitude (HA) represents an ideal model for evaluating the in vivo effects of hypobaric hypoxia. Taking advantage of the EV-K2-CNR Pyramid, this study was designed to evaluate whether acute and chronic hypoxia differently modulates the in vivo immune responses. METHODS:The study includes 13 healthy female moderately active volunteers participating to the Italian HA project EV-K2-CNR. Peripheral blood lymphocytes, collected at sea level and at HA in the Pyramid Laboratory of CNR, Nepal (5050 m), were immunologically characterized by flow cytometry and a series of molecular and functional analyses. RESULTS:Flow cytometric analyses showed that: a) CD3+ T lymphocytes significantly decreased during both acute and chronic exposure to HA, b) T-cell fall was totally due to CD4+ T-cell reduction, c) B lymphocytes were not influenced by the exposure to HA, and d) natural killer (NK) cells significantly increased during acute and chronic exposure. The evaluation of the Th1/Th2 pattern demonstrated a significant decrease of the expression of the Th1 cytokine interferon-gamma (IFN-gamma) by circulating T cells during acute and chronic exposure to HA. The expression by T cells of CXCR3, a chemokine receptor typically expressed by Th1/Tc1 cells, paralleled the decrease of IFN-gamma. On the contrary, the expression of IL-4 was not conditioned by the exposure to HA. Finally, functional studies showed a significant reduction of the proliferative activity in response to mitogen (PHA) both in acute and chronic HA exposure. Despite the increased number of NK cells, NK cytotoxic activity was not influenced by the HA exposure. CONCLUSIONS:Our results indicate that the in vivo exposure to HA leads to an impairment of the homeostatic regulation of Th1/Th2 immune balance that potentially could favor long-term immunological alterations and increase the risk of infections

Aerobic pyruvate metabolism sensitizes cells to ferroptosis primed by GSH depletion

Ferroptosis is a non-accidental, regulated form of cell death operated by lipid peroxidation under strict control of GPx4 activity. This is consistent with the notion that lipid peroxidation is initiated by radicals produced from decomposition of traces of pre-existing lipid hydroperoxides. The question, therefore, emerges about the formation of these traces of lipid hydroperoxides interacting with Fe2+. In the most realistic option, they are produced by oxygen activated species generated during aerobic metabolism. Screening for metabolic sources of superoxide supporting ferroptosis induced by GSH depletion, we failed to detect, in our cell model, a role of respiratory chain. We observed instead that the pyruvate dehydrogenase complex -as other \u3b1 keto acid dehydrogenases already known as a major source of superoxide in mitochondria- supports ferroptosis. The opposite effect on ferroptosis by silencing either the E1 or the E3 subunit of the pyruvate dehydrogenase complex pointed out the autoxidation of dihydrolipoamide as the source of superoxide. We finally observed that GSH depletion activates superoxide production, seemingly through the inhibition of the specific kinase that inhibits pyruvate dehydrogenase. In summary, this set of data is compatible with a scenario where the more electrophilic status produced by GSH depletion not only activates ferroptosis by preventing GPx4 activity, but also favors the formation of lipid hydroperoxides. In an attractive perspective of tissue homeostasis, it is the activation of energetic metabolism associated to a decreased nucleophilic tone that, besides supporting energy demanding proliferation, also sensitizes cells to a regulated form of death

Spatial Function of Influence on Center Optimal Location Based on L-p-Norms

We propose a sensitivity analysis using generalized L-p-norm (Minkowski distance) applied on center optimal location (1 facility). The results show that there exists in one dimension an underlying (log) linear relation between influence and distance of the demand points on the center. New L-p-norms are emphasized with interesting properties in statistics (e.g. with p = 3) although they are not used in location optimization. The law we enhance is of interest in both statistics and and spatial analysis domains and highlights in a new way the impact of the metrics choice on the center location, through the induced spatial influence function, those metrics aiming at spatial equity (L-8), equality (L-2) or efficiency (L-1)

Threshold robustness in discrete facility location problems: a bi-objective approach

The two best studied facility location problems are the p-median problem and the uncapacitated facility location problem (Daskin, Network and discrete location: models, algorithms, and applications. Wiley, New York, 1995; Mirchandani and Francis, Discrete location theory. Wiley, New York, 1990). Both seek the location of the facilities minimizing the total cost, assuming no uncertainty in costs exists, and thus all parameters are known. In most real-world location problems the demand is not certain, because it is a long-term planning decision, and thus, together with the minimization of costs, optimizing some robustness measure is sound. In this paper we address bi-objective versions of such location problems, in which the total cost, as well as the robustness associated with the demand, are optimized. A dominating set is constructed for these bi-objective nonlinear integer problems via the ε-constraint method. Computational results on test instances are presented, showing the feasibility of our approach to approximate the Pareto-optimal set