Cytoprotective effect of preparations from various parts of Punica granatum L. fruits in oxidatively injured mammalian cells in comparison with their antioxidant capacity in cell free systems

none9Pomegranate (Punica granatum L.) juice (PJ) is being increasingly proposed as a nutritional supplement to prevent atherosclerosis in humans. This therapeutically valuable potential has been attributed to PJ antioxidant capacity which has been mostly tested by means of cell-free assays: indeed, to the best of our knowledge, no study has focused on the direct antioxidant capacity of PJ in cultured cells. Here, the antioxidant capacity in cell free-systems of preparations from various parts of pomegranate has been compared with their cytoprotective – bona fide antioxidant – activity in cultured human cells (U937 promonocytes and HUVEC endothelial cells) exposed to an array of oxidizing agents. Pomegranate derivatives were PJ, arils only juice (AJ) and aqueous rinds extract (RE). In cell-free assays – 1,1-diphenyl-2-picrylhydrazyl (DPPH), chemiluminescence luminol/xanthine/xanthine oxidase and lipoxygenase assays – all the preparations displayed good antioxidant capacity, the relative potency order being RE > PJ > AJ. On the contrary, only RE was capable of preventing the deleterious effects – cytotoxicity, DNA damage and depletion of non protein sulphydrils (NPSH) pool – caused by treatment of cells with H2O2, tert-butylhydroperoxide (tB-OOH) or oxidized lipoproteins (Ox-LDL) via a mechanism which is likely to involve both direct scavenging of radical species and iron chelation. Surprisingly, AJ and PJ slightly sensitized cells to the cytotoxic effects of the three agents. Then it would appear that AJ, the major and tasty part of PJ, does not contain ellagic acid and punicalagin (i.e. the polyphenols highly represented in RE which are reputed to be responsible for the antioxidant capacity) in amounts sufficient to exert cytoprotection in oxidatively injured, living cells. Based on these results, the development and evaluation of rinds-only based derivatives for antiatherogenic preventive purposes in humans should be encouraged.openSESTILI P; MARTINELLI C; RICCI D; FRATERNALE D; BUCCHINI A; GIAMPERI L; CURCIO R; PICCOLI G; STOCCHI V.Sestili, Piero; Martinelli, Chiara; Ricci, Donata; Fraternale, Daniele; Bucchini, ANAHI ELENA ADA; Giamperi, Laura; Curcio, R; Piccoli, Giovanni; Stocchi, Vilbert

Early Denosumab for the prevention of osteoporotic fractures in breast cancer women undergoing aromatase inhibitors: A case-control retrospective study

BACKGROUND:Aromatase inhibitors (AIs) might have a detrimental impact on bone health in breast cancer (BC) women.Denosumab has been shown to reduce the risk of fractures, but the appropriate time for starting is yet to be clearly defined.OBJECTIVE:To evaluate the effects of early treatment with Denosumab (612 months after starting AIs) compared to a delayedtreatment in BC women.METHODS:In this retrospective case-control study, we included medical records of BC post-menopausal women, treated withAIs therapy; they were divided as: study group (starting Denosumab612 months after AIs) and control group (>12 months). Atthe baseline (T0) and at 18 months (T1), we evaluated the lumbar spine (LS) Tscore and femoral neck (FN) Tscore. Furthermore,at T1 we assessed the incident fragility fractures.RESULTS:Fifty-nine BC survivors (mean age: 61.5±11.5 years) were included: 28 with Early Denosumab and 31 with LateDenosumab. At T1, the study group did not show any incident hip or vertebral fragility fracture, whereas the Late Denosumabgroup showed 2 incident hip fractures (6.5%) and 4 (12.9%) vertebral fragility fractures. Early Denosumab showed a significantpositive effect on both LS (p=0.044) and FN (p=0.024) Tscore variations.CONCLUSION:Taken together, our findings suggest that an early start of Denosumab might be considered for the osteoporosismanagement in BC women undergoing AIs

La malattia renale cronica: qualità di vita, ansia e depressione in un gruppo di pazienti in fase pre-dialitica

Patients with chronic diseases frequently show a marked deterioration in their quality of life (QoL). This paper was aimed at investigating on both the prevalence of psychological disorders and the impact on QoL in patients with chronic renal failure. The survey was conducted on 155 patients, aged 77±11 years, 104/51 M/F, with renal failure on conservative treatment (stages IV-V) referring to Nephrology Unit in Mauriziano Hospital, Turin. 13 of them (8.4%) were aged 30-64 years, 63 (40.6%) were aged 65-79 years and 79 (51%) 80 years and older. Two validated questionnaires were administered, namely the SF-12 (general state of health) and the HADS (anxiety and depression). Sixty-five percent of patients believed to have a low QoL associated with health, finding difficulties in daily life activities. The prevalence of all psychologic disturbances was higher in females (p = 0.09) and in patients with more comorbidities (p = 0.05). Depression was more frequent in elderly (p = 0.05) and in females (p = 0.012). Among patients aged 80 years or over, we found a prevalence rate of 36% for anxiety and of 51% for depression. In all patients, anxiety and depression were strongly associated (p < 0.01). In conclusion, compared to the general population, patients with chronic renal failure have a higher rate of either anxiety or depression, or both, and present with lower QoL scores. Clinical teams dedicated to the management of chronic renal diseases should pursue an interdisciplinary approach to their patients, in order to provide them with a suitable monitoring of QoL and psychological support if needed

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Human matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn(2+) atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes

Le relazioni di potere fra polizia ed esercito e le dinamiche internazionali. Il caso degli Stati Uniti durante la guerra fredda.

The aim of my thesis is to demonstrate how the power relations between police and military influence -and are influenced by- the international context, with the specific case studies of United States. The theoretical background of my thesis is the Theory of Panopticon, which I apply to the international relations. During the Cold War, the United States tried to fulfill this model that permitted to “check the inside” in order to “control the outside” (and vice versa), while maintaining the balance achieved with the USSR. This theory helps explaining two intertwining process, policing the military and militarization of the police. In the first case, the army would no longer aim conquering new territories, but restoring the international order and maintaining it, as a policeman would do in a city: prevent and re-establish. During the Cold War the policing the military process led to an imbalance of the relations between military and police power in favor of the army, which culminated in the 1990's. This imbalance led to a increasing militarization both of the police and the entire society. The police aim is not only preventing crime, but fighting enemies, just as a military force would do on its mission: preventing and regaining

Comportamenti e motivazioni degli infermieri sulla ginnastica vescicale

Obiettivo. Valutare la variabilità di comportamenti degli infermieri nel ricorso alla ginnastica vescicale (GV) prima della rimozione del catetere e le motivazioni che supportano tale scelta. Metodo. È stata condotta un’indagine multicentrica con la somministrazione di un questionario a 338 infermieri di 28 reparti dei 6 maggiori ospedali dell’area torinese, nei servizi di medicina, chirurgia, urologia ed ortopedia Nel questionario venivano proposti 7 scenari che mostravano situazioni diverse e si chiedeva agli infermieri di specificare se avrebbero eseguito o meno la ginnastica vescicale e la motivazione. Risultati. Sono stati ritirati 240 questionari (71%). In generale, solo il 10% degli infermieri (24) utilizzano abitualmente la GV, il 24.2% (58) solo in rare occasioni, mentre il 65.8% (158) mai. Quando sono state analizzate le risposte alle singole situazioni, nel 63.3% (152) dei casi gli infermieri non userebbero la GV. La scelta di eseguire la GV non è associata alla formazione di base (p=0.43) o agli anni di esperienza (p=0.62), ma meno si conosce la situazione clinica del paziente, più frequente è il ricorso alla GV. Conclusioni. L’uso della GV è limitato, ma in assenza di prove di efficacia e di indicazioni, i comportamenti variano tra reparto. Anche nei reparti dove la ginnastica vescicale non viene eseguita, gli infermieri vi ricorrono in particolare nelle situazioni per le quali nel reparto si ha meno esperienz

Demonstration of a sensor-based app for self-monitoring of medicine intake

Accurate adherence to prescribed medications is essential for the effectiveness of therapies, but several studies show that when patients are responsible for treatment administration, poor adherence is prevalent. Existing apps to support self-administration of drugs may interfere with the normal routine of patients by providing unnecessary reminders. More sophisticated solutions, including the use of smart packaging and ingestible sensors, are currently restricted to patients involved in a few clinical studies. In this paper, we demonstrate a novel app to support self-administration of drugs without interfering with the patient's routines. The system relies on cheap wireless sensors attached to medicine boxes to detect medicine intake. The app uses machine learning to detect intake events, and active learning to improve recognition based on the user's feedback. In the demonstration, we show a working prototype of the system, which includes a Web dashboard for physicians to monitor the rate of intakes. Copyright is held by the author/owner(s)

Toward naturalistic self-monitoring of medicine intake

Since drug actions are dose-And time-dependent, adherence to prescribed medications is essential for the effectiveness of therapies. Unfortunately, several studies show that when patients are responsible for treatment administration, poor adherence is prevalent. Hence, it is necessary to devise effective methods to remotely assess medication compliance and support self-Administration of drugs. Existing methods include electronic reminders such as short message service reminders and pill reminder apps. Although those tools may help increasing adherence, they interfere with the normal routine of patients by providing unnecessary reminders, or providing the reminder at an unfortunate time. More sophisticated solutions include the use of smart packaging and ingestible sensors to quantify and monitor drug intake. While those solutions do not interfere with normal routines, currently they are restricted to patients involved in a few clinical studies. In this paper, we introduce a novel system to support self-Administration of drugs without interfering with the patient's routines. The system is based on a combination of cheap sensors and a smartphone. Tiny Bluetooth low energy sensors attached to medicine boxes communicate motion data to an app running on the patient's smartphone. Thanks to a machine learning algorithm, the app detects intake events, and reminds the user only when needed. Active learning is used to improve recognition rates thanks to the user's feedback. Preliminary experiments with a dataset acquired from volunteers show that the algorithm can detect most intake events with a few false positives. At the time of writing, we have developed a working prototype of the system, and we are beginning an experimental evaluation with a group of patients of an Italian hospital

Iron Bioavailability in the Extracellular Environment Is More Relevant Than the Intracellular One in Viability and Gene Expression: A Lesson from Oligodendroglioma Cells

Oligodendroglioma (OG) is a brain tumor that contributes to <1% of brain tumor diagnoses in the pediatric population. Unfortunately, pediatric OG remains without definitive molecular characteristics to aid in diagnosis, and little is known about the tumor microenvironment. Tumor cells’ metabolism and proliferation rate are generally higher than those of healthy cells, so their iron demand is also significantly higher. This consideration underlines the great importance of iron for tumor development and progression. In this context, this study aims to evaluate the effect of iron in a cellular in vitro model of human oligodendroglioma brain tumor. Cell morphology, the effect of siderotic medium on cell growth, iron uptake, and the expression of iron-metabolism-related genes were evaluated via optic microscopy, ICP-MS, confocal microscopy, and real-time PCR, respectively. This study underlines the great importance of iron for tumor development and progression and also the possibility of reducing the available iron concentration to determine an antiproliferative effect on OG. Therefore, every attempt can be promising to defeat OG for which there are currently no long-term curative therapies