Comparative gene expression profiling reveals partially overlapping but distinct genomic actions of different antiestrogens in human breast cancer cells.

Antiestrogens used for breast cancer (BC) treatment differ among each other for the ability to affect estrogen receptor (ER) activity and thereby inhibit hormone-responsive cell functions and viability. We used high-density cDNA microarrays for a comprehensive definition of the gene pathways affected by 17b-estradiol (E2), ICI 182,780 (ICI), 4OH- tamoxifen (Tamoxifen), and raloxifene (RAL) in ER-positive ZR-75.1 cells, a suitable model to investigate estrogen and antiestrogen actions in hormone-responsive BC. The expression of 601 genes was significantly affected by E2 in these cells; in silico analysis reveals that 86 among them include one or more potential ER binding site within or near the promoter and that the binding site signatures for E2F-1, NF-Y, and NRF-1 transcription factors are significantly enriched in the promoters of genes induced by estrogen treatment, while those for CAC-binding protein and LF-A1 in those repressed by the hormone, pointing to novel transcriptional effectors of secondary responses to estrogen in BC cells. Interestingly, expression of 176 E2- regulated mRNAs was unaffected by any of the antiestrogens tested, despite the fact that under the same conditions the transcriptional and cell cycle stimulatory activities of ER were inhibited. On the other hand, of 373 antiestrogen-responsive genes identified here, 52 were unresponsive to estrogen and 25% responded specifically to only one of the compounds tested, revealing non-overlapping and clearly distinguishable effects of the different antiestrogens in BC cells. As some of these differences reflect specificities of the mechanism of action of the antiestrogens tested, we propose to exploit this gene set for characterization of novel hormonal antagonists and selective estrogen receptor modulators (SERMs) and as a tool for testing new associations of antiestrogens, more effective against BC

Semisolid formulations containing dimethyl sulfoxide and alpha-tocopherol for the treatment of extravasation of antiblastic agents

The topical treatment with dimethyl sulfoxide (DMSO) and/or alpha-tocopherol (alpha-T) is widely used in order to prevent the local complications of extravasation of cytostatic drugs and protect patients against skin ulceration. Till now, DMSO and alpha-T have been mainly used in solution. The goal of this study was to formulate semisolid preparations for cutaneous application diVering in the hydrophilic and lipophilic properties and containing DMSO and alpha-T in combination. With respect to solutions, the use of semisolid preparations containing DMSO and alpha-T could be advantageous in patients having extravasation as DMSO and alpha-T can remain in contact with the skin over an extended period of time. As a consequence, the action of the active principles can be limited specifically on the injured skin area, reducing the cutaneous irritative effects of DMSO. The following types of semisolid formulations containing 50% m/m DMSO and 2.5% m/m alpha-T were prepared: hydrophilic ointment, o/w emulsion, hydrophilic gel and lipophilic gel. The ex vivo skin permeation of DMSO and alpha-T was evaluated by using modified Franz\u2019s diffusion cells and human stratum corneum and epidermis (SCE) as a membrane. The permeated and retained amounts of DMSO and alpha-T were determined. The oleogel preparation, the hydrophilic gel and the o/w emulsion were uniform in colour and aspect, without any evidences of phase separation over the period of the study. Hydrophilic ointments were discarded as they showed phase separation after 12 h. All formulations had a diVerent behaviour in terms of skin permeability. In particular, hydrogel and o/w emulsion showed the best control on the drug release considering the interactions of the vehicle components with the SCE and the drugs partition between the vehicle and the SCE. The DMSO permeated amount after 24 h was 4.1 mg/cm2 for hydrogel and 2.5 mg/cm2 for emulsion while the permeated amount of pure DMSO after 24 h was 47.5 mg/cm2. Therefore, aiming to reduce side eVects after the topical application of the antidotes DMSO and alpha-T, these results suggested that hydrogel and o/w emulsion could be considered the most promising formulations for further clinical evaluations in managing of extravasation of anthracycline

The reorganization of healthcare services from the perspective of appropriateness: The experience of the University Hospital "San Giovanni di Dio e Ruggi d'Aragona" in the management of Diagnosis-Related Group no. 127 - Heart failure and shock|La riorganizzazione delle prestazioni sanitarie in ottica di appropriatezza: L'esperienza dell'AOU “San Giovanni di Dio e Ruggi d'Aragona” nella gestione del DRG 127 - Insufficienza cardiaca e shock

The article proposes a care path intended to improve the standards of specialist care in the field of heart failure, in compliance with the criteria of effectiveness, efficiency and equity on which the Italian National Health Service (INHS) relies. A case study approach was undertaken. The attention was focused on the experience of the University Hospital “San Giovanni di Dio e Ruggi d'Aragona” located in Salerno, Southern Italy. In particular, data were collected from with the collaboration of the “Hospital Discharge Form” office. Examining a set of indicators - such as the average hospitalization and percentage of hospitalizations - about the Diagnosis-Related Group no. 127 “Heart failure and intensive cardiology shock” in the financial year 2017, we untangled the criticalities of the existing process and, adopting the Business Process Improvement (BPI) methodology, we proposed a process redesign. Technology, asset management, care paths, training, and monitoring were identified as the primary levers to enhance the standards of specialist care in the field of heart failure

"Senza essere" e "privo di niente". L'essere e l'ente a partire dall'evento (Ereignis)/a partire dall'inizio (Anfang).

I Trattati inediti degli anni Trenta e Quaranta propongono l'elaborazione della domanda sull'essere in maniera radicale, seguendo la stessa dinamica di superamento/involgimento dell'essere nella sua verità quale evento dell'inizio. In questo movimento di inabissamento dell'essere in direzione del carattere iniziale della sua essenza quale inizio è catturato anche l'ente e la sua differenza dall'essere. L'intento del contributo è quello di dar conto del modo in cui, soprattutto nei Trattati degli anni Quaranta ("Über Den Anfang" e "Das Ereignis"), Heidegger ripensi e ridefinisca il rapporto tra l'essere e l'ente

ALTERNATIVE AL CS2 PER L'ESTRAZIONE DI BTEX DA SUBSTRATI A BASE DI CARBONE ATTIVO

Nell’ambito di una ricerca mirata alla tutela della salute negli ambienti di lavoro si sono indagate procedure alternative al disolfuro di carbonio (CS2) nell’estrazione di benzene, toluene, etilbenzene e xyleni (BTEX) da substrati a base di carbone utilizzati per il monitoraggio della qualità dell’aria