Terapia ormonale sostitutiva e osteoporosi postmenopausale

SommarioL'osteoporosi postmenopausale è un processo per il quale il tessuto osseo sviluppa una fragilità risultando più suscettibile alle fratture anche per traumi che solitamente non comporterebbero tali eventi. La carenza estrogenica è un punto fondamentale nella patogenesi dell'osteoporosi. La TOS rappresenta un trattamento di scelta nella prevenzione della osteoporosi e delle fratture correlate, soprattutto nei primi anni di postmenopausa

Non-hormonal strategies for managing menopausal symptoms in cancer survivors: an update

Vasomotor symptoms, particularly hot flushes (HFs), are the most frequently reported symptom by menopausal women. In particular, for young women diagnosed with breast cancer, who experience premature ovarian failure due to cancer treatments, severe HFs are an unsolved problem that strongly impacts on quality of life. The optimal management of HFs requires a personalised approach to identify the treatment with the best benefit/risk profile for each woman. Hormonal replacement therapy (HRT) is effective in managing HFs but it is contraindicated in women with previous hormone-dependent cancer. Moreover, many healthy women are reluctant to take HRT and prefer to manage symptoms with non-hormonal strategies. In this narrative review, we provide an update on the current available non-oestrogenic strategies for HFs management for women who cannot, or do not wish to, take oestrogens. Since isoflavones have oestrogenic properties and it is not known if they can be safely consumed by women with previous hormonedependent cancer, they were excluded. Selective serotonin reuptake inhibitors/selective serotonin-norepinephrine reuptake inhibitors, as well as other neuroactive agents, some herbal remedies and behavioural strategies are considered

A Relay Pathway between Arginine and Tryptophan Metabolism Confers Immunosuppressive Properties on Dendritic Cells

Arginase 1 (Arg1) and indoleamine 2,3-dioxygenase 1\ua0(IDO1) are immunoregulatory enzymes catalyzing the degradation of L-arginine and L-tryptophan, respectively, resulting in local amino acid deprivation. In addition, unlike Arg1, IDO1 is also endowed with non-enzymatic signaling activity in dendritic cells (DCs). Despite considerable knowledge of their individual biology, no integrated functions of Arg1 and IDO1 have been reported yet. We found that IDO1 phosphorylation and consequent activation of IDO1 signaling in DCs was strictly dependent on prior expression of Arg1 and Arg1-dependent production of polyamines. Polyamines, either produced by DCs or released by bystander Arg1+ myeloid-derived suppressor cells, conditioned DCs toward an IDO1-dependent, immunosuppressive phenotype via activation of the Src kinase, which has IDO1-phosphorylating activity. Thus our data indicate that Arg1 and IDO1 are linked by an entwined pathway in immunometabolism and that their joint modulation could represent an important target for effective immunotherapy in several disease settings

Giustizia e letteratura II

The book explores and links different cultures, disciplines and perspectives, with a far more original and broad approach to the relations between “Justice” and “Literature” than more traditional works focused on “Law” and “Literature”. The many contributions from writers, literature and movie critics, psychologists, and criminal law practitioners and scholars, draw a complex and interdisciplinary path through primary texts of Italian and international literature, with the aim of prompting readers’ reflections about core issues related to law, crime, and responsibility. Through the analysis of masterpieces of literature, theatre and cinema, this book aims at stimulating dialogue and debate, as well as critical abilities and a deep-rooted sense of justice, amongst both law professionals and citizens at large. Literature and other forms of narration are presented here as a privileged key to approach long-standing questions about (amongst other) causes and consequences of crime; victimization and coping mechanisms; the role of criminal law and criminal proceedings; legalism and equity; law and ethics; the ‘time’ of justice; freedom, responsibility, culpability and forgiveness; rules, legality, socialization and culture; language and images as mediums for justice issues; the impact of prejudice and of existing balances of power on the application of the law; social and legal mechanisms of exclusion and inclusion; gender issues and legal systems; and so on. A whole section (Part V) is devoted to crimes against humanity and how the literary testimony may be understood both as a strategy to resist injustice and to seek justice, and as a way to prevent further horrors. Through this quest for justice in literature and arts, the volume proposes a wider cultural and research project which defies traditional formalistic and retributive approaches to criminal law, in order to open new perspectives for restorative and reintegrative strategies

La terapia ormonale sostitutiva oggi: un update

Dopo un lungo periodo di uso della terapia ormonale sostitutiva (TOS), basato su risultati globalmente positivi riportati in studi di tipo osservazionale, negli ultimi anni alcuni studi di tipo randomizzato e controllato con placebo (RCTs) hanno mostrato dati differenti ed a volte contrastanti rispetto a quelli di precedenti studi osservazionali. Uno dei motivi che possono spiegare tali differenze è l’età delle pazienti trattate: negli studi osservazionali, l’età media delle donne trattate con TOS è più giovane rispetto a quella delle donne trattate negli RCTs. Così, la risposta dei tessuti nelle donne più giovani potrebbe essere migliore rispetto a quella di donne più anziane. Attualmente, si preferisce iniziare precocemente la somministrazione di HRT e la scelta è di utilizzare le basse dosi all’inizio della terapia

Ethynilestradiol 20 mcg plus Levonorgestrel 100 mcg: Clinical Pharmacology

Estroprogestins (EPs) are combinations of estrogen and progestin with several actions on women’s health. The different pharmacological composition of EPs is responsible for different clinical effects. One of the most used low-dose EP associations is ethinylestradiol 20 mcg plus levonorgestrel 100 mcg in monophasic regimen (EE20/LNG100). This review summarizes clinical pharmacology, cycle control, and effects on lipid and glucose metabolism, coagulation, body weight/body composition, acne, and sexuality of EE20/LNG100. Overall, EE20/LNG100 combination is safe and well tolerated, and in several studies the incidence of adverse events in the treated group was comparable to that of the placebo group. Cycle control was effective and body weight/body composition did not vary among treated and untreated groups in most studies. The EE20/LNG100 combination shows mild or no effect on lipid and glucose metabolism. Lastly, EE20/LNG100 is associated with a low risk of venous thromboembolism (VTE). In conclusion, in the process of decision making for the individualization of EPs choice, EE20/LNG100 should be considered for its favorable clinical profile

Bone tissue: hormonal regulating systems, growth factors and remodeling as a target for therapeutic agents in osteoporosis

Bone regulating systems have received growing attention in recent years. Regulation of skeletal pathophysiology and modulation of osteoblast, osteoclast and osteocyte activity by hormones, cytokines, and growth factors are not only important features of bone biology, but also a target for old and new osteoporosis therapies. Molecules such as selective estrogen receptor modulators (SERMs, e.g. raloxifene and bazedoxifene), denosumab, or bisphosphonates may exert their effects through modulation of estrogen receptor, RANKL and osteoclast activity, respectively. Knowledge of the regulating systems is also the basis for developing future therapy. This review shows regulating systems as a basis for current and future therapies in the field of osteoporosi

The Tissue-Selective Estrogen Complex (Bazedoxifene/Conjugated Estrogens) for the Treatment of Menopause

The tissue-selective estrogen complex (TSEC) pairs conjugated estrogens (CE) with a selective estrogen receptor modulator (SERM), bazedoxifene acetate (BZA). A 2-year treatment with the TSEC improved vasomotor symptoms, quality of life, and vaginal atrophy in healthy postmenopausal women. In addition, the TSEC prevented vertebral and hip bone loss without increasing mammographic density, breast tenderness, the risk of myocardial infarction, stroke, or venous thromboembolism. Finally, the BZA 20 mg/CE 0.45 mg dose did not increase the risk of endometrial hyperplasia. Based on these findings, the TSEC can be considered as a first-line treatment for symptomatic postmenopausal women