Primary mediastinal lymphoma: diagnosis and treatment options.

Primary mediastinal large B-cell lymphoma (PMBCL) is a unique B-cell lymphoma variant that arises from a putative thymic medulla B cell. It constitutes 2-4% of non-Hodgkin lymphomas and occurs most frequently in young females. PMBCL is characterized by a diffuse proliferation of medium-to-large B cells associated with sclerosis. Molecular analysis shows that PMBCL is a distinct entity compared to other types of diffuse large B-cell lymphomas. PMBCL is characterized by a locally invasive anterior mediastinal bulky mass. The combination of rituximab with CHOP/CHOP-like regimens followed by mediastinal radiation therapy (RT) is associated with a 5-year progression-free survival of 75-85%. However, the role of consolidation RT still remains uncertain. More intensive regimens, such as DA-EPOCH-R without mediastinal RT, have shown very promising results. The conclusive role of PET-CT scan requires prospective studies and there is hope that this may allow to de-escalate RT and accordingly yield reliable prognostic information

Guinea-pig ileum as ex vivo model useful to characterize ligands displaying Imidazoline I2 and Adrenergic alpha2 mixed activity: a preliminary study

The lack of an effective analgesic treatment makes pain a clinical challenge and the need of a novel approach to identify new agents is urgent. In this scenario I2-ligands can be considered an alternative strategy in pain therapy. The development of an ex vivo model useful for the evaluation of functional activities at both a2 and I2-IBs (imidazoline binding sites) is an important task in pharmacological sciences since several I2 ligands display activity also towards a receptors. The present study aims to develop an ex vivo model for estimating the activity of I2-IBs ligands in a biological sample where a1 and a2 adrenergic receptors are present. For this purpose the imidalzoline endogenous ligand, harmane, reference compounds, 2BFI and BU224, and imidazoline derivatives 1-3 have been selected taking into account their in vitro activity towards IBs and adrenergic receptors. All compounds have been tested ex vivo in guinea pig-ileum where a2A-ARs are prejunctionally and I2-IBS postjunctionally localized. Adrenergic component has been identified by the studying the interference of compounds on the electrically-evoked contraction while I2-IBs activity by testing the ability of compounds to inhibit the carbachol-evoked contractions in the presence of prazosin to mask the a1 adrenoceptors. Compounds 1 and 2 were found I2-IBs antago nists (pIC50=4.2 and 4.0, respectively) whereas compound 3 was I2-IBs agonist (EC50=0.38 mM); All ligands were a2 adrenergic agonists. This paper suggests guinea-pig ileum as the first ex vivo approach for establishing both the intrinsic activity of I2-IBs ligands and the physiological correlation between IBs and adrenergic system

Il «buon costume» come limite ai diritti: prospettive e problematiche

This doctoral thesis concerns the concept of «good mores» as a limitation to constitutional rights. The goal of this research is to devise a definition of this concept that a secularized and pluralist society can accept. In the first part of the thesis I have examined the «good mores» within Italian legal system. I have singled out the legal sources that refer to «good mores», or to similar notions, and I have studied how these concepts live in the jurisprudence and in doctrinal opinions. In the second part of the thesis I have analyzed the «good mores» in a transnational context, and I took into account this clause in the European dimension and, in a comparative perspective, in a foreign legal system, namely that of U.S.A. In the last part of the work I attempted a definition of the «good mores». Since this concept has a content that belongs to the sphere of ethics and values, I held that the source of shared values in a liberal-democratic society might be its Constitution, and, within a pluralist Constitution, there might be an overlapping consensus on the value of human dignity. Therefore, I examined the possibility to link the «good mores» to human dignity, and I explored the consequences of that interpretive solution with regard to fundamental rights of the individual.

Calreticulin Enhances the Transcriptional Activity of Thyroid Transcription Factor-1 by Binding to Its Homeodomain

Transcription factors are often regulated by associated protein cofactors that are able to modify their activity by several different mechanisms. In this study we show that calreticulin, a Ca2+-binding protein with chaperone activity, binds to thyroid transcription factor-1 (TTF-1), a homeodomain-containing protein implicated in the differentiation of lung and thyroid. The interaction between calreticulin and TTF-1 appears to have functional significance because it results in increased transcriptional stimulation of TTF-1-dependent promoters. Calreticulin binds to the TTF-1 homeodomain and promotes its folding, suggesting that the mechanism involved in stimulation of transcriptional activity is an increase of the steady-state concentration of active TTF-1 protein in the cell. We also demonstrate that calreticulin mRNA levels in thyroid cells are under strict control by the thyroid-stimulating hormone, thus implicating calreticulin in the modulation of thyroid gene expression by thyroid-stimulating hormone

Epirubicin. A new entry in the list of fetal cardiotoxic drugs? Intrauterine death of one fetus in a twin pregnancy. Case report and review of literature

BACKGROUND: Current knowledge indicate that epirubicin administration in late pregnancy is almost devoid of any fetal cardiotoxicity. We report a twin pregnancy complicated by breast cancer in which epirubicin administration was causatively linked to the death of one twin who was small for gestational age (SGA) and in a condition of oligohydramnios and determined the onset of a transient cardiotoxicity of the surviving fetus/newborn. CASE PRESENTATION: A 38-year-old caucasic woman with a dichorionic twin pregnancy was referred to our center at 20 and 1/7 weeks for a suspected breast cancer, later confirmed by the histopathology report. At 31 and 3/7 weeks, after the second chemotherapy cycle, ultrasound examination evidenced the demise of one twin while cardiac examination revealed a monophasic diastolic ventricular filling, i.e. a diastolic dysfunction of the surviving fetus who was delivered the following day due to the occurrence of grade II placental abruption. The role of epirubicin cardiotoxicity in the death of the first twin was supported by post-mortem cardiac and placental examination and by the absence of structural or genomic abnormalities that may indicate an alternative etiology of fetal demise. The occurrence of epirubicin cardiotoxicity in the surviving newborn was confirmed by the report of high levels of troponin and transient left ventricular septal hypokinesia. CONCLUSION: Based on our findings we suggest that epirubicin administration in pregnancy should be preceded by the screening of some fetal conditions like SGA and oligohydramnios that may increase its cardiotoxicity and that, during treatment, the diastolic function of the fetal right ventricle should be specifically monitored by a pediatric cardiologist; also, epirubicin and desamethasone for lung maturation should not be closely administered since placental effects of glucocorticoids may increase epirubicin toxicity