The effect of pregnancy on subsequent relapse from Graves' disease after a successful course of antithyroid drug therapy.

OBJECTIVE: Pregnancy and the postpartum (PP) period are associated with profound changes of the immune system, which largely influence the clinical activity of autoimmune diseases. The aim of this study was to evaluate the effect of pregnancy and/or the PP period in driving a clinical relapse of hyperthyroidism in patients with Graves' disease (GD) who are in remission after antithyroid drug (ATD) treatment. Data were retrospectively collected from 150 female patients with GD, who were assigned to two groups according to the occurrence of a successful pregnancy after ATD withdrawal. RESULTS: Relapsing Graves' hyperthyroidism was observed in 70 of 125 patients in group I (no pregnancy after ATD withdrawal) (56.0%) and 21 of 25 patients in group II (pregnancy after ATD withdrawal) (84.0%) (P < 0.05). Logistic regression analysis (dependent variable: relapse/nonrelapse; covariates: age, positive family history for autoimmune thyroid disease, duration of treatment with ATD, number pregnancies at diagnosis, number of pregnancies after ATD withdrawal) showed a significant effect only for the number of pregnancies after ATD withdrawal [4.257 (1.315-13.782)]. The effect was ascribed to the PP period rather than to pregnancy itself because in 20 of 21 patients of group II (95.2%), the relapse of Graves' hyperthyroidism occurred between 4 and 8 months after delivery. CONCLUSIONS: The PP period is significantly associated with a relapse of hyperthyroidism in GD patients being in remission after ATD. We therefore recommend that patients with GD in remission after a course of ATD should have their thyroid function tested at 3 and 6 months after delivery

Specific Protein 1 and p53 Interplay Modulates the Expression of the KCTD-Containing Cullin3 Adaptor Suppressor of Hedgehog 2

The Hedgehog (Hh) signaling pathway plays a crucial role in normal embryonic development and adult tissue homeostasis. On the other end, dysregulated Hh signaling triggers a prolonged mitogenic response that may prompt abnormal cell proliferation, favoring tumorigenesis. Indeed, about 30% of medulloblastomas (MBs), the most common malignant childhood cerebellar tumors, exhibit improper activation of the Hh signaling. The oncosuppressor KCASH2 has been described as a suppressor of the Hh signaling pathway, and low KCASH2 expression was observed in Hh-dependent MB tumor. Therefore, the study of the modulation of KCASH2 expression may provide fundamental information for the development of new therapeutic approaches, aimed to restore physiological KCASH2 levels and Hh inhibition. To this end, we have analyzed the TATA-less KCASH2 proximal promoter and identified key transcriptional regulators of this gene: Sp1, a TF frequently overexpressed in tumors, and the tumor suppressor p53. Here, we show that in WT cells, Sp1 binds KCASH2 promoter on several putative binding sites, leading to increase in KCASH2 expression. On the other hand, p53 is involved in negative regulation of KCASH2. In this context, the balance between p53 and Sp1 expression, and the interplay between these two proteins determine whether Sp1 acts as an activator or a repressor of KCASH2 transcription. Indeed, in p53–/– MEF and p53 mutated tumor cells, we hypothesize that Sp1 drives promoter methylation through increased expression of the DNA methyltransferase 1 (DNMT1) and reduces KCASH2 transcription, which can be reversed by Sp1 inhibition or use of demethylating agents. We suggest therefore that downregulation of KCASH2 expression in tumors could be mediated by gain of Sp1 activity and epigenetic silencing events in cells where p53 functionality is lost. This work may open new venues for novel therapeutic multidrug approaches in the treatment of Hh-dependent tumors carrying p53 deficiency

Spatial resolution on a small animal RPC-PET prototype operating under magnetic field

It has been demonstrated in previous work that the RPC-PET technology is able to deliver radioisotope image resolutions approaching the physical limits of the PET principle. Here we study, by simulation, the effect of the magnetic field on the positron range to evaluate whether the spatial resolution of the RPC-PET could be improved by using an intense magnetic field. Six positron emitters of interest to small animal PET imaging (18F, 11C, 15O, 68G, 62Cu and 86Y) are considered. Results suggest that a three-fold improvement on the spatial resolution may be obtained under a magnetic field of 10 T for the higher energy radioisotopes like 86Y or 62Cu, and by about 20% for the lower energy ones, like 18F or 11C.http://www.sciencedirect.com/science/article/B6TVD-4KV4MR8-15/1/efa4356ba16a85fd7740937bd0e672a

Very high position resolution gamma imaging with resistive plate chambers

In this study we present experimental results from a first prototype of a positron emission tomography system based on the resistive plate chamber (RPC) technology. The system is composed of two counting heads, each one containing 16 single-gap RPC detectors capable of detecting the photon interaction point in the transaxial plane. Uniformity studies were performed for image resolution and sensitivity, yielding a rather uniform image resolution close to 0.3 mm FWHM across the field of view. The contribution of the photons noncolinearity effect to the intrinsic spatial resolution was also studied, causing a variation from 0.52 to 0.63 mm when the system diameter ranges from 60 to 120 mm, in agreement with calculations.http://www.sciencedirect.com/science/article/B6TJM-4K5HV7F-9/1/7b655e08199d2b28acc8050106c2271

MARTA: A high-energy cosmic-ray detector concept with high-accuracy muon measurement

A new concept for the direct measurement of muons in air showers is presented. The concept is based on resistive plate chambers (RPCs), which can directly measure muons with very good space and time resolution. The muon detector is shielded by placing it under another detector able to absorb and measure the electromagnetic component of the showers such as a water-Cherenkov detector, commonly used in air shower arrays. The combination of the two detectors in a single, compact detector unit provides a unique measurement that opens rich possibilities in the study of air showers.Comment: 11 page

Hydroxy-propil-β-cyclodextrin inclusion complexes of two biphenylnicotinamide derivatives: Formulation and anti-proliferative activity evaluation in pancreatic cancer cell models

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with poor outcomes largely due to its unique microenvironment, which is responsible for the low response to drugs and drug-resistance phenomena. This clinical need led us to explore new therapeutic approaches for systemic PDAC treatment by the utilization of two newly synthesized biphenylnicotinamide derivatives, PTA73 and PTA34, with remarkable antitumor activity in an in vitro PDAC model. Given their poor water solubility, inclusion complexes of PTA34 and PTA73 in Hydroxy-Propil-β-Cyclodextrin (HP-β-CD) were prepared in solution and at the solid state. Complexation studies demonstrated that HP-β-CD is able to form stable host–guest inclusion complexes with PTA34 and PTA73, characterized by a 1:1 apparent formation constant of 503.9 M−1 and 369.2 M−1, respectively (also demonstrated by the Job plot), and by an increase in aqueous solubility of about 150 times (from 1.95 µg/mL to 292.5 µg/mL) and 106 times (from 7.16 µg/mL to 762.5 µg/mL), in the presence of 45% w/v of HP-β-CD, respectively. In vitro studies confirmed the high antitumor activity of the complexed PTA34 and PTA73 towards PDAC cells, the strong G2/M phase arrest followed by induction of apoptosis, and thus their eligibility for PDAC therapy

Extreme Energy Cosmic Rays (EECR) Observation Capabilities of an "Airwatch from Space'' Mission

The longitudinal development and other characteristics of the EECR induced atmospheric showers can be studied from space by detecting the fluorescence light induced in the atmospheric nitrogen. According to the Airwatch concept a single fast detector can be used for measuring both intensity and time development of the streak of fluorescence light produced by the atmospheric shower induced by an EECR. In the present communication the detection capabilities for the EECR observation from space are discussed.Comment: 3 pages (LaTeX). To appear in the Proceedings of TAUP'9