Związek stosowania metforminy ze zmniejszoną zapadalnością na choroby nowotworowe u pacjentów z cukrzycą typu 2

Introduction: The objective of the study was to assess the influence of metformin on the prevalence of cancer and risk factors for the development of cancer, in patients with type 2 diabetes. Materials and methods: A total of 1063 patients, treated between October 2012 and March 2013 in the Diabetes and Endocrinology Centre in Bydgoszcz, were enrolled in the study. Only patients who were first diagnosed with diabetes and consecutively with cancer were included in the analysis. The final dataset compromised data from 1028 patients with type 2 diabetes, in whom retrospective analysis of the association between the occurrence of cancer and treatment with or without metformin was performed. Demographic data, medical history, physical assessment, diabetes history, diabetes complications, concomitant medication, and additional examination results were compared between two groups: those with cancer and those without cancer. Data were analysed using Student’s t-test, Chi-square test with Yates' continuity correction, and multiple logistic regression. Results: The most commonly observed cancer was breast cancer (24 patients; 22.5%), followed by uterine cancer (15 patients; 13.6%). Of the 75 diabetic patients with a cancer diagnosis, 18.7% were treated with metformin; of the 953 patients without cancer, 38% received metformin. Analysis of probability of cancer occurrence using Kaplan-Meier curves showed that the probability of cancer development was higher in groups of patients who were not treated with metformin (p = 0.006). Conclusions: Metformin treatment reduces the risk of cancer in type 2 diabetes patients.Wstęp: Metformina jest zalecana w profilaktyce raka u pacjentów z cukrzycą typu 2 (t2). Celem badania była ocena wpływu metforminy na częstość występowania raka i czynników ryzyka wystąpienia raka u pacjentów z cukrzycą typu 2. Materiał i metody: W badaniu wzięło udział 1063 pacjentów leczonych od października 2012 do marca 2013 w Bydgoskim Centrum Diabetologii i Endokrynologii. Do analizy włączono pacjentów, u których najpierw rozpoznano cukrzycę, a następnie raka. Ostatec­znie uzyskano dane od 1028 pacjentów z cukrzycą t2, na podstawie których przeprowadzono retrospektywną analizę związku między wystąpieniem nowotworu a stosowaniem metforminy. Grupy pacjentów z rakiem i bez raka porównano pod względem danych de­mograficznych, historii medycznej, wyników badania przedmiotowego, historii i powikłań cukrzycy, leków przyjmowanych z powodu chorób towarzyszących oraz wyników badań dodatkowych. Analizę statystyczną przeprowadzono za pomocą testu t Studenta, testu chi kwadrat z poprawką Yatesa na nieciągłość i wielokrotnej regresji logistycznej. Wyniki: Najczęściej obserwowanym rodzajem raka był rak sutka (N = 24; 22,5%), a następnie rak macicy (N = 15; 13,6%). Spośród 75 pacjentów chorujących na cukrzycę i nowotwór, 18,7% było leczonych metforminą, natomiast spośród 953 pacjentów bez nowotworu, metforminę przyjmowało 38%. Analiza prawdopodobieństwa wystąpienia raka za pomocą krzywych Kaplana-Meiera wykazała, że prawdopodobieństwo raka jest większe u pacjentów, którzy nie przyjmowali metforminy (p = 0,006). Wnioski: Metformina zmniejsza ryzyko raka u pacjentów z cukrzycą t2.

Flutamide induces alterations in the cell-cell junction ultrastructure and reduces the expression of Cx43 at the blood-testis barrier with no disturbance in the rat seminiferous tubule morphology

BACKGROUND: Present study was designed to establish a causal connection between changes in the cell-cell junction protein expression at the blood-testis barrier and alterations in the adult rat testis histology following an anti-androgen flutamide exposure. Particular emphasis was placed on the basal ectoplasmic specialization (ES) in the seminiferous epithelium and expression of gap junction protein, connexin 43 (Cx43). METHODS: Flutamide (50 mg/kg body weight) was administered to male rats daily from 82 to 88 postnatal day. Testes from 90-day-old control and flutamide-exposed rats were used for all analyses. Testis morphology was analyzed using light and electron microscopy. Gene and protein expressions were analyzed by real-time RT-PCR and Western blotting, respectively, protein distribution by immunohistochemistry, and steroid hormone concentrations by radioimmunoassay. RESULTS: Seminiferous epithelium of both groups of rats displayed normal histology without any loss of germ cells. In accord, no difference in the apoptosis and proliferation level was found between control and treated groups. As shown by examination of semi-thin and ultrathin sections, cell surface occupied by the basal ES connecting neighboring Sertoli cells and the number of gap and tight junctions coexisting with the basal ES were apparently reduced in flutamide-treated rats. Moreover, the appearance of unconventional circular ES suggests enhanced internalization and degradation of the basal ES. These changes were accompanied by decreased Cx43 and ZO-1 expression (p < 0.01) and a loss of linear distribution of these proteins at the region of the blood-testis barrier. On the other hand, Cx43 expression in the interstitial tissue of flutamide-treated rats increased (p < 0.01), which could be associated with Leydig cell hypertrophy. Concomitantly, both intratesticular testosterone and estradiol concentrations were elevated (p < 0.01), but testosterone to estradiol ratio decreased significantly (p < 0.05) in flutamide-treated rats compared to the controls. CONCLUSIONS: Short-term treatment with flutamide applied to adult rats exerts its primary effect on the basal ES, coexisting junctional complexes and their constituent proteins Cx43 and ZO-1, without any apparent morphological alterations in the seminiferous epithelium. In the interstitial compartment, however, short-term exposure leads to both histological and functional changes of the Leydig cells

Long-term allogeneic hematopoietic cells transplantation survivors proinflammatory cytokine profile compared to their respective donors and immunophenotype differences depending on GvHD history and infection status

Background In the course of allogeneic hematopoietic cell transplantation (allo-HCT) the donor’s hematopoietic progenitor cells are exposed to immense proliferative stress to reconstitute in the recipient the functional hematopoiesis. Moreover, recipients who develop infections or chronic GvHD are subjected to further proliferative stress, especially in the lymphocyte subset. We hypothesized that allo-HCT may induce changes in proinflammatory cytokines profile and immunophenotype in the allo-HCT recipients, especially in patients with cGVHD history. We compared the cytokine profile (Il-6, Il-10, and TNF-) between long-term allo-HCT recipients and their respective donors and we analyzed cytokines profile and the immunophenotype of lymphocytes in long-term recipients grouped according to the infection and GvHD history. Results We have found no differences in the proinflammatory cytokines between allo-HCT recipients and their respective donors, as well as between recipients grouped according to infectious risk status. Immunophenotyping of recipients grouped according to GvHD status revealed an increased percentage of B-cell presenting PD-1 in recipients without a history of GvHD. Conclusions Lack of differences in proinflammatory cytokines concentrations between recipients and donors of allo-HCT would suggest that allo-HCT does not induce acceleration of the inflammageing-resembling phenomenon. No differences in the cytokine profile and immunophenotype between recipients grouped according to infectious risk status suggest that infectious risk is not reflected by the immunophenotype and cytokine profile. Furthermore, the lack of significant differences in immunophenotype of the recipients grouped according to the history of GvHD may suggest that in long-term survivors the immune system tends to stabilize with time

Design status of ASPIICS, an externally occulted coronagraph for PROBA-3

The "sonic region" of the Sun corona remains extremely difficult to observe with spatial resolution and sensitivity sufficient to understand the fine scale phenomena that govern the quiescent solar corona, as well as phenomena that lead to coronal mass ejections (CMEs), which influence space weather. Improvement on this front requires eclipse-like conditions over long observation times. The space-borne coronagraphs flown so far provided a continuous coverage of the external parts of the corona but their over-occulting system did not permit to analyse the part of the white-light corona where the main coronal mass is concentrated. The proposed PROBA-3 Coronagraph System, also known as ASPIICS (Association of Spacecraft for Polarimetric and Imaging Investigation of the Corona of the Sun), with its novel design, will be the first space coronagraph to cover the range of radial distances between ~1.08 and 3 solar radii where the magnetic field plays a crucial role in the coronal dynamics, thus providing continuous observational conditions very close to those during a total solar eclipse. PROBA-3 is first a mission devoted to the in-orbit demonstration of precise formation flying techniques and technologies for future European missions, which will fly ASPIICS as primary payload. The instrument is distributed over two satellites flying in formation (approx. 150m apart) to form a giant coronagraph capable of producing a nearly perfect eclipse allowing observing the sun corona closer to the rim than ever before. The coronagraph instrument is developed by a large European consortium including about 20 partners from 7 countries under the auspices of the European Space Agency. This paper is reviewing the recent improvements and design updates of the ASPIICS instrument as it is stepping into the detailed design phase

Development of ASPIICS: a coronagraph based on Proba-3 formation flying mission

This paper presents the recent achievements in the development of ASPIICS (Association of Spacecraft for Polarimetric and Imaging Investigation of the Corona of the Sun), a solar coronagraph that is the primary payload of ESA&apos;s formation flying in-orbit demonstration mission PROBA-3. The PROBA-3 Coronagraph System is designed as a classical externally occulted Lyot coronagraph but it takes advantage of the opportunity to place the 1.4 meter wide external occulter on a companion spacecraft, about 150m apart, to perform high resolution imaging of the inner corona of the Sun as close as similar to 1.1 solar radii. Besides providing scientific data, ASPIICS is also equipped with sensors for providing relevant navigation data to the Formation Flying GNC system. This paper is reviewing the recent development status of the ASPIICS instrument as it passed CDR, following detailed design of all the sub-systems and testing of STM and various Breadboard models. ASPIICS is built by a large European consortium including about 20 partners from 7 countries under the auspices of the European Space Agency