Aprotinin reduces cardiac troponin I release and inhibits apoptosis of polymorphonuclear cells during off-pump coronary artery bypass surgery

Objectives: In addition to blood-sparing effects, aprotinin may have cardioprotective and anti-inflammatory effects during cardiopulmonary bypass-assisted cardiac surgery. In this study, the authors examined whether aprotinin had cardioprotective and/or anti-inflammatory effects in patients undergoing off-pump coronary artery bypass grafting. Design: A prospective randomized clinical trial. Setting: University hospital. Participants: Fifty patients were randomized to control (n = 25) or aprotinin treatment (n = 25) groups. Interventions: Aprotinin was given as a loading dose (2 x 10(6) KIU) followed by a continuous infusion at 5 x 10(5) KIU/h until skin closure. Measurements and Main Results: Blood samples for cardiac troponin I; interleukin-6, interleukin-8, and interleukin-10; tumor necrosis factor a; and elastase were taken after anesthesia induction, completion of revascularization, and 6 hours, 12 hours, and 24 hours after revascularization. Blood samples were taken to assess for apoptosis in polymorphonuclear cells. Baseline plasma levels for cardiac troponin I did not differ between groups but were significantly lower in aprotinin-treated patients at the time of revascularization (P = 0.03) and 6 hours (p = 0.004) and 24 hours (p = 0.03) later. Aprotinin significantly reduced apoptosis in polymorphonuclear cells compared with control-treated patients (p = 0.04). There were no differences in plasma cytokine or elastase levels between groups. Conclusions: The authors conclude that aprotinin reduces perioperative cardiac troponin I release and attenuates apoptosis in polymorphonuclear cells but has no significant effects on plasma cytokine levels in patients undergoing off-pump coronary artery bypass graft surgery

Evidence for position effects as a variant ETV6-mediated leukemogenic mechanism in myeloid leukemias with a t(4;12)(q11-q12;p13) or t(5;12)(q31;p13)

The ETV6 gene (first identified as TEL) is a frequent target of chromosomal translocations in both myeloid and lymphoid leukemias. At present, more than 40 distinct translocations have been cytogenetically described, of which 13 have now also been characterized at the molecular level. These studies revealed the generation of in-frame fusion genes between different domains of ETV6 and partner genes encoding either kinases or transcription factors. However, in a number of cases-including a t(6;12)(q23;p13), the recurrent t(5;12)(q31;p13), and some cases of the t(4;12)(q11-q12;p13) described in this work-functionally significant fusions could not be identified, raising the question as to what leukemogenic mechanism is implicated in these cases. To investigate this, we have evaluated the genomic regions at 4q11-q12 and 5q31, telomeric to the breakpoints of the t(4;12)(q11-q12;p13) and t(5;12)(q31;p13). The homeobox gene GSH2 at 4q11-q12 and the IL-3/CSF2 locus at 5q31 were found to be located close to the respective breakpoints. In addition, GSH2 and IL-3 were found to be ectopically expressed in the leukemic cells, suggesting that expression of GSH2 and IL-3 was deregulated by the translocation. Our results indicate that, besides the generation of fusion transcripts, deregulation of the expression of oncogenes could be a variant leukemogenic mechanism for translocations involving the 5' end of ETV6, especially for those translocations lacking functionally significant fusion transcripts

Histopathological study of JNK in venous wall of patients with chronic venous insufficiency related to osteogenesis process

Chronic venous insufficiency (CVI) is one of the most common vascular pathologies worldwide. One of the risk factors for the development of CVI is aging, which is why it is related to senile changes. The main trigger of the changes that occur in the venous walls in CVI is blood flow reflux, which produces increased hydrostatic pressure, leading to valve incompetence. The cellular response is one of the fundamental processes in vascular diseases, causing the activation of cell signalling pathways such as c-Jun N-terminal kinase (JNK). Metabolic changes and calcifications occur in vascular pathology as a result of pathophysiological processes. The aim of this study was to determine the expression of JNK in venous disease and its relationship with the role played by the molecules involved in the osteogenic processes in venous tissue calcification. This was a cross-sectional study that analyzed the greater saphenous vein wall in 110 patients with (R) and without venous reflux (NR), classified according to age. Histopathological techniques were used and protein expression was analysed using immunohistochemistry techniques for JNK and markers of osteogenesis (RUNX2, osteocalcin (OCN), osteopontin (OPN)). Significantly increased JNK, RUNX2, OCN, OPN and pigment epithelium-derived factor (PEDF) protein expression and the presence of osseous metaplasia and amorphous calcification were observed in younger patients (<50 years) with venous reflux. This study shows for the first time the existence of an osteogenesis process related to the expression of JNK in the venous wall.This study (FIS-PI18/00912) was supported by the Instituto de Salud Carlos III (Plan Estatal de I+D+i 2013-2016) and cofinanced by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF) and B2017/BMD-3804 MITIC-C

Ophrys fusca and Ophrys dyris (Orchidaceae) – constancy of tetraploidy amongst populations in Central Portugal

Ophrys is amongst the best known orchid genera and is an established system for the study of pollinatormediated floral evolution. Two species, Ophrys fusca s.l. and Ophrys dyris (= O. omegaifera subsp. dyris) belonging to Ophrys section Pseudophrys are the focus of this study. In the context of an integrative study of morphological and genetic diversity of O. fusca and O. dyris, genome size (GS) and cytotype diversity were surveyed from Portuguese populations. Flow cytometry methods were used to assess GS, and subsequently determine the ploidy level of 67 specimens, including the species and putative hybrids. Cytotypes were also confirmed based on chromosome counts from the roots of two specimens, one of each species. Constancy of nuclear DNA content (1C = 11.19 pg) and ploidy level (2n =4x = 72, 74) was documented among all the individuals analysed. Implications are considered, in terms of interpreting the origin and predicting the persistence of putative hybrids

Excitation of the molecular gas in the nuclear region of M82

We present high resolution HIFI spectroscopy of the nucleus of the archetypical starburst galaxy M82. Six 12CO lines, 2 13CO lines and 4 fine-structure lines are detected. Besides showing the effects of the overall velocity structure of the nuclear region, the line profiles also indicate the presence of multiple components with different optical depths, temperatures and densities in the observing beam. The data have been interpreted using a grid of PDR models. It is found that the majority of the molecular gas is in low density (n=10^3.5 cm^-3) clouds, with column densities of N_H=10^21.5 cm^-2 and a relatively low UV radiation field (GO = 10^2). The remaining gas is predominantly found in clouds with higher densities (n=10^5 cm^-3) and radiation fields (GO = 10^2.75), but somewhat lower column densities (N_H=10^21.2 cm^-2). The highest J CO lines are dominated by a small (1% relative surface filling) component, with an even higher density (n=10^6 cm^-3) and UV field (GO = 10^3.25). These results show the strength of multi-component modeling for the interpretation of the integrated properties of galaxies.Comment: Accepted for publication in A&A Letter

Chimeric Antigen Receptor T-Cell Therapy For Multiple Myeloma: A Consensus Statement From The European Myeloma Network

Adoptive cellular therapy using chimeric antigen receptor T-cell (CART) therapy is currently being evaluated in patients with relapsed / refractory multiple myeloma (MM). The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent phase I / II trials show promising preliminary results in patients with MM progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38. CAR-T cell therapy is a potentially life-threatening strategy that can only be administered in experienced centers. For the moment, CAR-T cell therapy for MM is still experimental, but once this strategy has been approved in relapsed/refractory MM, it will become one of the most important indications for this therapy in Europe and world-wide. This manuscript proposes practical considerations for the use of CAR-T cell therapy in MM, and discusses several important issues for its future development