Apoptosis represents a fundamental process during fetal/post-natal testis development. Therefore pro- and anti-apoptotic proteins are essential to regulate testis physiology. c-Flip
L is a known ...inhibitor of caspase 8/10 activity; in this study its perinatal expression in mouse male germ cells was investigated. In testis sections and seminiferous tubule whole mount c-Flip
L was found to be expressed in undifferentiated spermatogonia and to co-localize with germ stem cells markers. In vivo investigations in the vitamin-A deficient mouse, lacking differentiated germ cells, confirmed c-Flip
L expression in undifferentiated spermatogonia. Further analyses showed Fas expression but no significant caspase 8/10 activity when c-Flip
L was highly expressed. Altogether these data suggest that c-Flip may control the survival rate of undifferentiated spermatogonia.
An 80-years-old patient with permanent atrial fibrillation and symptomatic, paroxysmal atrioventricular blocks (AVBs) underwent leadless pacemaker (L-PM) implantation. Seven years after implantation, ...as a consequence of a progression of the AVB towards a persistent form, resulting in an increased need for pacing, he developed a pacing-induced cardiomyopathy. He then underwent a successful upgrade from L-PM to a transvenous pacemaker (T-PM) with left bundle branch area pacing (LBBAP). The L-PM did not interfere with the T-PM and was turned off and abandoned. One month after the upgrading the patient showed a significant improvement in cardiac function and functional capacity.
To study the effect of c-FLIP overexpression in testicular germ cells.
A novel transgenic mouse model overexpressing the apoptotic modulator c-FLIP in the testis was generated.
Animal facility and ...university research laboratory.
Transgenic mice overexpressing the long isoform of c-FLIP (c-FLIP(L)) under the transcriptional control of a 400 bp long regulatory region of the Stra8 promoter.
Spermatozoa motility and testis histological, immunohistochemical, and Western blot analyses were carried out in transgenic and control derived specimens.
Testis morphology, sperm motility, and germ cell apoptosis were assayed.
Stra8 promoter was found to activate the ectopic overexpression of c-FLIP(L) in round and elongated spermatids. As a consequence of such overexpression, a dramatic loss of germ cells was observed, resulting in testicular atrophy associated with reduced sperm motility.
The data show that c-FLIP(L) forced expression in haploid male germ cells has detrimental effects on spermatogenesis and sperm quality and reveal a possible mechanism underlying the onset of testicular atrophy.
The introduction of the GNSS positioning technology into the evolution of ERTMS/ETCS is based on the concept of virtual balise to minimize the impact onto existing ERTMS solutions. The detection of ...virtual balises is foreseen by using GNSS in combination with odometry information or other kinematic sensors. However, the presence of local GNSS threats (e.g, multipath, NLOS or interference) may lead to errors in the pseudorange measurement that cannot be neither corrected by local or wide-area augmentation systems nor properly bounded, and will lead ultimately to an error in the virtual balise position that cannot be bounded with the required integrity. In order to a priori prevent the risk of this hazardous situation, virtual balises must be logically located in areas where there are not local threats that may lead a Virtual Balise Transmission System on board the train to dynamically estimate unbounded virtual balise position errors. This paper summarizes the initial work performed in the H2020 GSA Project ERSAT-GGC with respect to the different techniques that can be used to detect local GNSS threats and that can support a later classification of railway areas as suitable or not suitable for placing virtual balises.
Inhibition of multiple myeloma (MM) plasma cells in their permissive bone marrow microenvironment represents an attractive strategy for blocking the tumor/vessel growth associated with the disease ...progression. However, target specificity is an essential aim of this approach. Here, we identified platelet-derived growth factor (PDGF)-receptor beta (PDGFRbeta) and pp60c-Src as shared constitutively activated tyrosine-kinases (TKs) in plasma cells and endothelial cells (ECs) isolated from MM patients (MMECs). Our cellular and molecular dissection showed that the PDGF-BB/PDGFRbeta kinase axis promoted MM tumor growth and vessel sprouting by activating ERK1/2, AKT, and the transcription of MMEC-released proangiogenic factors, such as vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8). Interestingly, pp60c-Src TK-activity was selectively induced by VEGF in MM tumor and ECs, and the use of small-interfering (si)RNAs validated pp60c-Src as a key signaling effector of VEGF loop required for MMEC survival, migration, and angiogenesis. We also assessed the antitumor/vessel activity of dasatinib, a novel orally bioactive PDGFRbeta/Src TK-inhibitor that significantly delayed MM tumor growth and angiogenesis in vivo, showing a synergistic cytotoxicity with conventional and novel antimyeloma drugs (ie, melphalan, prednisone, bor-tezomib, and thalidomide). Overall data highlight the biologic and therapeutic relevance of the combined targeting of PDGFRbeta/c-Src TKs in MM, providing a framework for future clinical trials.
This 3-day, multicenter, open-label, randomized, controlled trial was undertaken to assess the postoperative analgesic effect and therapeutic safety of intramuscular tramadol compared with ...intramuscular ketorolac in 48 patients undergoing orthopedic surgery and having postoperative pain assessed as 75 mm or more on a 100-mm visual analogue scale. Tramadol (100 mg/2 mL ampules) was administered as needed to a maximum of 400 mg/d, and ketorolac (30 mg/1 mL ampules) was given as needed up to 90 mg/d. Nine patients who received tramadol and six who received ketorolac needed only one dose of medication to achieve satisfactory analgesia. Tramadol had a more pronounced analgesic effect than did ketorolac. After 1 and 2 hours, respectively, 41.7% and 52.5% of the patients who received tramadol experienced relief, compared with 33.9% and 42.1% of the patients who received ketorolac. No adverse reactions were observed in either group, and the investigator's final opinion was positive (ie, effective analgesia in 19 patients 79.2% who received tramadol and in 14 patients 58.3% who received ketorolac). Intramuscular tramadol therefore appeared to be as effective as ketorolac against orthopedic postoperative pain and was well tolerated.
In patients with coronary artery disease, left ventricular performance during stress is affected by the degree of coronary stenosis. In order to verify whether there exists a relationship between the ...extent of wall motion abnormalities detectable during atrial pacing and the degree of coronary obstruction, 76 patients, without previous myocardial infarction, were studied. Each patient underwent cross-sectional echocardiography during transesophageal atrial pacing and exercise electrocardiography before coronary angiography. Of the 76 patients, 46 had significant coronary artery disease (stenosis greater than or equal to 75% of at least one major coronary vessel), while 30 had normal coronaries or a stenosis of less than 75%. Eighteen patients had single-, 14 had two- and 14 had three-vessel disease. For each patient a coronary score was obtained: the score used took into consideration the site, number and severity of the stenosis. This score was then correlated with the wall motion score, obtained from the analysis of 9 segments of the left ventricle. A weak correlation was obtained between wall motion score at rest and coronary score (r = -0.42), while the correlation between coronary score and the difference between wall motion score at rest and during transesophageal atrial pacing was slightly better (r = 0.53); this correlation further improved if wall motion score during pacing was considered (r = -0.63). If the patients with discordant diagnostic tests (echocardiography during transesophageal atrial pacing and exercise electrocardiography) were excluded, the correlation coefficient between coronary score and wall motion score during pacing increased even more (r = -0.77).
(1) analysis of wall motion of the left ventricle during atrial pacing is useful for the non-invasive evaluation of the severity of coronary disease; (2) cross-sectional echocardiography during atrial pacing, apart from being a useful diagnostic tool, is also a help in judging the degree of severity of coronary artery disease.
The aim of the present study was to investigate the expression of a number of angiogenic factors such as VEGF, VEGF-C, TGF-alpha and apoptosis in an attempt to relate these biological markers to TNM ...staging, lymph-node status and prognosis. Angiogenic factors and apoptosis were studied immunohistochemically in 72 gastric cancer cases. The search for micrometastases was performed with an immunohistochemical technique in 20 NO cases. Apoptosis determination was assessed with the TUNEL assay. The chi2 test according to Pearson was used for statistical analysis. The apoptotic index was related to both stage and prognosis: high expression cases showed an earlier stage (p < 0.02) and a better prognosis (p < 0.05). The determination of high neovessel density was related to poorer 5-year survival (p < 0.05). Only the expression of VEGF-C correlated inversely with prognosis (p < 0.05). The presence of micrometastases was unrelated to any of the biological markers studied. Our results partly confirm those reported in the literature. The present study revealed a number of biological markers that may be helpful for identifying particular subgroups of patients. More investigation with similar techniques in large prospective series is needed as a support to clinical practice.
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