High Pressure Assisted Coronary Stent Implantation Accomplished Without Intravascular Ultrasound Guidance and Subsequent Anticoagulation

AbstractObjectives. The purpose of this study was to determine the efficacy of treatment with antiplatelet therapy and no anticoagulation after high pressure assisted coronary stent implantation performed without intravascular ultrasound (IVUS) guidance.Background. Previous studies have shown that during IVUS-guided Palmaz-Schatz coronary stenting, it is safe to withhold anticoagulation when stent expansion has been optimized by high pressure balloon dilation.Methods. Patients that had successful coronary stenting without IVUS guidance were treated with ticlopidine, 500 mg/day, and aspirin, 325 mg/day, for 1 month and then received only aspirin, 325 mg/day, indefinitely. Patients were not treated with warfarin (Coumadin) or heparin after successful stenting. Clinical and angiographic events were assessed at 1 month.Results. A total of 201 intracoronary stents were implanted in 127 patients with 137 lesions. The average number of stents per lesion was 1.4 ± 0.8, and the average number of stents per patient was 1.6 ± 1.1. Stent deployment was performed for elective indications in 79% of procedures and for emergency indications in 21%. There were four stent thrombosis events for a per patient event rate of 3.1% and a per lesion event rate of 2.9%.Conclusions. After high pressure assisted stenting performed without IVUS guidance, there was an acceptable incidence of 3.1% of stent thrombosis with the combination of short-term ticlopidine and aspirin therapy and no anticoagulation. Although the study involved only 127 patients, the results support the relative safety of stenting without IVUS guidance and with antiplatelet therapy only in comparison to historical trials on stenting performed with postprocedure anticoagulation.(J Am Coll Cardiol 1977;29:21–7)

Insulin-like Growth Factor II mRNA-Binding Protein 1 Regulates Pancreatic Cancer Cell Growth through the Surveillance of CDC25A mRNA

: A number of data indicate that the sources of different kinds of PDAC may be discovered at the transcription/transduction stage. RNA metabolism is manipulated at various steps by different RNA-binding proteins (RBPs), and the deregulation or irregular activity of RBPs is known to contribute to tumor promotion and progression. The insulin-like growth factor 2 mRNA-binding protein family (IMPs), and IMP1 in particular, has been linked with a poor prognosis in PDAC patients; however, little is known about its contribution in PDAC carcinogenesis. In this study, we investigated the function of IMP1 in PDAC. To evaluate IMP1 expression and correlation with PDAC prognosis, we utilized several public databases. Using a specific siRNA IMP1, we analyzed cell death and cell cycle progression in PDAC cell lines and 3D spheroids. the role of IMP1 was also evaluated in vivo in a panc-1-derived tumor xenograft murine model. Public data suggest that PDAC patients with higher expression of IMP1 showed poor overall and progression-free survival. IMP1 silencing leads to reduced cell growth in PDAC cells and three-dimensional spheroids. Abrogation of IMP1 in PDAC cells showed lower levels of CDC25A, increased phosphorylation of the cyclin-dependent kinase (CDK)2, and accumulation of PDAC cells in the G1 phase. immunoprecipitation experiments revealed that IMP1 binds CDC25A mRNA, thus controlling cell-cycle progression. Ultimately, we proved that suppression of IMP1 blocked in vivo growth of Panc-1 transferred into immunodeficient mice. Our results indicate that IMP1 drives the PDCA cell cycle and represents a novel strategy for overcoming PDCA cell proliferation

Dysphagia: An unusual presentation of giant aneurysm of the right coronary artery and supravalvular aortic stenosis in Williams syndrome

Digitalitzat per Artypla

321. Sea Urchin sns Chromatin Insulator Prevents Silencing and Positional Effect Variegation of Oncoretroviral Vectors Transgene Expression in Murine Erythroid Cell Line

Silencing and position effect are considered significant obstacles to obtain a consistent level of transgene expression in viral gene therapy. Furthermore recent studies had shown that retroviruses tend to land on active genes with the potential consequence of insertional mutagenesis. The inclusion of elements, such as chromatin insulators, capable to insulate a gene from the surrounding chromatin effects at the integration site should improve both efficacy and safety of gene therapy vectors. We have previously characterized a 265 bp insulator element, termed sns, localized at the 3' end of the early histone H2A gene of the sea urchin Paracentrotus lividus. This sequence contains three cis-acting elements (Box A, Box B, and Box C+T) all needed for the enhancer blocking activity in both sea urchin and human cells. By colony assays, in human (K562) and mouse (Mel) erythroid cell lines, we have recently demonstrated that the sns insulator displays directional enhancer-blocking activity in that it interferes with the communication between the human beta-globin enhancer (LCR) and the gamma-globin promoter. By electrophoretic mobility shift assays (EMSA) we found bindings of sns insulator with the erythroid specific GATA1 and the ubiquitous Oct1, and Sp1 transcription factors

Rare case of an adrenocortical neoplasm: A case report and review of literature

Adrenocortical neoplasms (ACNs) are rare and poorly characterized in infants. The true incidence of ACNs is not well known and it appears to vary substantially across different geographical areas. ACNs are more common in females and two peaks of incidence have been identified: The first year of life and between the age of nine and 16 years. Due to the heterogeneity and rarity of ACNs, their pathological and prognostic classification is challenging. The current study describes the case of a seven‑year‑old male, who presented to the Department of Pediatric Surgery, University of Siena (Siena, Italy) with a feminization syndrome and increased somatic growth that was associated with a unilateral adrenal mass, which was diagnosed by magnetic resonance imaging. Surgical excision of the mass was performed and histological analysis determined that it was an ACN, with a low risk of malignity; however, the pathological classification of the tumor was challenging. At present, the future behavior of ACNs is unpredictable. Therefore, increasing the knowledge surrounding this type of tumor may aid in its diagnosis, treatment and prognosis. Due to the rarity of pediatric ACNs, no single pediatric oncology center has acquired extensive experience treating this type of tumor. Thus, the initiation of an international tumor registry may aid with the management of patients presenting with ACN

Smad7 Sustains Stat3 Expression and Signaling in Colon Cancer Cells

: Colorectal cancer (CRC) cells contain elevated levels of active signal transducer and the activator of transcription (Stat)-3, which exerts proliferative and anti-apoptotic effects. Various molecules produced in the CRC tissue can activate Stat3, but the mechanisms that amplify such an activation are yet to be determined. In this paper, we assessed whether Smad7, an inhibitor of Transforiming Growth Factor (TGF)-β1 activity, sustains Stat3 expression/activation in CRC cells. Both Smad7 and phosphorylated (p)/activated-Stat3 were more expressed in the tumoral areas of CRC patients, compared to the normal adjacent colonic mucosa of the same patients, and were co-localized in primary CRC cells and CRC cell lines. The knockdown of Smad7 with a Smad7 antisense oligonucleotide (AS) reduced p-Stat3 in both unstimulated and interleukin (IL)-6- and IL-22-stimulated DLD-1 and HCT116 cells. Consistently, reduced levels of BCL-xL and survivin, two downstream signaling targets of Stat3 activation, were seen in Smad7 AS-treated cells. An analysis of the mechanisms underlying Smad7 AS-induced Stat3 inactivation revealed that Smad7 AS reduced Stat3 RNA and protein expression. A chromatin immunoprecipitation assay showed the direct regulatory effect of Smad7 on the Stat3 promoter. RNA-sequencing data from the Tumor, Normal and Metastatic (TNM) plot database showed a positive correlation between Smad7 and Stat3 in 1450 CRC samples. To our knowledge, this is the first evidence supporting the theory that Smad7 positively regulates Stat3 function in CRC

The Sea Urchin sns5 Chromatin Insulator Improves the Likelihood of Lentiviral Vectors in Erythroid Milieu By Organizing an Independent Chromatin Domain at the Integration Site

Retroviral vectors are currently the most suitable vehicles for therapeutic gene transfer in hematopoietic stem cells. However, these vectors are known to integrate rather randomly throughout the genome, suffering the so called chromosomal position effects (PE). Such a critical occurrence most probably depends upon the ability of heterochromatin to spread in the inserted vector sequences. Moreover, the use of transgenes imply genotoxicity effects, since the cis-regulatory sequences harbored by the vector can disturb the proper transcription of the resident genes neighboring the integration site, potentially leading to malignant transformation. Due to their enhancer blocker activity, the incorporation of chromatin insulators in flanking position to the transferred unit can reduce the mentioned dangerous effects. Moreover, by acting as barriers to the spread of heterochromatin, chromatin insulators can also mitigate vector silencing. We have previously shown that the sea urchin sns5 chromatin insulator activity is conserved in mouse and human erythroid milieu: it blocks the βglobin-LCR-HS2 enhancer/globin promoter interaction when placed between them. In addition, when placed in flanking location of a γ-retrovirus vector, sns5 impedes PE variegation and improves vector-specific expression following integration in the erythroid genome. Importantly, by binding both erythroid-specific and ubiquitous factors, sns5 favors the accumulation inside the provirus locus of epigenetic marks commonly associated to an euchromatic state (Acuto S. et al., BCMD 2005; D'Apolito D. et al., 2009; Di Caro D. et al., J Mol Biol 2004; Cavalieri V. et al., NAR 2009). In this study we extend these findings, demonstrating that sns5 works as chromatin insulator also when placed in flanking position of a GFP transgene contained in a lentivirus vector (LV-GFP). A large panel of mouse erythroleukemic clones (MELC) was generated after transduction with uninsulated and sns5 -insulated LV-GFP. Individual clones were screened for single vector integrants (by Q-PCR), and for GFP-expression (by cytofluorimetry). Our results shown that the inclusion of the sns5 element in a forward orientation increased the fraction of vector expressing cells (89% for the insulated vector vs 42% for the uninsulated ones). The clonal variegation of expression, assessed as frequency of clones that showed a percentage of GFP-negative cells in the progeny, decreased in clones transduced with the insulated vectors (7.4% vs 13,9%). It has been suggested that chromatin insulators could shape the architecture of topologically independent chromosome domains. High resolution mapping of chromosomal domains in drosophila and higher eukaryotes highlighted that chromatin insulators play a critical role in shaping the architectural genome organization both in a local chromosome environment and in long range chromosomal interaction. Intriguingly, by using the Chromosome Conformation Capture (3C) technology, we demonstrated that the sns5 -flanked LV-GFP integrated at a single copy in the erythroid cell genome is organized into an independent chromatin loop at the integration site. Worth to mention, no looping was detected in the absence of sns5, indicating that the two flanking copies of sns5 are specifically involved in the reorganization of the chromatin structure at the provirus locus. In conclusion our results not only confirm the conserved and striking boundary function of sns5, but also provide a new clue concerning the molecular mechanism that allows this function to occur. On these basis, our findings reassure the use of sns5 to improve both efficacy and safety of lentiviral vectors for gene therapy

Long-Term Follow-Up of Testicular Microlithiasis in Children and Adolescents: Multicenter Prospective Cohort Study of the Italian Society of Pediatric Urology.

Introduction Testicular microlithiasis (TM), characterized by the presence of intratubular calcifications in a single or both the gonads, is an uncommon entity with unknown etiology and outcome in pediatric and adolescent age. In this study, the results of a multicenter long-term survey are presented. Materials and Methods From 11 units of pediatric urology/surgery, patients with TM were identified and yearly, followed up in a 7-year period, adopting a specific database. The recorded items were: age at diagnosis, presenting symptoms/associated abnormalities, ultrasonographic finding, surgery and histology at biopsy, if performed. Results Out of 85 patients, 81 were evaluated yearly (4 patients lost to follow-up). TM was bilateral in 66.6% of the patients. Associate genital abnormalities were present in 90%, more frequently undescended/retractile testis (23.4%) and varicocele (22.2%). TM remained unchanged at 4.7 years follow-up in 77 patients (93.8%) and was reduced in 4 patients after 1 to 5 years of inguinoscrotal surgery. Orchiectomy was performed in three patients (3.7%), one for severe testicular hypoplasia and two for seminoma (2.5%), respectively, concurrent and metachronous to diagnosis of TM. Tumorectomy with parenchymal sparing surgery was performed in a teratoma associated with TM. Conclusion TM is a controversial entity, often associated with several inguinogenital features, which rarely can recover. Testicular malignancy, although present in TM, has not proven definitively associated to microliths. Proper counseling, yearly ultrasound, and self-examination are long-term recommended

Bright light exposure reduces TH-positive dopamine neurons: Implications of light pollution in Parkinson\u27s disease epidemiology

This study explores the effect of continuous exposure to bright light on neuromelanin formation and dopamine neuron survival in the substantia nigra. Twenty-one days after birth, Sprague–Dawley albino rats were divided into groups and raised under different conditions of light exposure. At the end of the irradiation period, rats were sacrificed and assayed for neuromelanin formation and number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. The rats exposed to bright light for 20 days or 90 days showed a relatively greater number of neuromelanin-positive neurons. Surprisingly, TH-positive neurons decreased progressively in the substantia nigra reaching a significant 29% reduction after 90 days of continuous bright light exposure. This decrease was paralleled by a diminution of dopamine and its metabolite in the striatum. Remarkably, in preliminary analysis that accounted for population density, the age and race adjusted Parkinson's disease prevalence significantly correlated with average satellite-observed sky light pollution

Bright light exposure reduces TH-positive dopamine neurons: implications of light pollution in Parkinson's disease epidemiology.

This study explores the effect of continuous exposure to bright light on neuromelanin formation and dopamine neuron survival in the substantia nigra. Twenty-one days after birth, Sprague-Dawley albino rats were divided into groups and raised under different conditions of light exposure. At the end of the irradiation period, rats were sacrificed and assayed for neuromelanin formation and number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. The rats exposed to bright light for 20 days or 90 days showed a relatively greater number of neuromelanin-positive neurons. Surprisingly, TH-positive neurons decreased progressively in the substantia nigra reaching a significant 29% reduction after 90 days of continuous bright light exposure. This decrease was paralleled by a diminution of dopamine and its metabolite in the striatum. Remarkably, in preliminary analysis that accounted for population density, the age and race adjusted Parkinson's disease prevalence significantly correlated with average satellite-observed sky light pollution