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Journal Cover Karger Kompass
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   Full-text available via subscription Subscription journal
   ISSN (Print) 2296-0368 - ISSN (Online) 2296-0317
   Published by Karger Homepage  [101 journals]
  • Targeting HMGA2 in Retinoblastoma Cells in vitro Using the Aptamer
           Strategy
    • Abstract: High-mobility group A2 (HMGA2) protein regulates retinoblastoma (RB) cancer cell proliferation. Here, a stable phosphorothioate-modified HMGA2 aptamer was used to block HMGA2 protein function in RB cells. HMGA2-aptamer internalisation in RB cells (Y79, Weri Rb1) and non-neoplastic human retinal cells (MIO-M1) were optimised. Aptamer induced dose-dependent cytotoxicity in RB cancer cells (0.25-1.5 µM). Increased expression of TGFβ, SMAD4, CDH1, BAX, CASP 3, PARP mRNA and decreased SNAI1, Bcl2 mRNA levels in aptamer-treated RB cells suggests the activation of TGFβ-SMAD4-mediated apoptotic pathway. Synergistic effect with etoposide was observed in aptamer treated RB cells (p value ≤0.05). No significant toxicity was observed in non-neoplastic retinal cells.
      Ocul Oncol Pathol 2016;2:262-269
      PubDate: 2106-07-02T00:00:00+02:00
       
  • Coronary Artery Fistulas: Case Series and Literature Review
    • Abstract: Congenital coronary artery fistulas are rare anomalies. As coronary angiography and multidetector computed tomography have become more accessible, they have been increasingly used in the investigation of chest pain and heart failure. Coronary artery fistulas are often an incidental finding, which raises the question of how patients with this condition should be managed. Intervention with either transcatheter closure or surgical closure is often technically possible. Many patients are asymptomatic early after closure. However, follow-up studies have shown post-closure sequelae, such as residual leakage, thrombosis with or without myocardial infarction, and coronary stenosis. Therefore, there has been a shift from intervention towards watchful waiting in asymptomatic patients. In this article, we review the published literature on the natural history and treatment outcomes in individuals with coronary artery fistulas. We present case reports from our clinic and discuss the management of incidental findings of coronary artery fistulas.
      Cardiology 2017;136:93-101
      PubDate: 2017-08-30T00:00:00+02:00
       
  • Expression of Cyt-c-Mediated Mitochondrial Apoptosis-Related Proteins in
           Rat Renal Proximal Tubules during Development
    • Abstract: Background: Apoptosis regulates embryogenesis, organ metamorphosis and tissue homeostasis. Mitochondrial signaling is an apoptotic pathway, in which Cyt-c and Apaf-1 are transformed into an apoptosome, which activates procaspase-9 and triggers apoptosis. This study evaluated Cyt-c, Apaf-1 and caspase-9 expression during renal development. Methods: Kidneys from embryonic (E) 16-, 18-, and 20-day-old fetuses and postnatal (P) 1-, 3-, 5-, 7-, 14-, and 21-day-old pups were obtained. Immunohistochemical analysis, dual-labeled immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) technique assay and Western blot were performed in addition to histological analysis. Results: Immunohistochemistry showed that Cyt-c was strongly expressed in proximal and distal tubules (DTs) at all time points. Caspase-9 and Apaf-1 were strongly expressed in proximal tubules (PTs) but only weakly expressed in DTs. Dual-labeled immunofluorescence showed that most tubules expressed both Cyt-c and Apaf-1, except for some tubules that only expressed Cyt-c. The TUNEL assay showed a greater percentage of apoptotic cells in PTs compared to DTs. Apaf-1 and cleaved caspase-9 protein expression gradually increased during the embryonic period and peaked during the early postnatal period but apparently declined from P7. Cyt-c protein expression was weak during the embryonic period but obviously increased after P1. Conclusion: This study showed that PTs are more sensitive to apoptosis than DTs during rat renal development, even though both tubule segments contain a large number of mitochondria. Furthermore, Cyt-c-mediated mitochondrial apoptosis-related proteins play an important role in PTs during the early postnatal kidney development.
      Nephron
       
  • Circulating CXCL16 in Diabetic Kidney Disease
    • Abstract: Background/Aims: Chronic kidney disease and, specifically, diabetic kidney disease, is among the fastest increasing causes of death worldwide. A better understanding of the factors contributing to the high mortality may help design novel monitoring and therapeutic approaches. CXCL16 is both a cholesterol receptor and a chemokine with a potential role in vascular injury and inflammation. We aimed at identifying predictors of circulating CXCL16 levels in diabetic patients with chronic kidney disease. Methods: We have now studied plasma CXCL16 in 134 European patients with diabetic kidney disease with estimated glomerular filtration rate (eGFR) categories G1-G4 and albuminuria categories A1-A3, in order to identify factors influencing plasma CXCL16 in this population. Results: Plasma CXCL16 levels were 4.0±0.9 ng/ml. Plasma CXCL16 increased with increasing eGFR category from G1 to G4 (that is, with decreasing eGFR values) and with increasing albuminuria category. Plasma CXCL16 was higher in patients with prior cardiovascular disease (4.33±1.03 vs 3.88±0.86 ng/ml; p=0.013). In multivariate analysis, eGFR and serum albumin had an independent and significant negative correlation with plasma CXCL16. Conclusion: In diabetic kidney disease patients, GFR and serum albumin independently predicted plasma CXCL16 levels.
      Kidney Blood Press Res 2016;41:663-671
       
  • Tissue Engineering and Regenerative Medicine - New Initiatives for
           Individual Treatment Offers
    • Abstract:
      Transfus Med Hemother 2016;43:318-319
       
  • Cardio-Renal Syndrome Type 4: The Correlation Between Cardiorenal
           Ultrasound Parameters
    • Abstract: Bakground/Aims: Cardiovascular diseases represent the leading causes of morbidity and mortality in patients with cronich kidney disease (CKD). The pathogenesis includes a complex, bidirectional interaction between heart and kidney termed cardiorenal syndrome type 4. The aim of study was to evaluate the association between renal and cardiovascular ultrasonographic parameters and identify early markers of cardiovascular risk. Methods: A total of 35 patients with CKD and 25 healthy controls, were enrolled and we have evaluated inflammatory indexes, mineral metabolism, renal function, renal and cardiovascular ultrasonographic parameters. Results: Tricuspid anular plane systolic excursion (TAPSE) and estimated pulmonary artery systolic pressure (ePAPs) showed a statistically significant difference between CKD patients and healthy controls (p
       
  • Subtelomeric Copy Number Variations: The Importance of 4p/4q Deletions in
           Patients with Congenital Anomalies and Developmental Disability
    • Abstract: The most prevalent structural variations in the human genome are copy number variations (CNVs), which appear predominantly in the subtelomeric regions. Variable sizes of 4p/4q CNVs have been associated with several different psychiatric findings and developmental disability (DD). We analyzed 105 patients with congenital anomalies (CA) and developmental and/or intellectual disabilities (DD/ID) using MLPA subtelomeric specific kits (P036 /P070) and 4 of them using microarrays. We found abnormal subtelomeric CNVs in 15 patients (14.3%), including 8 patients with subtelomeric deletions at 4p/4q (53.3%). Additional genomic changes were observed at 1p36, 2q37.3, 5p15.3, 5q35.3, 8p23.3, 13q11, 14q32.3, 15q11.2, and Xq28/Yq12. This indicates the prevalence of independent deletions at 4p/4q, involving PIGG, TRIML2, and FRG1. Furthermore, we identified 15 genes with changes in copy number that contribute to neurological development and/or function, among them CRMP1, SORCS2, SLC25A4, and HELT. Our results highlight the association of genes with changes in copy number at 4p and 4q subtelomeric regions and the DD phenotype. Cytogenomic characterization of additional cases with distal deletions should help clarifying the role of subtelomeric CNVs in neurological diseases.
      Cytogenet Genome Res
       
  • Lesch-Nyhan Syndrome: Models, Theories, and Therapies
    • Abstract: Lesch-Nyhan syndrome (LNS) is a rare X-linked disorder caused by mutations in HPRT1, an important enzyme in the purine salvage pathway. Symptoms of LNS include dystonia, gout, intellectual disability, and self-mutilation. Despite having been characterized over 50 years ago, it remains unclear precisely how deficits in hypoxanthine and guanine recycling can lead to such a profound neurological phenotype. Several studies have proposed different hypotheses regarding the etiology of this disease, and several treatments have been tried in patients, though none have led to a satisfactory explanation of the disease. New technologies such as next-generation sequencing, optogenetics, genome editing, and induced pluripotent stem cells provide a unique opportunity to map the precise sequential pathways leading from genotype to phenotype.
      Mol Syndromol
       
  • A Randomized Trial on the Efficacy of Topical Anesthesia for Pain
           Reduction during Frame Placement for Gamma Knife Radiosurgery
    • Abstract: Background/Aims: Frame application for gamma knife radiosurgery (GKR) may be perceived as painful by patients. This study was designed to assess the efficacy of EMLA (2.5% lidocaine/2.5% prilocaine) in pain reduction. Methods: This was a prospective, randomized, and controlled trial approved by our institutional review board. Fifty-four patients undergoing outpatient GKR were divided into EMLA and placebo groups. Prior to frame placement, EMLA/placebo was applied to the patient's forehead. A visual analog scale (VAS) was used to measure pain during 4 intervals: frontal injections, occipital injections, frontal screw insertion, and overall discomfort. This study was designed to observe a difference of 1.0 on the VAS at a power of 95%. Results: VAS for EMLA versus placebo for frontal injections (5.2 ± 2.7 vs. 5.7 ± 2.0, respectively; p < 0.45), back injections, (6.5 ± 2.2 vs. 5.9 ± 2.3, respectively; p < 0.30), frontal pins (4.6 ± 2.7 vs. 4.6 ± 2.2, respectively; p < 0.99), and overall discomfort (p < 0.29) were not significantly different. A comparison between back and frontal injections for EMLA (6.54 vs. 5.19, respectively; p < 0.16) and placebo (5.89 vs. 5.68, respectively; p < 0.69) showed no significant difference between group and location (p < 0.21). Conclusion: Application of EMLA did not significantly reduce pain when used preoperatively for frame fixation. EMLA is no longer used as part of our routine for patients undergoing GKR.
      Stereotact Funct Neurosurg 2016;94:259-264
       
  • The Cross-Link between Adipokines, Insulin Resistance and Obesity in
           Offspring of Diabetic Pregnancies
    • Abstract: Background/Aims: Intrauterine exposure to hyperglycemia might impact the risk for future metabolic deteriorations. The aim was to characterize the association between different adipokines and neuropeptides and insulin resistance and BMI-SDS in children affected by diabetes during pregnancy. Methods: 76 children (mean age: 6 years, male:female = 36:40) born to mothers with gestational or pregestational diabetes and nondiabetic women were consecutively included for clinical assessments comprising anthropometrics and metabolic characterization [2-hour glucose tolerance test, leptin, peptide YY (PYY), neuropeptide Y (NPY), ghrelin, growth differentiation factor 15 (GDF-15), and adiponectin]. Results: The level of insulin resistance was associated with BMI-SDS (p < 0.001), leptin (p < 0.001), ghrelin (p = 0.002), age (p < 0.002) and negatively with GDF-15 (p = 0.005). BMI-SDS, leptin and GDF-15 were shown to have independent effects on insulin resistance by using a multiple regression model (additionally including age, and maternal diabetes status), whereas ghrelin lost significance (p = 0.345). No differences were present in adipokines and insulin resistance when children were evaluated by maternal glucometabolic status. However, we observed more strengthened associations between insulin resistance and covariates BMI-SDS and leptin in offspring of diabetic pregnancies. Conclusions: Young children with elevated BMI or leptin are affected by higher indices of insulin resistance, particularly those who were born to mothers with diabetes during pregnancy. The impact of this special risk constellation should be considered in future studies.
      Horm Res Paediatr
       
 
 
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