Design and synthesis of novel organometallic complexes using boronated phenylalanine derivatives as potential anticancer agents

Drug design and discovery studies are important because of the prevalence of diseases without available medical cures. New anticancer agents are particularly urgent because of the high mortality rate associated with cancer. A series of mononuclear gold (III) and platinum (II) complexes based on boronated phenylalanine (BPA) were designed and synthesized using 4,4’-dimethyl-2,2’-dipyridyl (L1) or 1,10-phenanthroline-5,6-dion (L2) ligands to obtain promising anticancer drug candidates. Proton nuclear magnetic resonance, infrared, mass spectrometry, and elemental analyses were utilized for chemical characterizations. Cell viability, cancer cell colony formation, endothelial tube formation, and cytoskeleton staining assays were performed using A549 lung adenocarcinoma and human umbilical vein endothelial cells (HUVECs) to investigate preliminary pharmacological activities. L1-based platinum (II) complex (BPA-L1-Pt) was the most promising complex, and has similar activity with the approved chemotherapy drug cis-platinum. Half maximal inhibitory concentration values for BPA-L1-Pt were 9.15 µM on A549s and 16.61 µM on HUVECs; the values for cis-platinum were 5.24 µM on A549s and 23.14 µM on HUVECs. Consequently, further synthesis studies should be performed to boost the cancer cell selectivity feature of BPA by varying metal and ligand types.     

Surgery for Hepatolithiasis: Single Center Experience of 12 Patients

Hellenic Journal of Surgery - Hepatolithiasis is the presence of stones within the intrahepatic bile ducts, regardless of common bile duct and gallbladder stones. It is rarely seen in our country...     

Decreased dehydroepiandrosterone sulphate levels in adolescents with post-traumatic stress disorder after single sexual trauma

Background: Recent evidence shows that the hypothalamic–pituitary–adrenal (HPA) axis can be dysregulated in chronic sexual abuse victims with post-traumatic stress disorder (PTSD). We hypothesized that PTSD in adolescents exposed to a single sexual trauma may function as a chronic stressor leading to HPA-axis dysregulation. Aims: The objective of this study was to assess dehydroepiandrosterone sulphate (DHEA-S) and cortisol levels in female adolescents |with single sexual trauma-related PTSD compared to healthy controls. Method: We assessed 20 female adolescent (age 12–18) single sexual trauma victims with PTSD from the Ondokuz Mayis University Department of Child and Adolescent Psychiatry between December 2013 and December 2014. PTSD symptoms were assessed using the Child Depression Inventory (CDI) and Child Posttraumatic Stress Reaction Index (CPSRI). Blood cortisol and DHEA-S were measured in 20 female adolescent sexual abuse victims with PTSD and 20 healthy adolescents after 12-h fasting using the chemiluminescence method. Results: Compared to age-matched controls, female adolescent sexual abuse victims with PTSD had significantly lower DHEA-S levels (U = 70.00, Z = ? 3.517, p = 0.01, r = 0.55). There was also a significant negative correlation between DHEA-S and CDI scores (Spearman r = ? 0.522, p < 0.01). Conclusions: Decreased DHEA-S levels and correlation with depressive symptoms are evidence for a dysregulated HPA-axis in female adolescent single sexual trauma victims with PTSD. Further research is now recommended with large patient groups in order to maximize generalizations.     

The Clinical Features of Comorbid Pediatric Bipolar Disorder in Children with Autism Spectrum Disorder

The aim of this study was to describe clinical features of PBD comorbidity in children with ASD. Forty children with ASD and PBD aged 6–18 years, and 40 age- and sex-matched ASD subjects with no affective episodes were included in the study. Autism Behavior CheckList, Abberant Behavior CheckList, and Young Mania Rating Scale-Parent Version were completed. This study shows that PBD comorbidity in children with ASD involves a highly episodic course, with manic episodes, subsyndromal symptoms and interepisodic periods commonly being described in the manic symptom profile of these children. These findings need to be repeated with large samples, together with controlled studies concerning therapeutic interventions directed toward PBD comorbidity in children with ASD.     

MRI quantification techniques in fatty liver: the diagnostic performance of hepatic T1, T2, and stiffness measurements in relation to the proton density fat fraction

PURPOSENonalcoholic fatty liver disease (NAFLD) can progress to liver cirrhosis and is predicted to become the most frequent indication for liver transplantation in the near future. Noninvasive assessment of NAFLD is important for diagnosis and patient management. This study aims to prospectively determine the liver stiffness and T1 and T2 values in patients with NAFLD and to compare the diagnostic performance of magnetic resonance elastography (MRE) and mapping techniques in relation to the proton density fat fraction (PDFF).METHODSEighty-three patients with NAFLD and 26 participants with normal livers were imaged with a 1.5 T scanner. PDFF measurements obtained from the multiecho Dixon technique were used to quantify the liver fat. MRE, native T1 mapping (modified Look-Locker inversion recovery [MOLLI] schemes 5(3)3, 3(3)3(3)5, and 3(2)3(2)5 and the B1-corrected variable flip angle [VFA] method), and T2 mapping values were correlated with PDFF. The diagnostic performance of MRE and the mapping techniques were analyzed and compared.RESULTST1 values measured with the MOLLI schemes and the B1-corrected VFA (p < 0.001), and the stiffness values from MRE (p = 0.047) were significantly higher in the NAFLD group. No significant difference was found between the groups in terms of T2 values (p = 0.127). In differentiation of the NAFLD and control groups, the B1-corrected VFA technique had slightly higher accuracy and area under the curve (AUC) than the MOLLI schemes. In the NAFLD group, there was a good correlation between the PDFF, MOLLI 3(3)3(3)5 and 3(2)3(2)5, and VFA T1 measurements (r=0.732; r=0.735; r=0.716, p < 0.001, respectively).CONCLUSIONLiver T1 mapping techniques have the potential to distinguish steatotic from nonsteatotic livers, and T1 values seem to have a strong correlation with the liver fat content.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease, with an estimated worldwide prevalence of around 25% (1). It may range from simple steatosis, which is considered a benign condition, to nonalcoholic steatohepatitis (NASH), which can progress to fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. NAFLD is also known to be associated with metabolic syndrome, which is a risk factor for cardiovascular disease and type II diabetes mellitus (2–4).The gold standard method for diagnosing NAFLD and distinguishing its different patterns is a liver biopsy which has considerable limitations, including sampling errors, its invasive nature and associated complication risks, small sample size, and inter- and intraobserver variability (5, 6). These drawbacks constrain its utility for clinical monitoring and make it unsuitable as a screening method. Therefore, there is an urgent clinical need for an accurate noninvasive approach in the assessment of NAFLD. Accordingly, both the European Association for the Study of the Liver and the American Association for the Study of Liver Disease propose magnetic resonance imaging (MRI) as a noninvasive diagnostic tool for NAFLD (7, 8). Proton density fat fraction (PDFF)-based MRI and magnetic resonance spectroscopy (MRS) techniques are considered the most accurate noninvasive methods for the quantification of liver fat (9–12). The PDFF is accepted as a standardized biomarker of hepatic steatosis. Studies suggest that this biomarker is equivalent to the hepatic “signal fat fraction” (FF) after correcting all the confounding factors (13). However, PDFF measurement is not suitable for the assessment of any inflammation or fibrosis in NAFLD (13). On the other hand, recent studies have shown that other quantitative MRI techniques such as magnetic resonance elastography (MRE) and T1–T2 mapping can be useful in detecting hepatic inflammatory and fibrotic changes (14, 15–21). Thus, the application of a multiparametric MRI protocol might be helpful in liver tissue characterization and thereby in the risk stratification and therapeutic management of patients with NAFLD.In this prospective study, we aimed to determine liver stiffness and T1 and T2 values in patients with NAFLD and nonsteatotic subjects and compare the diagnostic performance of MRE and mapping techniques in relation to the FF.     

Effect of Recombinant Human Granulocyte/Macrophage Colony-Stimulating Factor on the Healing of Colonic Anastomosis in Rats

The purpose of this study was to investigate the efficacy of recombinant human granulocyte/macrophage colony-stimulating factor (rHuGM-CSF) on the wound healing of colonic anastomosis in rats. In total, 40 male Wistar rats were taken into this study. The control group (n = 20) received subcutaneous saline injection. The experiment group (n