Growth hormone secretagogue receptor signalling affects high‐fat intake independently of plasma levels of ghrelin and LEAP2, in a 4‐day binge eating model

The growth hormone secretagogue receptor (GHSR) is a G protein‐coupled receptor that is highly expressed in the central nervous system. GHSR acts as a receptor for ghrelin and for liver‐expressed antimicrobial peptide 2 (LEAP2), which blocks ghrelin‐evoked activity. GHSR also displays ligand‐independent activity, including a high constitutive activity that signals in the absence of ghrelin and is reduced by LEAP2. GHSR activity modulates a variety of food intake‐related behaviours, including binge eating. Previously, we reported that GHSR‐deficient mice daily and time‐limited exposed to a high‐fat (HF) diet display an attenuated binge‐like HF intake compared to wild‐type mice. In the present study, we aimed to determine whether ligand‐independent GHSR activity affects binge‐like HF intake in a 4‐day binge‐like eating protocol. We found that plasma levels of ghrelin and LEAP2 were not modified in mice exposed to this binge‐like eating protocol. Moreover, systemic administration of ghrelin or LEAP2 did not alter HF intake in our experimental conditions. Interestingly, we found that central administration of LEAP2 or K‐(D‐1‐Nal)‐FwLL‐NH₂, which are both blockers of constitutive GHSR activity, reduced binge‐like HF intake, whereas central administration of ghrelin or the ghrelin‐evoked GHSR activity blockers [D‐Lys3]‐GHRP‐6 and JMV2959 did not modify binge‐like HF intake. Taken together, current data indicate that GHSR activity in the brain affects binge‐like HF intake in mice independently of plasma levels of ghrelin and LEAP2.     

Bypass Surgery or Stenting for Left Main Coronary Artery Disease in Patients With Diabetes

Background

The randomized EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial reported a similar rate of the 3-year composite primary endpoint of death, myocardial infarction (MI), or stroke in patients with left main coronary artery disease (LMCAD) and site-assessed low or intermediate SYNTAX scores treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Whether these results are consistent in high-risk patients with diabetes, who have fared relatively better with CABG in most prior trials, is unknown.

Pro-Inflammatory Diet Is Associated with Adiposity during Childhood and with Adipokines and Inflammatory Markers at 11 Years in Mexican Children

There is limited evidence about the inflammatory potential of diet in children. The aim of this study was to evaluate the association between the Children’s Dietary Inflammatory Index (C-DII) from 5 to 11 years with adiposity and inflammatory biomarkers in Mexican children. We analyzed 726 children from a birth cohort study with complete dietary information and measurements to evaluate adiposity at 5, 7 and 11 y and 286 children with IL-6, hsCRP, leptin and adiponectin information at 11 y. C-DII trajectories were estimated using latent class linear mixed models. We used linear mixed models for adiposity and logistic and multinomial regression for biomarkers. In girls, each one-point increase in C-DII score was associated with greater adiposity (abdominal-circumference 0.41%, p = 0.03; skinfold-sum 1.76%, p = 0.01; and BMI Z-score 0.05, p = 0.01). At 11 y the C-DII was associated with greater leptin (34% ≥ 13.0 ng/mL, p = 0.03) and hsCRP concentrations (29% ≥ 3.00 mg/L, p = 0.06) and lower adiponectin/leptin ratio (75% < 2.45, p = 0.02). C-DII trajectory 3 in boys was associated with a 75.2% (p < 0.01) increase in leptin concentrations and a 37.9% decrease (p = 0.02) in the adiponectin/leptin ratio. This study suggests that the inflammatory potential of diet may influence adiposity in girls and the homeostasis of adipose tissue and chronic subclinical inflammation in 11-year-old children.     

A comparative study of the lipids of plasma membranes of normal cells and those infected and transformed by rous sarcoma virus

Comparative studies of the phospholipids of Rous sarcoma virus (RSV)-transformed chicken embryo cells, uninfected normal cells, and cells infected but not transformed by the transformation-defective mutant of RSV td105, were done. Phospholipids of whole cells as well as those of isolated plasma membranes were analyzed by thin-layer and gas-liquid chromatography. The plasma membrane preparations used were significantly enriched in 5′-nucleotidase enzyme activity over that of whole cell homogenates. Our results indicated that transformation by RSV and infection by td105 do not significantly alter the molar ratios of the various phospholipids compared to uninfected normal cells. However, comparison of the fatty acyl chains of total phospholipid as well as isolated specific phospholipids revealed that the phospholipids of transformed cells have higher percentages of unsaturated fatty acyl chains than those of uninfected normal cells; phosphatidylethanolamine (PE), phosphatidylinositol (PI), and sphingomyelin (SP) have higher percentages of unsaturated fatty acyl chains, while phosphatidylcholine (PC) and phosphatidylserine (PS) remained unchanged. The percentages of unsaturated fatty acyl chains of PE and PI of td 105-infected cells increased, while that of PC and PS decreased resulting in no overall change. These results are consistent with the concept that altered fluidity of membranes of transformed cells is due to the selection of phospholipids with specific fatty acyl chains by new or modified proteins incorporated into the membranes of transformed and/or virus-producing cells.     

Modified transurethral resection of the prostate for the management of BPH-related refractory lower urinary tract symptoms in patients with a history of pelvic fracture urethral injury reconstruction

International Urology and Nephrology - To evaluate the impact of a modified transurethral resection of prostate (mTURP) in patients with a history of pelvic fracture urethral injury (PFUI) status...     

C-kit expression in human osteosarcoma and in vitro assays

Biologic agents targeting oncogenes have encourage researchs trying to correlate the role of tyrosine kinase in the pathogenesis of tumours. Osteosarcoma is a high grade aggressive neoplasm with poor survival. Our aim was to investigate c-kit immunoexpression, its prognostic relevance for patients with osteosarcoma, and the effect of imatinib mesylate (STI571) on proliferation and invasion of the human osteosarcoma cell line.A retrospective immu-nohistochemical study was performed on archival formalin-fixed paraffin-embedded specimens from 52 patients with high-grade primary osteosarcoma of extremities treated at the Pediatric Oncology Institute (IOP, GRAAC) and archived in the Department of Pathology, Federal University of São Paulo. Only pre-chemotherapy specimens were analyzed. Strongly stained cytoplasm and membrane cells were taken as positive. Human osteosarcoma cells from line MG-63 were incubated and the inhibitory effect of imatinib mesylate (STI571) on cell proliferation and invasion was studied. In 24 cases (46.15%), c-kit was expressed by the cells and c-kit-positive tumors exhibited lower necrosis post-chemotherapy. No correlation was found between c-kit expression and overall and disease-free survival. Imatinib mesylate decreased the rates of cell growth of osteosarcoma cells in low doses and invasion in high doses C-kit-positive tumors had worse response to chemotherapy and imatinib mesylate can play a role in blocking or decreasing the rate of growth of osteosarcoma cells, but not the invasive capacity of these neoplastic cells. These data suggested that imatinib mesylate could be a therapeutic target of strategies against osteosarcoma tumors. Further studies are necessary to confirm this indication.