Angiogenesis and chronic kidney disease

The number of patients requiring renal replacement therapy due to end-stage renal disease (ESRD) is increasing worldwide. The prevalence of chronic kidney disease (CKD), and the importance of CKD as a risk factor in development of ESRD and in complicating cardiovascular disease (CVD) have been confirmed. In recent years, the involvement of angiogenesis-related factors in the progression of CKD has been studied, and the potential therapeutic effects on CKD of modulating these factors have been identified. Vascular endothelial growth factor (VEGF)-A, a potent pro-angiogenic factor, is involved in the development of the kidney, in maintenance of the glomerular capillary structure and filtration barrier, and in the renal repair process after injury. VEGF-A is also involved in the development of early diabetic nephropathy, demonstrated by the therapeutic effects of anti-VEGF-A antibody. Angiopoietin (Ang)-1 induces the maturation of newly formed blood vessels, and the therapeutic effects of Ang-1 in diabetic nephropathy have been described. In experimental models of diabetic nephropathy, the therapeutic effects of angiogenesis inhibitors, including angiostatin, endostatin and tumstatin peptides, the isocoumarin NM-3, and vasohibin-1, have been reported

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Biaxial flexural strength of Turkom-Cera core compared to two other all-ceramic systems

Advances in all-ceramic systems have established predictable means of providing metal-free aesthetic and biocompatible materials. These materials must have sufficient strength to be a practical treatment alternative for the fabrication of crowns and fixed partial dentures. OBJECTIVES: The aim of this study was to compare the biaxial flexural strength of three core ceramic materials. MATERIAL AND METHODS: Three groups of 10 disc-shaped specimens (16 mm diameter x 1.2 mm thickness - in accordance with ISO-6872, 1995) were made from the following ceramic materials: Turkom-Cera Fused Alumina [(Turkom-Ceramic (M) Sdn Bhd, Puchong, Selangor, Malaysia)], In-Ceram (Vita Zahnfabrik, Bad Säckingen, Baden-Württemberg, Germany) and Vitadur-N (Vita Zahnfabrik, Bad Säckingen, Baden-Württemberg, Germany), which were sintered according to the manufacturer's recommendations. The specimens were subjected to biaxial flexural strength test in an universal testing machine at a crosshead speed of 0.5 mm/min. The definitive fracture load was recorded for each specimen and the biaxial flexural strength was calculated from an equation in accordance with ISO-6872. RESULTS: The mean biaxial flexural strength values were: Turkom-Cera: 506.8±87.01 MPa, In-Ceram: 347.4±28.83 MPa and Vitadur-N: 128.7±12.72 MPa. The results were analyzed by the Levene's test and Dunnett's T3 post-hoc test (SPSS software V11.5.0 for Windows, SPSS, Chicago, IL, USA ) at a preset significance level of 5% because of unequal group variances (P<0.001). There was statistically significant difference between the three core ceramics (P<0.05). Turkom-Cera showed the highest biaxial flexural strength, followed by In-Ceram and Vitadur-N. CONCLUSIONS: Turkom-Cera core had significantly higher flexural strength than In-Ceram and Vitadur-N ceramic core materials

Temporal metabolomic responses of cultured HepG2 liver cells to high fructose and high glucose exposures

High fructose consumption has been implicated with deleterious effects on human health, including hyperlipidemia elicited through de novo lipogenesis. However, more global effects of fructose on cellular metabolism have not been elucidated. In order to explore the metabolic impact of fructose-containing nutrients, we applied both GC-TOF and HILIC-QTOF mass spectrometry metabolomic strategies using extracts from cultured HepG2 cells exposed to fructose, glucose, or fructose + glucose. Cellular responses were analyzed in a time-dependent manner, incubated in media containing 5.5 mM glucose + 5.0 mM fructose in comparison to controls incubated in media containing either 5.5 mM glucose or 10.5 mM glucose. Mass spectrometry identified 156 unique known metabolites and a large number of unknown compounds, which revealed metabolite changes due to both utilization of fructose and high-carbohydrate loads independent of hexose structure. Fructose was shown to be partially converted to sorbitol, and generated higher levels of fructose-1-phosphate as a precursor for glycolytic intermediates. Differentially regulated ratios of 3-phosphoglycerate to serine pathway intermediates in high fructose media indicated a diversion of carbon backbones away from energy metabolism. Additionally, high fructose conditions changed levels of complex lipids toward phosphatidylethanolamines. Patterns of acylcarnitines in response to high hexose exposure (10.5 mM glucose or glucose/fructose combination) suggested a reduction in mitochondrial beta-oxidation