Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

Growing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5' phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as α-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer

The corporate brand and strategic direction: Senior business school managers’ cognitions of corporate brand building and management

This revelatory study focuses on top Financial Times (FT) ranked British business school managers cognitions of corporate brand building and management. The study insinuates there is a prima facie bilateral link between corporate branding and strategic direction. Among this genus of business school, the data revealed corporate brand building entailed an on-going concern with strategic management, stakeholder management, corporate communications, service focus, leadership, and commitment. These empirical findings, chime with the early conceptual scholarship on corporate brand management dating back to the mid-1990s. These foundational articles stressed the multi-disciplinary and strategic nature of corporate brand management and stressed the significant role of the CEO. As such, this research adds further credence to the above in terms of best-practice vis-à-vis corporate brand management. Curiously, whilst senior managers espouse a corporate brand orientation, corporate brand management is seemingly not accorded a similar status in the curriculum. Drawing on general embedded case study methodological approach, data was collected within eight leading (FT-ranked) business schools in Great Britain at Oxford, Cambridge, Durham, Bradford, Cranfield, Warwick, Lancaster and City (London) Universities. Each of these eight British business schools can be deemed as ‘top’ business schools by virtue of their inclusion in the influential Financial Times (FT) worldwide list of top business schools. The primary mode of qualitative data collection was the 37 in-depth interviews with business school Deans, Associate Deans and other senior faculty members and other managers

From global to local: reshoring for sustainability

The UK clothing industry has seen the extensive offshoring of manufacturing, which has created fragmented global supply chains; these present a range of supply issues and challenges, including many related to sustainability. Reshoring is a reversion of a previous offshoring decision, thereby ‘bringing manufacturing back home’ (Gray et al. J Supply Chain Management 49(2):27–33, 2013), and can be motivated by increased costs and supply management problems. While not a new phenomenon, the reshoring of activities is growing in practice and there is an imperative for academic research (Fratocchi et al. J Purch Supply Manag 20:54–59, 2014). Through an in-depth longitudinal case study, this paper explores how sustainability can be addressed through reshoring; the studied UK-based clothing SME has strong principles and is explicitly committed to bringing its supply chain ‘home’. There is a recognised need for more OM research using a social lens (Burgess and Singh Oper Manag Res 5:57–68, 2012), so Social Network Theory (SNT) is employed to examine the reshoring decision-making process. SNT applies a relational, qualitative approach to understand the interactions between network actors, and focuses on the types and strengths of relationships and how they provide context for decisions (Galaskiewicz J Supply Chain Manag 47(1):4–8, 2011). The findings demonstrate the importance of socially complex, long-term relationships in managing a sustainable supply network. These relationships contribute to the resources that a firm can harness in its supply practices, and SNT extends this with its emphasis on the strength of ties with suppliers, and the trust, reciprocity and shared meanings it engenders. For the studied firm these advantages are derived through its localised supply chain, and collaborative supplier relationships, and its progressive reshoring of activities is integral to achieving its sustainability principles

Nutraceutical therapies for atherosclerosis

Atherosclerosis is a chronic inflammatory disease affecting large and medium arteries and is considered to be a major underlying cause of cardiovascular disease (CVD). Although the development of pharmacotherapies to treat CVD has contributed to a decline in cardiac mortality in the past few decades, CVD is estimated to be the cause of one-third of deaths globally. Nutraceuticals are natural nutritional compounds that are beneficial for the prevention or treatment of disease and, therefore, are a possible therapeutic avenue for the treatment of atherosclerosis. The purpose of this Review is to highlight potential nutraceuticals for use as antiatherogenic therapies with evidence from in vitro and in vivo studies. Furthermore, the current evidence from observational and randomized clinical studies into the role of nutraceuticals in preventing atherosclerosis in humans will also be discussed

Amiodarone disrupts cholesterol biosynthesis pathway and causes accumulation of circulating desmosterol by inhibiting 24-dehydrocholesterol reductase

Background We have earlier reported that amiodarone, a potent and commonly used antiarrhythmic drug increases serum desmosterol, the last precursor of cholesterol, in 20 cardiac patients by an unknown mechanism. Objective Here, we extended our study to a large number of cardiac patients of heterogeneous diagnoses, evaluated the effects of combining amiodarone and statins (inhibitors of cholesterol synthesis at the rate-limiting step of hydroxy-methyl-glutaryl CoA reductase) on desmosterol levels and investigated the mechanism(s) by which amiodarone interferes with the metabolism of desmosterol using in vitro studies. Methods and Results We report in a clinical case-control setting of 236 cardiac patients (126 with and 110 without amiodarone treatment) that amiodarone medication is accompanied by a robust increase in serum desmosterol levels independently of gender, age, body mass index, cardiac and other diseases, and the use of statins. Lipid analyses in patient samples taken before and after initiation of amiodarone therapy showed a systematic increase of desmosterol upon drug administration, strongly arguing for a direct causal link between amiodarone and desmosterol accumulation. Mechanistically, we found that amiodarone resulted in desmosterol accumulation in cultured human cells and that the compound directly inhibited the 24-dehydrocholesterol reductase (DHCR24) enzyme activity. Conclusion These novel findings demonstrate that amiodarone blocks the cholesterol synthesis pathway by inhibiting DHCR24, causing a robust accumulation of cellular desmosterol in cells and in the sera of amiodarone-treated patients. It is conceivable that the antiarrhythmic potential and side effects of amiodarone may in part result from inhibition of the cholesterol synthesis pathway.Peer reviewe

Accumulation of 99mTc-low-density lipoprotein in human malignant glioma.

Low-density lipoprotein (LDL) uptake in gliomas was studied to find out if LDL has potential as a drug carrier of boron, especially for boron neutron capture therapy. Single photon emission tomography (SPET) was performed 2 h and 20 h after intravenous injection of autologous 99mTc-labelled LDL in four patients with untreated and five patients with recurrent glioma. 99mTc-LDL uptake was compared with the uptake of 99mTc-labelled human serum albumin (HSA), an established blood pool marker. The intra- and peritumoral distributions of radioactivity in the SPET images were not identical for radiolabelled LDL and HSA. The mean LDL tumour to brain ratio, determined from transversal SPET slices at 20 h post injection, was 1.5 in untreated and 2.2 in recurrent gliomas; the corresponding ratios for HSA were 1.6 and 3.4. The brain to blood ratio remained constant at 2 h and 20 h in both types of tumours. These data are not consistent with highly selective, homogeneous uptake of LDL in gliomas. However, the different tumoral distribution and rate of uptake of 99mTc-LDL, as compared with 99mTc-HSA, indicate that the uptake of LDL is different from that of HSA and that further studies on the mechanism of LDL uptake in glioma are warranted

Mild obstructive sleep apnea does not modulate baroreflex sensitivity in adult patients

Peer reviewe

Saturated fat is more metabolically harmful for the human liver than unsaturated fat or simple sugars

Objective Weight gain predisposes to increased intrahepatic triglycerides (IHTG) and insulin resistance (IR), but these do not occur in all obese subjects. Adipose tissue lipolysis and hepatic de novo lipogenesis (DNL) are the main pathways contributing to IHTG, while ceramides, which synthesis is induced by saturated fatty acids and endotoxin, are key mediators of IR. We hypothesized that dietary macronutrient composition influences the mechanisms and magnitude of weight gain-induced changes in IHTG and IR. Research Design and Methods We overfed 38 overweight subjects (age 48±2, BMI 31±1 kg/m2, liver fat 4.7±0.9%) 1000 extra kilocalories/day of either saturated or unsaturated fat or simple sugars for 3 weeks. We measured IHTG (1H-MRS), pathways contributing to IHTG (lipolysis ([2H5]glycerol) and DNL (2H2O) basally and during euglycemic hyperinsulinemia), IR, plasma ceramides (UPLC-MS) and endotoxemia at 0 and 3 weeks. Results Overfeeding saturated fat increased IHTG more (+55%) than unsaturated fat (+15%) or simple sugars (+33%) despite similar increases in body weight. Simple sugars increased DNL (+98%) whilst saturated fat increased lipolysis (+11%). Saturated fat but not other diets induced IR (+23%), endotoxemia (+9%) and increased multiple plasma ceramides (+32 to +63%). Conclusions These data demonstrate that the macronutrient composition of the diet overconsumed matters. Saturated fat exerts greater metabolic harm on the liver than unsaturated fat or simple sugars