NOVEL ANTENNAE FOR THE SENSITIZATION AND PROTECTION OF LANTHANIDE CATIONS EMITTING IN THE VISIBLE AND NEAR-INFRARED

Several lanthanide cations are luminescent in the visible and in the near-infrared (NIR) regions, with unique and advantageous luminescence properties compared to organic fluorophores, which make luminescent lanthanide complexes desirable for a range of applications including light amplification, optical telecommunications, biological imaging and bioanalytical techniques. To overcome the limitation of low absorptivity and weak luminescence of free lanthanide cations in solution, lanthanide complexes are formed with chromophoric groups that are capable of absorbing incident light, and transferring the resulting energy to the lanthanide cation thus sensitizing luminescence ("antenna effect"). Additionally, lanthanide cations must be protected from solvent molecules whose vibrational overtones efficiently deactivate lanthanide cation excited states through non-radiative routes. The research work presented here has focused on developing lanthanide species with improved photophysical properties, utilizing a variety of approaches to reach two main goals: providing efficient sensitization of lanthanide cations via the antennae effect and superior protection against non-radiative deactivation. In a relatively traditional coordination chemistry approach, natural product molecules of the flavonoid family were used as antennae for NIR emitting lanthanide cations. Using a nanomaterials approach to achieve improved protection from quenching, visible emitting lanthanide cations were incorporated into CdSe semiconductor crystals, which bring their own electronic properties, including broad absorbance bands with high epsilon values and size dependent band gaps. Thus, the nanocrystals are used to provide protection from quenching as well as sensitize lanthanide cations through the antennae effect. In an alternate nanomaterials approach NIR emitting Yb3+ and Nd3+ were incorporated into NaYF4 inorganic nanoparticle matrices that were coated with organic tropolonate sensitizing groups. The nanoparticle matrix protects the lanthanide cations from non-radiative deactivation while the surface bound chromophores provide antennae effect sensitization. In addition, upconverting NaYF4:Yb,Er nanocrystals were synthesized and their potential to serve as energy acceptors from a naphthalimide based antenna or energy donors to Quantum Dots were investigated. Finally, metal-organic frameworks (MOFs) were explored as method to sensitize NIR and visible emitting lanthanide cations by incorporating the lanthanide cations at metal sites in the MOF structure and/or as occupants of the pores of zinc based MOFs

Enzymatic Determination of Diglyceride Using an Iridium Nano-Particle Based Single Use, Disposable Biosensor

A single use, disposable iridium-nano particle contained biosensor had been developed for the determination of diglyceride (DG). In this study hydrogen peroxide, formed through the enzymatic breakdown of DG via lipase, glycerol kinase and glycerol 3-phosphate oxidase, was electrochemically oxidized at an applied potential of +0.5 V versus the Ag/AgCl reference electrode. The oxidation current was then used to quantify the diglyceride concentration. Optimum enzyme concentrations and the surfactant loading used were established for successful sensor response. Good linear performance was observed over a DG concentration range of 0 to 25 μM in phosphate buffer and bovine serum media

Diacylglycerol oil for the metabolic syndrome

Excess adiposity has been shown to play a crucial role in the development of the metabolic syndrome. The elevated fasting and postprandial triglyceride-rich lipoprotein levels is the central lipid abnormality observed in the metabolic syndrome. Recent studies have indicated that diacylglycerol (DAG) is effective for fasting and postprandial hyperlipidemia and preventing excess adiposity by increasing postprandial energy expenditure. We will here discuss the mechanisms of DAG-mediated improvements in hyperlipidemia and in postprandial energy expenditure, and effects of DAG oil on lipid/glucose metabolism and on body fat. Further, the therapeutic application of DAG for the metabolic syndrome will be considered

Vitamin A Deficiency after Gastric Bypass Surgery: An Underreported Postoperative Complication

Introduction. Few data are available on vitamin A deficiency in the gastric bypass population. Methods. We performed a retrospective chart review of gastric bypass patients (n = 69, 74% female). The relationship between serum vitamin A concentration and markers of protein metabolism at 6-weeks and 1-year post-operative were assessed. Results. The average weight loss at 6-weeks and 1-year following surgery was 20.1 ± 9.1 kg and 44.1 ± 17.1 kg, respectively. At 6 weeks and 1 year after surgery, 35% and 18% of patients were vitamin A deficient, (<325 mcg/L). Similarly, 34% and 19% had low pre-albumin levels (<18 mg/dL), at these time intervals. Vitamin A directly correlated with pre-albumin levels at 6 weeks (r = 0.67, P < 0.001) and 1-year (r = 0.67,  P < 0.0001). There was no correlation between the roux limb length measurement and pre-albumin or vitamin A serum concentrations at these post-operative follow-ups. Vitamin A levels and markers of liver function testing were also unrelated. Conclusion. Vitamin A deficiency is common after bariatric surgery and is associated with a low serum concentration of pre-albumin. This fat-soluble vitamin should be measured in patients who have undergone gastric bypass surgery and deficiency should be suspected in those with evidence of protein-calorie malnutrition

A Chronic Oral Toxicity Study of Marine Collagen Peptides Preparation from Chum Salmon (Oncorhynchus keta) Skin Using Sprague-Dawley Rat

Due to the increased consumption of marine collagen peptides preparation (MCP) as ingredients in functional foods and pharmaceuticals, it was necessary to carry out safety requirements in the form of an oral chronic toxicity assessment. In order to define the oral chronic toxicity of MCP, a 24-month feeding study of MCP was carried out. Sprague-Dawley (S-D) rats at the age of four-week of both sexes were treated with MCP at the diet concentrations of 0%, 2.25%, 4.5%, 9% and 18% (wt/wt). The actual food intake and bodyweight of the individual animals were recorded periodically until sacrifice. Blood and urine samples were collected for serum chemistry evaluations and urinalysis. Throughout the experimental period, there was no toxicologically significant difference between the vehicle and MCP-treated animals with respect to the survival rate, body weight, food consumption, urinalysis, clinical biochemistry parameter and relative organ weight in either sex. Moreover, incidences of non-neoplastic lesions in MCP-treated groups did not significantly increase compared with the control group. Under the present experimental conditions, no higher risk of chronic toxic effects was observed in MCP-treated rats at the diet concentrations of 2.25%, 4.5%, 9% and 18% (wt/wt) than in the rats fed with basal rodent diet

A 28-day oral dose toxicity study enhanced to detect endocrine effects of hexabromocyclododecane in wistar rats

A 28-day repeated dose study in rats (OECD407) enhanced for endocrine and immune parameters was performed with hexabromocyclododecane (HBCD). Rats were exposed by daily gavage to HBCD dissolved in corn oil in 8 dose groups with doses ranging between 0 and 200 mg/kg bw per day (mkd). Evaluation consisted of dose-response analysis with calculation of a benchmark dose at the lower 95% one-sided confidence bound (BMDL) at predefined critical effect sizes (CESs) of 10-20%. The most remarkable findings were dose-related effects on the thyroid hormone axis, that is, decreased total thyroxin (TT4, BMDL 55.5 mkd at CES--10%), increased pituitary weight (29 mkd at 10%) and increased immunostaining of TSH in the pituitary, increased thyroid weight (1.6 mkd at 10%), and thyroid follicle cell activation. These effects were restricted to females. Female rats also showed increased absolute liver weights (22.9 mkd at 20%) and induction of T4-glucuronyl transferase (4.1 mkd at 10%), suggesting that aberrant metabolization of T4 triggers feedback activation of the thyroid hormone system. These effects were accompanied by possibly secondary effects, including increased cholesterol (7.4 mkd at 10%), increased tibial bone mineral density (> 49 mkd at 10%), both in females, and decreased splenocyte counts (0.3-6.3 mkd at 20%; only evaluated in males). Overall, female rats appeared to be more sensitive to HBCD than male rats, and an overall BMDL is proposed at 1.6 mkd, based on a 10% increase of the thyroid weight, which was the most sensitive parameter in the sequence of events

Subcutaneous unfractionated heparin for the initial treatment of venous thromboembolism

Background: Venous thromboembolism (VTE) is a prevalent and serious condition. Its medical treatment requires anticoagulation, usually with either unfractionated or low molecular weight heparin (LMWH). Administration of unfractionated heparin (UFH) is usually intravenous (IV) but can be subcutaneous as well. This is an update of a review first published in 2009. Objectives: To assess the effects of subcutaneous UFH versus intravenous UFH, subcutaneous LMWH or any other anticoagulant drug for the initial treatment of venous thromboembolism. Search methods: For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (last searched 30 November 2016) and CENTRAL (2016, Issue 10). The Cochrane Vascular Information Specialist also searched trials registries for details of ongoing or unpublished studies. Selection criteria: Randomised controlled trials comparing subcutaneous UFH to control, such as subcutaneous LMWH, continuous intravenous UFH or other anticoagulant drugs in participants with acute venous thromboembolism. Data collection and analysis: Two review authors (JS and LR) independently extracted data and assessed the risk of bias in the trials. We used meta-analyses when we considered heterogeneity low. The primary outcomes were symptomatic recurrent venous thromboembolism (deep vein thrombosis and/or pulmonary embolism), VTE-related mortality, adverse effects of treatment including major bleeding, and all-cause mortality. We calculated all outcomes using an odds ratio (OR) with a 95% confidence interval (CI). Main results: We included one additional study in this update, bringing the total number of studies in the review to 16 randomised controlled trials, with a total of 3593 participants (1745 participants in the intervention group and 1848 participants in the control group). Eight trials used intravenous UFH as the control treatment, seven trials used LMWH, and one trial had three arms with both drugs as the controls. We did not identify trials comparing subcutaneous UFH with other anticoagulant drugs. We downgraded the quality of the evidence to low due to lack of blinding in studies, which led to a risk of performance bias, and also for imprecision, as reflected by the wide confidence intervals. When comparing subcutaneous versus IV UFH, there was no difference in the incidence of symptomatic recurrent VTE at three months (odds ratio (OR) 1.66, 95% confidence interval (CI) 0.89 to 3.10; 8 studies; N = 965; low-quality evidence), symptomatic recurrent deep vein thrombosis (DVT) at three months (OR 3.29, 95% CI 0.64 to 17.06; 1 study; N = 115; low-quality evidence), pulmonary embolism (PE) at three months (OR 1.44, 95% CI 0.73 to 2.84; 9 studies; N = 1161; low-quality evidence), VTE-related mortality at three months (OR 0.98, 95% CI 0.20 to 4.88; 9 studies; N = 1168; low-quality evidence), major bleeding (OR 0.91, 95% CI 0.42 to 1.97; 4 studies; N = 583; low-quality evidence) or all-cause mortality (OR 1.74, 95% CI 0.67 to 4.51; 8 studies; N = 972; low-quality evidence). There were no episodes of asymptomatic VTE occurring within three months of the commencement of treatment. When comparing subcutaneous UFH versus LMWH, there was no difference in the incidence of recurrent VTE at three months (OR 1.01, 95% CI 0.63 to 1.63; 5 studies; N = 2156; low-quality evidence), recurrent DVT at three months (OR 1.38, 95% CI 0.73 to 2.63; 3 studies; N = 1566; low-quality evidence), PE (OR 0.84, 95% CI 0.36 to 1.96; 5 studies, N = 1819; low-quality evidence), VTE-related mortality (OR 0.53, 95% CI 0.17 to 1.67; 8 studies; N = 2469; low-quality evidence), major bleeding (OR 0.72, 95% CI 0.43 to 1.20; 5 studies; N = 2300; low-quality evidence) or all-cause mortality (OR 0.73, 95% CI 0.50 to 1.07; 7 studies; N = 2272; low-quality evidence). There were no episodes of asymptomatic VTE occurring within three months of the commencement of treatment. Authors' conclusions: There is no evidence of a difference between subcutaneous versus intravenous UFH for preventing VTE recurrence, VTE-related or all-cause mortality, and major bleeding. According to GRADE criteria, the quality of the evidence was low. There is also no evidence of a difference between subcutaneous UFH and LMWH for preventing VTE recurrence, VTE-related or all-cause mortality or major bleeding

Green tea extract inhibits chemokine production, but up-regulates chemokine receptor expression, in rheumatoid arthritis synovial fibroblasts and rat adjuvant-induced arthritis

Objective. Evaluation of the efficacy of green tea extract (GTE) in regulating chemokine production and chemokine receptor expression in human RA synovial fibroblasts and rat adjuvant-induced arthritis (AIA). Methods. Fibroblasts isolated from human RA synovium were used in the study. Regulated upon activation normal T cell expressed and secreted (RANTES)/CCL5, monocyte chemoattractant protein (MCP)-1/CCL2, growth-regulated oncogene (GRO)a/CXCL1 and IL-8/CXCL8 production was measured by ELISA. Western blotting was used to study the phosphorylation of protein kinase C (PKC)d and c-Jun N-terminal kinases (JNK). Chemokine and chemokine receptor expression was determined by quantitative RT–PCR. The benefit of GTE administration in rat AIA was determined. Results. GTE (2.5–40 mg/ml) inhibited IL-1b-induced MCP-1/CCL2 (10 ng/ml), RANTES/CCL5, GROa/CXCL1 and IL-8/CXCL8 production in human RA synovial fibroblasts (P<0.05). However, GTE inhibited MCP-1/CCL2 and GROa/CXCL1 mRNA synthesis in RA synovial fibroblasts. Furthermore, GTE also inhibited IL-1b-induced phosphorylation of PKCd, the signalling pathway mediating IL-1b-induced chemokine production. Interestingly, GTE preincubation enhanced constitutive and IL-1b-induced CCR1, CCR2b, CCR5, CXCR1 and CXCR2 receptor expression. GTE administration (200 mg/kg/day p.o.) modestly ameliorated rat AIA, which was accompanied by a decrease in MCP-1/CCL2 and GROa/CXCL1 levels and enhanced CCR-1, -2, -5 and CXCR1 receptor expression in the joints of GTE administered rats. Conclusions. Chemokine receptor overexpression with reduced chemokine production by GTE may be one potential mechanism to limit the overall inflammation and joint destruction in RA.NIHPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77485/1/Marotte, et al. Green tea extract...Rheumatology 2010.pdf-

Risk to human health related to the presence of perfluoroalkyl substances in food

Acknowledgements: The Panel wishes to thank the following for their support provided to this scientific output as Hearing experts: Klaus Abraham, Esben Budtz-Jørgensen, Tony Fletcher, Philippe Grandjean, Hans Mielke and Hans Rumke and EFSA staff members: Davide Arcella, Marco Binaglia, Petra Gergelova, Elena Rovesti and Marijke Schutte. The Panel wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output. The Panel would also like to thank the following authors and co-authors for providing additional information in relation to their respective studies: Berit Granum, Margie M Peden-Adams, Thomas Webster.Peer reviewedPublisher PD