Upregulation of Oxidative Stress Markers in Human Microvascular Endothelial Cells by Complexes of Serum Albumin and Digestion Products of Glycated Casein

The extent of absorption of dietary advanced glycation end products (AGEs) is not fully known. The possible physiological impact of these absorbed components on inflammatory processes has been studied little and was the aim of this investigation. Aqueous solutions of bovine casein and glucose were heated at 95 degrees C for 5 h to give AGE-casein (AGE-Cas). Simulated stomach and small intestine digestion of AGE-Cas and dialysis (molecular mass cutoff of membrane = 1 kDa) resulted in a low molecular mass (LMM) fraction of digestion products, which was used to prepare bovine serum albumin (BSA)-LMM-AGE-Cas complexes. Stimulation of human microvascular endothelial cells with BSA-LMM-AGE-Cas complexes significantly increased mRNA expression of the receptor of AGE (RAGE), galectin-3 (AGE-113), tumor necrosis factor alpha, and a marker of the mitogen-activated protein kinase pathway (MAPK-1), as well as p65NF-kappa B activation. Cells treated with LMM digestion products of AGE-Cas significantly increased AGE-R3 mRNA expression. Intracellular reactive oxygen species production increased significantly in cells challenged with BSA-LMM-AGE-Cas and LMM-AGE-Cas. In conclusion, in an in vitro cell system, digested dietary AGEs complexed with serum albumin play a role in the regulation of RAGE and down-stream inflammatory pathways. AGE-R3 may protect against these effects.

Exploring the perspective of midwives involved in offering serum screening for Down's syndrome in Northern Ireland

Aims. To explore the perspective of midwives offering serum screening for Down’s syndrome.

Background. Previous literature has indicated that the offer and discussion of prenatal serum screening tests with women is complex, and health professionals may influence women’s decisions to accept or decline screening. Midwives are usually the key professional to offer serum screening for Down’s syndrome in the UK but their perspective is relatively neglected in the literature.

Design. An explorative qualitative interview study with 15 midwives employed in a maternity unit in Northern Ireland involved in offering prenatal screening to pregnant women. Data were collected from 1 July 2005–31 October 2005.

Methods. A focused ethnographic approach was used to explore the perspective of midwives.

Results. Midwives reported difficulty in explaining the test to women and felt unable to provide the necessary information to adequately inform women within their appointment time. The test offered (the triple test) and potential pathway of subsequent care, were identified as sources of professional and personal conflict by midwives. The expectation that midwives would provide a universal offer of Down’s syndrome serum screening but be unable to support women regarding termination of pregnancy also created dissonance.

Conclusions. The feasibility of proceeding with a universal serum screening programme for Down’s syndrome is questionable in countries which legally or culturally oppose termination of pregnancy. Professionals practising within environments such as this experience conflict in their role, which affects communication with women when discussing screening tests.

Relevance to clinical practice. As midwives are often, the primary health professional providing information to women, it is important that midwives are key participants in ongoing planning and discussions about screening policy to ensure programmes are implemented successfully.

Binding of serum albumin to the anthelmintic drugs albendazole, triclabendazole and their sulphoxides

The binding of drugs to plasma proteins – especially serum albumin – is an important factor in controlling the availability and distribution of these drugs. In this study we have investigated the binding of two drugs commonly used to treat liver fluke infections, albendazole (ABZ) and triclabendazole (TCBZ), and their sulphoxide metabolites to bovine serum albumin (BSA). Both ABZ and TCBZ caused shifts in the mobility of BSA in native gel electrophoresis. No such changes were observed with the sulphoxides under identical conditions. The drugs, and their sulphoxides, caused quenching of the intrinsic tryptophan fluorescence of BSA, indicating association between the drugs and this protein. Quantification of this quenching suggested a 5–10-fold reduction in affinity of the sulphoxides compared to the parent compounds. These results are discussed in respect to previous work on the pharmacodynamics of these fasciolicides and will inform the design of novel anthelmintics.

Rheological Evaluation of the Isothermal Cure Characteristics of Medical Grade Silicone Elastomers

Silicone elastomer systems have been shown to offer potential for the fabrication of medical devices and sustained release drug delivery devices comprising low molecular weight drugs and protein therapeutics. For drug delivery systems in particular, there is often no clear rationale for selection of the silicone elastomer grade, particularly in respect of optimizing the manufacturing conditions to ensure thermal stability of the active agent and short cycle times. In this study, the cure characteristics of a range of addition-cure and condensation-cure, low-consistency, implant-grade silicone elastomers, either as supplied or loaded with the model protein bovine serum albumin (BSA) and the model hydrophilic excipient glycine, were investigated using oscillatory rheology with a view to better understanding the isothermal cure characteristics. The results demonstrate the influence of elastomer type, cure temperature, protein loading, and glycine loading on isothermal cure properties. By measuring the cure time required to achieve tan delta values representative of early and late-stage cure conditions, a ratio t(1)/t(2) was defined that allowed the cure characteristics of the various systems to be compared. Sustained in vitro release of BSA from glycine-loaded silicone elastomer covered rod devices was also demonstrated over 14 days. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 116: 2320-2327, 2010

Leptin concentrations in maternal serum and cord blood in diabetic and nondiabetic pregnancy

OBJECTIVE: The purpose of this study was to examine the relationships between maternal and cord leptin concentrations, maternal and neonatal outcomes, and measures of glycemic control in diabetic and nondiabetic pregnancy.

Association of serum AACT levels and AACT signal polymorphism with late-onset Alzheimer's disease in Northern Ireland

alpha 1-antichymotrypsin (AACT) is a serine protease inhibitor that has been associated with amyloid plaques in the brains of patients with Alzheimer's disease (AD). It has been reported that AACT serum levels are higher in AD patients than in age and sex matched controls. In addition, polymorphisms in the signal peptide and 5' of the AACT gene have been reported to increase the risk of developing AD, Serum AACT has also been suggested to be associated with cognitive decline in elderly subjects. Our objective was to investigate whether a relationship existed between serum AACT levels, AACT genotypes and risk for AD in a case control association study using 108 clinically well defined late onset AD cases and 108 age and sex matched controls from Northern Ireland. We also wished to determine whether higher serum AACT affected levels of cognition as had been previously reported. Serum AACT levels were found to bet significantly raised in cases compared to controls (t = 3.8, df = 209, p

Meta analysis of the effects of lithium usage on serum creatinine levels

There is conflicting evidence concerning lithium’s effect on renal function. The aim is to clarify whether lithium affects kidney function and at what stage of treatment any effect may occur. Systematic review identified 23 studies split into three groups on which meta-analysis was performed to identify the following: A) lithium’s effect on renal function in cross-sectional case-control studies, B) studies of renal function before and after commencement on lithium, C) studies of longer term effect in those already established on lithium therapy. Group A showed a statistically significant increase of 5.7 µmol/L in creatinine in the study population compared with controls. Group B showed a non-statistically significant rise in creatinine (2.9 µmol/L) after a mean follow-up of 86 months. Group C showed a statistically significant increase in creatinine of 7.0 µmol/L over a mean duration of 64 months. An increase in creatinine of an average of 1.6 µmol/L/year on lithium was also identified in this group. Any lithium-associated increase in serum creatinine is quantitatively small and of questionable clinical significance. However, routine renal function monitoring of patients on lithium is essential.

Fast, copper-free click chemistry: a convenient solid-phase approach to oligonucleotide conjugation

Solid-phase oligonucleotide conjugation by nitrile oxide-alkyne click cycloaddition chemistry has been successfully demonstrated; the reaction, compatible with all nucleobases, requires no metal catalyst and proceeds under physiological conditions.

Hapten synthesis and antibody production for the development of a melamine immunoassay

The incorporation of melamine into food products is banned but its misuse has been widely reported in both animal feeds and food. The development of a rapid screening immunoassay for monitoring of the substance is an urgent requirement. Two haptens of melamine were synthesized by introducing spacer arms of different lengths and structures on the triazine ring of the analyte molecular structure. 6-Aminocaproic acid and 3-mercaptopropionic acid were reacted with 2-chloro-4,6-diamino-1,3,5-triazine (CAAT) to produce hapten 1[3-(4,6-diamino-1,6-dihydro-1,3,5-triazin-2-ylamino) hexanoic acid] and hapten 2[3-(4,6-diamino-1,6-dihydro-1,3,5-triazin-2-ylthio) propanoic acid]. respectively. The molecular structures of the two haptens were identified by I H nuclear magnetic resonance spectrometry, mass spectrometry and infrared spectrometry. An immunogen was prepared by coupling hapten 1 to bovine serum albumin (BSA). Two plate coating antigens were prepared by coupling both haptens to egg ovalbumin (OVA). A competitive indirect enzyme-linked immunosorbent assay (ciELISA) was developed to evaluate homogeneous and heterogeneous assay formats. The results showed that polyclonal antibodies with high titers were obtained, and the heterogeneous immunoassay format demonstrated a better performance with an IC50 of 70.6 ng mL(-1), a LOD of 2.6 ng mL(-1) and a LOQ of 7.6 ng mL(-1). Except for cyromazine, no obvious cross-reactivity to common compounds was found. The data showed that the hapten synthesis was successful and the resultant antisera could be used in an immunoassay for the rapid and sensitive detection of this banned chemical. (C) 2010 Elsevier B.V. All rights reserved.

Rapid screening for monensin residues in poultry plasma by a dry reagent dissociation enhanced lanthanide fluoroimmunoassay.

Monensin, a carboxylic acid ionophore, is commonly fed to poultry to control coccidiosis. A method for rapid analysis of unextracted poultry plasma samples has been developed based on a novel immunoassay format: one-step all-in-one dry reagent time resolved fluorimetry. All assay specific components were pre-dried onto microtitration plate wells. Only addition of the serum sample diluted in assay buffer was required to perform analysis. Results were available one hour after sample addition. The limit of detection (mean + 3s) of the assay calculated from the analysis of 23 known negative samples was 14.2 ng ml(-1). Intra- and inter-assay RSD were determined as 15.2 and 7.4%, respectively, using a plasma sample fortified with 50 ng ml(-1) monensin. Eight broiler chickens were fed monensin at a dose rate of 120 mg kg(-1) feed for one week, blood sampled then slaughtered without drug withdrawal. Plasma monensin concentrations, as determined by the fluoroimmunoassay ranged from 101-297 ng ml(-1). This compared with monensin liver concentrations, determined by LC-MS, which ranged fi om 13-41 ng g(-1). The fluoroimmunoassay described is extremely user friendly, gives particularly rapid results and is suitable for the detection and quantification of plasma monensin residues. Data from medicated poultry suggest that analysis of plasma may be useful in predicting the extent of monensin liver residues.

Carbon chemistry in Galactic bulge planetary nebulae

Galactic bulge planetary nebulae show evidence of mixed chemistry with emission from both silicate dust and polycyclic aromatic hydrocarbons (PAHs). This mixed chemistry is unlikely to be related to carbon dredge-up, as third dredge-up is not expected to occur in the low-mass bulge stars. We show that the phenomenon is widespread and is seen in 30 nebulae out of 40 of our sample, selected on the basis of their infrared flux. Hubble Space Telescope (HST) images and Ultraviolet and Visual Echelle Spectrograph (UVES) spectra show that the mixed chemistry is not related to the presence of emission-line stars, as it is in the Galactic disc population. We also rule out interaction with the interstellar medium (ISM) as origin of the PAHs. Instead, a strong correlation is found with morphology and the presence of a dense torus. A chemical model is presented which shows that hydrocarbon chains can form within oxygen-rich gas through gas-phase chemical reactions. The model predicts two layers, one at A_V~ 1.5, where small hydrocarbons form from reactions with C+, and one at A_V~ 4, where larger chains (and by implication, PAHs) form from reactions with neutral, atomic carbon. These reactions take place in a mini-photon-dominated region (PDR). We conclude that the mixed-chemistry phenomenon occurring in the Galactic bulge planetary nebulae is best explained through hydrocarbon chemistry in an ultraviolet (UV)-irradiated, dense torus.

A click chemistry approach to C3 symmetric, G-quadruplex stabilising ligands.

Described is the structure-based design and synthesis of a series of tris-triazole G-quadruplex binding ligands utilising the copper catalysed azide–alkyne ‘click’ reaction. The results of G-quadruplex stabilisation by the ligands are reported and discussed.