Incorporation of n-3 PUFA and γ-linolenic acid in blood lipids and red blood cell lipids together with their influence on disease activity in patients with chronic inflammatory arthritis--a randomized controlled human intervention trial.

Background And Aim: Marine n-3 fatty acids and γ-linolenic acid both have anti-inflammatory effects and may be useful to help treat inflammatory diseases. The effects of these alone or combined were examined in patients with arthritis in a randomized controlled trial.

Design: Patients with rheumatoid arthritis or psoriatic arthritis were randomized into four groups in a double-blind, placebo-controlled parallel designed study.

Stereoselective binding of chiral anti-diabetic drug nateglinide to plasma proteins.

The binding of nateglinide (NA) enantiomers with human plasma (HP), human serum albumin (HSA) and bovine serum albumin (BSA) was investigated. The protein binding was studied over a drug concentration range of 5-100 μM at a protein concentration of 600 μM. Unbound drug concentrations were determined by direct chiral liquid chromatography using chiralcel OJ-RH column.

In patients with aortic stenosis increased flow-mediated dilation is independently associated with higher peak jet velocity and lower asymmetric dimethylarginine levels.

Background: Recently, it has been shown that endothelial dysfunction and aortic stenosis (AS) share several risk factors. Endothelial function represents a crucial factor for the regulation of vascular tonus and its malfunction influences the formation of thrombosis and inflammation. However, the role of endothelial dysfunction in AS remains unclear.

NADPH oxidase and eNOS control cardiomyogenesis in mouse embryonic stem cells on ascorbic acid treatment.

Ascorbic acid (AA) increases cardiomyogenesis of embryonic stem (ES) cells. Herein we show that treatment of mouse ES cells with AA enhanced cardiac differentiation accompanied by an upregulation of the NADPH oxidase isoforms NOX2 and NOX4, phosphorylation of endothelial nitric oxide synthase (eNOS), and cyclic GMP (cGMP) formation, indicating that reactive oxygen species (ROS) as well as nitric oxide (NO) may be involved in cardiomyogenesis. In whole mount embryoid bodies as well as isolated Flk-1-positive (Flk-1(+)) cardiovascular progenitor cells ROS elevation by AA was observed in early stages of differentiation (Days 4-7), and absent at Day 10.

Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune-mediated arthritis.

Objective: Clinical and preclinical evidence suggests that somatostatin exhibits potent antiinflammatory and antinociceptive properties. However, it is not known which of the 5 somatostatin receptor subtypes (SSTRs 1-5) is involved in these actions. The purpose of this study was to assess the effects of the stable somatostatin analogs octreotide and pasireotide (SOM230) in a mouse model of antigen-induced arthritis (AIA).

Real-time PCR and quantitative culture for monitoring of experimental Aspergillus fumigatus intracranial infection in neutropenic mice.

The central nervous system (CNS) is the most common site of dissemination during Aspergillus infection. PCR has the potential to facilitate early diagnosis of CNS aspergillosis, which could assist in reducing disease mortality. In two experiments, neutropenic CD-1 male mice were infected intracranially with 5×10⁶ conidia of Aspergillus fumigatus.

Detection of thiopurine methyltransferase activity in lysed red blood cells by means of lab-on-a-chip surface enhanced Raman spectroscopy (LOC-SERS).

In this contribution, the great potential of surface enhanced Raman spectroscopy (SERS) in a lab-on-a-chip (LOC) device for the detection of analyte molecules in a complex environment is demonstrated. Using LOC-SERS, the enzyme activity of thiopurine S-methyltransferase (TPMT) is analysed and identified in lysed red blood cells. The conversion of 6-mercaptopurine to 6-methylmercaptopurine catalysed by TPMT is observed as it gives evidence for the enzyme activity.

Structural determinants of agonist-selective signaling at the sst(2A) somatostatin receptor.

The clinically used somatostatin (SS-14) analogs octreotide and pasireotide (SOM230) stimulate distinct species-specific patterns of sst(2A) somatostatin receptor phosphorylation and internalization. Like SS-14, octreotide promotes the phosphorylation of at least six carboxyl-terminal serine and threonine residues, namely S341, S343, T353, T354, T356, and T359, which in turn leads to a robust endocytosis of both rat and human sst(2A) receptors. Unlike SS-14, pasireotide fails to induce any substantial phosphorylation or internalization of the rat sst(2A) receptor.

Semi-synthetic polysaccharide sulfates as anticoagulant coatings for PET, 1--cellulose sulfate.

In the present study, blood-compatible PET surfaces were prepared by coating with anticoagulant cellulose sulfates that were synthesized homogeneously in ionic liquids. The adsorption behavior of polysaccharides on PET films was investigated using QCM-D. It was demonstrated that pre-coating with different amino-group-containing polysaccharides improves the affinity toward cellulose sulfate.

Selection of reliable reference genes during THP-1 monocyte differentiation into macrophages.

Background: Reliable reference genes are a vital prerequisite for any functional study employing quantitative real-time RT-PCR (RT-qPCR) for analyzing gene expression. Yet a proper selection and assessment of the chosen reference genes is only rarely included into a study. To date, no reference genes have been validated for differentiation of THP-1 monocytes.

Individual variability of response and non-response to acetyl salicylic acid after cardiac surgery.

Insufficient inhibition of platelet function by acetyl salicylic acid (ASA) or other platelet inhibitors is a risk factor for arterial thrombosis in cardiovascular patients. We wanted to collect and analyse information on the frequency and probable causes of non-response to ASA in patients prior to and after cardiac surgery. One hundred and one patients (mean age 68 ± 9 years) undergoing cardiac surgery (98 patients with coronary bypass grafting, 18 cases had combined valve replacement, and three patients with only valve replacement) were enrolled.

Parenchymal and pleural findings in pulmonary embolism visualized by multi-channel detector computed tomography.

Background: A normal computed tomography (CT) scan of the pulmonary arteries in the presence of parenchymal and pleural abnormalities may indicate a false-negative diagnosis of pulmonary embolism (PE). Multi-channel detector CT (MDCT) with thinner collimation may improve the detection of small peripheral PEs causing such abnormalities.

Purpose: To investigate parenchymal and pleural findings visualized by contrast-enhanced MDCT in patients with and without PE, and to identify possible predictors of PE.

Proapoptotic effects of long-chain vitamin E metabolites in HepG2 cells are mediated by oxidative stress.

Although the metabolism of vitamin E has been extensively studied in cell culture, animals, and humans, biochemical analyses of intermediate metabolites are scarce. We here describe the synthesis and proapoptotic properties of long-chain metabolites of α- and δ-tocopherol. Several long-chain vitamin E metabolites, namely 13'-hydroxy- and 13'-carboxychromanols, were synthesized from garcinoic acid, a δ-tocotrienol derivative extracted from the African bitter nut Garcinia kola.

Impurity profiling of dexamphetamine sulfate by cyclodextrin-modified microemulsion electrokinetic chromatography.

A CD-modified microemulsion electrokinetic chromatography method has been developed and validated for dexamphetamine sulfate which allows the simultaneous determination of charged and uncharged impurities of the drug including the levorotary (R)-enantiomer. The optimized background electrolyte consisted of 1.5% w/w SDS, 0.

Fluoride-dependent conversion of organic compounds mediated by manganese peroxidases in the absence of Mn(2+) ions.

Manganese peroxidase generally mediates the oxidation of Mn(2+) to Mn(3+) with H(2)O(2) as an oxidant. Several manganese peroxidases purified from different lignin-degrading fungi were found to mediate a fluoride-dependent conversion of organic substrates such as monochlorodimedone or 2,6-dimethoxyphenol in the absence of manganese ions. Using the manganese peroxidase MnP-1 from Bjerkandera adusta strain Ud1, these fluoride-dependent reactions were studied with respect to different substrates converted, reaction products, and kinetic properties to shed some light on the reaction mechanism of manganese peroxidase.

CE assay for simultaneous determination of charged and neutral impurities in dexamphetamine sulfate using a dual CD system.

A CE assay for the simultaneous determination of charged and uncharged potential impurities (1S,2S-(+)-norpseudoephedrine, 1R,2S-(-)-norephedrine, phenylacetone and phenylacetone oxime) of dexamphetamine sulfate including the stereoisomer levoamphetamine was developed and validated. The optimized background electrolyte consisted of a 50 mM sodium phosphate buffer, pH 3.0, containing 80 mg/mL sulfobutylether-beta-CD and 25 mg/mL sulfated beta-CD.

n-3 LC-PUFA-enriched dairy products are able to reduce cardiovascular risk factors: a double-blind, cross-over study.

Background: &

Aims: The effects of n-3 LC-PUFA-supplemented dairy products on cardiovascular risk factors in mildly hypertriacylglycerolemic patients (TAG: ≥1.5 mmol/L) were determined.

Methods: Fifty-one patients (25 f, 26 m) were included in the double-blind, placebo-controlled cross-over study and were randomly divided into two groups.

Phenotypic and genotypic characterization of acyclovir-resistant clinical isolates of herpes simplex virus.

Sixteen herpes simplex virus type 1 (HSV-1) and four type 2 (HSV-2) isolates resistant to acyclovir (ACV) were characterized retrospectively for drug resistance. Phenotypic testing was performed by means of tetrazolium reduction assay and genotypic analysis was carried out by sequencing of thymidine kinase (TK) and DNA-polymerase (pol) genes. All strains were characterized as cross-resistant to penciclovir, brivudin and susceptible to cidofovir.

Analysis of vitamin E metabolites in biological specimen.

Vitamin E is known as the most important lipid antioxidant and is widely used to prevent age-associated diseases. Despite increasing knowledge about human vitamin E metabolism, little is known to justify its widespread use. As meta-analyses revealed even harmful effects of high vitamin E doses, a profound understanding of vitamin E metabolism is mandatory.

Pasireotide and octreotide stimulate distinct patterns of sst2A somatostatin receptor phosphorylation.

Pasireotide (SOM230) is currently under clinical evaluation as a successor compound to octreotide for the treatment of acromegaly, Cushing's disease, and carcinoid tumors. Whereas octreotide acts primarily via the sst(2A) somatostatin receptor, pasireotide was designed to exhibit octreotide-like sst(2A) activity combined with enhanced binding to other somatostatin receptor subtypes. In the present study, we used phophosite-specific antibodies to examine agonist-induced phosphorylation of the rat sst(2A) receptor.

Phenotyping with sulfasalazine - time dependence and relation to NAT2 pharmacogenetics.

Objective: N-acetyltransferase 2 (NAT2) genotype-phenotype relation with sulfasalazine as probe drug by means of detailed genotype analysis and kinetic data evaluation.

Background: Though phenotype analysis of sulfasalazine metabolism has been described before, genotype investigations in this regard are scarce. The influence of different single point mutations on the metabolism of the sulfasalazine metabolite sulfapyridine (SP) should give more insight into the functionality of different alleles especially with those still under discussion.

Studies on the boronation of methyl-beta-D-cellobioside--a cellulose model.

The conversion of phenylboronic acid (PBA) with methyl-beta-D-cellobioside (Me-beta-D-clb) and cellodextrins (DP(w) 12) was investigated to gain a basic understanding of the interactions of boric acid derivatives with oligo- and polyglucans. By means of MS and NMR experiments, it was possible to show a first stage formation of a six-membered ring at C-4 and C-6 of the non-reducing glucose occurs as in the case of monosaccharides. If the amount of reagent is increased the formation of seven-membered rings at the secondary OH moieties is observed.