[Overview on omega-3 polyunsaturated fatty acids and heart failure].

Despite aggressive pharmacotherapy, heart failure is still clinical problem. Current therapies improve clinical symptoms and slow progression to heart failure, but overall the prognosis remains poor. Evidence from epidemiological, clinical and experimental studies indicates a beneficial role of the omega-3 polyunsaturated fatty acids (omega-3 PUFA) found in fish oils in the prevention and management of heart failure.

Microfluidic hydrodynamic cellular patterning for systematic formation of co-culture spheroids.

This paper describes a microfluidic method to form co-culture spheroids of various geometries and compositions in order to manipulate cell-cell interaction dynamics. The cellular patterning is performed in a two-layered microfluidic device that sandwiches a semi-porous membrane so that flow occurs from the top channel through the membrane to the bottom channel. Arbitrary cellular arrangements are enabled by regulating the geometric features of the bottom channel so that as culture media drains, the flow hydrodynamically focuses (aggregates) cells onto the membrane only over the regions of the bottom channel.

The low prevalence Rh antigen Be(a) (Rh36) is associated with RHCE*ce 662C>G in exon 5, which is predicted to encode Rhce 221Arg.

Background And Objectives: The low prevalence antigen, Be(a), is produced by a complex that also produces weak c, e and f (ce). We report here the molecular basis associated with Be(a) antigen expression.

Materials And Methods: Peripheral blood samples from four Be(a+) probands were tested.

A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test.

The present study determined regional serotonin (5-HT) synthesis and metabolism changes associated with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine (L-NA) and the influence of 5-HT receptor blockade in the antidepressant-like actions of L-NA in the forced swimming test (FST). Regional effects of L-NA (5,10 and 20mg/kg i.p.

The complications of septic arthritis in the elderly.

Background And Aims: An epidemiological analysis of cases of spontaneous community acquired septic arthritis in an elderly population at a university teaching hospital.

Methods: Confirmed cases of spontaneous septic arthritis in the over-65 population were studied. Patients with prosthetic joint infections were excluded from the study.

UV and solar TiO(2) photocatalysis of brevetoxins (PbTxs).

Karenia brevis, the harmful alga associated with red tide, produces brevetoxins (PbTxs). Exposure to these toxins can have a negative impact on marine wildlife and serious human health consequences. The elimination of PbTxs is critical to protect the marine environment and human health.

Advanced oxidation and reduction process chemistry of methyl tert-butyl ether (MTBE) reaction intermediates in aqueous solution: 2-methoxy-2-methyl-propanal, 2-methoxy-2-methyl-propanol, and 2-methoxy-2-methyl-propanoic acid.

Absolute rate constants for the reaction of three important degradation products of methyl-tert-butyl ether (MTBE) with the hydroxyl radical, hydrated electron and hydrogen atom were determined in aqueous solution at room temperature. These three intermediate species; 2-methoxy-2-methyl propanal (MMP), 2-methoxy-2-methyl-propanol (MMP-OH) and 2-methoxy-2-methyl-propionic acid (MMP-acid), are formed in the degradation of MTBE under advanced oxidation and reduction process conditions. The rate constants for their hydroxyl radical oxidation of (3.

Pseudomonas fluorescens contamination of a feline packed red blood cell unit and studies of canine units.

Background: While screening programs have reduced the risk of infectious disease transmission by donors in human and veterinary blood banking, bacterial contamination of blood products has emerged as a major complication in human medicine.

Objectives: To describe a Pseudomonas fluorescens (Pf)-contaminated feline packed RBC (pRBC) unit and experimentally investigate Pf-contaminated canine pRBCs.

Methods: Canine pRBCs were inoculated with Pf-rich pRBCs from the sentinel feline unit and stored at 4 degrees C or 20 degrees C for 72 hours.

A high-fat diet increases adiposity but maintains mitochondrial oxidative enzymes without affecting development of heart failure with pressure overload.

A high-fat diet can increase adiposity, leptin secretion, and plasma fatty acid concentration. In hypertension, this scenario may accelerate cardiac hypertrophy and development of heart failure but could be protective by activating peroxisome proliferator-activated receptors and expression of mitochondrial oxidative enzymes. We assessed the effects of a high-fat diet on the development of left ventricular hypertrophy, remodeling, contractile dysfunction, and the activity of mitochondrial oxidative enzymes.

Dietary omega-3 fatty acids alter cardiac mitochondrial phospholipid composition and delay Ca2+-induced permeability transition.

Consumption of omega-3 fatty acids from fish oil, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), decreases risk for heart failure and attenuates pathologic cardiac remodeling in response to pressure overload. Dietary supplementation with EPA + DHA may also impact cardiac mitochondrial function and energetics through alteration of membrane phospholipids. We assessed the role of EPA + DHA supplementation on left ventricular (LV) function, cardiac mitochondrial membrane phospholipid composition, respiration, and sensitivity to mitochondrial permeability transition pore (MPTP) opening in normal and infarcted myocardium.

L1 retrotransposition in human neural progenitor cells.

Long interspersed element 1 (LINE-1 or L1) retrotransposons have markedly affected the human genome. L1s must retrotranspose in the germ line or during early development to ensure their evolutionary success, yet the extent to which this process affects somatic cells is poorly understood. We previously demonstrated that engineered human L1s can retrotranspose in adult rat hippocampus progenitor cells in vitro and in the mouse brain in vivo.

The cardioprotective effects of fish oil during pressure overload are blocked by high fat intake: role of cardiac phospholipid remodeling.

Supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil may prevent development of heart failure through alterations in cardiac phospholipids that favorably impact inflammation and energy metabolism. A high-fat diet may block these effects in chronically stressed myocardium. Pathological left ventricle (LV) hypertrophy was generated by subjecting rats to pressure overload by constriction of the abdominal aorta.

Development and validation of an LC-MS/MS method for determination of methanesulfonamide in human urine.

A sensitive and selective liquid chromatographic method coupled with tandem mass spectrometry (LC-MS/MS) was developed and validated for the quantification of methanesulfonamide (MSA) in human urine. MSA is a potential in vivo metabolite of reparixin, a specific inhibitor of the CXCL8 biological activity. In this study, a simple derivatization procedure with a new reagent, N-(4-methanesulfonyl-benzoyl)-imidazole, was set up to enable MSA and the internal standard (I.

Microfluidic culture of single human embryonic stem cell colonies.

We have developed a miniaturized microfluidic culture system that allows experimentation on individual human embryonic stem cell (hESC) colonies in dynamic (flow applied) or static (without flow) conditions. The system consists of three inlet channels that converge into a cell-culture channel and provides the capability to spatially and temporally deliver specific treatments by using patterned laminar fluid flow to different parts of a single hESC colony. We show that microfluidic culture for 96 h with or without flow results in similar maintenance of hESC self-renewal, the capability to differentiate into three germ cell lineages, and to maintain a normal karyotype, as in standard culture dishes.

omega-3 polyunsaturated fatty acid supplementation for the treatment of heart failure: mechanisms and clinical potential.

Heart failure (HF) is a complex clinical syndrome with multiple aetiologies. Current treatment options can slow the progression to HF, but overall the prognosis remains poor. Clinical studies suggest that high dietary intake of the omega-3 polyunsaturated fatty acids (omega-3PUFA) found in fish oils (eicosapentaenoic and docosahexaenoic acids) may lower the incidence of HF, and that supplementation with pharmacological doses prolongs event-free survival in patients with established HF.

Radiolysis studies on the destruction of microcystin-LR in aqueous solution by hydroxyl radicals.

In this study, steady-state and time-resolved radiolysis methods were used to determine the primary reaction pathways and kinetic parameters for the reactions of hydroxyl radical with microcystin-LR (MC-LR). The fundamental kinetic data is critical for the accurate evaluation of hydroxyl-radical based technologies for the destruction of this problematic class of cyanotoxins. The bimolecular rate constant for the reaction of hydroxyl radical with MC-LR is 2.

5-Aminomethylbenzimidazoles as potent ITK antagonists.

Benzamide 1 demonstrated good potency as a selective ITK inhibitor, however the amide moiety was found to be hydrolytically labile in vivo, resulting in low oral exposure and the generation of mutagenic aromatic amine metabolites. Replacing the benzamide with a benzylamine linker not only addressed the toxicity issue, but also improved the cellular and functional potency as well as the drug-like properties. SAR studies around the benzylamines and the identification of 10n and 10o as excellent tools for proof-of-concept studies are described.

Free-radical-induced oxidative and reductive degradation of N,N'-diethyl-m-toluamide (DEET): Kinetic studies and degradation pathway.

N,N'-Diethyl-m-toluamide (DEET) is widely used as an insect repellent and has therefore been detected as a contaminant in numerous waste and surface waters. In this study we have determined the absolute reaction rate constants of DEET with the hydroxyl radical and the hydrated electron in aqueous solution as (4.95+/-0.

Glutamatergic neuronal differentiation of mouse embryonic stem cells after transient expression of neurogenin 1 and treatment with BDNF and GDNF: in vitro and in vivo studies.

Differentiation of the pluripotent neuroepithelium into neurons and glia is accomplished by the interaction of growth factors and cell-type restricted transcription factors. One approach to obtaining a particular neuronal phenotype is by recapitulating the expression of these factors in embryonic stem (ES) cells. Toward the eventual goal of auditory nerve replacement, the aim of the current investigation was to generate auditory nerve-like glutamatergic neurons from ES cells.

Fish oil, but not flaxseed oil, decreases inflammation and prevents pressure overload-induced cardiac dysfunction.

Aims: Clinical studies suggest that intake of omega-3 polyunsaturated fatty acids (omega-3 PUFA) may lower the incidence of heart failure. Dietary supplementation with omega-3 PUFA exerts metabolic and anti-inflammatory effects that could prevent left ventricle (LV) pathology; however, it is unclear whether these effects occur at clinically relevant doses and whether there are differences between omega-3 PUFA from fish [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and vegetable sources [alpha-linolenic acid (ALA)].

Methods And Results: We assessed the development of LV remodelling and pathology in rats subjected to aortic banding treated with omega-3 PUFA over a dose range that spanned the intake of humans taking omega-3 PUFA supplements.

The antioxidant tempol attenuates pressure overload-induced cardiac hypertrophy and contractile dysfunction in mice fed a high-fructose diet.

We have previously shown that high-sugar diets increase mortality and left ventricular (LV) dysfunction during pressure overload. The mechanisms behind these diet-induced alterations are unclear but may involve increased oxidative stress in the myocardium. The present study examined whether high-fructose feeding increased myocardial oxidative damage and exacerbated systolic dysfunction after transverse aortic constriction (TAC) and if this effect could be attenuated by treatment with the antioxidant tempol.

Analysis of the factors that limit the ability of feeder cells to maintain the undifferentiated state of human embryonic stem cells.

Human embryonic stem cell (hESC) culture is routinely performed using inactivated mouse embryonic fibroblasts (MEFs) as a feeder cell layer (FL). Although these cells maintain pluripotency of hESCs, the molecular basis for this is unknown. Objectives of this study were to determine whether timing between MEF inactivation and their use as a FL influenced hESC growth and differentiation, and to begin defining the mechanism(s) involved.

State of the art in developmental toxicity screening methods and a way forward: a meeting report addressing embryonic stem cells, whole embryo culture, and zebrafish.

A meeting was convened so that users of three models for in vitro developmental toxicity (embryonic stem cells, whole embryo culture, and zebrafish) could share their experiences with each model, and explore the areas for improvement. We present a summary of this meeting and the recommendations of the group.