A simple cultural method for the presumptive detection of the yeasts Brettanomyces/Dekkera in wines

The development of a simple and reliable procedure, compatible with routine use in wineries, for the presumptive detection of Brettanomyces/Dekkera from wine and wine-environment samples. Methods and Results: The method of detection of these yeasts employs a selective enrichment medium. The medium contains glucose (10 g l⁻¹1) as carbon and energy source, cycloheximide (20 mg l⁻¹1) to prevent growth of Saccharomyces, chloramphenicol (200 mg l⁻¹1) to prevent growth of bacteria and p-coumaric acid (20 mg l⁻¹1) as the precursor for the production of 4-ethyl-phenol. After the inoculation with wine, the medium is monitored by visual inspection of turbidity and by periodic olfactive analysis. Contaminated wines will develop visible turbidity in the medium and will produce the 4-ethyl-phenol off-odour, which can be easily detected by smelling. Conclusions: A selective enrichment liquid medium was developed to differentially promote the growth and activity of Brettanomyces/Dekkera. The method is simple to execute, employing a simple-to-prepare medium and a periodic olfactive detection. Significance and Impact of the Study: The characteristics of the procedure make it particularly applicable in a wine-making environment thus presenting important advantages to the wine industry

Does cardiac resynchronization therapy restore peripheral circulatory homeostasis?

Aims: To evaluate whether peripheral circulatory ‘remodeling’ as measured by changes in vascular compliance and in markers of nitric oxide signaling contributes to patient response to cardiac resynchronization therapy (CRT)  Methods and results: Effects of CRT were evaluated in 33 patients pre- and 6 months post- procedure. Peak oxygen consumption (VO2 max), six-minute walk distance (6MWD), NYHA class, and quality of life score (QOL) were evaluated. Augmentation index (AIX) and its interactions with nitric oxide (NO) were evaluated by applanation tonometry. Platelet NO responsiveness and content of thioredoxin-interacting protein (TXNIP) were assessed. Plasma concentrationsof NT-proBNP, asymmetric and symmetric dimethylarginine (ADMA and SDMA), high sensitivity C-reactive protein, catecholamines and matrix metalloproteinases-2 and -9 were assessed. Despite significant improvement in 6MWD (p=0.005), NYHA class (p<0.001), QOL (p=0.001), and all echocardiographic parameters post CRT, there were no significant changesin AIx measurements, TXNIP content and platelet NO response. Significant falls in NTproBNP (p=0.008) and SDMA (p=0.013; independent of renal function) occurred. Falls in SDMA predicted reduction in hs-CRP (p=0.04) and increases in VO2max (p=0.04). There were no correlations between changes in echocardiographic parameters and those in vascular function.  Conclusions: These data suggest that the beneficial effects of CRT over 6 months are independent of any change in peripheral NO-related signaling. However there is evidence that suppression of inflammation occurs and its magnitude predicts extent of clinical improvement

Perhexiline Therapy in Patients with Type 2 Diabetes: Incremental Insulin Resistance despite Potentiation of Nitric Oxide Signaling

Published: 23 September 2022Perhexiline (Px) inhibits carnitine palmitoyltransferase 1 (CPT1), which controls uptake of long chain fatty acids into mitochondria. However, occasional cases of hypoglycaemia have been reported in Px-treated patients, raising the possibility that Px may also increase sensitivity to insulin. Furthermore, Px increases anti-aggregatory responses to nitric oxide (NO), an effect which may theoretically parallel insulin sensitization. We therefore sought to examine these relationships in patients with stable Type 2 diabetes (T2D) and cardiovascular disease (n = 30). Px was initiated, and dosage was titrated, to reach the therapeutic range and thus prevent toxicity. Investigations were performed before and after 2 weeks, to examine changes in insulin sensitivity and, utilizing aggregometry in whole blood, platelet responsiveness to the anti-aggregatory effects of the NO donor sodium nitroprusside (SNP). Other parameters that affect may affect NO signalling were also evaluated. Px substantially potentiated inhibition of platelet aggregation by SNP (from 16.7 ± 3.0 to 27.3 ± 3.7%; p = 0.005). Px did not change fasting blood glucose concentrations but reduced insulin sensitivity (HOMA-IR score increased from median of 4.47 to 6.08; p = 0.028), and increased fasting plasma insulin concentrations (median 16.5 to 19.0 mU/L; p = 0.014). Increases in SNP responses tended (r = −0.30; p = 0.11) to be reciprocally related to increases in HOMA-IR, and increases in HOMA-IR were greater (p = 0.002) in patients without NO-sensitizing effects. No patient developed symptomatic hypoglycaemia, nor was there any other short-term toxicity of Px. Thus, in patients with stable T2D and cardiovascular disease, Px increases anti-aggregatory responsiveness to NO, but is not an insulin sensitizer, and does not induce hypoglycaemia. Absence of NO-sensitizing effect occurs in approximately 30% of Px-treated patients with T2D, and is associated with induction of insulin resistance in these patients.Cher-Rin Chong, Saifei Liu, Hasan Imam, Tamila Heresztyn, Benedetta C. Sallustio, Yuliy Y. Chirkov, and John D. Horowit

On the Chemistry, Toxicology and Genetics of the Cyanobacterial Toxins, Microcystin, Nodularin, Saxitoxin and Cylindrospermopsin

The cyanobacteria or “blue-green algae”, as they are commonly termed, comprise a diverse group of oxygenic photosynthetic bacteria that inhabit a wide range of aquatic and terrestrial environments, and display incredible morphological diversity. Many aquatic, bloom-forming species of cyanobacteria are capable of producing biologically active secondary metabolites, which are highly toxic to humans and other animals. From a toxicological viewpoint, the cyanotoxins span four major classes: the neurotoxins, hepatotoxins, cytotoxins, and dermatoxins (irritant toxins). However, structurally they are quite diverse. Over the past decade, the biosynthesis pathways of the four major cyanotoxins: microcystin, nodularin, saxitoxin and cylindrospermopsin, have been genetically and biochemically elucidated. This review provides an overview of these biosynthesis pathways and additionally summarizes the chemistry and toxicology of these remarkable secondary metabolites

Endothelial dysfunction and glycocalyx shedding in heart failure:insights from patients receiving cardiac resynchronisation therapy

To determine (a) whether chronic heart failure with reduced ejection fraction (HFrEF) is associated with increased glycocalyx shedding; (b) whether glycocalyx shedding in HFrEF with left ventricular dyssynchrony is related to inflammation, endothelial dysfunction and/or redox stress and is ameliorated by cardiac resynchronisation therapy. Glycocalyx shedding has been reported to be increased in heart failure and is a marker of increased mortality. Its role in dyssynchronous systolic heart failure and the effects of cardiac resynchronisation therapy (CRT) are largely unknown. Twenty-six patients with dyssynchronous HFrEF were evaluated before and 6 months after CRT insertion. Echocardiographic septal to posterior wall delay (SPWD) assessed intra-ventricular mechanical dyssynchrony, and quality of life, integrity of nitric oxide (NO) signalling, inflammatory and redox-related biomarkers were measured. Glycocalyx shedding was quantitated via plasma levels of the glycocalyx component, syndecan-1. Syndecan-1 levels pre-CRT were inversely correlated with LVEF (r = - 0.45, p = 0.02) and directly with SPWD (r = 0.44, p = 0.02), QOL (r = 0.39, p = 0.04), plasma NT-proBNP (r = 0.43, p = 0.02), and the inflammatory marker, symmetric dimethylarginine (SDMA) (r = 0.54, p = 0.003). On multivariate analysis, syndecan-1 levels were predicted by SPWD and SDMA (β = 0.42, p = 0.009 and β = 0.54, p = 0.001, respectively). No significant correlation was found between syndecan-1 levels and other markers of endothelial dysfunction/inflammatory activation. Following CRT there was no significant change in syndecan-1 levels. In patients with dyssynchronous HFrEF, markers of glycocalyx shedding are associated with the magnitude of mechanical dyssynchrony and elevation of SDMA levels and inversely with LVEF. However, CRT does not reverse this process

Impact of volatile phenols and their precursors on wine quality and control measures of Brettanomyces/Dekkera yeasts

Volatile phenols are aromatic compounds and one of the key molecules responsible for olfactory defects in wine. The yeast genus Brettanomyces is the only major microorganism that has the ability to covert hydroxycinnamic acids into important levels of these compounds, especially 4-ethylphenol and 4-ethylguaiacol, in red wine. When 4-ethylphenols reach concentrations greater than the sensory threshold, all wine’s organoleptic characteristics might be influenced or damaged. The aim of this literature review is to provide a better understanding of the physicochemical, biochemical, and metabolic factors that are related to the levels of p-coumaric acid and volatile phenols in wine. Then, this work summarizes the different methods used for controlling the presence of Brettanomyces in wine and the production of ethylphenols

An overview of plasma concentrations of asymmetric dimethylarginine (ADMA) in health and disease and in clinical studies: Methodological considerations

Copyright © 2006 Elsevier B.V. All rights reserved.Recent studies among patients including those with known coronary disease demonstrate that small elevations in asymmetric dimethylarginine (ADMA) concentrations in plasma are predictive of adverse outcomes. The precision of current methodologies for quantitation of ADMA such as HPLC, MS and ELISA is discussed with respect to many reports which appear to over-estimate ADMA levels and quote broad concentration ranges. While plasma ADMA concentrations tend to increase with age, the mean for a healthy population is between 0.4 and 0.6 microM. ADMA levels may fluctuate in normal subjects, and this needs to be considered in light of the relatively small differences in ADMA concentration between healthy normal subjects and patients.John D. Horowitz and Tamila Heresztynhttp://www.elsevier.com/wps/find/journaldescription.cws_home/643040/description#descriptio

Determination of L-arginine and NG,NG- and NG,NG'-dimethyl-L-arginine in plasma by liquid chromatography as AccQ-FluorTM fluorescent derivatives

© 2004 Elsevier B.V. All rights reserved.A new HPLC assay for the detection of L-arginine, NG, NG-dimethyl-L-arginine (ADMA) and NG, NG' -dimethyl-L-arginine (SDMA) in plasma using the derivatisation reagent AccQ-Fluor (6-aminoquinolyl-N-hydroxysuccinimidyl carbamate) is described. The fluorescent derivatives produced are extremely stable enabling routine processing of large numbers of samples. Arginine and its metabolites are extracted from plasma on strong cation exchange (SCX) cartridges with NG-monomethyl-L-arginine (NMMA) as internal standard, derivatised and separated on a C18 column with acetonitrile in 0.1M sodium acetate buffer pH 6. Separation of the stereoisomers ADMA and SDMA was excellent and improvements to the solid phase extraction (SPE) procedure enabled good recovery (>80%) of arginine, ADMA and SDMA. The utility of the method is exemplified by comparison of plasma concentrations of ADMA, SDMA and arginine in healthy volunteers and diabetic/ischaemic patients.Tamila Heresztyn, Matthew I. Worthley, John D. Horowit