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Beer is a beverage consumed worldwide. It is produced from cereals (barley or wheat) and contains a wide array of bioactive phytochemicals and nutraceutical compounds. Specifically, high melatonin concentrations have been found in beer. Beers with high alcohol content are those that present the greatest concentrations of melatonin and vice versa. In this study, gel filtration chromatography and ELISA were combined for melatonin determination. We brewed beer to determine, for the first time, the beer production steps in which melatonin appears. We conclude that the barley, which is malted and ground in the early process, and the yeast, during the second fermentation, are the largest contributors to the enrichment of the beer with melatonin. [ABSTRACT FROM AUTHOR]

Texturizing products by protein setting reinforced by Microbial Transglutaminase (MTGase), which forms covalent bonds between proteins, makes it possible to obtain minimally processed products in a raw state that can be commercialized in fresh or cooked products. In the present paper, microbiological analysis determined that restructured products would have a shelf life of up to 14 days (at 2C) if the pH of the samples were 6.0. The physicochemical properties of restructured fish muscle with added MTGase (0.5–1.0%) set at 5C for 48 h at different pH (6 and 6.8) and sodium chloride concentrations (0.5, 1.5 and 4.0%) were studied. pH had the greatest effect on the raw product's mechanical properties at low or medium NaCl concentrations, while at high NaCl concentrations, no differences between either pH were found. More than 0.5% MTGase had very little effect on the mechanical properties of restructured muscle. PRACTICAL APPLICATIONS The main aim is to establish bases for using fish fillet trimmings and minced muscle to prepare restructured products that can be commercialized in a raw state. One possibility is to process this kind of products with technologies normally used in whole fish muscle such as smoked fish fillets, carpaccios or marinated products. In addition, these raw restructured products can be commercialized to be cooked as a normal fresh fish fillet or pieces of fillet in a variety of preparations. Nowadays, most restructured products are thermically treated and this limits their consumption. One way of achieving raw restructured products is to use Microbial Transglutaminase to bind small pieces of the muscle. Knowledge of the effect of the combined action of salt and Transglutaminase on fish muscle would be important to develop products with the right consistence. It would also be important for these products to have a low pH to extend their shelf life. [ABSTRACT FROM AUTHOR]

Intensive monitoring of adherence in patients with uncontrolled hypertension was evaluated over a 6-month period. After that period, only patients well characterized as having resistant hypertension were followed for 12 months. The goal of this study was to evaluate whether adherence to a drug regimen helps to identify patients with resistant hypertension. Forty-four hypertensive patients resistant to a 3-drug regimen (average blood pressure [BP] mm Hg, mean +/- standard deviation) were studied prospectively. Each patient was followed for a 12-month period. Adherence to treatment was evaluated through self-report, applying Morisky's questionnaire and the pill count method. Ambulatory BP monitoring and office BP measures were performed. By pill count, 63.6% of the patients were adherent to treatment at the start of the survey and 94% at the end, although 59% of the patients still did not reach normal BP levels. We found that non-adherence was not associated with resistance to antihypertensive treatment. Therefore, after investigation, we concluded that patients who presented with uncontrolled arterial BP may be truly resistant hypertensive to treatment. [ABSTRACT FROM AUTHOR]

Branched nodal roots comprise the largest portion of the root system mass in Chloris gayana Kunth and the effects of high salinity on nodal root appearance and elongation rates were analysed in cv. Boma in greenhouse experiments. Roots from salt-treated plants (0·2 mol l–1 NaCl) were smaller than controls, and accumulated higher concentrations of soluble sugars and reserve lipids. The number of nodal roots was reduced by the saline treatment. Leaf, tiller and nodal root appearance were delayed by salinity but the correlation among these processes was maintained, indicating that the developmental pattern was not altered by this level of salinity, only its rate. Initial nodal root growth rates varied as a function of plant size and were decreased by salinity only after 2 weeks of treatment. When shoots of non-salinized plants were cut, a drastic reduction in nodal root appearance was observed, suggesting emerging leaves were stronger sinks than roots for available reserves. However, when the shoots of salt-treated plants were cut, the already depressed root appearance rate was not further reduced. This suggests that, under salinity, alterations in root ability to metabolize reserves could have been more significant than reserve availability for controlling elongation. [ABSTRACT FROM AUTHOR]

Topoisomerase 3α (TOP3A) is an enzyme that removes torsional strain and interlinks between DNA molecules. TOP3A localises to both the nucleus and mitochondria, with the two isoforms playing specialised roles in DNA recombination and replication respectively. Pathogenic variants in TOP3A can cause a disorder similar to Bloom syndrome, which results from bi-allelic pathogenic variants in BLM, encoding a nuclear-binding partner of TOP3A. In this work, we describe 11 individuals from 9 families with an adult-onset mitochondrial disease resulting from bi-allelic TOP3A gene variants. The majority of patients have a consistent clinical phenotype characterised by bilateral ptosis, ophthalmoplegia, myopathy and axonal sensory-motor neuropathy. We present a comprehensive characterisation of the effect of TOP3A variants, from individuals with mitochondrial disease and Bloom-like syndrome, upon mtDNA maintenance and different aspects of enzyme function. Based on these results, we suggest a model whereby the overall severity of the TOP3A catalytic defect determines the clinical outcome, with milder variants causing adult-onset mitochondrial disease and more severe variants causing a Bloom-like syndrome with mitochondrial dysfunction in childhood., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

With molecular treatments coming into reach for spinocerebellar ataxia type 3 (SCA3), easily accessible, cross-species validated biomarkers for human and preclinical trials are warranted, particularly for the preataxic disease stage. We assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in ataxic and preataxic subjects of two independent multicentric SCA3 cohorts and in a SCA3 knock-in mouse model. Ataxic SCA3 subjects showed increased levels of both NfL and pNfH. In preataxic subjects, NfL levels increased with proximity to the individual expected onset of ataxia, with significant NfL elevations already 7.5 years before onset. Cross-sectional NfL levels correlated with both disease severity and longitudinal disease progression. Blood NfL and pNfH increases in human SCA3 were each paralleled by similar changes in SCA3 knock-in mice, here also starting already at the presymptomatic stage, closely following ataxin-3 aggregation and preceding Purkinje cell loss in the brain. Blood neurofilaments, particularly NfL, might thus provide easily accessible, cross-species validated biomarkers in both ataxic and preataxic SCA3, associated with earliest neuropathological changes, and serve as progression, proximity-to-onset and, potentially, treatment-response markers in both human and preclinical SCA3 trials., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

Congenital cataract (CC) is a significant cause of childhood blindness worldwide. CC is a genetically heterogeneous disease because mutations in over 40 genes have been demonstrated to cause the disorder and up to 40% of cases arise from single-gene mutations. Hence, next generation sequencing (NGS) of deoxyribonucleic acid is a suitable approach for CC molecular diagnosis. In this study, we used commercially available inherited disease NGS panels including 50 CC genes for the genetic diagnosis of 11 probands with hereditary CC. Causal variants were recognized in six families. A novel CRYGC variant, p.(Phe6Ser), was identified in two apparently unrelated families. Two additional novel variants in the crystallin genes CRYBB2 (p.[Gly149Asp]) and CRYGA (p.[Arg48Cys]) were also identified. One family carried the novel p.[Gly8_Leu11del] variant in GJA8, while another family exhibited the previously reported c.2826-9G>A pathogenic change in EPHA2. Our results illustrate the utility of NGS for diagnosing CC in our population, and our results contribute to expand the mutational spectrum with four novel pathogenic variants in known CC genes., (© 2018 Wiley Periodicals, Inc.)

Background: Nearly 50% of patients with heart failure (HF) have preserved LV ejection fraction, with interstitial fibrosis and cardiomyocyte hypertrophy as early manifestations of pressure overload. However, methods to assess both tissue characteristics dynamically and noninvasively with therapy are lacking. We measured the effects of mineralocorticoid receptor blockade on tissue phenotypes in LV pressure overload using cardiac magnetic resonance (CMR)., Methods and Results: Mice were randomized to l-nitro-ω-methyl ester (l-NAME, 3 mg/mL in water; n=22), or l-NAME with spironolactone (50 mg/kg/day in subcutaneous pellets; n=21). Myocardial extracellular volume (ECV; marker of diffuse interstitial fibrosis) and the intracellular lifetime of water (τic; marker of cardiomyocyte hypertrophy) were determined by CMR T1 imaging at baseline and after 7 weeks of therapy alongside histological assessments. Administration of l-NAME induced hypertensive heart disease in mice, with increases in mean arterial pressure, LV mass, ECV, and τic compared with placebo-treated controls, while LV ejection fraction was preserved (>50%). In comparison, animals receiving both spironolactone and l-NAME ("l-NAME+S") showed less concentric remodeling, and a lower myocardial ECV and τic, indicating decreased interstitial fibrosis and cardiomyocyte hypertrophy (ECV: 0.43 ± 0.09 for l-NAME versus 0.25 ± 0.03 for l-NAME+S, P<0.001; τic: 0.42 ± 0.11 for l-NAME groups versus 0.12 ± 0.05 for l-NAME+S group). Mice treated with a combination of l-NAME and spironolactone were similar to placebo-treated controls at 7 weeks., Conclusions: Spironolactone attenuates interstitial fibrosis and cardiomyocyte hypertrophy in hypertensive heart disease. CMR can phenotype myocardial tissue remodeling in pressure-overload, furthering our understanding of HF progression., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Aims: Recent reports, largely in animal models, have suggested that either inhibition of nitric oxide (NO) synthase or endothelium removal in arteries inhibits the response to isoprenaline, a beta-adrenoceptor agonist, and also enhances the response to sodium nitroprusside, a nitrovasodilator. This in vivo study was designed to determine whether N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis, influences relaxation of human hand veins mediated by isoprenaline or by sodium nitroprusside., Methods: Using the dorsal hand vein technique, full dose-response curves to bradykinin (0.27-278 ng min(-1), n=6), isoprenaline (2.12-271 ngmin(-1), n=8) and sodium nitroprusside (0.01-634 ng min(-1) n=7) were generated on separate occasions before and after L-NMMA co-infusion (50 microg min(-1))., Results: In veins preconstricted with the alpha1-adrenoceptor-selective agonist phenylephrine, the three vasodilators induced maximal responses (Emax) of 119+/-35, 72+/-18 and 103+/-17%, respectively. L-NMMA inhibited relaxation to bradykinin by 64% (P=0.014) but did not influence relaxation induced by isoprenaline. The sensitivity to sodium nitroprusside was significantly enhanced by L-NMMA co-infusion (concentration shift of 2.3, P=0.031). CONCLUSIONS; We conclude that in human veins, spontaneously released NO does not play a major role in isoprenaline-induced relaxation. Our results also suggest that the effects of sodium nitroprusside in this vascular bed may be attenuated by endothelium-derived NO.

Background: The addition of omeprazole to classical triple therapy for eradication of H. pylori may enhance compliance through reducing ulcer symptoms and side-effects. The aim of this study was to investigate the effects of a 5-day administration of omeprazole on metronidazole pharmacokinetics., Methods: Fourteen healthy male volunteers were selected. The study had an open, randomized, two-period crossover design with a 21-day washout period between the phases. Plasma concentrations of metronidazole and its hydroxy-metabolite were measured by reversed-phase HPLC with ultraviolet detection., Results: Administration of omeprazole did not affect the pharmacokinetic parameters of orally administered metronidazole., Conclusion: Our results indicate that short-term treatment with omeprazole in healthy volunteers does not alter the extent or the rate of metronidazole absorption, and does not affect metronidazole clearance.