The lack of knowledge about the onset and progression of Parkinson's disease (PD) hampers its early diagnosis and treatment. Metabolomics might shed light on the PD imprint seeking a broader view of ...the biochemical remodeling induced by this disease in an early and pre-symptomatic stage and unveiling potential biomarkers. To achieve this goal, we took advantage of the great potential of the European Prospective Study on Nutrition and Cancer (EPIC) cohort to apply metabolomics searching for early diagnostic PD markers. This cohort consisted of healthy volunteers that were followed for around 15 years until June 2011 to ascertain incident PD. For this untargeted metabolomics-based study, baseline preclinical plasma samples of 39 randomly selected individuals that developed PD (Pre-PD group) and the corresponding control group were analyzed using a multiplatform approach. Data were statistically analyzed and exposed alterations in 33 metabolites levels, including significantly lower levels of free fatty acids (FFAs) in the preclinical samples from PD subjects. These results were then validated by adopting a targeted HPLC-QqQ-MS approach. After integrating all the metabolites affected, our finding revealed alterations in FFAs metabolism, mitochondrial dysfunction, oxidative stress, and gut-brain axis dysregulation long before the development of PD hallmarks. Although the biological purpose of these events is still unknown, the remodeled metabolic pathways highlighted in this work might be considered worthy prognostic biomarkers of early prodromal PD. The findings revealed by this work are of inestimable value since this is the first study conducted with samples collected many years before the disease development.
Parkinson's disease (PD) is a progressive neurodegenerative disorder, diagnosed according to the clinical criteria that occur in already advanced stages of PD. The definition of biomarkers for the ...early diagnosis of PD represents a challenge that might improve treatment and avoid complications in this disease. Therefore, we propose a set of reliable samples for the identification of altered metabolites to find potential prognostic biomarkers for early PD.
This case-control study included plasma samples of 12 patients with PD and 21 control subjects, from the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC)-Navarra cohort, part of the EPIC-Spain study. All the case samples were provided by healthy volunteers who were followed-up for 15.9 (±4.1) years and developed PD disease later on, after the sample collection. Liquid chromatography coupled to tandem mass spectrometry was used for the analysis of samples.
Out of 40 that were selected and studied due to their involvement in established cases of PD, seven significantly different metabolites between PD cases and healthy control subjects were obtained in this study (benzoic acid, palmitic acid, oleic acid, stearic acid, myo-inositol, sorbitol, and quinolinic acid). These metabolites are related to mitochondrial dysfunction, the oxidative stress, and the mechanisms of energy production.
We propose the samples from the EPIC study as reliable and invaluable samples for the search of early biomarkers of PD. Likewise, this study might also be a starting point in the establishment of a well-founded panel of metabolites that can be used for the early detection of this disease.
The aim of this work was to determine and study the concentration of different groups of disinfection by-products (DBPs): trihalomethanes, haloacetic acids, haloacetonitriles, haloacetones and ...combined chlorine (as an indicator of chloramine levels), in the water of 175 public swimming pools in Gipuzkoa (Basque Country, Spain). The study included chlorinated and brominated pools, indoor and outdoor, used for recreational and sports purposes, and filled with water from calcareous and siliceous soils. The most abundant were haloacetic acids, followed by trihalomethanes, with chlorinated or brominated forms predominating depending on whether the pools were disinfected by chlorination or bromination, respectively. All the 75th percentiles of DBPs were below the limits established by the European Chemical Agency (ECHA), although the maximum values of trihalomethanes exceeded them. The same was true for dichloroacetonitrile in chlorinated pools and dibromoacetonitrile in brominated pools. All families of DBPs showed positive associations with each other, all being significant except for combined chlorine. Their mean levels were higher in outdoor pools than in indoor pools, significantly so in all except combined chlorine. Recreational pools showed higher levels of haloacetic acids and combined chlorine than sports pools. The concentrations of the different groups of DBPs were higher in the pools than in the mains water that fed them. This increase, especially that of the haloacetonitriles, as well as the high concentrations of brominated forms in the pools disinfected by bromination, make it necessary to focus on their toxicological implication. The differences in the DBP profiles of the filling network water were not transferred to the pool water.
Many of the infectious diseases that affect livestock have bacteria as etiological agents. Thus, therapy is based on antimicrobials that leave the animal’s tissues mainly via urine, reaching the ...environment through slurry and waste water. Once there, antimicrobial residues may lead to antibacterial resistance as well as toxicity for plants, animals, or humans. Hence, the objective was to describe the rate of antimicrobial excretion in urine in order to select the most appropriate molecule while reducing harmful effects. Thus, 62 pigs were treated with sulfamethoxypyridazine, oxytetracycline, and enrofloxacin. Urine was collected through the withdrawal period and analysed via LC-MS/MS. Oxytetracycline had the slowest rate of degradation (a half-life time of 4.18 days) and the most extended elimination period in urine (over 2 months), followed by enrofloxacin (a half-life time of 1.48 days, total urine elimination in ca. 3 weeks) and sulfamethoxypyridazine (a half-life time of 0.49 days, total urine elimination in ca. 1 week). Bacterial sensitivity and recommendations for responsible use are limiting when selecting the treatment. Nevertheless, with similar effectiveness, sulfamethoxypyridazine would be the choice, as waste treatment would only need to be implemented for 1 week after treatment. Thus, more in-depth knowledge regarding antibacterial elimination would improve resource management, while protecting animals and consumers’ health.
The introduction of antimicrobial residues in the food chain has a significant impact on human health. An innovative solution to avoid their presence in meat is the adaptation of current control ...methods for use with in vivo matrixes. Thus, the aim was to obtain paired blood and muscle samples from pigs treated with some of the main antimicrobials currently used in veterinary medicine (oxytetracycline, sulfamethoxypyridazine, enrofloxacin, amoxicillin), and to compare their rate of depletion in both matrixes. Antimicrobial concentrations in paired samples of blood and muscle were determined by liquid chromatography with tandem mass spectrometry (LC-MS/MS) or high performance liquid chromatography with fluorescence detection (HPLC-FLD). A comparison between values obtained in muscle and blood showed a similar distribution in both matrixes for oxytetracycline; for sulfamethoxypyridazine, a similar decrease rate but a concentration three times higher in blood compared to muscle was found; for enrofloxacin, we found significant differences in the rate of depletion, with similar antimicrobial concentrations in both matrixes with values close to the maximum residue limit (MRL) and higher amounts in muscle for values that lay considerably over the MRL. Conversely, amoxicillin depletion was so rapid that its appearance in carcasses does not seem to pose a risk. Therefore, blood would be a feasible matrix for the development of new in vivo tests.
Dioxins and polychlorinated biphenyls (PCBs) are toxic, endocrine disruptors and persistent chemicals for which the main exposure source is diet due to their bioaccumulation and biomagnification in ...food chains. Cohort studies in the general populations have reported inconsistent associations between these chemicals in serum/plasma and mortality. Our objective was to study the association between dietary intake of 17 dioxins and 35 PCBs and all-cause, cancer-specific and cardiovascular-specific mortalities were assessed in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Dietary intake of dioxins and PCBs was assessed combining EPIC food consumption data with European food contamination data provided by the European Food Safety Authority. We applied multivariable Cox regressions. The analysis included 451,390 adults (mean ± SD age:51.1 ± 9.7 years) with 46,627 deaths and a median follow-up of 17.4 years (IQR = 15.2-19.1). A U-shaped non-linear association with all-cause mortality for dietary intake of dioxins (P
<0.0001), DL-PCB (P
= 0.0001), and NDL-PCBs (P
<0.01) was observed. For example, the hazard ratios (95%Confidance interval) for all-cause mortality obtained with the spline model was equal to 1.03 (1.02-1.05) for low levels of intake to dioxins (7 pg TEQ/day), 0.93 (0.90-0.96) for moderate levels of intake (25 pg TEQ/day), while for high levels of intake (55 pg TEQ/day) it was 1.03 (0.97-1.09). Intake of dioxins, DL-PCBs and NDL-PCBs was not associated with cardiovascular mortality. There was no association between intakes of dioxins and cancer mortality, but a U-shaped association was observed for intake of DL-PCBs and intakes of NDL-PCBs and cancer mortality. The PCBs and dioxins are known to have endocrine disrupting properties which can lead to non-monotonic dose responses. These results need to be interpreted with caution and further studies are needed to better clarify the association between dietary intake of dioxins and PCB and mortality in the general population.
Volatile composition and aroma compounds of Idiazabal PDO cheeses made in winter and spring were compared. In these seasons flock management differs: concentrate and conserved forages are fed in ...winter whereas a part-time grazing system is used in spring. Commercial cheeses from ten farmhouses were analysed during ripening. Acids, carbonyl compounds, esters, and alcohols were the main volatiles in both seasons. The shift from winter to spring management led to a higher proportion of esters and alcohols, and a lower proportion of ketones and aldehydes. More than 30 odour-active compounds were identified by olfactometry with butanoic acid, ethyl butanoate, ethyl hexanoate and 2-heptanone being the principal ones. Coinciding with fresh pasture grazing in spring, the odour impact ratios of esters and alcohols increased, indicating that spring cheeses might have more intense fruity and sweet overtones in comparison with winter cheeses.
HS-SPME analysis of terpenes does usually have inherent quantification problems when working with complex samples, especially due to the matrix effect of the substrate or the calibration solution. ...Three different terpene carrier matrices were compared: methanol, synthetic oil and milk fat obtained by centrifugation from milk cream. Considerable differences in calibration sensitivity parameters were observed depending on the matrix used and on the type of terpene standard analysed. For milk sample quantification purposes internal standard method was preferred using milk fat as calibration matrix. Linearity range, repeatability, recovery and limits of detection and quantification were determined. Validation parameters were different depending on the concentration and molecular structure of each terpene analysed, particularly between mono- and sesquiterpenes. The method was useful to determine in an accurate manner the terpene content in milk samples from pasture fed animals, and it will help to establish objective terpene levels to differentiate milks from specific production systems.
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