21 research outputs found
Sterolomics in biology, biochemistry, medicine
In mammalian systems “sterolomics” can be regarded as the quantitative or semi-quantitative profiling of all metabolites derived from cholesterol and its cyclic precursors. The system can be further complicated by metabolites derived from ingested phytosterols or pharmaceuticals, but this is beyond the scope of this article. “Sterolomics” can be performed on either an unbiased global format, or more usually, exploiting a targeted format. Here we discuss the different mass spectrometry-based analytical techniques used in “sterolomics” giving specific examples in the context of neurodegenerative disease and for the diagnosis of inborn errors of metabolism. We pay particular attention to the profiling of cholesterol metabolites in the bile acid biosynthesis pathways, although the analytical techniques discussed are also appropriate for analysis of hormonal steroids
Intestinal permeability, microbiota composition, and expression of genes related to intestinal barrier function of broiler chickens fed different methionine sources supplemented at varying concentrations
ABSTRACT: Intestinal health of broiler chickens is influenced by the concentration of dietary amino acids but data are limited on the role of dietary methionine (Met). Two experiments were conducted to investigate the implications of different Met sources for performance, gut barrier function, and intestinal microbiota in broilers. In the first experiment, Ross 308 off-sex birds (n = 900) were assigned to 10 dietary treatments each replicated 9 times in a 35-day study. Three sources of Met included DL-Met, L-Met, or Met hydroxy analog free acid (MHA-FA), each supplemented at suboptimal (SUB) at 80%, adequate (ADE) at 100% and over-requirement (OVR) at 120% of the specifications against a deficient (DEF) diet with no added Met. The second experiment used 96 Ross 308 broilers in a 2 × 4 factorial arrangement. Four diets included 3 sources of Met supplemented at ADE level plus the DEF treatment. On d 17, 19, and 23, half of the birds in each dietary treatment were injected with dexamethasone (DEX) to induce leaky gut. In the first experiment, without an interaction, from d 0 to 35, birds fed DL-Met and L-Met performed similarly for BWG, feed intake, and FCR but birds fed MHA-FA had less feed intake and BWG (P < 0.05). At d 23, mRNA expression of selected tight junction proteins was not affected except for claudin 2. Ileal microbiota of DEF treatment was different from DL-MET or L-MET supplemented birds (P < 0.05). However, microbiota of MHA-FA treatments was only different at OVR from the DEF group. The abundance of Peptostreptococcus increased in DEF treatment whereas Lactobacillus decreased. In the second experiment, DEX independently increased (P < 0.001) intestinal permeability assayed by fluorescein isothiocyanate dextran, but diet had no effect. DL-Met and L-Met fed birds had a higher level of claudin 3 only in DEX-injected birds (P < 0.05). In conclusion, unlike the level of supplementation, DL-Met, L-Met, and MHA-FA were largely similar in their limited impacts on intestinal barrier function and gut microbiota in broilers
Varietal differences among the flavonoid profiles of white grape cultivars studied by high-performance liquid chromatography
In order to develop a method that allows to distinguish between white grape cultivars, the flavonoid profiles of 10 white accessions from the “Misión Biológica de Galicia” germplasm collection were studied during years 2003, 2004 and 2005 by high-performance liquid chromatography (HPLC). Twenty-four flavonoids (15 flavonols and 9 dihydroflavonols) were totally or partly identified, and significant differences between the studied flavonoid markers were found. With this method all the cultivars examined could be easily distinguished from each other, and we may conclude that this has been proved to be of great value for white grape cultivar recognition.This study was financially supported by the project
XUGA40301B94 from the Galician government (Spain). M.V.
was supported by a I3P contract financed by the CSIC-European
Social Fund.Peer reviewe
Recommendations for the detection and diagnosis of Niemann-Pick disease type C An update
Purpose of review: Niemann-Pick disease type C (NP-C) is a neurovisceral disorder that may be more prevalent than earlier estimates. Diagnosis of NP-C is often delayed; a key aim for clinical practice is to reduce this delay. Recently, substantial progress has been made in the field of NP-C screening and diagnosis, justifying an update to the existing recommendations for clinical practice. Recent findings: New biomarker profiling and genetic analysis technologies are included as first-line diagnostic tests for NP-C. Most diagnoses can now be confirmed by combination of biomarker and genetic analyses. Filipin staining may facilitate diagnosis in uncertain cases. Recommendations are provided for psychiatrists, neuro-ophthalmologists, and radiologists, and on screening within specific at-risk patient cohorts. The NP-C diagnostic algorithm has been updated and simplified. Summary: This publication provides expert recommendations for clinicians who may see patients presenting with the signs and symptoms of NP-C, including general practitioners, pediatricians, neurologists, and psychiatrists
Implementation of a cost-effective HPLC/UV-approach for medical routine quantification of donepezil in human serum
The hidden Niemann-Pick type C patient:Clinical niches for a rare inherited metabolic disease
Background: Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups (clinical niches) have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. Methods: Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. Findings: Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. Conclusions: Several clinical niches have been identified that harbor patients at increased risk of NP-C
Bioaccumulation of therapeutic drugs by human gut bacteria
Bacteria in the gut can modulate the availability and efficacy of therapeutic drugs. However, the systematic mapping ofthe interactions between drugs and bacteria has only started recently' and the main underlying mechanism proposed is the chemical transformation of drugs by microorganisms (biotransformation). Here we investigated the depletion of 15 structurally diverse drugs by 25 representative strains of gut bacteria. This revealed 70 bacteria-drug interactions, 29 of which had not to our knowledge been reported before. Over half of the new interactions can be ascribed to bioaccumulation; that is, bacteria storing the drug intracellularly without chemically modifying it, and in most cases without the growth ofthe bacteria being affected. As a case in point, we studied the molecular basis of bioaccumulation of the widely used antidepressant duloxetine by using click chemistry, thermal proteome profiling and metabolomics. We find that duloxetine bindsto several metabolic enzymes and changes the metabolite secretion of the respective bacteria. When tested in a defined microbial community of accumulators and non-accumulators, duloxetine markedly altered the composition of the community through metabolic cross-feeding. We further validated our findings in an animal model, showing that bioaccumulating bacteria attenuate the behavioural response of Caenorhabditis elegansto duloxetine. Together, our results show that bioaccumulation by gut bacteria may be a common mechanism that alters drug availability and bacterial metabolism, with implications for microbiota composition, pharmacokinetics, side effects and drug responses, probably in an individual manner