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The Clinical Biochemist. Reviews Aug 2008* Interference occurs when a substance or process falsely alters an assay result. * Interferences are classified as endogenous or exogenous. Endogenous interference...
* Interference occurs when a substance or process falsely alters an assay result. * Interferences are classified as endogenous or exogenous. Endogenous interference originates from substances present in the patient's own specimen. Exogenous interferences are substances introduced into the patient's specimen. * To perform interference studies, proper planning is required. * Interference from haemolysis, icterus and lipaemia are most frequently studied. Haemolysis affects more analytes than does any other type of interference. * Protein interferences are most often associated with paraproteins and predominantly with IgM or IgG and rarely with IgA. * Drug interference may be due to the parent drug, metabolite(s) or additives in the drug preparation. * Collection tube components can affect determination of analytes. * Carryover interference typically occurs when analyte from a high concentration sample (or reagent) is incompletely removed by the analytical system's washing process, whether probe, mixer or cuvette washing. * Immunoassay interferences are most commonly due to antibodies (generally polyclonal). They may be autoantibodies (e.g. in thyroid disease) or heterophile antibodies that predominantly interfere in two-site immunometric (sandwich) assays, forming a bridge between capture and detection antibodies. * Determining if interference is significant requires deviation limits from the original result. * Once interferences are identified during method evaluation or in general use, there is a need to establish procedures for handling affected results as part of the quality system.
PubMed: 18852856
DOI: No ID Found -
Physiological Genomics Apr 2018In 2015, a genome-wide association study described 59 independent signals that showed strong associations with 85 fasting metabolite concentrations as measured by the...
In 2015, a genome-wide association study described 59 independent signals that showed strong associations with 85 fasting metabolite concentrations as measured by the Biocrates AbsoluteIDQ p150 kit. However, the human body resides in a nonfasting state for the greater part of the day, and the genetic basis of postprandial metabolite concentrations remains largely unknown. We systematically examined these previously identified genetic associations in postprandial metabolite concentrations after a mixed meal. Of these 85 metabolites, 23 were identified with significant changes after the meal, for which 38 gene-metabolite associations were analyzed. Of these 38 associations, 31 gene-metabolite associations were replicated with postprandial metabolite concentrations. These data indicate that the genetics of fasting and postprandial metabolite levels are significantly overlapping.
Topics: Fasting; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide; Postprandial Period
PubMed: 29373077
DOI: 10.1152/physiolgenomics.00101.2017 -
The Plant Genome Jun 2022Plant metabolites are important traits for plant breeders seeking to improve nutrition and agronomic performance yet integrating selection for metabolomic traits can be...
Plant metabolites are important traits for plant breeders seeking to improve nutrition and agronomic performance yet integrating selection for metabolomic traits can be limited by phenotyping expense and degree of genetic characterization, especially of uncommon metabolites. As such, developing generalizable genomic selection methods based on biochemical pathway biology for metabolites that are transferable across plant populations would benefit plant breeding programs. We tested genomic prediction accuracy for >600 metabolites measured by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) in oat (Avena sativa L.) seed. Using a discovery germplasm panel, we conducted metabolite genome-wide association study (mGWAS) and selected loci to use in multikernel models that encompassed metabolome-wide mGWAS results or mGWAS from specific metabolite structures or biosynthetic pathways. Metabolite kernels developed from LC-MS metabolites in the discovery panel improved prediction accuracy of LC-MS metabolite traits in the validation panel consisting of more advanced breeding lines. No approach, however, improved prediction accuracy for GC-MS metabolites. We ranked model performance by metabolite and found that metabolites with similar polarity had consistent rankings of models. Overall, testing biological rationales for developing kernels for genomic prediction across populations contributes to developing frameworks for plant breeding for metabolite traits.
Topics: Genome-Wide Association Study; Genomics; Mass Spectrometry; Metabolomics; Plant Breeding
PubMed: 35470586
DOI: 10.1002/tpg2.20205 -
Phytochemistry Reviews : Proceedings of... 2022Plants generate a wide variety of organic components during their different growth phases. The majority of those compounds have been classified as primary and secondary... (Review)
Review
UNLABELLED
Plants generate a wide variety of organic components during their different growth phases. The majority of those compounds have been classified as primary and secondary metabolites. Secondary metabolites are essential in plants' adaptation to new changing environments and in managing several biotic and abiotic stress. It also invests some of its photosynthesized carbon as secondary metabolites to establish a mutual relationship with soil microorganisms in that specific niche. As soil harbors both pathogenic and beneficial microorganisms, it is essential to identify some specific metabolites that can discriminate beneficial and pathogenic ones. Thus, a detailed understanding of metabolite's architectures that interact with beneficial microorganisms could open a new horizon of ecology and agricultural research. Flavonoids are used as classic examples of secondary metabolites in this study to demonstrate recent developments in understanding and realizing how these valuable metabolites can be controlled at different levels. Most of the research was focused on plant flavonoids, which shield the host plant against competitors or predators, as well as having other ecological implications. Thus, in the present review, our goal is to cover a wide range of functional and signalling activities of secondary metabolites especially, flavonoids mediated selective cross-talk between plant and its beneficial soil microbiome. Here, we have summarized recent advances in understanding the interactions between plant species and their rhizosphere microbiomes through root exudates (flavonoids), with a focus on how these exudates facilitate rhizospheric associations.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s11101-022-09806-3.
PubMed: 35221830
DOI: 10.1007/s11101-022-09806-3 -
Toxicological Sciences : An Official... Aug 2021Impregnating military uniforms and outdoor clothing with the insecticide permethrin is an approach to reduce exposure to insect borne diseases and to repel pests and...
Impregnating military uniforms and outdoor clothing with the insecticide permethrin is an approach to reduce exposure to insect borne diseases and to repel pests and disease vectors such as mosquitos and sandflies, but the practice exposes wearers to prolonged dermal exposure to the pesticide. Key metabolite(s) from a low dose dermal exposure of permethrin were identified using accelerator mass spectrometry. Metabolite standards were synthesized and a high performance liquide chromatography (HPLC) elution protocol to separate individual metabolites in urine was developed. Six human subjects were exposed dermally on the forearm to 25 mg of permethrin containing 1.0 µCi of 14C for 8 h. Blood, saliva and urine samples were taken for 7d. Absorption/elimination rates and metabolite concentrations varied by individual. Average absorption was 0.2% of the dose. Serum concentrations rose until 12-24 h postdermal application then rapidly declined reaching predose levels by 72 h. Maximum saliva excretion occurred 6 h postdosing. The maximum urinary excretion rate occurred during 12-24 h; average elimination half-life was 56 h. 3-Phenoxybenzyl alcohol glucuronide was the most abundant metabolite identified when analyzing elution fractions, but most of the radioactivity was in still more polar fractions suggesting extensive degradative metabolism and for which there were no standards. Analyses of archived urine samples with the ultra performance liquid chromatography-accelerator mass spectrometry-mass spectrometry (UPLC-AMS-MS) system isolated a distinct polar metabolite but it was much diminished from the previous analyses a decade earlier.
Topics: Animals; Biomarkers; Chromatography, High Pressure Liquid; Humans; Insecticides; Mass Spectrometry; Permethrin
PubMed: 34460930
DOI: 10.1093/toxsci/kfab082 -
Toxins Oct 2022Mycotoxins are secondary metabolites produced by fungi. Food/feed contamination by mycotoxins is a great threat to food safety. The contamination can occur along the... (Review)
Review
Mycotoxins are secondary metabolites produced by fungi. Food/feed contamination by mycotoxins is a great threat to food safety. The contamination can occur along the food chain and can cause many diseases in humans and animals, and it also can cause economic losses. Many detoxification methods, including physical, chemical, and biological techniques, have been established to eliminate mycotoxins in food/feed. The biological method, with mycotoxin detoxification by microorganisms, is reliable, efficient, less costly, and easy to use compared with physical and chemical ones. However, it is important to discover the metabolite's toxicity resulting from mycotoxin biodegradation. These compounds can be less or more toxic than the parent. On the other hand, mechanisms involved in a mycotoxin's biological control remain still unclear. Mostly, there is little information about the method used by microorganisms to control mycotoxins. Therefore, this article presents an overview of the most toxic mycotoxins and the different microorganisms that have a mycotoxin detoxification ability. At the same time, different screening methods for degradation compound elucidation are given. In addition, the review summarizes mechanisms of mycotoxin biodegradation and gives some applications.
Topics: Humans; Animals; Mycotoxins; Food Contamination; Mycotoxicosis; Fungi; Food
PubMed: 36355979
DOI: 10.3390/toxins14110729 -
Frontiers in Microbiology 2016Given that: (1) the worldwide consumption of antimicrobial drugs (AMDs) used in food-producing animals will increase over the coming decades; (2) the prudent use of AMDs... (Review)
Review
Given that: (1) the worldwide consumption of antimicrobial drugs (AMDs) used in food-producing animals will increase over the coming decades; (2) the prudent use of AMDs will not suffice to stem the rise in human antimicrobial resistance (AMR) of animal origin; (3) alternatives to AMD use are not available or not implementable, there is an urgent need to develop novel AMDs for food-producing animals. This is not for animal health reasons, but to break the link between human and animal resistomes. In this review we establish the feasibility of developing for veterinary medicine new AMDs, termed "green antibiotics," having minimal ecological impact on the animal commensal and environmental microbiomes. We first explain why animal and human commensal microbiota comprise a "turnstile" exchange, between the human and animal resistomes. We then outline the ideal physico-chemical, pharmacokinetic, and pharmacodynamic properties of a veterinary green antibiotic and conclude that they can be developed through a rational screening of currently used AMD classes. The ideal drug will be hydrophilic, of relatively low potency, slow clearance and small volume of distribution. It should be eliminated principally by the kidney as inactive metabolite(s). For oral administration, bioavailability can be enhanced by developing lipophilic pro-drugs. For parenteral administration, slow-release formulations of existing eco-friendly AMDs with a short elimination half-life can be developed. These new eco-friendly veterinary AMDs can be developed from currently used drug classes to provide alternative agents to those currently used in veterinary medicine and mitigate animal contributions to the human AMR problem.
PubMed: 27536285
DOI: 10.3389/fmicb.2016.01196 -
Nature Communications Jun 2023Mycobacterium tuberculosis is one of the global leading causes of death due to a single infectious agent. Pretomanid and delamanid are new antitubercular agents that...
Mycobacterium tuberculosis is one of the global leading causes of death due to a single infectious agent. Pretomanid and delamanid are new antitubercular agents that have progressed through the drug discovery pipeline. These compounds are bicyclic nitroimidazoles that act as pro-drugs, requiring activation by a mycobacterial enzyme; however, the precise mechanisms of action of the active metabolite(s) are unclear. Here, we identify a molecular target of activated pretomanid and delamanid: the DprE2 subunit of decaprenylphosphoribose-2'-epimerase, an enzyme required for the synthesis of cell wall arabinogalactan. We also provide evidence for an NAD-adduct as the active metabolite of pretomanid. Our results highlight DprE2 as a potential antimycobacterial target and provide a foundation for future exploration into the active metabolites and clinical development of pretomanid and delamanid.
Topics: Antitubercular Agents; Molecular Targeted Therapy; Mycobacterium tuberculosis; Alcohol Oxidoreductases; Nitroimidazoles; Cell Wall; Drug Resistance; Prodrugs; Spectrophotometry; NAD; Kinetics
PubMed: 37380634
DOI: 10.1038/s41467-023-39300-z -
Journal of Fungi (Basel, Switzerland) Nov 2022mushroom is a traditional medicinal fungus with anti-cancer, antioxidation, and immunomodulatory activities, and it is used in folk medicine as a treatment for...
mushroom is a traditional medicinal fungus with anti-cancer, antioxidation, and immunomodulatory activities, and it is used in folk medicine as a treatment for indigestion, cancer, diabetes, and gastric illnesses. Although is recognized as a rare edible medicinal macrofungi, its genomic sequence and biosynthesis potential of secondary metabolites have not been investigated. In this study, using Illumina NovaSeq combined with the PacBio platform, we sequenced and assembled the whole genome of NPCB_001, a wild isolate from the Aksu area of Xinjiang Province, China. Comparative genomic and phylogenomic analyses reveal interspecific differences and evolutionary traits in the genus . Bioinformatics analysis identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary metabolite biosynthesis. Additionally, molecular networks of metabolites exhibit differences in chemical composition and content between fruiting bodies and mycelium, as well as association clusters of related compounds. The deciphering of the genome of will deepen the understanding of the biosynthesis of bioactive components, open the path for future biosynthesis research, and promote the application of in the fields of drug research and functional food manufacturing.
PubMed: 36547578
DOI: 10.3390/jof8121245 -
Environmental Health Perspectives Mar 1983Phenacetin can be metabolized to reactive metabolites by a variety of mechanisms. (1) Phenacetin can be N-hydroxylated, and the resulting N-hydroxyphenacetin can be... (Review)
Review
Phenacetin can be metabolized to reactive metabolites by a variety of mechanisms. (1) Phenacetin can be N-hydroxylated, and the resulting N-hydroxyphenacetin can be sulfated or glucuronidated. Whereas phenacetin N-O sulfate immediately rearranges to form a reactive metabolite which may covalently bind to protein, phenacetin N-O glucuronide slowly rearranges to form reactive metabolites. Incubation of the purified phenacetin N-O glucuronide under a variety of conditions suggests that N-acetyl-p-benzoquinone imine is a reactive metabolite. This metabolite covalently binds to protein, reacts with glutathione to form an acetaminophen-glutathione conjugate, is reduced by ascorbate to acetaminophen or is partially hydrolyzed to acetamide. (2) Phenacetin can be O-deethylated to acetaminophen, and acetaminophen can be converted directly to a reactive metabolite which may be also N-acetyl-p-benzoquinone imine. (3) Phenacetin can be sequentially N-hydroxylated and O-deethylated to N-hydroxyacetaminophen which spontaneously dehydrates to N-acetyl-p-benzoquinone imine. (4) Phenacetin can be 3, 4-epoxidated to form an alkylating and an arylating metabolite. In the presence of glutathione, a S-ethylglutathione conjugate and an acetaminophen-glutathione conjugate are formed. In the absence of glutathione, the alkylating metabolite may bind to protein and the arylating metabolite is completely hydrolyzed to acetamide and another arylating metabolite which may bind to protein. The structures of the alkylating and arylating metabolites are unknown. Control experiments have shown that in pathway (1) the phenolic oxygen of the acetaminophenglutathione conjugate is derived from water, whereas in pathways (2) and (3) the phenolic oxygen of this metabolite is derived from phenacetin. In pathway (4) the phenolic oxygen was 50% derived from molecular oxygen and 50% from phenacetin. Administration of [p-(18)0]phenacetin to hamsters revealed only a 10% loss of (18)0 in the acetaminophen mercapturic acid (the further metabolic product of the glutathione conjugate) which suggests that, in the hamster, pathways (2) and/or (3) are the primary mechanism of conversion of phenacetin to reactive metabolites in vivo.
Topics: Acetaminophen; Animals; Benzoquinones; Biotransformation; Cricetinae; Epoxy Compounds; Glucuronates; Glutathione; Hydroxylation; Imines; Microsomes, Liver; Phenacetin; Protein Binding; Rats; Sulfates
PubMed: 6339229
DOI: 10.1289/ehp.834971