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  • Oxford University Press (OUP)  (4)
  • 1
    In: Brain, Oxford University Press (OUP), Vol. 145, No. 2 ( 2022-04-18), p. 569-583
    Abstract: The identification of intestinal dysbiosis in patients with neurological and psychiatric disorders has highlighted the importance of gut–brain communication, and yet the question regarding the identity of the components responsible for this cross-talk remains open. We previously reported that relapsing remitting multiple sclerosis patients treated with dimethyl fumarate have a prominent depletion of the gut microbiota, thereby suggesting that studying the composition of plasma and CSF samples from these patients may help to identify microbially derived metabolites. We used a functional xenogeneic assay consisting of cultured rat neurons exposed to CSF samples collected from multiple sclerosis patients before and after dimethyl fumarate treatment to assess neurotoxicity and then conducted a metabolomic analysis of plasma and CSF samples to identify metabolites with differential abundance. A weighted correlation network analysis allowed us to identify groups of metabolites, present in plasma and CSF samples, whose abundance correlated with the neurotoxic potential of the CSF. This analysis identified the presence of phenol and indole group metabolites of bacterial origin (e.g. p-cresol sulphate, indoxyl sulphate and N-phenylacetylglutamine) as potentially neurotoxic and decreased by treatment. Chronic exposure of cultured neurons to these metabolites impaired their firing rate and induced axonal damage, independent from mitochondrial dysfunction and oxidative stress, thereby identifying a novel pathway of neurotoxicity. Clinical, radiological and cognitive test metrics were also collected in treated patients at follow-up visits. Improved MRI metrics, disability and cognition were only detected in dimethyl fumarate-treated relapsing remitting multiple sclerosis patients. The levels of the identified metabolites of bacterial origin (p-cresol sulphate, indoxyl sulphate and N-phenylacetylglutamine) were inversely correlated to MRI measurements of cortical volume and directly correlated to the levels of neurofilament light chain, an established biomarker of neurodegeneration. Our data suggest that phenol and indole derivatives from the catabolism of tryptophan and phenylalanine are microbially derived metabolites, which may mediate gut–brain communication and induce neurotoxicity in multiple sclerosis.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1474117-9
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2020
    In:  Schizophrenia Bulletin Vol. 46, No. Supplement_1 ( 2020-05-18), p. S55-S55
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 46, No. Supplement_1 ( 2020-05-18), p. S55-S55
    Abstract: Schizophrenia and Bipolar I disorder patients lack the ability to identify emotional expressions, which is characterized by poor social and professional functions. Facial affect recognition is a complex function that includes cortical and limbic connections, providing an essential source of information during face-to-face communication. In this study, the Facial Labeling Task, which can evaluate Koreans’ ability to recognize emotions using facial expressions, is used to compare defects in face emotional recognition in patients with remitted schizophrenia patients, euthymic bipolar I disorder patients, and normal controls. Methods Three groups were included in this study: remitted patients with schizophrenia (n=75), patients in euthymic states of bipolar I disorder (n=70), and healthy controls (n=59) who were matched on age, sex, years of education. Facial Labeling Task was used to examine face emotional recognition defects the standardized happy, fearful, disgust, anger, sad, contempt, surprise and neutral faces from actors (4 males, 4 females) were used (emotional intensity 100%). Accuracy (commission error rates), correct response times of each trial were calculated. All subjects had to satisfy the inclusion criteria(absence of substance abuse, head trauma, mental retardation) and subjects with above mild level of psychiatric symptoms [BPRS(Brief Psychiatric Rating Scale) & gt;31, K-MADRS(Korean version Montgomery-Asberg Depression Scale) Score & gt;9, YMRS(Young Mania Rating Scale Korean version) Score & gt;7] were excluded. All of patients group had to be in remitted state at least 3 months. All of subjects in normal control group were interviewed before the test using Structured Clinical Interview for DSM-IV Axis-1 Disorder to rule out psychiatric history. We used Korean version-Wechsler Adult Intelligence Scale. Psychomotor performance was examined using Finger Tapping Test. Results There were no differences on demographic data between three groups. Although psychopathologies in all groups were within the criteria, there were group differences. The scoring of BPRS, YMRS, MADRS were higher in schizophrenia patients. Intelligence was low in schizophrenia and Bipolar I disorder patients. There was no difference among the group in the psychomotor speed. Two patients groups were significantly higher error rates for sadness (p & lt; 0.01), anger (p & lt; 0.001),, and neutral (p & lt; 0.01). Schizophrenia group showed significantly higher error rates for contempt to normal controls (p & lt; 0.05). Happy and neutral face had significantly more delayed correct response times in two patient groups than in the healthy controls (p & lt; 0.05). Discussion These finds suggest that the patients with schizophrenia and bipolar I disorder have a defects in the perception and response of specific emotions in the remitted states, and schizophrenia is more emotionally impaired than bipolar disease. Therefore, it is thought that a defects in facial recognition should be considered in the process of assessing and treating patients with bipolar I disorder as well as those with schizophrenia.
    Type of Medium: Online Resource
    ISSN: 0586-7614 , 1745-1701
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2180196-4
    SSG: 15,3
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  • 3
    In: Clinical Chemistry, Oxford University Press (OUP), Vol. 49, No. 12 ( 2003-12-01), p. 2078-2081
    Type of Medium: Online Resource
    ISSN: 0009-9147 , 1530-8561
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2003
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  • 4
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2013
    In:  Journal of AOAC INTERNATIONAL Vol. 96, No. 5 ( 2013-09-01), p. 1059-1064
    In: Journal of AOAC INTERNATIONAL, Oxford University Press (OUP), Vol. 96, No. 5 ( 2013-09-01), p. 1059-1064
    Abstract: A rapid method for the simultaneous determination of flavonol aglycones in food using ultra-high-performance LC (u-HPLC) coupled with a heating-block acidic hydrolysis method was validated in terms of precision, accuracy, and linearity. The u-HPLC separation was performed on an RP C18 column (particle size 2 μm id, 2 mm, length 100 mm) with a photodiode array detector. The LOD and LOQ of the u-HPLC analyses were 0.15 and 0.47 mg/kg for myricetin, 0.09 and 0.28 mg/kg for quercetin, 0.16 and 0.49 mg/kg for kaempferol, and 0.08 and 0.25 mg/kg for isorhamnetin. The intraday and interday precisions of the individual flavonol aglycones were less than 9.31%. All calibration curves exhibited good linearity (r2 = 0.99) within the tested ranges. Total run time of u-HPLC was 13 min. The rapid u-HPLC method presented herein significantly improved the speed, sensitivity, and resolution of the analyses of myricetin, quercetin, kaempferol, and isorhamnetin in food.
    Type of Medium: Online Resource
    ISSN: 1060-3271 , 1944-7922
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2013
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